2024.2

1.      Contrasting Phenotypes of Neutrophils During Asymptomatic Versus Symptomatic Leishmania braziliensis Infection. J Infect Dis. 2024 Dec ani

Conceição JA(1)(2)(3), Carneiro PP(2), Dórea AS(2), Oliveira WN(2), Muniz AC(2),
Carvalho EM(4)(5), Wilson ME(1)(3)(6), Bacellar O(2)(5).

Afiliação:
(1)   Department of Internal Medicine, University of Iowa, Iowa City.
(2)   Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
(3)   Medical Service, Veterans' Affairs Medical Center, Iowa City.
(4)   Instituto Gonçalo Moniz, Fiocruz Bahia.
(5)   Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais, The National Council for Scientific and Technological Development/Ministry of Science and Technology, Salvador, Brazil.
(6)   Department of Microbiology and Immunology, University of Iowa, Iowa City.

Resumo:
The mechanisms that mediate immune protection in individuals with subclinical (SC) or asymptomatic infection with Leishmania braziliensis are largely unknown. Neutrophils (polymorphonuclear leukocytes [PMNs]) have been implicated in progressive symptomatic cutaneous leishmaniasis (CL), but their potential participation in maintenance of subclinical infection is unexplored. The aim of this study was to compare the phenotypic and functional profiles of PMNs in individuals with SC infection versus patients with symptomatic CL due to L braziliensis. METHODS: Subjects were recruited in the endemic region of Corte de Pedra, Bahia, Brazil. Surface markers to define activation status were characterized by flow cytometry. Functional responses of PMNs including phagocytic capacity, production of oxidative species, and oxidative killing of intracellular parasites were studied in vitro. RESULTS: PMNs from individuals with SC infection displayed a more activated phenotype and greater ability to control the infection than PMNs from patients with CL. In contrast, PMNs from patients with CL exhibited higher expression of HLA-DR and higher production of oxidative species than PMNs from subjects with SC infection. CONCLUSIONS: PMNs from individuals with SC infection can control the infection more efficiently than PMNs from patients with CL, despite the lower production of oxidants. Our observations suggest that L braziliensis may evade microbicidal mechanisms of PMNs from patients with CL, contributing to parasite dissemination and the establishment of disease.

2.      The Brazilian association of hematology, hemotherapy, and cell therapy (ABHH) and its absolute commitment to ethics and absence of conflicts of interest. Hematol Transfus Cell Ther. 2024 Jul-Sep;46(3):219-220. doi: 10.1016/j.htct.2024.05.003.

de Souza CA(1), Rego EM(2), Ribeiro GN(3), Magalhães SMM(4), da Silva CAR(5),
Passos LNDM(6), Covas DT(7), Tavares RS(8), Hungria VTM(9), Crusoé EQ(10), ...

Afiliação:
(1)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
(2)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
(3)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
(4)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
(5)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Universidade Federal de São Paulo (UNIFESP), Sao Paulo, SP, Brazil.
(6)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Fundação de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, AM, Brazil.
(7)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Hemocentro de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil.
(8)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Hospital das Clínicas da Universidade Federal de Goiás (HC UFG), Goiania, GO, Brazil.
(9)   Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP), São Paulo, SP, Brazil.
(10)  Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), São Paulo, SP, Brazil; Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil.
...

3.      Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. N Engl J Med. 2024 Nov 27. doi: 10.1056/NEJMoa2411858.

Kelley CF(1), Acevedo-Quiñones M(1), Agwu AL(1), Avihingsanon A(1), Benson P(1), Blumenthal J(1), Brinson C(1), Brites C(1), Cahn P(1), ...; PURPOSE 2 Study Team.

Afiliação:
(1)From the Hope Clinic of the Emory University School of Medicine, Decatur (C.F.K.), and Grady Health System (C.F.K.), and the Division of Infectious Diseases, Emory University-Ponce de Leon Center Clinical Research Site, HIV/AIDS Clinical Trials Unit (V.D.C.), Atlanta - all in Georgia; the Divisions of Pediatric and Adult Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore (A.L.A.); Be Well Medical Center, Berkley, MI (P.B.); the Department of Medicine, University of California, San Diego, San Diego (J.B.), the Department of Medicine, University of California, Los Angeles (J.C.), Ruane Clinical Research (P.J.R.), and Drew Center for AIDS Research, Education, and Services, Charles R. Drew University (L.Y.S.), Los Angeles, Optimus Medical Group/StudyOps, San Francisco (S.H.), Mills Clinical Research, West Hollywood (A.M.), Bios Clinical Research, Palm Springs (P.S.), and Gilead Sciences, Foster City (S.C., R.E., P.W., R.S., L.B.B., C.C.C., M.D., J.M.B.) - all in California; ...; Complexo Hospitalar Universitário Professor Edgard Santos, Salvador, ...}

