2023.1

1 - Hepatobiliary disease after bone marrow transplant. Expert Rev Gastroenterol Hepatol. 2023 Feb;17(2):129-143. doi: 10.1080/17474124.2023.2169671.
Dezan MGF(1)(2), Cavalcante LN(1)(2), Cotrim HP(2), Lyra AC(1)(2).

Afiliação:
(1) Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil.
(2) Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil.

Resumo
INTRODUCTION: Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-BMT patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischemic and fulminant hepatitis, among others.AREA COVERED: Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation.EXPERT OPINION: Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis.

2 -  Safety and effectiveness of adding fentanyl or sufentanil to spinal anesthesia: systematic review and meta-analysis of randomized controlled trials. Braz J Anesthesiol. 2023 Mar-Apr;73(2):198-216. doi: 10.1016/j.bjane.2021.10.010.
Fonseca NM(1), Guimarães GMN(2), Pontes JPJ(3), Azi LMTA(4), de Ávila Oliveira R(5).

Afiliação:
(1)    Universidade Federal de Uberlândia (UFU), Faculdade de Medicina; Sociedade Brasileira de Anestesiologia, Brazil; Comitê para o Estudo do Equipamento Respiratório e Anestesia de ABNT, Brazil; Revista Brasileira de Anestesiologia, Brazil.
2)    Universidade de Brasília (UnB), Faculdade de Medicina, Departamento de Clínica Cirúrgica, Brasília, DF, Brazil.
(3)    Complexo Hospitalar Santa Genoveva de Uberlândia, Departamento de Anestesiologia, Uberlândia, MG, Brazil.
(4)    Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Departamento de Anestesiologia e Cirurgia, Salvador, BA, Brazil; Complexo Hospitalar Universitário Professor Edgard Santos, Salvador, BA, Brazil.
(5)    Universidade Federal de Uberlândia (UFU), Faculdade de Medicina, Disciplina de Cirurgia Vascular, Uberlândia, MG, Brazil; Universidade Federal de Uberlândia (UFU), Departamento de Cirurgia, Uberlândia, MG, Brazil.

Resumo
INTRODUCTION: Spinal infusions of either fentanyl or sufentanil have been reported in international reports, articles, and scientific events worldwide. This study aimed to determine whether intrathecal fentanyl or sufentanil offers safety in mortality and perioperative adverse events. METHODS: MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane library databases), gray literature, hand-searching, and clinicaltrials.gov were systematically searched. Randomized controlled trials with no language, data, or status restrictions were included, comparing the effectiveness and safety of adding spinal lipophilic opioid to local anesthetics (LAs). Data were pooled using the random-effects models or fixed-effect models based on heterogeneity. RESULTS: The initial search retrieved 4469 records; 3241 records were eligible, and 3152 articles were excluded after reading titles and abstracts, with a high agreement rate (98.6%). After reading the full texts, 76 articles remained. Spinal fentanyl and sufentanil significantly reduced postoperative pain and opioid consumption, increased analgesia and pruritus. Fentanyl, but not sufentanil, significantly reduced both postoperative nausea and vomiting, and postoperative shivering; compared to LAs alone. The analyzed studies did not report any case of in-hospital mortality related to spinal lipophilic opioids. The rate of respiratory depression was 0.7% and 0.8% when spinal fentanyl or sufentanil was added and when it was not, respectively. Episodes of respiratory depression were rare, uneventful, occurred intraoperatively, and were easily manageable. CONCLUSION: There is moderate to high quality certainty that there is evidence regarding the safety and effectiveness of adding lipophilic opioids to LAs in spinal anesthesia.

3 - Efficacy of silymarin in patients with non-alcoholic fatty liver disease - the Siliver trial: a study protocol for a randomized controlled clinical trial. Trials. 2023 Mar 10;24(1):177. doi: 10.1186/s13063-023-07210-6.
de Avelar CR(1), Nunes BVC(2), da Silva Sassaki B(2), Dos Santos Vasconcelos M(2), de Oliveira LPM(2), Lyra AC(3), Bueno AA(4), de Jesus RP(2).

Afiliação:
(1)    Department of Nutrition Sciences, Federal University of Bahia, Bahia, 32 Araújo Pinho Street, Canela, Salvador, Bahia, 40.110-150, Brazil.
(2)    Department of Nutrition Sciences, Federal University of Bahia, Bahia, 32 Araújo Pinho Street, Canela, Salvador, Bahia, 40.110-150, Brazil.
(3)    Gastrohepatology Service, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Bahia, Brazil.
(4)    College of Health, Life and Environmental Sciences, University of Worcester, Worcester, WR2 6AJ, UK.

Resumo:
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases globally. Pharmacological treatments for NAFLD are still limited. Silymarin, a compound extracted from Silybum marianum, is an herbal supplement traditionally used in folk medicine for liver disorders. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the efficacy of silymarin supplementation in the adjuvant treatment of NAFLD in adult patients. METHOD: This is a randomized double-blind placebo-controlled clinical trial recruiting adult NAFLD patients in therapy on an outpatient basis. Participants are randomized to an intervention (I) or control (C) group. Both groups receive identical capsules and are followed for 12 weeks. I receives 700mg of silymarin + 8mg vitamin E + 50mg phosphatidylcholine daily, while C receives 700mg maltodextrin + 8mg vitamin E + 50mg phosphatidylcholine daily. Patients undergo a computerized tomography (CT) scan and blood tests at the beginning and end of the study. Monthly face-to-face consultations and weekly telephone contact are carried out for all participants. The primary outcome assessed will be change in NAFLD stage, if any, assessed by the difference in attenuation coefficient between liver and spleen, obtained by upper abdomen CT. DISCUSSION: The results of this study may provide a valuable opinion on whether silymarin can be used as adjuvant therapy for the management or treatment of NAFLD. The data presented on the efficacy and safety of silymarin may provide more foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION: This study has been approved by the Research Ethics Committee of the Professor Edgard Santos University Hospital Complex, Salvador BA, Brazil, under protocol 2.635.954. The study is carried out according to guidelines and regulatory standards for research involving humans, as set out in Brazilian legislation. Trial registration – Clinical Trials.gov : NCT03749070. November 21, 2018. 

4 - Social support among individuals with bipolar disorder during euthymic phase: A systematic review. Clin Psychol Psychother. 2023 Mar;30(2):270-280. doi: 10.1002/cpp.2805.

Studart-Bottó P(1)(2), Léda-Rêgo G(1)(2), Abbade P(3), Bandeira ID(2)(4), Miranda-Scippa Â(1)(2)(5).

Afiliação:
(1) Mood and Anxiety Disorders Program (CETHA), Psychiatry Service of Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil.
(2) Postgraduate Program in Medicine and Health, Federal University of Bahia, Salvador, Brazil.
(3) Bahia Medical School, Federal University of Bahia, Salvador, Brazil.(4) Neuropsychopharmacology Laboratory, Psychiatry Service of Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil.
(5) Department of Neurosciences and Mental Health, Medical School, Federal University of Bahia, Salvador, Brazil.

Resumo:
INTRODUCTION: In spite of the recent increase in scientific publications showing an expressive interest in studies about social support, there are still scarce publications regarding this thematic and bipolar disorder, mostly when evaluating the individuals in the state of euthymia. Euthymia referred a state that a bipolar patient does not have signs/symptoms of (hipo)mania or depression, thus assessing individuals in this state may reduce response bias. OBJECTIVE: The objective of this study is to identify the impact of social support on bipolar disorder in patients in the euthymic phase. METHODS: A systematic search of observational studies on PubMed/Medline, PsycINFO, EMBASE, Scopus and Web of Science databases was performed from February 2021 to August 2022. RESULTS: In total, seven studies fulfilled the eligibility criteria. According to three studies, bipolar disorder patients had lower social support than healthy controls. Contrastingly, one study showed bipolar patients did not have different social support compared to healthy controls. CONCLUSIONS: Even though few papers with low or middle risk of bias were included in this review, we found that not only does social support could act as a protective factor for bipolar patients but also that clinical manifestations of the disorder seem to affect social support. This systematic review suggests the narrowed evidence field with different measures and type of evaluation from studies on social support and bipolar disorder, which highlights the need for further investigations on this theme.

5 -  Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil. J Pediatr (Rio J). 2023 Jan-Feb;99(1):23-30. doi: 10.1016/j.jped.2022.04.002.

Godoy C(1), Paixão DC(2), Boa-Sorte NCA(3), Amorim T(4), da Silva Filho LVRF(5),Souza EL(6).

Afiliação:
(1) Faculdade de Medicina da Bahia, Programa de Pós-graduação em Medicina e Saúde, Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil; Universidade do Estado da Bahia (UNEB), Salvador, BA, Brazil.
(2) Universidade do Estado da Bahia (UNEB), Salvador, BA, Brazil.
(3) Universidade do Estado da Bahia (UNEB), Salvador, BA, Brazil; Universidade Federal da Bahia (UFBA), Unidade de tecnologia em saúde, Hospital Universitário Professor Edgard Santos (HUPES), Salvador, BA, Brazil; Associação de Pais e Amigos dos Excepcionais de Salvador (APAE Salvador), Salvador, BA, Brazil.
(4) Universidade do Estado da Bahia (UNEB), Salvador, BA, Brazil; Associação de Pais e Amigos dos Excepcionais de Salvador (APAE Salvador), Salvador, BA, Brazil.
(5) Faculdade de Medicina, Hospital das Clínicas, Instituto da Criança, Universidade de São Paulo (HC/ FM/ USP), São Paulo, SP, Brazil; Hospital Albert Einstein, São Paulo, SP, Brazil.(6) Faculdade de Medicina da Bahia, Programa de Pós-graduação em Medicina e Saúde, Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil.

Resumo:
OBJECTIVE: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state.METHOD: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. RESULTS: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. CONCLUSIONS: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

 6 -  Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection. NEJM Evid. 2023 Mar;2(3):10.1056/evidoa2200302. doi: 10.1056/evidoa2200302.

Lundgren JD(1), Babiker AG(2), Sharma S(3), Grund B(4), Phillips AN(5), Matthews G(6), Kan VL(7), Aagaard B(1), Abo I(8), Alston B(9), Arenas-Pinto A(2), Avihingsanon A(10), Badal-Faesen S(11), Brites C(12), Carey C(6), Casseb J(13), et al.; INSIGHT Strategic Timing of AntiRetroviral Treatment (START) Study Group.

Afiliação:
(1)    CHIP Centre of Excellence for Health, Immunity, and Infections, Department of Infectious Diseases, Rigshospitalet, Copenhagen.
(2)    Medical Research Council Clinical Trials Unit, University College London, London.
(3)    Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis.
(4)    School of Statistics, University of Minnesota, Minneapolis.
(5)    Institute for Global Health, University College London, London.
(6)    Kirby Institute, Sydney.
(7)    VA Medical Center, Washington, D.C.
(8)    Helsinki University Central Hospital, Helsinki.
(9)    Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD.
(10)             Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
(11)            Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg.
(12)            Hospital Universitario Professor Edgard Santos, School of Medicine, Federal University of Bahia, Salvador, Brazil.
(13)            Laboratory of Medical Investigation - LIM56, Faculty of Medicine, Department of Dermatology, University of São Paulo, São Paulo.

Resumo:
BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS: The Strategic Timing of Anti Retroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.

7 - Introduction of chikungunya virus in coastal northeast Brazil. Lancet Microbe. 2023 Jun 26:S2666-5247(23)00176-3. doi: 10.1016/S2666-5247(23)00176-3.

Postigo-Hidalgo I(1), Jo WK(1), Pedroso C(2), Brites C(2), Drexler JF(3).

Afiliação:
(1)    Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, 10117 Berlin, Germany.
(2)    Hospital Universitário Professor Edgard Santos, Universidade Federal de Bahia, Salvador, Brazil.
3)    Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, 10117 Berlin, Germany; German Centre for Infection Research (DZIF), associated partner Charité-Universitätsmedizin Berlin, Berlin, Germany.

Correspondência:
We read the article by William M de Souza and colleagues with great interest. Their study traces chikungunya virus (CHIKV) since its introduction in Brazil around 2013, and highlights spatial variability in viral spread. Among other laboratory tests, they consider people with CHIKV IgG or IgM antibodies as having confirmed infections. However, alphaviral antigenic relatedness can compromise serological diagnosis of past CHIKV infections. In northeast Brazil, the 600 000-inhabitant city of Feira de Santana, located in the hinterland of the Brazilian state Bahia, is a CHIKV hot spot. To probe CHIKV introduction into coastal northeast Brazil, we analysed CHIKV-specific antibodies in 2074 serum samples from asymptomatic patients attending the HIV outpatient clinic at Hospital Universitário Professor Edgard Santos, Salvador, for antiretroviral therapy and CD4 cell count monitoring from 2007 to 2021. Salvador is about 100 km from Feira de Santana and the biggest city in northeast Brazil with about 3 million inhabitants, ecologically highly suitable for Aedes-borne infections as illustrated by the explosive spread of Zika virus. Our results showed that CHIKV IgG ELISA detection rates increased during 2014 onwards compared with 2007–13; from 2·0% (n=12; 95% CI 2·0–3·4) to 18·0 % (n=262; 17·9–20·0; χ2, p<0·0001). The increase in IgG seroprevalence and the detection of two epidemic CHIKV waves paralleled notified cases from Bahia, suggesting robustness of our data (appendix p 1). Using a custom-made pan-alphavirus immunofluorescence IgG assay (IFA) for ELISA-positive sera, we found cross-reactivity with Mayaro virus (MAYV), Ross River virus (RRV), and O’nyong’nyong virus (ONNV) at lower dilution steps (1:10) in serum samples from both periods (appendix p 2). Endpoint titration improved specificity but was not enough to diagnose CHIKV confidently, as cross-reactivity with ONNV or MAYV was still present at higher dilutions (1:100) and no reactivity overall was detectable at 1:1000 serum dilution (appendix p 2). All ELISA-positive samples before 2014 were negative by CHIKV-specific plaque reduction neutralisation tests (PRNT)50; in contrast, 30 (78·9%, 95% CI 63·6–88·9; Fisher's exact test p<0·0001) of a randomly selected subset of 38 post-2014 ELISA-positive samples were positive by CHIKV PRNT50 at a median endpoint titre of 1:102 (range 1:23–540). Likewise, post-2013 samples yielded significantly higher CHIKV IgG ELISA ratios (Welch's t-test p=0·029), which is consistent with the onset of CHIKV circulation and false-positive ELISA results pre-2014. One IgG ELISA-reactive sample from 2016 yielding equal IFA reactivity patterns for CHIKV, ONNV, and MAYV at 1:10 serum dilution showed a MAYV-specific PRNT titre of 1:180, whereas no neutralisation of CHIKV was detected (appendix p 3). Comparing all ELISA results validated by PRNT (appendix p 3), we found a low positive predictive value (60·0%, 95% CI 45·2–73·6) and a high negative predictive value (96·0%, 78·9–99·9) for IgG ELISA. Those data were consistent with high false-positive ELISA rates in febrile patients from Salvador during low CHIKV circulation.5 In addition to cross-reactivity of alphaviral immune responses, false-positive ELISA results in our cohort could be due to HIV-induced polyclonal B-cell activation.6 Altogether, our data emphasise the necessity of confirmation of results from less specific tests such as ELISA by PRNT—while acknowledging lower sensitivity of the latter—particularly beyond epidemics, since IFA testing also did not yield unambiguous results. Our results suggest CHIKV introduction into Salvador during late 2013 to 2014 followed by gradually increased circulation, which is consistent with the first notified chikungunya case from Bahia during September, 2014 (appendix p 1). Our data align with the authors’ data on spatial spread variance, and underline the necessity of addressing serological cross-reactivity for precise alphavirus infection diagnostics, particularly in areas of co-endemicity of different alphaviruses, such as MAYV and CHIKV in Latin America. We declare no competing interests. This study was supported by the DFG project COALITION (project number DR 810/6-1), the European Union's Horizon 2020 Research and Innovation Program through the ZIKAlliance project (grant number 734548), and the Host Switching Pathogens, Infectious Outbreaks and Zoonosis (HONOURS) innovative training network (grant number 721367). All samples were collected and tested under permit number 1.408.499 issued by the Federal University of Bahia research ethics board Climério de Oliveira.