Resumo:
Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.METHODS: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF). The primary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with the background HIV incidence in the screened population. The secondary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with that in the F/TDF group. RESULTS: Among 3265 participants who were included in the modified intention-to-treat analysis, HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years; 95% confidence interval [CI], 0.01 to 0.37) and in 9 participants in the F/TDF group (0.93 per 100 person-years; 95% CI, 0.43 to 1.77). The background HIV incidence in the screened population(4634 participants) was 2.37 per 100 person-years (95% CI, 1.65 to 3.42). The incidence of HIV infection in the lenacapavir group was significantly lower than both the background incidence (incidence rate ratio, 0.04; 95% CI, 0.01 to 0.18; P<0.001) and the incidence in the F/TDF group (incidence rate ratio, 0.11; 95% CI, 0.02 to 0.51; P = 0.002). No safety concerns were identified. A total of 26 of 2183 participants (1.2%) in the lenacapavir group and 3 of 1088 (0.3%) in the F/TDF group discontinued the trial regimen because of injection-site reactions. CONCLUSIONS: The HIV incidence with twice-yearly lenacapavir was significantly lower than the background incidence and the incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 2 ClinicalTrials.gov number, NCT04925752.).

4.      Acute heart failure due to myocarditis in Takayasu's arteritis. Reumatismo. 2024 Sep 24;76(4). doi: 10.4081/reumatismo.2024.1681.

Castro de Oliveira Figueirôa MDL(1), Moura Costa MC(2), Rocha Lobo P(2), Souza
Pedreira AL(3), Barreto Santiago M(4).

Afiliação:
(1)   BAHIANA - School of Medicine and Public Health, Salvador; Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador.
(2)   Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador.
(3)   BAHIANA - School of Medicine and Public Health, Salvador.
(4)   Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador; Specialized Rheumatology Services in Bahia (SER), Salvador.

Resumo:
Takayasu's arteritis (TA) is a granulomatous vasculitis that involves the aortic artery and its branches, resulting in stenosis, occlusion, and aneurysmal dilatation. Cardiovascular involvement is one of the main complications and a major cause of mortality in these patients. Herein, we describe the case of a woman with TA who presented with severe acute heart failure secondary to myocarditis and responded well to immunosuppressive therapy.

5.      Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: A randomized controlled trial. Int J Infect Dis. 2024 Oct;147:107206. doi: 10.1016/j.ijid.2024.107206.

Lago T(1), Peixoto F(2), Mambelli F(3), Carvalho LP(4), Guimarães LH(5), Carvalho AM(6), Cardoso L(7), Machado PRL(7), Scott P(8), Lago J(1), Andrade JM(3), Fahel JS(3), Oliveira SC(9), Carvalho EM(10).

Afiliação:
(1)   Immunology Service of University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil; Post Graduate Program of Health Sciences, Federal University of Bahia, Salvador, Bahia, Brazil.
(2)   Gonçalo Moniz Institute, Fiocruz, Salvador, Bahia, Brazil.
(3)   Federal University of Minas Gerais, Belo Horizonte, Brazil.
(4)   Immunology Service of University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil; Post Graduate Program of Health Sciences, Federal University of Bahia, Salvador, Bahia, Brazil; National Institute of Science and Technology of Tropical Diseases (INCT-DT), Ministry of Science, Technology, Innovations and Communications, CNPq, Brasília, Distrito Federal, Brazil; Health Science Institute, Federal University of Bahia, Salvador, Bahia, Brazil; Gonçalo Moniz Institute, Fiocruz, Salvador, Bahia, Brazil.
(5)   National Institute of Science and Technology of Tropical Diseases (INCT-DT), Ministry of Science, Technology, Innovations and Communications, CNPq, Brasília, Distrito Federal, Brazil; Federal University of the Recôncavo da Bahia, Cruz das Almas, Bahia, Brazil.
(6)   National Institute of Science and Technology of Tropical Diseases (INCT-DT), Ministry of Science, Technology, Innovations and Communications, CNPq, Brasília, Distrito Federal, Brazil; Gonçalo Moniz Institute, Fiocruz, Salvador, Bahia, Brazil.
(7)   Immunology Service of University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil; National Institute of Science and Technology of Tropical Diseases (INCT-DT), Ministry of Science, Technology, Innovations and Communications, CNPq, Brasília, Distrito Federal, Brazil.
(8)   Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, PA, USA.
(9)   Federal University of Minas Gerais, Belo Horizonte, Brazil; National Institute of Science and Technology of Tropical Diseases (INCT-DT), Ministry of Science, Technology, Innovations and Communications, CNPq, Brasília, Distrito Federal, Brazil; University of São Paulo, São Paulo, Brazil.
(10)   Immunology Service of University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil; National Institute of Science and Technology of Tropical Diseases (INCT-DT), Ministry of Science, Technology, Innovations and Communications, CNPq, Brasília, Distrito Federal, Brazil; Gonçalo Moniz Institute, Fiocruz, Salvador, Bahia, Brazil.