8 - Role of paraoxonase 1 activity and PON1 gene polymorphisms in sickle cell disease. Sci Rep. 2023 May 3;13(1):7215. doi: 10.1038/s41598-023-34396-1.

Menezes JF(1)(2)(3), Carvalho MOS(1)(4), Rocha LC(3), Dos Santos FM(5), Adorno EV(2), de Souza CC(1), Santiago RP(1), da Guarda CC(1), de Oliveira RM(1), Figueiredo CVB(1), Carvalho SP(1), Yahouédéhou SCMA(1), Fiuza LM(1), Adanho CSA(1), Pitanga TN(1), Lyra IM(3)(6), Nascimento VML(3), Noronha-Dutra AA(4), Goncalves MS(7)(8).

Afiliação:
(1) Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil.
(2) Departamento de Toxicologias e Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(3) Fundação de Hematologia e Hemoterapia do Estado da Bahia (HEMOBA), Salvador, Bahia, Brazil.
(4) University College of London, UCL, London, UK.
(5) Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(6) Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(7) Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil. marilda.goncalves@fiocruz.br.
(8) Departamento de Toxicologias e Análises Clínicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

Resumo:
Sickle cell disease (SCD) patients often exhibit a dyslipidemic sub-phenotype. Paraoxonase 1 (PON 1) is a serum glycoprotein associated with the high-density lipoproteins cholesterol (HDL-C), and variability in PON1 activity depends on the PON1 genotypes. We investigated the influence of PON1c.192Q > R and PON1c.55L > M polymorphisms on PON1 activity and laboratory parameters and the association between PON1 activity and clinical manifestations in SCD patients. We recruited 350 individuals, including 154 SCD patients and 196 healthy volunteers, which comprised the control group. Laboratory parameters and molecular analyses were investigated from the participants' blood samples. We have found increased PON1 activity in SCD individuals compared to the control group. In addition, carriers of the variant genotype of each polymorphism presented lower PON1 activity. SCD individuals carrying the variant genotype of PON1c.55L > M polymorphism had lower platelet and reticulocyte counts, C-reactive protein, and aspartate aminotransferase levels; in addition to higher creatinine levels. SCD individuals carrying the variant genotype of PON1c.192Q > R polymorphism had lower triglyceride, VLDL-c, and indirect bilirubin levels. Furthermore, we observed an association between PON1 activity history of stroke and splenectomy. The present study confirmed the association between PON1c.192Q > R and PON1c.55L > M polymorphisms and PON1 activity, in addition to demonstrate their effects on markers of dislipidemia, hemolysis and inflammation, in SCD individuals. Moreover, data suggest PON1 activity as a potential biomarker related to stroke and splenectomy.

9 - CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil. Hematol Transfus Cell Ther. 2023 Apr-Jun;45(2):266-274. doi: 10.1016/j.htct.2022.08.002.

Hungria V(1), Piérola AA(2), Filho JS(3), Crusoe E(4), Filho RJPM(5), Maiolino A(6), Rodríguez-Otero P(7).

Afiliação:
(1)    Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, SP, Brazil; Clínica São Germano, São Paulo, Brazil.
(2)    Clinica Universidad de Navarra, IDISNA, Pamplona, Spain.
(3)    A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
(4)    Hospital Universitário Professor Edgar Santos da Universidade Federal da Bahia (HUPES), Salvador, BA, Brazil; Rede D'or Oncologia, Salvador, Brazil.
(5)    Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
(6)    Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil; Oncologia Américas, Rio de Janeiro, Brazil.
(7)    Clinica Universidad de Navarra, IDISNA, Pamplona, Spain.

Resumo:
INTRODUCTION: Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. METHODS: A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. RESULTS: This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. CONCLUSION: We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.

10 - Angiolymphoid Hyperplasia With Temporal Artery Eosinophilia: A Case Report. Vasc Endovascular Surg. 2023 Jun 28:15385744231184333. doi: 10.1177/15385744231184333.

Carvalho Lujan RA(1), de Melo Mascarenhas DA(1), de Amorim Aquino M(1), Costa Menezes A(1), Pereira de Souza Filho ML(2), Costa Sampaio Silva F(3), Godeiro Fernandez M(4), Silveira Alves CA(1), Aras Júnior R(3).

Afiliação:
(1)    Vascular Surgery Division, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Bahia, Brazil.
(2)    Pathology Division, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Bahia, Brazil.
(3)    Postgraduate Program in Medicine and Health, Faculty of Medicine of Bahia, Federal University of Bahia, Salvador, Bahia, Brazil.
(4)    Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil.

Resumo:
Angiolymphoid Hyperplasia with Eosinophilia (ALHE) is a benign vascular proliferative disorder with uncertain etiology and pathogenesis. The aim of this paper is to report a case of ALHE in the temporal artery and discuss the general aspects of this pathology. A 29-year-old female black patient sought the Vascular Surgery Outpatient Service, complaining of bulging in the right temporal region, associated with pain and local discomfort. Physical examination revealed pulsatile bulging in the right temporal region measuring approximately 2.5 × 1.5 cm. Nuclear Magnetic Resonance showed an expansive fusiform lesion in the superficial soft parts of the right temporal region, measuring 2.9 cm in the longest longitudinal axis. Surgical excision proved to be the best therapeutic option for the patient in this case. Histopathological sections showed the proliferation of vessels of different sizes, covered by swollen endothelium, prominent inflammatory infiltrate composed of lymphocytes, plasma cells, eosinophils, and scarce histiocytes. Immunohistochemical analysis of the lesion showed positivity for CD31, corroborating the diagnosis of ALHE.

 11 - A thermosensitive PCNA allele underlies an ataxia-telangiectasia-like disorder. J Biol Chem. 2023 May;299(5):104656. doi: 10.1016/j.jbc.2023.104656.

Magrino J(1), Munford V(2), Martins DJ(2), Homma TK(3), Page B(1), Gaubitz C(1), Freire BL(3), Lerario AM(4), Vilar JB(2), Amorin A(5), Leão EKE(6), Kok F(7), Menck CF(2), Jorge AA(8), Kelch BA(9).

Afiliação:
(1)    Department of Biochemistry and Biotechnology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
(2)    Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
(3)    Genetic Endocrinology Unit, Cellular and Molecular Endocrinology Laboratory LIM25, Endocrinology Discipline of the Faculty of Medicine of the University of São Paulo, São Paulo, Brazil; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM42, Faculty of Medicine of the University of São Paulo, São Paulo, Brazil.
(4)    Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM42, Faculty of Medicine of the University of São Paulo, São Paulo, Brazil; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan, USA.
(5)    Neurogenetics, Neurology Department, Faculty of Medicine of the University of São Paulo, São Paulo, Brazil.
(6)    Medical Genetics Service of the Professor Edgard Santos University Hospital - Federal University of Bahia, Salvador, Brazil.
(7)    Neurogenetics, Neurology Department, Faculty of Medicine of the University of São Paulo, São Paulo, Brazil; Mendelics Genomic Analysis, São Paulo, São Paulo, Brazil.
(8)    Genetic Endocrinology Unit, Cellular and Molecular Endocrinology Laboratory LIM25, Endocrinology Discipline of the Faculty of Medicine of the University of São Paulo, São Paulo, Brazil.
(9)    Department of Biochemistry and Biotechnology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.

Resumo:
Proliferating cell nuclear antigen (PCNA) is a sliding clamp protein that coordinates DNA replication with various DNA maintenance events that are critical for human health. Recently, a hypomorphic homozygous serine to isoleucine (S228I) substitution in PCNA was described to underlie a rare DNA repair disorder known as PCNA-associated DNA repair disorder (PARD). PARD symptoms range from UV sensitivity, neurodegeneration, telangiectasia, and premature aging. We, and others, previously showed that the S228I variant changes the protein-binding pocket of PCNA to a conformation that impairs interactions with specific partners. Here, we report a second PCNA substitution (C148S) that also causes PARD. Unlike PCNA-S228I, PCNA-C148S has WT-like structure and affinity toward partners. In contrast, both disease-associated variants possess a thermostability defect. Furthermore, patient-derived cells homozygous for the C148S allele exhibit low levels of chromatin-bound PCNA and display temperature-dependent phenotypes. The stability defect of both PARD variants indicates that PCNA levels are likely an important driver of PARD disease. These results significantly advance our understanding of PARD and will likely stimulate additional work focused on clinical, diagnostic, and therapeutic aspects of this severe disease.

12 - T cell-and non T cell-mediated delayed hypersensitivity to dupilumab. J Eur Acad Dermatol Venereol. 2023 May 12. doi: 10.1111/jdv.19182.

de Magalhães AR(1)(2), Machado GU(2), Lefèvre MA(3), Garreau AC(4), Nicolas JF(3)(4), Vocanson M(4), Mosnier A(3), Pralong P(5), Nosbaum A(3)(4).

Afiliação:
(1)    Serviço de Dermatologia, Universidade Federal da Bahia, Complexo Hospitalar Universitário Professor Edgard Santos, Salvador, Bahia, Brazil.
(2)    Serviço de Imunologia, Universidade Federal da Bahia, Complexo Hospitalar Universitário Professor Edgard Santos, Salvador, Bahia, Brazil.
(3)    CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
(4)    Service d'Allergologie et Immunologie Clinique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France.
(5)    Department of Dermatology, Allergology and Photobiology, Centre Hospitalier Universitaire Grenoble Alpes, La Tronche, France.

Resumo não disponível.

13 - Genetic analysis of osteogenesis imperfecta in a large Brazilian cohort. Bone. 2023 Apr;169:116683. doi: 10.1016/j.bone.2023.116683.

Holtz AP(1), Souza LT(2), Ribeiro EM(3), Acosta AX(4), Lago RMRS(4), Simoni G(5), Llerena JC Jr(6), Félix TM(7).

Afiliação:
(1)    Post Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Genomic Medicine Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
(2)    Genomic Medicine Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
(3)    Genetics Service, Hospital Infantil Albert Sabin, Fortaleza, Brazil.
(4)    Pediatric Department, Hospital Universitário Prof. Edgar Santos, Salvador, Brazil.
(5)    Pediatric Endocrinology Department, Hospital Infantil Joana de Gusmão, Florianópolis, Brazil.
(6)    Medical Genetics Department, Instituto Nacional Fernandes Figueira - Fiocruz, Rio de Janeiro, Brazil.
(7)    Post Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Genomic Medicine Laboratory, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.

Resumo:
INTRODUCTION: Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder caused by disruption of type I collagen synthesis. Previous Brazilian molecular OI studies have been restricted to case reports or small cohorts. The Brazilian OI Network (BOIN) is a multicenter study collecting clinical OI treatment data from five reference centers in three regions of Brazil. OBJECTIVE: To describe the molecular analysis of a large cohort of OI registered at BOIN. METHODS: Targeted next-generation sequencing (NGS) was performed at a centralized laboratory with the Ion Torrent platform, covering 99.6 % of the coding regions of 18 OI-associated genes. Clinical information was obtained from a clinical database. RESULTS: We included 156 subjects in the molecular analyses. Variants were detected in 121 subjects: 65 (53.7 %) in COL1A1, 42 (34.7 %) in COL1A2, 2 (1.7 %) in IFITM5, one (0.8 %) in CRTAP, three (2.5 %) in P3H1, two (1.7 %) in PPIB, four (3.3 %) FKBP10, one (0.8 %) in SERPINH1, and one (0.8 %) in TMEM38B. Ninety-one distinct variants were identified, of which 26 were novel. Of the 107 variants identified in COL1A1 and COL1A2, 24.5 % cause mild OI, while the remaining 75.5 % cause moderate, severe, or lethal OI, of which 49.3 % are glycine to serine substitutions. A single variant in FKBP10 (c.179A>C; p.Gln60Pro) was found in three unrelated and non-consanguineous participants living in the same geographic area in Northeast Brazil, suggesting a possible founder effect. CONCLUSION: Consistent with the literature, 88.4 % of the subjects had a variant in the COL1A1 and COL1A2 genes, with 10 % inherited in an autosomal recessive manner. Notably, one variant in FKBP10 with a potential founder effect requires further investigation. Data from this large cohort improves our understanding of genotype-phenotype correlations for OI in Brazil.

14 - Chimerism 47,XY, + 8/46,XX: Follow-up for 11 Years. J Pediatr Genet. 2020 Dec 7;12(1):81-85. doi: 10.1055/s-0040-1721440.

de Carvalho AFL(1), Pitanga PML(1)(2), Alves ES(2)(3), Miguel DSCG(2), Santo LDE(1)(2), de Araújo AEF(1), Ornellas ACP(2), Toralles MBP(2)(3).

Afiliação:
(1)    Laboratory of Human Genetics and Mutagenesis, Institute of Biology, Federal University of Bahia, Salvador, Bahia, Brazil.
(2)    DNA Laboratory - Laboratory Center for Genetics and Molecular Biology, Salvador, Bahia, Brazil.
(3)    Department of Medical Genetics, Edgard Santos Teaching Hospital Academic, Federal University of Bahia, Salvador, Bahia, Brazil.

Resumo:
Approximately 30 sex chromosome discordant chimera cases have been reported to date. In particular, there are few reported cases of chimerism involving coexisting normal and abnormal lineages that each carries a distinct sex chromosome complement. To our knowledge, this is the first case of sexual chimerism with a simultaneous chromosomal aneuploidy involving chromosome 8. This report represents the data from 11 years of follow-up.

15 - Factors associated with diet quality among Brazilian individuals with cardiovascular diseases. J Hum Nutr Diet. 2023 Jun 7. doi: 10.1111/jhn.13184.

Brito L(1), Sahade V(2), Weber B(3), Bersch-Ferreira ÂC(4), Marcadenti A(5), Torreglosa C(4), Kovacs C(6), Moreira ASB(7), Torres RS(8), Marinho H(9), Matos C(10), Abib R(11), Souza GC(12), Shirmann GDS(13), Nagano FEZ(14), Ramos MEM(15), Poloni S(16), El Kik RM(17), Feres NH(18), Dutra ES(19), Ferreira Carvalho APP(20), David MM(21), Galvão I(22), Sousa ACS(23), Dantas CF(24), Gonçalves A(24), Pinheiro JMF(25), Vasconcelos SML(26), Penafort A(27), de Oliveira Carlos DM(28), Luna A(29), Neto JAF(30), Dias L(31), Moriguchi EH(32), Bruscato N(32), Izar MC(33), Lopes S(34), Backes LM(35), Bressan J(36), Raimondi S(37), Kumbier M(38), Daltro C(39).

Afiliação:
(1)    Programa de Pós-Graduação em Medicina e Saúde da UFBA, Complexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal da Bahia (UFBA), Empresa Brasileira de Serviços Hospitalares (EBSERH), Salvador, Bahia, Brazil.
(2)    Departamento de Nutrição da Escola de Nutrição da UFBA, Salvador, Bahia, Brazil.
(3)    Hospital do Coração (HCor), São Paulo, Brazil.
(4)    Hospital do Coração, São Paulo, Brazil.
(5)    Instituto de Pesquisa, Hospital do Coração, São Paulo, Brazil.
(6)    Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil.
(7)    Instituto Nacional de Cardiologia (INC), Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.

Resumo:
BACKGROUND: An individual's dietary pattern contributes in different ways to the prevention and control of recurrent cardiovascular events. However, the quality of the diet is influenced by several factors. The present study aimed to evaluate the quality of the diet of individuals with cardiovascular diseases and determine whether there is an association between sociodemographic and lifestyle factors. METHODS: This is a cross-sectional study carried out with individuals with atherosclerosis (coronary artery disease, cerebrovascular disease or peripheral arterial disease) recruited from 35 reference centres for the treatment of cardiovascular disease in Brazil. Diet quality was assessed according to the Modified Alternative Healthy Eating Index (mAHEI) and stratified into tertiles. For comparing two groups, the Mann-Whitney or Pearson's chi-squared tests were used. However, for comparing three or more groups, analysis of variance or Kruskal-Wallis was used. For the confounding analysis, a multinomial regression model was used. p < 0.05 was considered statistically significant. RESULTS: In total, 2360 individuals were evaluated: 58.5% male and 64.2% elderly. The median (interquartile range [IQR]) of the mAHEI was 24.0 (20.0-30.0), ranging from 0.4 to 56.0 points. When comparing the odds ratios (ORs) for the low (first tertile) and medium (second tertile) diet quality groups with the high-quality group (third tertile), it was observed that there was an association between diet quality with a family income of 1.885 (95% confidence intervals [CI] = 1.302-2.729) and 1.566 (95% CI = 1.097-2.235), as well as physical activity of 1.391 (95% CI = 1.107-1.749) and 1.346 (95% CI = 1.086-1.667), respectively. In addition, associations were observed between diet quality and region of residence. CONCLUSIONS: A low-quality diet was associated with family income, sedentarism and geographical area. These data are extremely relevant to assist in coping with cardiovascular disease because they enable an assessment of the distribution of these factors in different regions of the country.

16 - Malaria and COVID-19 coinfection in a non-malaria-endemic area in Brazil. Rev Soc Bras Med Trop. 2023 May 22;56:e05982022. doi: 10.1590/0037-8682-0598-2022.

Rocha VD(1), Brasil LW(2)(3), Gomes EO(4)(5), Khouri R(6)(7), Ferreira GJ(1), Vasconcelos B(6), Gouveia MS(8), Santos TS(8), Reis MG(6)(9)(10), Lacerda MVG(2)(3)(4).

Afiliação:
(1)    Instituto Couto Maia, Salvador, BA, Brasil.
(2)    Instituto de Pesquisa Clínica Carlos Borborema, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM, Brasil.
(3)    Instituto Leônidas & Maria Deane, Fiocruz, Manaus, AM, Brasil.
(4)    Universidade do Estado do Amazonas, Manaus, AM, Brasil.
(5)    Instituto Nacional de Pesquisas da Amazônia, Manaus, AM, Brasil.
(6)    Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brasil.
(7)    Universidade Federal da Bahia, Salvador, BA, Brasil.
(8)    Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Salvador, BA, Brasil.
(9)    Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil.
(10)                       Yale School of Public Health, Yale University, New Haven, Connecticut, United States.

Resumo:
Differential diagnosis of coronavirus disease 2019 (COVID-19) from other febrile diseases is one of several challenges imposed by the pandemic. We present a case of severe malaria and COVID-19 coinfection in a non-malaria-endemic region. A 44-year-old female with malaise, fever, hypotension, jaundice, and enlarged liver and spleen was admitted to the intensive care unit. Reverse transcription-quantitative PCR results for severe acute respiratory syndrome coronavirus 2 were positive. Rapid tests, microscopy, and quantitative PCR were positive for Plasmodium vivax. Cytokine storm profiles were identified. We could not determine whether the severe vivax malaria in our patient was triggered by COVID-19 coinfection.

17- Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group. Arq Neuropsiquiatr. 2023 Mar;81(3):284-295. doi: 10.1055/s-0043-1761434.

Sampaio LPB(1), Manreza MLG(1), Pessoa A(2), Gurgel-Giannetti J(3), Coan AC(4), Júnior HVL(5), Embiruçu EK(6), Henriques-Souza AMM(7), Kok F(1).

Afiliação:
(1)    Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
(2)    Universidade Estadual do Ceará, Hospital Infantil Albert Sabin, Fortaleza CE, Brazil.
(3)    Universidade Federal de Minas Gerais, Faculdade de Medicina, Hospital das Clínicas, Belo Horizonte MG, Brazil.
(4)    Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas SP, Brazil.
(5)    Instituto de Neurologia de Goiânia, Goiânia GO, Brazil.
(6)    Universidade do Estado da Bahia, Hospital Universitário Professor Edgard Santos, Salvador BA, Brazil.
(7)    Instituto de Medicina Integral Professor Fernando Figueira, Recife PE, Brazil.

Resumo:
Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease hat affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigate and confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.

18 - Arketamine for bipolar depression: Open-label, dose-escalation, pilot study. J Psychiatr Res. 2023 Aug;164:229-234. doi: 10.1016/j.jpsychires.2023.06.028.

Bandeira ID(1), Leal GC(2), Correia-Melo FS(3), Souza-Marques B(2), Silva SS(2), Lins-Silva DH(3), Mello RP(2), Vieira F(2), Dorea-Bandeira I(3), Faria-Guimarães D(3), Carneiro B(2), Caliman-Fontes AT(2), Kapczinski F(4), Miranda-Scippa Â(5), Lacerda ALT(6), Quarantini LC(7).

Afiliação:
(1)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, United States.
(2)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.
(3)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
(4)    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada.
(5)    Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.
(6)    Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de São Paulo, São Paulo, Brazil; Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil; Instituto Sinapse de Neurociências Clínicas, Campinas, Brazil.
(7)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.

Resumo:
There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at least four weeks. Four subjects were female (66.66%), and the mean age was 45.33 (±12.32). Subjects received adjunct treatment with two arketamine intravenous infusions one week apart-0.5 mg/kg first and then 1 mg/kg. The mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score was 36.66, which decreased to 27.83 24h after the first infusion of 0.5 mg/kg of arketamine (p = 0.036). In respect of the 1 mg/kg dose, the mean MADRS total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p < 0.001). Arketamine appears to have rapid-acting antidepressant properties, consistent with previous animal studies on major depression. All individuals tolerated both doses, exhibiting nearly absent dissociation, and no manic symptoms. To the best of our knowledge, this pilot trial is the first to test the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) for bipolar depression.

19 - Anorectal function and clinical characteristics associated with fecal incontinence in patients with Crohn's disease. J Crohns Colitis. 2023 Mar 23:jjad048. doi: 10.1093/ecco-jcc/jjad048.

de Codes LMG(1)(2), de Jesus ACC(3), de Codes JJG(4), Ferreira RF(3), da Silva Beda Sacramento C(5), da Cruz IDM(2), de Castro Ribeiro Fidelis F(2), de Carvalho AL(2), Motta MP(5), de Oliveira Alves C(5), Netto EM(1), Santana GO(1)(6).

Afiliação:
(1)    Medicine and Health Science Postgraduate Program, Universidade Federal da Bahia, Salvador, Brazil.
(2)    Department of Surgery, Hospital Universitário Professor Edgard Santos, Salvador, Brazil.
(3)    Medical School, Universidade do Estado da Bahia, Salvador, Brazil.
(4)    Hospital Ana Nery, Salvador, Brazil.
(5)    Department of Gastroenterology, Hospital Universitário Professor Edgard Santos, Salvador, Brazil.
(6)    Department of Life Sciences, Universidade do Estado da Bahia, Salvador, Brazil.

Resumo:
BACKGROUND AND AIMS: Fecal incontinence is an important complaint reported by patients with Crohn's disease and it is associated with several disease-related mechanisms, including anorectal functional disorders. This study aimed to assess the anorectal function and clinical characteristics to identify parameters associated with fecal incontinence in Crohn's disease patients. METHODS: This is a cross-sectional study of 104 patients with Crohn's disease, aged 18 years or older, from a referral center between August 2019 and May 2021. Patients responded to a specific questionnaire, and underwent medical record review, proctological examination, and anorectal functional assessment with anorectal manometry. RESULTS: Of the 104 patients, 49% were incontinent. Patients with incontinence had a lower mean resting pressure (43.5 mmHg versus 53.1 mmHg; p = 0.038), lower mean squeeze pressure (62.1 mmHg versus 94.1 mmHg; p = 0.036), and lower maximum rectal capacity (140 ml versus 180 ml; p < 0.001). Fecal incontinence was also associated with disease activity (p < 0.001), loose stools (p = 0.02), perianal disease (p = 0.006), previous anoperineal surgery (p = 0.048), and the number of anorectal surgeries (p = 0.036). CONCLUSIONS: This is the largest reported study describing manometric findings of Crohn's disease patients with and without fecal incontinence. Our results identified an association between FI and functional disorders, in addition to clinical features in these patients. Functional assessment with anorectal manometry may help choose the best treatment for FI in patients with CD.

20 - Evolution of erectile dysfunction in individuals infected with human T-lymphotropic virus 1: a prospective cohort study. J Sex Med. 2023 Feb 27;20(3):269-276. doi: 10.1093/jsxmed/qdac050.

de Oliveira CJV(1)(2), Neto JAC(1)(2), Liberato de Matos SNF(1)(2), Oliveira P(2), Tannus M(2), Castro N(2), Rocha PN(1)(3), Carvalho EM(2)(4)(5)(6).

Afiliação:
(1)    Post Graduate Program of Health Sciences, Federal University of Bahia, Salvador, Bahia, CEP 40026-010, Brazil.
(2)    Ambulatório Multidisciplinar de HTLV-1, Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, CEP 40110-060, Brazil.
(3)    School of Medicine of Bahia, Federal University of Bahia, Salvador, Bahia, CEP 40110-100, Brazil.
(4)    Gonçalo Moniz Institute, Fiocruz, Salvador, Bahia, CEP 40296-710, Brazil.
(5)    Immunology Service of University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, CEP 40110-060, Brazil.
(6)    National Institute of Science and Technology of Tropical Diseases, Salvador, Bahia, CEP 40296-710, Brazil.

Resumo:
BACKGROUND: Virtually all patients with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have some degree of erectile dysfunction (ED), but ED is also found in a large percentage of HTLV-1 carriers. AIM: To evaluate the evolution of ED in individuals infected with HTLV-1 who were followed for up to 15 years. METHODS: This prospective cohort study included men infected with HTLV-1 who had ED, were aged 18 to 70 years, and were followed from January 2004 to December 2019. We used the International Index of Erectile Function-5 (IIEF-5), the Expanded Disability Status Scale and Osame Motor Disability Scale, and the Overactive Bladder Symptom Score (OABSS) to define and stratify ED, neurologic disability, and bladder dysfunction, respectively. OUTCOMES: Time to development of severe ED was the main outcome. RESULTS: We studied 90 men with ED (mean ± SD age, 52.8 ± 9.78 years). At baseline, 42 were carriers, 16 had probable HAM/TSP, and 32 had definite HAM/TSP. IIEF-5 was highest among carriers and lowest in patients with definite HAM/TSP, whereas OABSS was lowest in carriers and highest in patients with definite HAM/TSP. Median (IQR) follow-up was 8.50 years (3.00-12.00). IIEF-5 fell significantly from baseline to last follow-up among carriers and patients with probable and definite HAM/TSP. There was an inverse correlation between the IIEF-5 and the OABSS at last follow-up (r = -0.62, P < .001). In survival analysis, the time to development of severe ED was significantly shorter in patients with definite HAM/TSP when compared with carriers (P = .001) and those with probable HAM/TSP (P = .014). The presence of definite HAM/TSP at baseline was independently associated with the development of severe ED, after adjustment for baseline age and proviral load (hazard ratio, 6.74; P = .008). CLINICAL IMPLICATIONS: Formal assessment of erectile function should be part of the routine clinical assessment of individuals infected with HTLV-1; worsening erectile function should alert clinicians to the possibility of neurologic deterioration. STRENGTHS AND LIMITATIONS: This is the first prospective cohort study to describe the course of ED in men infected with HTLV-1. The small sample size and absence of seronegative controls are limitations. CONCLUSION: ED is a slowly progressive clinical manifestation of HTLV-1 infection, and the degree of neurologic compromise at baseline is the main predictor of time to progression to severe ED.

21 - Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study. J Affect Disord. 2023 Jun 1;330:7-15. doi: 10.1016/j.jad.2023.02.151.

Leal GC(1), Souza-Marques B(1), Mello RP(1), Bandeira ID(2), Caliman-Fontes AT(1), Carneiro BA(1), Faria-Guimarães D(3), Guerreiro-Costa LNF(1), Jesus-Nunes AP(1), Silva SS(1), Lins-Silva DH(3), Fontes MA(1), Alves-Pereira R(1), Cordeiro V(1), Rugieri-Pacheco S(3), Santos-Lima C(1), Correia-Melo FS(1), Vieira F(1), Sanacora G(4), Lacerda ALT(5), Quarantini LC(6).

Afiliação:
(1)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.
(2)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, USA.
(3)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
(4)    Department of Psychiatry, Yale University School of Medicine, New Haven, USA.
(5)    Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de São Paulo, São Paulo, Brazil.
(6)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil. Electronic address: lcq@ufba.br.

Resumo:
BACKGROUND: Racemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled trial of arketamine for treatment-resistant depression (TRD) and to assess its efficacy and safety compared to placebo. METHODS: This is a, randomized, double-blind, crossover, pilot trial (n = 10). All participants received saline and arketamine (0.5 mg/kg) with a one-week interval. Treatment effects were analyzed with a linear mixed effects (LME) model. RESULTS: Our analysis suggested the presence of a carryover effect, so the main efficacy analysis was limited to the first week, which demonstrated a main effect of time (p = 0.038) but not for treatment (p = 0.40) or their interaction (p = 0.95). This indicates that depression improved over time, but without significant difference between arketamine and placebo. Analyzing the two weeks together, findings were the same. Dissociation and other adverse events were minimal. LIMITATIONS: This was a pilot study with a small sample and underpowered. CONCLUSIONS: Arketamine was not superior to placebo for TRD but demonstrated to be extremely safe. Our findings reinforce the importance of continuing studies with this drug, with better powered clinical trials, perhaps considering a parallel design with higher or flexible doses and repeated administrations.

22 - Functional status of individuals with osteogenesis imperfecta: data from a reference center. J Pediatr (Rio J). 2023 Jan-Feb;99(1):94-98. doi: 10.1016/j.jped.2022.07.002.

Carvalho PAF(1), Regis TS(2), Faiçal AVB(3), Lago RMRDS(4), Terse-Ramos R(5), Acosta AX(5).

Afiliação:
(1)    Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brasil; Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil.
(2)    Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil.
(3)    Universidade Federal da Bahia, Salvador, BA, Brasil.
(4)    Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil; Universidade Federal do Recôncavo da Bahia, BA, Brasil.
(5)    Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brasil; Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil; Departamento de Pediatria da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brasil.

Resumo:
OBJECTIVE: To evaluate the functional status of individuals with Osteogenesis Imperfecta (OI) followed up at a reference center in the state of Bahia. MATERIALS AND METHODS: This is an observational, cross-sectional, descriptive study, which evaluated individuals with OI, based on a non-probabilistic sampling. To assess motor function, the Motor Function Measure (MFM) score was used, in addition to the measurement of muscle strength using the Medical Research Council (MRC) score. Functional performance was measured using the Pediatric Assessment of Disability Inventory, Computerized Adaptive Testing (PEDI-CAT). RESULTS: Thirty-one individuals aged between two and 18 years old were evaluated. The overall score of MFM was 74.2%, and the lowest score was found in participants with type III OI (56.3%). The median of the MRC index was 80. The mobility domain was the most affected in the PEDI-CAT evaluation, with a mean T score of 23.9, (14.2 in type III OI). CONCLUSIONS: Among the evaluated individuals, functional alterations were identified, reduced global gross motor functionality and muscle strength, impacting the mobility domain, with the most relevant findings in individuals with type III OI.

23 - Cutaneous leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study. PLoS Negl Trop Dis. 2023 Jan 23;17(1):e0011029. doi: 10.1371/journal.pntd.0011029.

Castro MDM(1)(2), Rode J(3), Machado PRL(4), Llanos-Cuentas A(5), Hueb M(6), Cota G(7), Rojas IV(8), Orobio Y(1)(2), Oviedo Sarmiento O(1)(2), Rojas E(9), Quintero J(10), Pimentel MIF(11), Soto J(12), Suprien C(4), Alvarez F(5), Ramos AP(5), Arantes RBDS(6), da Silva RE(7), Arenas CM(8), Vélez ID(10), Lyra MR(11), Saravia NG(1)(2), Arana B(13), Alexander N(1)(2).

Afiliação:
(1) Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.
(2) Universidad Icesi, Cali, Colombia.
(3) Drugs for Neglected Diseases initiative (DNDi), Rio de Janeiro, Brazil.
(4) Servico de Imunologia, Hospital Universitário Prof. Edgar Santos, Universidade Federal da Bahia, Salvador, Brazil.
(5) Unidad de Leishmaniasis y Malaria, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, and Hospital Cayetano Heredia, Lima, Perú.
(6) Universidade Federal de Mato Grosso, Hospital Universitário Júlio Müller (HUJM), Cuiabá, Mato Grosso, Brazil.
(7) Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
(8) Centro Dermatológico Federico Lleras Acosta E.S.E (CDFLA), Bogotá, Colombia.
(9) Centro Universitario de Medicina Tropical-Universidad Mayor de San Simón (CUMT), Cochabamba, Bolivia.
(10) PECET-Programa de Estudio y Control de Enfermedades Tropicales, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
(11) Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
(12) FUNDERMA (Fundación Nacional de Dermatología), Santa Cruz de la Sierra, Bolivia.
(13) Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.

Resumo:
BACKGROUND: Treatment guidance for children and older adult patients affected by cutaneous leishmaniasis (CL) is unclear due to limited representation of these groups in clinical trials. METHODS: We conducted a collaborative retrospective study to describe the effectiveness and safety of antileishmanial treatments in children ≤ 10 and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in Latin America.RESULTS: 2,037 clinical records were assessed for eligibility. Of them, the main reason for non-inclusion was lack of data on treatment follow-up and therapeutic response (182/242, 75% of children and 179/468, 38% of adults). Data on 1,325 eligible CL patients (736 children and 589 older adults) were analyzed. In both age groups, disease presentation was mild, with a median number of lesions of one (IQR: 1-2) and median lesion diameter of less than 3 cm. Less than 50% of the patients had data for two or more follow-up visits post-treatment (being only 28% in pediatric patients). Systemic antimonials were the most common monotherapy regimen in both age groups (590/736, 80.2% of children and 308/589, 52.3% of older adults) with overall cure rates of 54.6% (95% CI: 50.5-58.6%) and 68.2% (95% CI: 62.6-73.4%), respectively. Other treatments used include miltefosine, amphotericin B, intralesional antimonials, and pentamidine. Adverse reactions related to the main treatment were experienced in 11.9% (86/722) of children versus 38.4% (206/537) of older adults. Most adverse reactions were of mild intensity. CONCLUSION: Our findings support the need for greater availability and use of alternatives to systemic antimonials, particularly local therapies, and development of strategies to improve patient follow-up across the region, with special attention to pediatric populations.

24 - High Concordance between D:A:Dr and the Framingham Risk Score in Brazilians Living with HIV. Viruses. 2023 Jan 26;15(2):348. doi: 10.3390/v15020348.

Souza V(1), Valadares V(1), Dias T(1), Brites C(1)(2).

Afiliação:
(1) Department of Medicine, Medical School, Federal University of Bahia, Salvador 40110-060, BA, Brazil.
(2) Hospital Universitário Professor Edgard Santos, UFBA-EBSEHR, Salvador 40110-060, BA, Brazil.

Resumo:
People living with HIV (PLHIV) have twice the risk of developing cardiovascular diseases, making it essential to identify high cardiovascular risk (CVR). However, there is no validated CVR calculator for PLHIV in Brazil. We performed a cross-sectional study with 265 individuals living with HIV, aged 40 to 74 years, to assess the agreement between three CVR scores: Framingham Risk Score (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score, and a specific for PLHIV, Reduced Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:Dr). We assessed agreement using the weighted Kappa coefficient and the Bland-Altman plot. The median age was 52 years (47-58), 58.9% were men, 34% were hypertensive and 8.3% had a detectable viral load. There was an almost perfect agreement between D:A:Dr x FRS (k = 0.82; 95% CI 0.77-0.87; p < 0.001), and substantial agreement between FRS vs. ASCVD (k = 0.74; 95% CI 0.69-0.79; p < 0.001) and between D:A:Dr vs. ASCVD (k = 0.70; 95% CI 0.64-0.76; p < 0.001). The Bland-Altman plot revealed greater discordance between scores as the CVR increased. Our results suggest that the FRS and the D:A:Dr are adequate to classify the CVR in this population, and the D:A:Dr score can be used as an alternative to the FRS in Brazil, as other international guidelines have already advocated.

25 - Mental Health and Emotional Disorders During the COVID-19 Pandemics: Prevalence and Extent in PICU Staff. Pediatr Crit Care Med. 2023 Apr 1;24(4):277-288. doi: 10.1097/PCC.0000000000003119.

Lima-Setta F(1)(2)(3), de Moraes CL(3)(4), Silami PHNC(2)(5)(6), Reichenheim ME(3), de Mello E Silva JF(1), Stochero L(7), de Oliveira MBG(1), Robaina JR(1), Rodrigues-Santos G(1), de Almeida CG(8), Amoretti CF(9), et al.; Brazilian Research Network in Pediatric Intensive Care (BRnet-PIC).

Afiliação:
(1)    Department of Pediatrics, Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, RJ, Brazil.
(2)    Pediatric Intensive Care Unit, Instituto Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
(3)    Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, RJ, Brazil.
(4)    Postgraduate Program in Family Health, Universidade Estácio de Sá, Rio de Janeiro, RJ, Brazil.
(5)    Pediatric Intensive Care Unit, Hospital Estadual da Criança, Rio de Janeiro, RJ, Brazil.
(6)    Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
(7)    Sergio Arouca National School of Public Health, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
(8)    Pediatric Intensive Care Unit, Hospital Assunção, São Bernardo do Campo, SP, Brazil.
(9)    Pediatric Intensive Care Unit, Hospital Universitário Professor Edgard Santos, Salvador, BA, Brazil.

Resumo:
OBJECTIVES: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8-24] and 40 [IQR, 33-44], respectively) whereas low in the depersonalization one (2 [IQR, 0-5]), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p < 0.001), and depression symptoms (32.5% vs 15%; p < 0.001), with superior PCL-5 scores for PTSD ( p < 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p < 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p < 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.

26 - Setting references for daily intake of micronutrients: A study on magnesium. Nutrition. 2023 Feb;106:111903. doi: 10.1016/j.nut.2022.111903.

Guimarães R(1), Andrade FCD(2), Costa GNO(3), Rocha ADS(4), Barreto ML(4), Salles C(5).

Afiliação:
(1)    International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil; Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign.
(2)    School of Social Work, University of Illinois at Urbana-Champaign.
(3)    UNIFACS: Universidade Salvador, Laureate International Universities, Salvador, Bahia, Brazil; Centro de Integração de Dados e Conhecimentos para Saúde, Fundação Oswaldo Cruz - FIOCRUZ, Salvador, Bahia, Brazil.
(4)    Centro de Integração de Dados e Conhecimentos para Saúde, Fundação Oswaldo Cruz - FIOCRUZ, Salvador, Bahia, Brazil.
(5)    International Center on Clinical Sleep Medicine and Research, Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil; Professor Edgard Santos University Hospital Complex, Federal University of Bahia- Ebserh Network, Salvador, Bahia, Brazil.

Resumo:
OBJECTIVES: The Institute of Medicine stratifies the references for daily nutrient intake into age and sex groups, considering that the basal metabolic rate varies according to these aspects, and in most cases, it extrapolates the values calculated for adults to children, because their body weights are different. In this context, this study aimed to evaluate the recommendation for magnesium in children according to energy expenditure. METHODS: This was an observational study using the database of the Social Changes, Asthma and Allergy in Latin America (SCAALA) cohort, which randomly collected information from 1445 children ages 4 to 11 y. Of these, 480 (33%) were part of the present study (children between 7 and 11 y old with eutrophic body mass index and adequate growth). Information on food intake was obtained from the child's parents or legal guardians through a 24-h recall. The population was characterized using static analyses such as the Student t test, Pearson correlation coefficient, and linear regression. RESULTS: The mean age of the sample was 8.5 ± 0.96 y, and 54% were males. The mean magnesium intake was 149 ± 70 mg, with a high correlation observed between energy expenditure and magnesium intake (boys: R, 0.716; P <0.001; girls: R, 0.641; P < 0.001). CONCLUSIONS: The metabolic rate can be considered a reference variable for recommending the daily intake of the studied nutrient, aiming to avoid deficiencies and food poisoning because of poor intake.

27 - Multi-center Integrating Radiomics, Structured Reports, and Machine Learning Algorithms for Assisted Classification of COVID-19 in Lung Computed Tomography. J Med Biol Eng. 2023;43(2):156-162. doi: 10.1007/s40846-023-00781-4.

Machado MAD(1)(2), Silva RRE(2)(3), Namias M(4), Lessa AS(5), Neves MCLC(6), Silva CTA(1), Oliveira DM(7)(8)(9), Reina TR(10), Lira AAB(7), Almeida LM(11), Zanchettin C(11)(12), Netto EM(13).

Afiliação:
(1)    Department of Radiology, Complexo Hospitalar Universitário Prof. Edgard Santos/ Ebserh, Universidade Federal da Bahia, Salvador, Bahia 40110-040 Brazil.
(2)    Radtec Serviços em Física Médica, Salvador, Bahia 40060-330 Brazil.
(3)    Department of Systems and Computing, Universidade Federal de Campina Grande, Campina Grande, Paraíba 58429-900 Brazil.
(4)    Department of Medical Physics, Nuclear Diagnostic Center Foundation, C1417CVE Buenos Aires, Argentina.
(5)    Department of Radiology, Hospital Universitário Gaffrée e Guinle, Universidade do Rio de Janeiro (UNIRIO), Rio de Janeiro, 20270-004 Brazil.
(6)    Department of Pneumology, Complexo Hospitalar Universitário Prof. Edgard Santos/ Ebserh, Universidade Federal da Bahia, Salvador, Bahia 40110-040 Brazil.
(7)    Department of Radiology, Hospital Universitário Alcides Carneiro/ Ebserh, Universidade Federal de Campina Grande, Campina Grande, Paraíba 58400-398 Brazil.
(8)    Northeast Regional Nuclear Science Centre (CRCN-NE), Recife, Pernambuco 50840-545 Brazil.
(9)    Nuclear Energy Department, Universidade Federal de Pernambuco, Recife, Pernambuco 50740-540 Brazil.
(10) Department of Radiology, Hospital Universitário da Universidade Federal de Juiz de Fora/ Ebserh, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36038-330 Brazil.
(11) Centro de Informática, Universidade Federal de Pernambuco, Recife, Pernambuco 50720-001 Brazil.
(12) Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208 USA.
(13) Infectious Disease Research Laboratory, Complexo Hospitalar Universitário Prof. Edgard Santos/ Ebserh, Universidade Federal da Bahia, Salvador, Bahia 40110-040 Brazil.

Resumo:
PURPOSE: To evaluate the classification performance of structured report features, radiomics, and machine learning (ML) models to differentiate between Coronavirus Disease 2019 (COVID-19) and other types of pneumonia using chest computed tomography (CT) scans. METHODS: Sixty-four COVID-19 subjects and 64 subjects with non-COVID-19 pneumonia were selected. The data was split into two independent cohorts: one for the structured report, radiomic feature selection and model building (n = 73), and another for model validation (n = 55). Physicians performed readings with and without machine learning support. The model's sensitivity and specificity were calculated, and inter-rater reliability was assessed using ohen's Kappa agreement coefficient. RESULTS: Physicians performed with mean sensitivity and specificity of 83.4 and 64.3%, respectively. When assisted with machine learning, the mean sensitivity and specificity increased to 87.1 and 91.1%, respectively. In addition, machine learning improved the inter-rater reliability from moderate to substantial. CONCLUSION: Integrating structured reports and radiomics promises assisted classification of COVID-19 in CT chest scans.

 28 - Evaluation of 2D and 3D Erythroid Differentiation Protocols Using Sickle Cell Disease and Healthy Donor Induced Pluripotent Stem Cells. Cells. 2023 Apr 10;12(8):1121. doi: 10.3390/cells12081121.

Martins GLS(1)(2), Nonaka CKV(2)(3), Rossi EA(1)(2), de Lima AVR(1)(2), Adanho CSA(1)(2), Oliveira MS(2), Yahouedehou SCMA(1), de Souza CLEM(4), Gonçalves MS(1), Paredes BD(2)(3), Souza BSF(1)(2)(3).

Afiliação:
(1)    Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, Brazil.
(2)    Center for Biotechnology and Cell Therapy (CBTC), São Rafael Hospital (HSR), Salvador 41253-190, Brazil.
(3)    D'Or Institute for Research and Education (IDOR), Salvador 41253-190, Brazil.
(4)    Hospital Universitário Professor Edgard Santos, Federal University of Bahia (UFBA), Salvador 40110-060, Brazil.

Resumo:
BACKGROUND: Sickle cell disease (SCD) is a highly prevalent genetic disease caused by a point mutation in the HBB gene, which can lead to chronic hemolytic anemia and vaso-occlusive events. Patient-derived induced pluripotent stem cells (iPSCs) hold promise for the development of novel predictive methods for screening drugs with anti-sickling activity. In this study, we evaluated and compared the efficiency of 2D and 3D erythroid differentiation protocols using a healthy control and SCD-iPSCs. METHODS: iPSCs were subjected to hematopoietic progenitor cell (HSPC) induction, erythroid progenitor cell induction, and terminal erythroid maturation. Differentiation efficiency was confirmed by flow cytometry analysis, colony-forming unit (CFU) assay, morphological analyses, and qPCR-based gene expression analyses of HBB and HBG2.
RESULTS: Both 2D and 3D differentiation protocols led to the induction of CD34+/CD43+ HSPCs. The 3D protocol showed good efficiency (>50%) and high productivity (45-fold) for HSPC induction and increased the frequency of BFU-E, CFU-E, CFU-GM, and CFU-GEMM colonies. We also produced CD71+/CD235a+ cells (>65%) with a 630-fold cell expansion relative to that at the beginning of the 3D protocol. After erythroid maturation, we observed 95% CD235a+/DRAQ5-enucleated cells, orthochromatic erythroblasts, and increased expression of fetal HBG2 compared to adult HBB. CONCLUSION: A robust 3D protocol for erythroid differentiation was identified using SCD-iPSCs and comparative analyses; however, the maturation step remains challenging and requires further development.

 29 - Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America. Gastroenterology. 2023 May 30:S0016-5085(23)00806-5. doi: 10.1053/j.gastro.2023.05.033.

Farias AQ(1), Curto Vilalta A(2), Momoyo Zitelli P(1), Pereira G(3), Goncalves LL(4), Torre A(5), Diaz JM(6), Gadano AC(7), Mattos AZ(8), Mendes LSC(9), Alvares-da-Silva MR(10), Bittencourt PL(11), Benitez C(12), Alves Couto C(13), Mendizabal M(14), Toledo CL(15), Mazo DFC(16), Castillo Barradas M(17), Uson Raposo EM(2), Padilla-Machaca PM(18), Zarela Lozano Miranda A(19), Malé-Velázquez R(20), Castro Lyra A(21), Dávalos-Moscol MB(22), et al.; ACLARA Study Collaborators.

Afliação:
(1) The Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil.
(2) European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.
(3) Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital, Ministry of Health, Rio de Janeiro, Brazil; Estácio de Sá University, School of Medicine, Rio de Janeiro, Brazil.
(4) Gastroenterology and Hepatology Unit, Hospital Universitário Cassiano Antônio Moraes, Universidade Federal do Espírito Santo, Vitória, Brazil.
(5) Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, Mexico.
(6) European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain; Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
(7) Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
(8) Federal University of Health Sciences of Porto Alegre, and Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil.
(9) Hospital de Base do Distrito Federal, Brasilia, Brazil.
(10) Gastrointestinal and Liver Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
(11) Hospital Português da Bahia, Salvador, Brazil.
(12) Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
(13) Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
(14) Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina.
(15) Universidad Austral de Chile, Hospital Valdivia, Valdivia, Chile.
(16) Division of Gastroenterology, University of Campinas, Campinas, Brazil.
(17) Servicio de Gastroenterología y Hepatología, Hospital de Especialidades Centro Médico Nacional La Raza Instituto Mexicano del Seguro Social, Mexico City, Mexico.
(18) Hospital Nacional Guillermo Almenara, and Universidad Nacional de San Marcos, Lima, Peru.
(19) Unidad de Hígado, Hospital Nacional Arzobispo Loayza, Lima, Peru.
(20) Instituto de Salud Digestiva y Hepática, Guadalajara, Mexico.
(21) Hospital Universtário Professor Edgard Santos, Salvador, Brazil; Hospital São Rafael, Salvador, Brazil.
(22) Hospital Nacional Edgardo Rebagliati Martins-EsSalud, Lima, Peru.

Resumo:
BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

 30 - Analysis of false positive PI-RADS 4 lesions: experience from a single nonacademic center using cognitive fusion. Int Urol Nephrol. 2023 May;55(5):1081-1085. doi: 10.1007/s11255-023-03508-1.

de Souza BCA(1)(2)(3), Novaes MAS(4), de Souza MF(5)(6), do Amaral MEP(5), Mota A(7), Athanazio DA(8)(9).

Afiliação:
(1)    Federal University of Bahia/Hospital Universitário Professor Edgard Santos, R. Augusto Viana, s/n - Canela, Salvador, 40301-155, Brazil.
(2)    Rede D'or Bahia. Av. São Rafael, 2152 - São Marcos, Salvador, BA, 41253-190, Brazil.
(3)    Hospital Aristides Maltez.Av. Dom João VI, 332 - Brotas, Salvador, BA, 40285-001, Brazil.
(4)    Multimagem Clinic, Av. Manoel Dias da Silva, 675 - Pituba, Salvador, 41830-000, Brazil.
(5)    Imagepat Laboratory, Rua Lucaia, 209 - Edf. Eventus Empresarial, Rio Vermelho, Salvador, 41940-660, Brazil.
(6)    Departamento de Patologia e Medicina Legal, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Praça XV de Novembro, s/n - Largo do Terreiro de .
(7)    AMO Clinic, Rua João Gomes, 225 - Rio Vermelho, Salvador, 41950-640, Brazil.
(8)    Imagepat Laboratory, Rua Lucaia, 209 - Edf. Eventus Empresarial, Rio Vermelho, Salvador, 41940-660, Brazil.
(9)    Departamento de Patologia e Medicina Legal, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Praça XV de Novembro, s/n - Largo do Terreiro de Jesus, Salvador, BA, 40025-010, Brazil.

Resumo:
BACKGROUND: We evaluated pathological findings in targeted biopsies of PI-RADS4 and PI-RADS5 lesions, and clinical data that could predict those patients with benign findings. MATERIALS AND METHODS: A retrospective study was conducted to summarize the experience from a single nonacademic center using cognitive fusion and a 1.5 or 3.0 Tesla scanner. RESULTS: We found a false positive rate of 29 and 3.7% for any cancer in PI-RADS 4 and 5 lesions, respectively. Diverse histologic patterns were observed among target biopsies. At multivariate analysis, size ≤ 6 mm and previous negative biopsy were independent predictors of false positive PI-RADS4 lesions. The small number of false PI-RADS5 lesions precluded further analyses. CONCLUSION: Benign findings are common in PI-RADS4 lesions and most of them do not show obvious glandular or stromal hypercellularity as expected in hyperplastic nodules. Size ≤ 6 mm and previous negative biopsy predict a higher probability of false positive results in patients with PI-RADS 4 lesions.

 31- Brief communication: Vitamin D serum levels in American tegumentary leishmaniasis from an endemic area in Northeast Brazil. Braz J Infect Dis. 2023 Jan-Feb;27(1):102720. doi: 10.1016/j.bjid.2022.102720.

Figueiredo LP(1), Cerqueira-Silva T(2), Magalhães A(3), Lago EL(3), Lessa MM(4).

Afiliação:
(1)    Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brazil; Universidade Federal da Bahia, Serviço de Imunologia do Hospital Universitário Professor Edgard Santos, Salvador, BA, Brazil.
(2)    Universidade Federal da Bahia, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brazil.
(3)    Universidade Federal da Bahia, Serviço de Imunologia do Hospital Universitário Professor Edgard Santos, Salvador, BA, Brazil.
(4)    Universidade Federal da Bahia, Serviço de Imunologia do Hospital Universitário Professor Edgard Santos, Salvador, BA, Brazil; Universidade Federal da Bahia, Serviço de Otorrinolaringologia do Hospital Universitário Professor Edgard Santos, Salvador, BA, Brazil.

Resumo:
INTRODUCTION: The pathogenesis of cutaneous and mucosal leishmaniasis is associated with different immune responses. Vitamin D may modulate the immune system. Here we evaluate the association of vitamin D levels with the severity of the clinical forms of cutaneous and mucosal leishmaniasis. METHODS: We conducted an observational study evaluating the association between vitamin D levels, disease severity and therapeutic response in patients with cutaneous and mucosal leishmaniasis. Additionally, we conducted a cross-sectional study to compare vitamin D levels in patients with leishmaniasis and healthy subjects. Hypovitaminosis D was defined as a serum level of 25 (OH) D < 30 ng/mL. RESULTS: In patients with leishmaniasis, vitamin D serum levels were 38.5 ± 11.54 ng/mL, and 37.5 ± 10.43 ng/mL in healthy subjects The prevalence of hypovitaminosis D was 23.3% and 20.0%, respectively (p = 0.72). There was no correlation between vitamin D serum levels, disease severity, and healing time in the mucosal leishmaniasis group. CONCLUSION: Vitamin D levels are not associated with neither susceptibility nor severity of tegumentary leishmaniasis.

32 - Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group. Arq Neuropsiquiatr. 2023 Jun;81(6):597-606. doi: 10.1055/s-0043-1768676.

de Brito Sampaio LP(1), Henriques-Souza AMM(2), Lin K(3), Neri LCL(1), Inuzuka LM(4), Uchôa LIL(5), Gregório MMO(6), Guilhoto LM(6)(7), Montenegro MA(8), Lunardi M(9), Veiga M(10), de Lima PA(11), Braatz V(12).

Afiliação:
(1) Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Instituto da Criança e Adolescente, São Paulo SP, Brazil.
(2) Instituto de Medicina Integral Professor Fernando Figueira, Centro de Terapias Cetogênicas do IMIP, Recife PE, Brazil.
(3) Universidade Federal de Santa Catarina, Departamento de Medicina Interna, Divisão de Neurologia, Florianópolis SC, Brazil.
(4) Hospital Sirio Libanês, Departamento de Neurofisiologia, São Paulo SP, Brazil.
(5) Hospital Materno-Infantil de Brasília, Brasília DF, Brazil.
(6) Universidade Federal de São Paulo, Departamento de Neurologia, São Paulo, Brazil.
(7) Universidade de São Paulo, Hospital Universitário, Divisão de Clínica Pediátrica, São Paulo SP, Brazil.
(8) Universidade Estadual de Campinas, Departamento de Neurologia, São Paulo SP, Brazil.
(9) Universidade Federal de Santa Catarina, Programa de Pós-Graduação em Ciências Médicas, Florianópolis SC, Brazil.
(10) Hospital Universitário Professor Edgard Santos, Salvador BA, Brazil.
(11) Universidade Anhanguera, São Paulo SP, Brazil.
(12) Universidade da Região de Joinville, Departamento de Medicina, Divisão de Neurologia, Joinville SC, Brazil.

Resumo:
Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil. Publisher: As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.

33 - Outcomes of recurrent stroke in patients with atrial fibrillation according to presumed etiology. Arq Neuropsiquiatr. 2023 Jul;81(7):616-623. doi: 10.1055/s-0043-1769124.

Pedreira BB(1)(2), Zachrison KS(3), Singhal A(1), Yan Z(1), Oliveira-Filho J(2), Schwamm LH(1).

Afiliação:
(1)    Harvard Medical School, Massachusetts General Hospital, Department of Neurology, Boston, United States.
(2)    Universidade Federal da Bahia, Hospital Universitario Professor Edgard Santos, Programa de Pós-Graduação em Ciências da Saúde, Salvador BA, Brazil.
(3)    Harvard Medical School, Massachusetts General Hospital and Boston, Department of Emergency Medicine, Boston, United States.

Resumo:
BACKGROUND: Atrial fibrillation (AF) is a potent risk factor for stroke. The presence of competing etiologies can modify disease outcomes and demand different treatment strategies.OBJECTIVES: The primary purpose of the study was to examine the differences in outcomes for patients with AF admitted with a recurrent stroke, stratified according to the presumed etiology of the stroke.METHODS: We analyzed AF patients admitted for a recurrent ischemic stroke in an academic comprehensive stroke center. Recurrent strokes were categorized as "Cardioembolic", meaning AF without any competing mechanism, versus "Undetermined" etiology due to competing mechanisms. We used logistic regression to test the association between recurrent stroke etiology and favorable outcome (discharge home), after accounting for important covariates. RESULTS: We included 230 patients, with a mean age 76.9 (SD ± 11.3), 52.2% male, median National Institute of Health Stroke Scale (NIHSS) score of 7 (IQR 2-16). Patients with cardioembolic stroke (65.2%) had higher median NIHSS 8.5 (3-18) versus 3 (1-8) and were more likely to be treated with reperfusion therapies. The favorable outcome was reached by 64 patients (27.8%), and in-hospital mortality was 15.2% overall. After adjustment, there was no difference in outcome between patients with cardioembolic versus undetermined stroke etiology (odds ratio for discharge home: 1.41; 95% CI: 0.65-3.15). CONCLUSIONS: In this single-center sample of AF patients with history of stroke, there was no difference in discharge outcomes between those with cardioembolic and those with undetermined stroke etiology. This question warrants examination in larger samples to better understand the importance of the stroke mechanism and secondary prophylaxis.

34 - Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors of Leishmania infection. Front Trop Dis. 2023;3:1011124. doi: 10.3389/fitd.2022.1011124.

Kavouris JA(1), McCall LI(2), Giardini MA(2), De Muylder G(3), Thomas D(2), Garcia-Pérez A(4), Cantizani J(4), Cotillo I(4), Fiandor JM(4), McKerrow JH(2)(3), De Oliveira CI(5), Siqueira-Neto JL(2)(3), González S(4), Brown LE(1), Schaus SE(1).

Afiliação:
(1)    Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts, United States of America.
(2)    Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America.
(3)    Department of Pathology, Sandler Center for Drug Discovery, University of California San Francisco, San Francisco, California, United States of America.
(4)    Global Health Medicines R&D, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Madrid, Spain.
(5)    HUPES, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT) -Salvador, Brazil; Instituto de Investigação em Imunologia (iii-INCT), São Paulo, Brazil.

Resumo:
INTRODUCTION: Leishmaniasis is a parasitic disease that affects more than 1 million people worldwide annually, predominantly in resource-limited settings. The challenge in compound development is to exhibit potent activity against the intracellular stage of the parasite (the stage present in the mammalian host) without harming the infected host cells. We have identified a compound series (pyrazolopyrrolidinones) active against the intracellular parasites of Leishmania donovani and L. major; the causative agents of visceral and cutaneous leishmaniasis in the Old World, respectively. METHODS: In this study, we performed medicinal chemistry on a newly discovered antileishmanial chemotype, with over 100 analogs tested. Studies included assessments of antileishmanial potency, toxicity towards host cells, and in vitro ADME screening of key drug properties. RESULTS AND DISCUSSION: Members of the series showed high potency against the deadliest form, visceral leishmaniasis (approximate EC50 ≥ 0.01 μM without harming the host macrophage up to 10.0 μM). In comparison, the most efficient monotherapy treatment for visceral leishmaniasis is amphotericin B, which presents similar activity in the same assay (EC50 = 0.2 μM) while being cytotoxic to the host cell at 5.0 μM. Continued development of this compound series with the Discovery Partnership with Academia (DPAc) program at the GlaxoSmithKline Diseases of the Developing World (GSK DDW) laboratories found that the compounds passed all of GSK's criteria to be defined as a potential lead drug series for leishmaniasis. CONCLUSION: Here, we describe preliminary structure-activity relationships for antileishmanial pyrazolopyrrolidinones, and our progress towards the identification of candidates for future in vivo assays in models of visceral and cutaneous leishmaniasis.

35 - Development of a new non invasive prognostic stroke scale (NIPSS) including triage elements for sleep apnea and peripheral artery disease. J Stroke Cerebrovasc Dis. 2023 Jan;32(1):106864. doi: 10.1016/j.jstrokecerebrovasdis.2022.106864.

Oliveira AS(1), Dantas MC(2), de Jesus PAP(3), Farias DS(4), de Almeida BM(5), Santos CSO(5), Santos CSLA(3), Blumetti CR(5), de Faria CD(5), Costa CC(5), Fernandes DP(5), Nogueira EB(5), Fonseca GQ(5), Pinto JPM(5), Oliveira IJW(5), Barcelos LS(5), Velloso LUF(5), Lucio MJP(5), Pimenta MD(4), Leopoldino OCS(5), de Medeiros RC(5), Junior TML(5), Santana TA(5), Lacerda VR(5), Alcantara YFV(5), Oliveira-Filho J(6).

Afiliação:
(1)    Post-Graduate Program in Health Sciences (PPgCS), Federal University of Bahia, Brazil (UFBA), Neurology Service, Hospital Universitario Professor Edgard Santos, UFBA, Sala 421, Rua Reitor Miguel Calmón, Sem Número, Bairro Canela, Salvador 40110-100, Brazil.
(2)    Post-Graduate Program in Health Sciences (PPgCS), Federal University of Bahia, Brazil (UFBA), Neurology Service, Hospital Universitario Professor Edgard Santos, UFBA, Sala 421, Rua Reitor Miguel Calmón, Sem Número, Bairro Canela, Salvador 40110-100, Brazil.
(3)    Stroke Unit, Hospital Geral Roberto Santos, Brazil.
(4)    Neurology Service, Hospital Universitario Professor Edgard Santos, UFBA, Brazil.
(5)    Universidade Faculdade de Salvador (UNIFACS), Bahia, Brazil. Post-Graduate Program in Health Sciences (PPgCS), Federal University of Bahia, Brazil (UFBA), Neurology Service, Hospital Universitario Professor Edgard Santos, UFBA, Sala 421, Rua Reitor Miguel Calmón, Sem Número, Bairro Canela, Salvador 40110-100, Brazil.

Resumo:
BACKGROUND: Although sleep apnea and peripheral artery disease are prognostic factors for stroke, their added benefit in the acute stage to further prognosticate strokes has not been evaluated. OBJECTIVES: We tested the accuracy in the acute stroke stage of a novel score called the Non-Invasive Prognostic Stroke Scale (NIPSS).PATIENTS AND METHODS: Prospective cohort with imaging-confirmed ischemic stroke. Clinical data, sleep apnea risk score (STOPBANG) and blood pressure measures were collected at baseline. Primary outcome was the 90-day modified Rankin Scale (mRS), with poor outcome defined as mRS 3-6. Area under the ROC curve (AUC) was calculated for NIPSS and compared to six other stroke prognostic scores in our cohort: SPAN-100 index, S-SMART, SOAR, ASTRAL, THRIVE, and Dutch Stroke scores. RESULTS: We enrolled 386 participants. After 90 days, there were 56% with poor outcome, more frequently older, female predominant and with higher admission National Institute of Health Stroke Scale (NIHSS). Four variables remained significantly associated with primary endpoint in the multivariable model: age (OR 1.87), NIHSS (OR 7.08), STOPBANG category (OR 1.61), and ankle-braquial index (OR 2.11). NIPSS AUC was 0.86 (0.82-0.89); 0.83 (0.79-0.87) with bootstrapping. When compared to the other scores, NIPSS, ASTRAL, S-SMART and DUTCH scores had good abilities in predicting poor outcome, with AUC of 0.86, 0.86, 0.83 and 0.82, respectively. THRIVE, SOAR and SPAN-100 scores were fairly predictive. DISCUSSION AND CONCLUSIONS: Non-invasive and easily acquired emergency room data can predict clinical outcome after stroke. NIPSS performed equal to or better than other prognostic stroke scales.

36 - Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries. Arch Toxicol. 2023 Feb;97(2):593-602. doi: 10.1007/s00204-022-03419-7.

Bessone F(1), Ferrari A(2), Hernandez N(3), Mendizabal M(4), Ridruejo E(5), Zerega A(6), Tanno F(2), Reggiardo MV(2), Vorobioff J(2), Tanno H(2), Arrese M(7), Nunes V(8), Tagle M(9), et al.

Afiliação:
(1)    Hospital Provincial del Centenario, Rosario, Argentina.
(2)    Hospital Provincial del Centenario, Rosario, Argentina.
(3)    Hospital de Clínicas, Montevideo, Uruguay.
(4)    Hospital Universitario Austral, Buenos Aires, Argentina.
(5)    Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina.
(6)    Hospital Allende, Ciudad de Córdoba, Argentina.
(7)    Pontificia Universidad Católica de Chile, Santiago, Chile.
(8)    Hospital Universitário Prof. Edgard Santos-UFBA, Salvador, Brazil.
(9)    Clínica Anglo Americana, Lima, Peru.

Resumo:
Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96-760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57-141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis.

37 - Systemic Inflammatory Molecules Are Associated with Advanced Fibrosis in Patients from Brazil Infected with Hepatitis Delta Virus Genotype 3 (HDV-3). Microorganisms. 2023 May 12;11(5):1270. doi: 10.3390/microorganisms11051270.

Souza Campos M(1)(2), Villalobos-Salcedo JM(3), Vieira Dallacqua DS(3), Lopes Borges Andrade C(1)(4)(5), Meyer Nascimento RJ(1)(4)(5), Menezes Freire S(1)(4)(5), Paraná R(1)(6), Schinoni MI(1)(2)(6).

Afiliação:
(1)    Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil.
(2)    Programa de Pós-Graduação em Processos Interativos de Órgãos e Sistemas, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil.
(3)    Fundação Oswaldo Cruz (FIOCRUZ), Porto Velho 76812-245, Brazil.
(4)    Programa de Pós-Graduação em Imunologia, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Brazil.
(5)    Laboratório de Imunologia e Biologia Molecular, Instituto Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300,Brazil.
(6)    Hospital Universitario Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110-060, Brazil.

Resumo:
BACKGROUND AND AIMS: Hepatitis Delta virus (HDV) genotype 3 is responsible for outbreaks of fulminant hepatitis in Northeastern South America. This study investigates if systemic inflammatory molecules are differentially expressed in patients with advanced fibrosis chronically infected with Hepatitis Delta virusgenotype 3(HDV-3). METHODS: Sixty-one patients from the north of Brazil coinfected with hepatitis B virus (HBV)/HDV-3 were analyzed. HDV quantification and genotyping were performed by semi-nested real-time polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) methodologies. Ninety-two systemic inflammatory molecules (SIMs) were measured by Proximity Extension Assay (PEA) technology. The Shapiro-Wilk, Student's t-test, Mann-Whitney tests, and logistic regression analysis were used when appropriate. RESULTS: The median age was 41 years, and all patients were HBeAg negative. Advanced fibrosis or cirrhosis was diagnosed by histological staging in 17 patients, while 44 presented with minimal or no fibrosis. Advanced necroinflammatory activity correlated positively with serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Established non-invasive fibrosis scores (APRI, FIB-4, and AST/ALT ratio) revealed low sensitivities and positive predictive values (PPVs) with an AUROC maximum of 0.586. Among the 92 SIMs analyzed, MCP.4, CCL19, EN.RAGE, SCF, and IL18 showed a positive correlation with fibrosis stage. A combined score including CCL19 and MCP.4 revealed a sensitivity of 81% and an odds ratio of 2.202 for advanced fibrosis. CONCLUSIONS: Standard non-invasive fibrosis scores showed poor performance in HDV-3 infection. We here suggest that the determination of CCL19 and MCP.4 may be used to identify patients with advanced fibrosis. Moreover, this study gives novel insights into the immunopathogenesis of HDV-3 infection.

38 - Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies. PLoS Pathog. 2023 Mar 20;19(3):e1011230. doi: 10.1371/journal.ppat.1011230.

Pilling OA(1), Reis-Cunha JL(2), Grace CA(2), Berry ASF(1), Mitchell MW(3), Yu JA(4), Malekshahi CR(1), Krespan E(1), Go CK(1), Lombana C(1), Song YS(4)(5), Amorim CF(1), Lago AS(6)(7), Carvalho LP(6)(7), Carvalho EM(6)(7), Brisson D(3), Scott P(1), Jeffares DC(2), Beiting DP(1).

Afiliação:
(1)    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
(2)    Department of Biology, York Biomedical Research Institute, University of York, York, United Kingdom.
(3)    Department of Biology, School of Arts & Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
(4)    Computer Science Division, University of California, Berkeley, Berkeley, California, United States of America.
(5)    Department of Statistics, University of California, Berkeley, Berkeley, California, United States of America.
(6)    Serviço de Imunologia, Complexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(7)    Laboratório de Pesquisas Clínicas do Instituto de Pesquisas Gonçalo Moniz, Fiocruz Bahia, Brazil.

Resumo:
In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.

39 - Clear Cell Papillary Renal Cell Tumors: A Study of 42 Tumors with Emphasis on the Fibrous Capsule, Cystic Component, and GATA3 Immunohistochemistry. Int J Surg Pathol. 2023 Feb;31(1):38-45. doi: 10.1177/10668969221091583.

da Paz AR(1)(2), de Souza MF(3)(4), Santana CMM(1), Athanazio DA(3)(4)(5).

Afiliação:
(1)    Hospital Napoleão Laureano, João Pessoa, Brazil.
(2)    Universidade Federal da Paraíba, João Pessoa, Brazil.
(3)    Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil.
(4)    Imagepat, Laboratory of Pathology, Brazil.
(5)    Hospital Universitário Professor Edgard Santos / Federal University of Bahia, Brazil.

Resumo:
Clear cell papillary renal cell tumor is a common and sometimes underdiagnosed renal cell neoplasm. Its proper recognition is important because its diagnosis implies a remarkably high probability of indolent behavior. This study aimed to evaluate the frequency of a fibrous capsule, a cystic component, and a GATA3 expression in clear cell papillary renal cell tumors. We assessed 419 renal cell neoplasms from three institutions located in northeastern Brazil and identified 42 clear cell papillary renal cell tumors (from 39 patients), which were the fourth most common renal cell neoplasm. These tumors commonly exhibited fibrous capsules (all showed complete or partial capsules) and cystic component (93%). Eighteen out of 42 tumors (43%) showed some expression of GATA3, and weak and focal staining was common among the positive tumors. Clear cell papillary renal cell tumor must always be included in the differential diagnosis of predominantly cystic renal cell neoplasms. As GATA3 is inconsistently expressed in clear cell papillary renal cell tumors, it is not useful in this diagnosis.

40 - Brazilian Guidelines for Cardiac Implantable Electronic Devices. Arq Bras Cardiol. 2023 Jan 23;120(1):e20220892. doi: 10.36660/abc.20220892.

Teixeira RA(1), Fagundes AA(2), Baggio Junior JM(3), Oliveira JC(4), Medeiros PTJ(5), Valdigem BP(5), Teno LAC(6), Silva RT(7)(8), Melo CS(9), Elias Neto J(10), Moraes Júnior AV(11)(12), Pedrosa AAA(13), Porto FM(14), Brito Júnior HL(15), Souza TGSE(16), Mateos JCP(5), Moraes LGB(17), Forno ARJD(18), D'Avila ALB(18), Cavaco DAM(19), Kuniyoshi RR(20)(21), Pimentel M(22), Camanho LEM(23), Saad EB(23)(24), Zimerman LI(25), Oliveira EB(26), Scanavacca MI(13), Martinelli Filho M(13), Lima CEB(27)(28), Peixoto GL(29), Darrieux FCDC(13), Duarte JOP(30), Galvão Filho SDS(31), et al.

Afiliação:
(1) Hospital Renascentista, Pouso Alegre, MG – Brasil.
(2) Hospital Ana Nery, Salvador, BA – Brasil.
(3) Instituto de Cardiologia do Distrito Federal, Brasília, DF – Brasil.
(4) Universidade Federal de Mato Grosso (UFMT),Cuiabá, MT – Brasil.
(5) Instituto Dante Pazzanese de Cardiologia, São Paulo, SP – Brasil.
(6) Clínica Cardiovascular Ribeirão Preto, Ribeirão Preto, SP – Brasil.
(7) Universidade de Franca (UNIFRAN), Franca, SP – Brasil.
(8) Centro Universitário Municipal de Franca (Uni-FACEF), Franca, SP – Brasil.
(9) Clínica de Marca-passos Cardíacos, Uberaba, MG – Brasil.
(10) Universidade Federal do Espírito Santo (UFES), Vitória, ES – Brasil.
(11) Santa Casa de Ribeirão Preto, Ribeirão Preto, SP – Brasil.
(12) Unimed de Ribeirão Preto, Ribeirão Preto, SP – Brasil.
(13)  Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP – Brasil.
(14) Pontifícia Universidade Católica de Campinas, Campinas, SP – Brasil.(15)                       Universidade Federal de Juiz de Fora, Juiz de Fora, MG – Brasil.
(16) Hospital Universitário da Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, MG – Brasil.
(17) Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ – Brasil.
(18) Hospital SOS Cárdio, Florianópolis, SC – Brasil.
(19) Hospital de Santa Cruz, Lisboa – Portugal.
(20) Centrocor Vitória, Vitória, ES – Brasil.
(21) Vitória Apart Hospital, Vitória, ES – Brasil.
(22) Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS – Brasil.
(23) Hospital Pró-Cardíaco, Rio de Janeiro, RJ – Brasil.
(24) Hospital Samaritano, Rio de Janeiro, RJ – Brasil.
(25) Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS – Brasil.
(26) Hospital Mãe de Deus, Porto Alegre, RS – Brasil.
(27) Hospital Universitário da Universidade Federal do Piauí (UFPI), Teresina, PI – Brasil.
(28) Empresa Brasileira de Serviços Hospitalares (EBSERH), Brasília, DF – Brasil.
(29) DentCor Clínica Médica e Odontológica, Santo André, SP – Brasil.
(30) Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia (UFBA), Salvador, BA – Brasil.
(31) Centro Avançado de Ritmologia e Eletrofisiologia (CARE), Vista, SP – Brasil.

Resumo não disponível.

41 - Efficacy of intralesional meglumine antimoniate in the treatment of canine tegumentary leishmaniasis: A Randomized controlled trial. PLoS Negl Trop Dis. 2023 Feb 15;17(2):e0011064. doi: 10.1371/journal.pntd.0011064.

Lago J(1)(2), Fraga D(3), Guimarães LH(4), Lago T(1)(2), Silva YJ(3), Lago E(1)(5), Werneck GL(6)(7), Bacellar O(1)(2)(5), Carvalho EM(1)(2)(3)(5).

Afiliação:
(1)    Immunology Service, Professor Edgard Santos University Hospital Complex, Federal University of Bahia, Salvador, Bahia, Brazil.
(2)    Post-Graduate Course in Health Sciences, Federal University of Bahia Medical School. Salvador, Bahia, Brazil.
(3)    Gonçalo Moniz Institute (IGM), Fiocruz, Salvador, Bahia, Brazil.
(4)    Federal University of Southern Bahia, Teixeira de Freitas, Bahia, Brazil.
(5)    Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Ministério da Ciência e Tecnologia e Inovação (MCTI), CNPq, Salvador, Bahia, Brazil.
(6)    Department of Epidemiology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
(7)    Institute for Public Health Studies, Federal University of Rio de Janeiro. Federal.

Resumo:
Dogs living in areas of Leishmania (Viannia) braziliensis transmission may present canine tegumentary leishmaniasis (CTL) characterized by cutaneous or muzzle ulcers as well as asymptomatic L. braziliensis infection. It is not clear if dogs participate in the transmission chain of L. braziliensis to humans. However, dogs may remain with chronic ulcers for a long time, and as there are no public policies about CTL, these animals die or are sacrificed. Here we compare the efficacy of intralesional meglumine antimoniate with intralesional 0.9% NaCl solution in CTL treatment. This randomized control study included 32 dogs with cutaneous or muzzle lesions who had L. braziliensis DNA detected by PCR in tissue biopsied. Group one received 5ml of intralesional Glucantime, and group two received 5ml 0.9% NaCl solution, both applied in the four cardinal points on days 0, 15, and 30. Cure was defined as complete healing of the ulcers in the absence of raised borders on day 90. There was no difference in animals' demographic and clinical features in the two groups (p >.05). While at the endpoint, the cure rate was 87.5% in the group test, and in those who received 0.9 NaCl the cure rate was only 12.5%. As important as the high cure rate, the healing time was faster in dogs treated with antimony than in those treated with saline (p < .001). Intralesional meglumine antimoniate is effective in the treatment of dogs with L. braziliensis infection and accelerates the healing time of CTL.

42 - Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome. Ann Hepatol. 2023 Jul-Aug;28(4):101105. doi: 10.1016/j.aohep.2023.101105.

Braga MH(1), Cançado GGL(2), Bittencourt PL(3), Couto CA(4), Guedes LV(1), Lima AMC(4), Ferraz MLG(5), Villela-Nogueira CA(6), Nardelli MJ(4), Faria LC(4), Gomes NMF(5), Oliveira EMG(7), Rotman V(6), Oliveira MB(8), da Cunha SMCF(9), Cunha-Silva M(10), Mendes LSC(11), et al; Members of the Brazilian Cholestasis Study Group Consortium.

Afiliação:
(1) Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil.
(2) Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
(3) Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil; Hospital Português, Salvador, Bahia, Brazil.
(4) Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
(5) Disciplina de Gastroenterologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
(6) Hospital Universitário Clementino Fraga Filho e Departamento de Clínica Médica da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
(7) Centro Universitário Lusíada - UNILUS, Santos, São Paulo, Brazil.
(8) Ambulatório Municipal de Hepatites Virais de São José dos Campos, São José dos Campos, São Paulo, Brazil.
(9) Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(10) Divisão de Gastroenterologia (Gastrocentro), Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.

Resumo:
INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. MATERIALS AND METHODS: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. RESULTS: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. CONCLUSIONS: The prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

43 - Rhinal and hippocampal event-related potentials as epileptogenic zone markers in the pre-surgical evaluation of temporal epilepsies: a systematic review. Arq Neuropsiquiatr. 2023 May;81(5):492-501. doi: 10.1055/s-0043-1761493.

Morange DA(1)(2), Amaral MTR(3), Martinez-Silveira MS(4), Trébuchon A(1)(5).

Afiliação:
(1)    Institut de Neurosciences des Systèmes, Université d'Aix-Marseille, Marseille, France.
(2)    Hospital Universitário Prof. Edgard Santos, Departamento de Neurofisiologia Clínica, Salvador BA, Brazil.
(3)    Universidade Estadual de Feira de Santana, Departamento de Ciências Exatas, Salvador BA, Brazil.
(4)    Fundação Oswaldo Cruz, Instituto Gonçalo Muniz, Salvador BA, Brazil.
(5)    Neurophysiologie Clinique, Assistance Publique - Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France.

Resumo:
BACKGROUND: Cognitive event-related potentials (ERPs) allow for lateralization of the epileptogenic zone (EZ) to estimate the reserve of memory in the contralateral non-epileptogenic hemisphere, and to investigate the prognosis of temporal lobe seizure control in unilateral temporal lobe epilepsy (TLE). OBJECTIVE: To define the accuracy of cognitive evoked anterior mesial temporal lobe (AMTL-N400) and P600 potentials in detecting the epileptogenic zone in temporal lobe epilepsy (TLE), and second, to evaluate the possibility of using them as markers of cognitive outcome. METHODS: The systematic review using Medline/PubMed, Embase, and Lilacs database was conducted in September 2021. Only articles published in English from 1985 to June 2021 were included. We searched for studies with: (1) depth intracranial electroencephalography (iEEG) recordings analysis of rhinal and hippocampal activity (2) correlations between ERP results obtained in the mesial temporal regions (AMTL-N400 and P600) and the epileptogenic zone. RESULTS: Six out of the seven studies included in this review defined the laterality of the epileptogenic zone (EZ) during presurgical investigation using ERPs. One study showed that the contralateral AMTL-N400 predicts seizure control. Another study found correlation between the amplitudes of the right AMTL-N400 and postoperative memory performance. CONCLUSIONS: There is evidence that the reduced amplitude of the AMTL-N400 has high accuracy in identifying the epileptogenic zone, as it does in estimating the extent of seizure control and memory impairment in postoperative patients.

44 - Implementation of a re-linkage to care strategy in patients with chronic hepatitis C who were lost to follow-up in Latin America. J Viral Hepat. 2023 Jan;30(1):56-63. doi: 10.1111/jvh.13758.

Mendizabal M(1), Thompson M(1), Gonzalez-Ballerga E(2), Anders M(3), Castro-Narro GE(4), Pessoa MG(5), Cheinquer H(6), Mezzano G(7), Palazzo A(8), Ridruejo E(9), Descalzi V(10), Velarde-Ruiz Velasco JA(11), Marciano S(12), Muñoz L(13), Schinoni MI(14), Poniachik J(15), et al.

Afiliação:
(1) Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina.
(2) Sección Hepatología, Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.
(3) Unidad de Hepatología y Trasplante Hepático, Hospital Alemán, Buenos Aires, Argentina.
(4) Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de Mexico, Mexico.
(5) Divisão de Gastroenterologia e Hepatologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
(6) Departamento de Gastroenterología y Hepatología, Universidad Federal do Rio Grande do Sul e do Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
(7) Sección de Gastroenterología, Hospital El Salvador, Santiago, Chile.
(8) Servicio de Gastroenterología, Sección de Hepatología, Hospital Padilla, Tucumán, Argentina.
(9) Sección Hepatología, Departamento de Medicina, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Buenos Aires, Argentina.
(10)  Unidad de Hígado y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
(11) Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico.
(12) Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
(13) Hospital Universitario "Dr. José E. González", Monterrey, Mexico.
(14) Núcleo de Hepatología, Hospital Universitario Prof. Edgard Santos, Universidad Federal de Bahia, Salvador, Brazil.
(15) Sección de Gastroenterología, Departamento de Medicina, Hospital Clínico de la Universidad de Chile, Santiago, Chile.

Resumo:
To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.

45 - Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model. Lancet Glob Health. 2023 May;11(5):e781-e790. doi: 10.1016/S2214-109X(23)00065-7.

Rosadas C(1), Senna K(2), da Costa M(3), Assone T(4), Casseb J(4), Nukui Y(5), Cook L(6), Mariano L(5), Galvão Castro B(7), Rios Grassi MF(8), Penalva de Oliveira AC(9), Caterino-de-Araujo A(10), Malik B(11), Boa-Sorte N(12), Peixoto P(13), Puccioni-Sohler M(14), Santos M(2), Taylor GP(15).

Afiliação:
(1) Section of Virology, Department of Infectious Disease, Imperial College London, London, UK.
(2) Núcleo de Avaliação de Tecnologias em Saúde, Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil.
(3) Núcleo de Avaliação de Tecnologias em Saúde, Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
(4) Departamento de Dermatologia, Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
(5) Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
(6) National Centre for Human Retrovirology, Imperial College Healthcare NHS Trust, London, UK.
(7) Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil.
(8) Instituto Gonçalo Muniz, Fundação Oswaldo Cruz, Salvador, Brazil.
(9) Instituto de Infectologia Emílio Ribas, São Paulo, Brazil.
(10) Centro de Imunologia, Instituto Adolfo Lutz, São Paulo, Brazil.
(11) Centre for Economics of Obesity, Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
(12) Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil; Health Technology Assessment Unit, Hospital Universitário Professor Edgar Santos, Universidade Federal da Bahia, Salvador, Brazil.
(13) Faculdade de Medicina Veterinária, Universidade Estácio de Sá, Rio de Janeiro, Brazil.
(14) Departamento de Medicina Geral, Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; Programa de Pós-graduação em Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
(15) Section of Virology, Department of Infectious Disease, Imperial College London, London, UK; National Centre for Human Retrovirology, Imperial College Healthcare NHS Trust, London, UK.

Resumo:
BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. METHODS: In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. FINDINGS: The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. INTERPRETATION: HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide

46 - Virologic response to antiretroviral therapy in people with HIV and tuberculosis in high-TB burden countries. AIDS. 2023 Feb 17. doi: 10.1097/QAD.0000000000003521.

De Castro N(1)(2), Chazallon C(1), Brites C(3), Messou E(4)(5)(6), Khosa C(7), Laureillard D(8)(9), Chau GD(10), Pilotto JH(11), Eholie S(4)(6), Delaugerre C(12)(13)(14), Molina JM(2)(13)(14), Wittkop L(15)(16)(17), Grinsztejn B(18), Marcy O(1).

Afiliação:
(1) University of Bordeaux, National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, Bordeaux, France.
(2) Infectious Diseases Department, AP-HP-Hôpital Saint-Louis Lariboisière, Paris, France.
(3) Laboratório de Pesquisa em Doenças Infecciosas, Hospital Universitário Prof Edgar Santos,Bahia, Brazil.
(4) Programme PACCI/ANRS Research Center, Abidjan, Côte-d'Ivoire.
(5) Centre de Prise en Charge de Recherche et de Formation, CePReF-Aconda-VS, Abidjan, Cote D'Ivoire.
(6) Département de Dermatologie et d'Infectiologie, UFR des Sciences Médicales, Université Félix Houphouët Boigny, Abidjan, Cote d'Ivoire.
(7) Instituto Nacional de Saúde, Marracuene, Mozambique.
(8) Department of Infectious and Tropical Diseases, Nimes University Hospital, Nimes, France.
(9) Research Unit 1058, Pathogenesis and Control Chronical Infections, INSERM, French Blood Center, University of Montpellier, Montpellier, France.
(10) Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam.
(11) Laboratorio de AIDS e Imunologia Molecular-IOC/Fiocruz, Rio de Janeiro, Brazil.
12) Virology department, APHP-Hôpital Saint-Louis, Paris.
(13) INSERM U944, Paris.
(14) Université Paris Cité, Paris, France.
(15) University Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401, F-33000, Bordeaux, France.
(16) INRIA SISTM team, Talence.
(17) CHU de Bordeaux, Service d'information médicale, INSERM, Institut Bergonié, CIC-EC 1401, F-33000 Bordeaux, France.
(18) National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.

Resumo:
OBJECTIVES: We sought to compare virologic outcomes on ART between people with HIV (PWH) also treated for tuberculosis in the different countries who participated to two randomized trials. DESIGN: Pooled analysis of two randomized clinical trials. METHODS: In the phase II Reflate TB and phase III Reflate TB2 trials in Brazil, Côte d'Ivoire, Mozambique and Vietnam, ART-naïve PWH treated for tuberculosis were randomized to receive raltegravir or efavirenz. We assessed country differences in baseline characteristic using Wilcoxon tests and chi-square, or Fisher's exact test. We used logistic regression to analyze determinants of virologic success, defined as week-48 plasma HIV-1 RNA <50 copies/mL. RESULTS: Of 550 participants (140 from Brazil, 170 from Côte d'Ivoire, 129 from Mozambique and 111 from Vietnam) with median baseline HIV-1 RNA of 5.4 log10 copies/mL, 362 (65.8%) achieved virologic success at week 48. Virologic success rates were: 105/140 (75.0%) in Brazil, 99/170 (58.2%) in Côte d'Ivoire, 84/129 (65.1%) in Mozambique and 74/111 (66.7%) in Vietnam (P = 0.0233). Baseline HIV-1 RNA, but not the country, was independently associated with virologic success: reference HIV-1 RNA≥500, 000 copies/mL, HIV RNA <100,000 copies/mL OR: 3.12 (95%CI 1.94; 5.01) and HIV-1 RNA 100,000-499,999 copies/mL OR: 1.80 (95% CI 1.19; 2.73). Overall, 177/277 (63.9%) patients treated with raltegravir and 185/273 (67.9%) patients treated with efavirenz had a plasma HIV-1 RNA <50 copies/mL at week 48. CONCLUSIONS: Virologic response to antiretroviral therapy in PWH with TB varied across countries but was mainly driven by levels of pretreatment HIV-1 RNA.

47 - Epidemiological profile of rosacea in dermatology outpatient clinics in Brazil: an observational report from the Brazilian study group on rosacea. Eur J Dermatol. 2023 Feb 1;33(1):6-11. doi: 10.1684/ejd.2023.4405. 

Suarez MV(1), Francesconi F(2), Gonçalves H(3), Dal Forno T(4), Ribeiro BM(5), Mulinari-Brenner F(6), Costa IMC(7), Filho JWA(8), Cunha MG(9), Follador I(10), Cotrim P(11), Neves JR(12), Brito MFM(13), Francesconi VA(2), Pontes MAA(3), Queiroz AJR(7), Rego V(10), Zink BS(11), Marques LP(12).

Afiliação:
(1) Hospital do Servidor Público Municipal de São Paulo. Rua Castro Alves 60, 5° andar sala 52, São Paulo, SP, 01532001, Brazil.
(2) Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Av. Pedro Teixeira, s/n - Manaus - AM - 69040-000, Brazil.
(3) Centro de Dermatologia Dona Libania. R. Pedro I, 1033 - Fortaleza - CE - 60035-100, Brazil.
(4) Hospital São Lucas da PUCRS. Av. Ipiranga, 6681 - Porto Alegre - RS - 90619-900, Brazil.
(5) Hospital Regional da Asa Norte. Setor Médico Hospitalar Norte Q 2 - Brasília - DF - 70710-100, Brazil.
(6) Universidade Federal do Paraná. Rua João Negrão, 280 - Curitiba - Paraná - 80010-200, Brazil.
(7) Hospital Universitário de Brasília. Setor de Grandes Áreas Norte 605 - Brasília - DF - 70840-901, Brazil.
(8) Serviço de Dermatologia do Hospital Universitário Walter Cantidio-UFCE. Rua Pastor Samuel Munguba, 1290 - Fortaleza - CE - 60430-370, Brazil.
(9) Fundação do ABC - Faculdade de Medicina do ABC. Av. Lauro Gomes, 2000 - Santo André - SP -09060-870, Brazil.
(10) Universidade Federal da Bahia - Hospital Universitário Professor Edgar Santos. R. Dr. Augusto Viana, s/n - Salvador - BA - 40110-060, Brazil.
(11) Serviço de Dermatologia do Hospital Federal de Bonsucesso. Av. Londres, 616 - prédio 6 - 2° andar - Rio de Janeiro - RJ - 21041-030, Brazil.
(12) Setor de Dermatologia do Hospital de Força Aérea do Galeão. Estrada do Galeão, 4101 - Rio de Janeiro - RJ -21941-353, Brazil.
(13) Universidade Federal de Pernambuco - Serviço de Dermatologia. Av. Prof. Moraes Rego, 1235 - Recife - PE - Brazil, 50670-901, Brazil.

Resumo:
BACKGROUND: Rosacea prevalence varies worldwide and there is a lack of information in Brazil. OBJECTIVES: To describe the epidemiological profile of rosacea in subjects who consulted in dermatological outpatient clinics in Brazil. MATERIALS & METHODS: A cross-sectional study was conducted in 13 dermatological outpatient clinics across the country. Patients with rosacea diagnosis were eligible for the study according to the investigator's clinical assessment. Clinical, social and demographic data were collected. The overall and regional rosacea prevalence was calculated, and association with baseline characteristics was analysed. RESULTS: A total of 3,184 subjects were enrolled, and rosacea prevalence was 12.7%. The southern region of Brazil presented a higher prevalence, followed by the southeast. The subjects in the rosacea group were older than those without rosacea (52.5 ±14.9 vs. 47.5 ±17.5; p<0.001). Moreover, the rosacea group was associated with Fitzpatrick's phototypes I and II, Caucasian ethnicity, a family history of rosacea, and facial erythema, however, no association with gender was found. The most prevalent clinical sign and clinical subtype in rosacea patients were erythema and erythematotelangiectatic, respectively. CONCLUSION: Rosacea is highly prevalent in Brazil, mostly in the southern region, associated with phototypes I and II and a family history.

48 - Psychopathological symptoms in parents and siblings of people on the autism spectrum: A systematic review and meta-analysis. Psychiatry Res. 2023 May;323:115145. doi: 10.1016/j.psychres.2023.115145.

Bispo-Torres AC(1), Lucena R(2), Tavares-Rodrigues IC(1), Barouh JL(3), Lins-Silva DH(3), Dorea-Bandeira I(4), Souza LS(3), Faria-Guimarães D(3), Tolentino A(1), Miranda-Scippa Â(2), Hermens DF(5), Sampaio AS(6), Quarantini LC(6), Glozier N(7), Hickie IB(8), Bandeira ID(9).

Afiliação:
(1)    Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40025010, Brazil.
(2)    Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40025010, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40110060, Brazil.
(3)    Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40025010, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110060, Brazil.
(4)    Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110060, Brazil.
(5)    Sunshine Coast Mind and Neuroscience Thompson Institute, University of the Sunshine Coast, Sunshine Coast 4575, Australia.
(6)    Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40025010, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador 40110060, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia.
(7)    Brain and Mind Centre, The University of Sydney, Sydney 2050, Australia; Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney 2050, Australia.
(8)    Brain and Mind Centre, The University of Sydney, Sydney 2050, Australia.
(9)    Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto 94305, United States. Electronic address: igordbandeira@gmail.com.

Resumo:
Parents and siblings of children on the autism spectrum experience significant distress, and for this reason, it is essential to understand the most prevalent psychopathological symptoms among this population. This work aims to establish the prevalence of psychopathological symptoms in parents and siblings of individuals on the autism spectrum, following the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) criteria. Searches were carried out using the PubMed/Medline, Embase, PsycINFO, SciELO, and Biblioteca Virtual em Saúde (BVS) databases. Twenty-three articles were included in this review. Depressive symptoms were the most frequently reported conditions, with a higher prevalence in mothers of children on the autism spectrum. In the meta-analysis, mothers of children on the autism spectrum scored higher by 0.42 standard deviations on the symptom scales (SMD 0.42; CI 0.25-0.59), with low statistical heterogeneity (I2 0%, p = 0.5) when compared with mothers of children with atypical development. The psychopathological symptoms of relatives should be investigated as part of the follow-up procedures for the child on the autism spectrum to facilitate their treatment.

49 - SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease - 2023Arq Bras Cardiol. 2023 Jun 26;120(6):e20230269. doi: 10.36660/abc.20230269.

Marin-Neto JA(1), Rassi A Jr(2), Oliveira GMM(3), Correia LCL(4), Ramos Júnior AN(5), Luquetti AO(6), Hasslocher-Moreno AM(7), Sousa AS(7), Paola AAV(8), Sousa ACS(9)(10), Ribeiro ALP(11), Correia Filho D(9), Souza DDSM(12), Cunha-Neto E(13), Ramires FJA(14), Bacal F(14), Nunes MDCP(11), Martinelli Filho M(14), Scanavacca MI(14), Saraiva RM(7), Oliveira Júnior WA(15), Lorga-Filho AM(16)(17), Guimarães AJBA(18)(19), Braga ALL(20), Oliveira AS(14), Sarabanda AVL(21), Pinto AYDN(7), Carmo AALD(22), Schmidt A(1), Costa ARD(7), Ianni BM(14), Markman Filho B(23), Rochitte CE(14)(24), Macêdo CT(25), et al.

Afiliação:
(1) Universidade de São Paulo , Faculdade de Medicina de Ribeirão Preto , Ribeirão Preto , SP - Brasil.
(2) Hospital do Coração Anis Rassi , Goiânia , GO - Brasil.
(3) Universidade Federal do Rio de Janeiro , Rio de Janeiro , RJ - Brasil.
(4) Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador , BA - Brasil.
(5) Universidade Federal do Ceará , Faculdade de Medicina , Fortaleza , CE - Brasil.
(6) Centro de Estudos da Doença de Chagas , Hospital das Clínicas da Universidade Federal de Goiás , Goiânia , GO - Brasil.
(7) Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ - Brasil.
(8) Universidade Federal de São Paulo , São Paulo , SP - Brasil.
(9) Universidade Federal de Sergipe , São Cristóvão , SE - Brasil.
(10) Hospital São Lucas , Rede D`Or São Luiz , Aracaju , SE - Brasil.
(11) Universidade Federal de Minas Gerais , Belo Horizonte , MG - Brasil.(12)                       Universidade Federal do Pará , Belém , PA - Brasil.}
(13) Universidade de São Paulo , Faculdade de Medicina da Universidade, São Paulo, SP - Brasil.
(14) Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil.
(15) Universidade de Pernambuco , Faculdade de Ciências Médicas , Recife , PE - Brasil.
(16) Instituto de Moléstias Cardiovasculares , São José do Rio Preto , SP - Brasil.
(17) Hospital de Base de Rio Preto , São José do Rio Preto , SP - Brasil.
(18) Secretaria de Saúde do Distrito Federal , Brasília , DF - Brasil.
(19) Escola Superior de Ciências da Saúde , Brasília , DF - Brasil.
(20) Hospital Universitário Professor Edgard Santos , Universidade Federal da Bahia , Salvador , BA - Brasil.
(21) Instituto de Cardiologia do Distrito Federal , Brasília , DF - Brasil.
(22) Hospital das Clínicas da Universidade Federal de Minas Gerais , Belo Horizonte , MG - Brasil.
(23)Hospital das Clínicas da Universidade Federal de Pernambuco , Recife , PE - Brasil.
(24) Hcor, Associação Beneficente Síria , São Paulo , SP - Brasil.
(25) Hospital São Rafael, Fundação Monte Tabor , Salvador , BA - Brasil.

Resumo não disponível.

50 - Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries. Liver Int. 2023 Aug;43(8):1749-1760. doi: 10.1111/liv.15623.

García-Cortés M(1)(2), Ortega-Alonso A(1)(2), Matilla-Cabello G(1), Medina-Cáliz I(1), Castiella A(3)(4), Conde I(5), Bonilla-Toyos E(1)(6), Pinazo-Bandera J(1), Hernández N(7), Tagle M(8), Nunes V(9), Parana R(10), Bessone F(11), Kaplowitz N(12), Lucena MI(1)(2)(6), Alvarez-Alvarez I(1)(2)(6), Robles-Díaz M(1)(2), Andrade RJ(1)(2).

Afiliação:
(1)    Servicios de Aparato Digestivo and Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Universidad de Málaga, Málaga, Spain.
(2)    Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
(3)    Servicio de Gastroenterología, Hospital Universitario de Donostia, San Sebastián, Spain.
(4)    Servicio de Gastroenterología, Hospital de Mendaro, Mendaro, Spain.
(5)    Servicio de Aparato Digestivo, Hospital Universitari i Politècnic La Fe, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
(6)    Platform ISCIII for Clinical Research and Clinical Trials UICEC-IBIMA, Málaga, Spain.
(7)    Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.
(8)    Universidad Peruana Cayetano Heredia, Lima, Peru.
(9)    Hospital Universitario Prof. Edgard Santos, Salvador de Bahia, Brazil.
(10)  Universidad Federal de Bahia, Bahia, Brazil.
(11)  Hospital Provincial del Centenario, Facultad de Medicina, Universidad Nacional de Rosario, Rosario, Argentina.
(12)  University of Southern California Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Resumo:
BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (DILI) with autoimmune features is a liver condition with laboratory and histological characteristics similar to those of idiopathic autoimmune hepatitis (AIH), which despite being increasingly reported, remains largely undefined. We aimed to describe in-depth the features of this entity in a large series of patients from two prospective DILI registries. METHODS: DILI cases with autoimmune features collected in the Spanish DILI Registry and the Latin American DILI Network were compared with DILI patients without autoimmune features and with an independent cohort of patients with AIH. RESULTS: Out of 1,426 patients with DILI, 33 cases with autoimmune features were identified. Female sex was more frequent in AIH patients than in the other groups (p = .001). DILI cases with autoimmune features had significantly longer time to onset (p < .001) and resolution time (p = .004) than those without autoimmune features. Interestingly, DILI patients with autoimmune features who relapsed exhibited significantly higher total bilirubin and transaminases at onset and absence of peripheral eosinophilia than those who did not relapse. The likelihood of relapse increased over time, from 17% at 6 months to 50% 4 years after biochemical normalization. Statins, nitrofurantoin and minocycline were the drugs most frequently associated with this phenotype. CONCLUSIONS: DILI with autoimmune features shows different clinical features than DILI patients lacking characteristics of autoimmunity. Higher transaminases and total bilirubin values with no eosinophilia at presentation increase the likelihood of relapse in DILI with autoimmune features. As the tendency to relapse increases over time, these patients will require long-term follow-up.

51 - Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial. Trends Psychiatry Psychother. 2023 Mar 7;45:e20210298. doi: 10.47626/2237-6089-2021-0298.

Caliman-Fontes AT(1), Leal GC(2), Correia-Melo FS(3), Paixão CS(4), Carvalho MS(5), Jesus-Nunes AP(3), Vieira F(3), Magnavita G(6), Bandeira ID(3), Mello RP(3), Beanes G(3), Silva SS(7), Echegaray M(6), Carvalho LP(4), Machado P(4), Sampaio AS(1), Cardoso TA(8), Kapczinski F(9), Lacerda ALT(5), Quarantini LC(10).

Afiliação:
(1)    Faculdade de Medicina da Bahia, Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil. Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil.
(2)    Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil. Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, UFBA, Salvador, BA, Brazil. Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil.
(3)    Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil. Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil.
(4)    Laboratório de Pesquisas Clínicas, Instituto Gonçalo Moniz, Fiocruz, Salvador, BA, Brazil. Serviço de Imunologia, UFBA, Salvador, BA, Brazil.
(5)    Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de São Paulo, São Paulo, Brazil.
(6)    Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil.
(7)    Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil. Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, UFBA, Salvador, BA, Brazil.
(8)    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
(9)    Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
(10)  Faculdade de Medicina da Bahia, Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil. Laboratório de Neuropsicofarmacologia, Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil. Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, FBA, Salvador, BA, Brazil. Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, UFBA, Salvador, BA, Brazil.

Resumo:
OBJECTIVES: Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). METHODS: Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. RESULTS: There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. CONCLUSION: There was no significant treatment impact on BDNF serum levels - neither with ketamine nor esketamine - despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion.

52 - Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis. Dig Dis Sci. 2023 Feb;68(2):514-520. doi: 10.1007/s10620-022-07654-x.

Cançado GGL(1)(2), Couto CA(3), Terrabuio DRB(4), Cançado ELR(4), Villela-Nogueira CA(5), Ferraz MLG(6), Braga MH(4), Nardelli MJ(3), Faria LC(3), de Faria Gomes NM(6), Oliveira EMG(7), Rotman V(5), Oliveira MB(8), da Cunha SMCF(9), Cunha-Silva M(10),et al.; Members of the Brazilian Cholestasis Study Group Consortium.

Afiliação:
(1)    Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Av. Professor Alfredo Balena 110, Belo Horizonte, Minas Gerais, 30130-100, Brazil.
(2)    Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
(3)    Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
(4)    Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil.
(5)    Hospital Universitário Clementino Fraga Filho e Departamento de Clínica Médica da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
(6)    Disciplina de Gastroenterologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
(7)    Centro Universitário Lusíada - UNILUS, Santos, São Paulo, Brazil.
(8)    Ambulatório Municipal de Hepatites Virais de São José dos Campos, São José dos Campos, São Paulo, Brazil.
(9)    Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(10)  Divisão de Gastroenterologia (Gastrocentro), Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.

Resumo:
BACKGROUND: Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies.AIMS: This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. METHODS: Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC.RESULTS: 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001). CONCLUSIONS: After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.