Resumo: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1β play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down-modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL. METHODS: In this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20 mg/kg/weight) for 20 days. Group 1 used topical rSm29 (10 µg), group 2 a placebo topically applied, and group 3 received only MA. RESULTS: The cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P < 0.05). There was a decrease in GzmB and an increase in IFN-γ (P < 0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P < 0.05) in patients who received rSm29. CONCLUSION: rSm29 associated with MA reduces GzmB levels, is more effective than MA alone, and decreases CL healing time.

6.      The importance of secondary cancer screening programs in Hodgkin lymphoma survivors. Haematologica. 2024 Oct 1;109(10):3100-3102. doi: 10.3324/haematol.2023.284609.

Salvino MA(1), Domingo-Domènech E(2), Sureda A(3).

Afiliação:
(1)   Complexo Hospitalar Universitário Professor Edgard, Universidade Federal de Bahia (HUPES UFBA), Salvador, BA, Brazil; Hospital San Rafael Rede D'or Oncologia, Salvador, BA.
(2)   Clinical Hematology Department, Institut Català d'Oncologia - L'Hospitalet, Institut d'Investigació de Ciències Biomèdiques de Bellvitge (IDIBELL), Barcelona.
(3)   Clinical Hematology Department, Institut Català d'Oncologia - L'Hospitalet, Institut d'Investigació de Ciències Biomèdiques de Bellvitge (IDIBELL), Universitat de Barcelona, Barcelona.

Sem resumo

7.      Description of the new HIV-1 intersubtype B/C circulating recombinant form (CRF146_BC) detected in Brazil. Mem Inst Oswaldo Cruz. 2024 Sep 23;119:e230214. doi: 10.1590/0074-02760230214.

Oliveira RC(1), Martin D(2), de Souza JSM(1), Alcântara LCJ(3), Guimarães ML(4),
Brites C(5), Monteiro-Cunha JP(1).

Afiliação:
(1)   Universidade Federal da Bahia, Departamento de Bioquímica e Biofísica, Núcleo de Bioinformática, Salvador, BA, Brasil.
(2)   University of Cape Town, Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Computational Biology Group, Cape Town, South Africa.
(3)   Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Flavivírus, Rio de Janeiro, RJ, Brasil.
(4)   Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de AIDS e Imunologia Molecular, Rio de Janeiro, RJ, Brasil.
(5)   Universidade Federal da Bahia, Complexo Hospitalar Prof Edgard Santos, Laboratório de Pesquisa em Infectologia, Salvador, BA, Brasil.

Resumo: The human immunodeficiency virus 1 (HIV-1) infections in Brazil are predominantly caused by two subtypes, B and C. OBJECTIVES: Here we present the characterisation of a novel HIV-1 recombinant form, indicating a new Brazilian CRF_BC, named CRF146_BC. METHODS: RDP, JphMM and Simplot recombination tools were used to evaluate the mosaic pattern. FINDINGS: In this work, we identified three HIV-1 nucleotide sequences previously classified as unique recombinant forms (URFs), plus one new partial genome sharing the same BC recombination pattern. The mosaic genome is almost entirely represented by the subtype C sequence, with a small subtype B recombination region in the pol gene, at the Integrase level. The phylogenetic  analyses strongly indicate a common origin between the strains, which were isolated in Rio Grande do Sul, Rio de Janeiro and Bahia states. MAIN CONCLUSIONS: Thus, the new HIV-1 CRF146_BC is circulating in three different Brazilian regions: South, Southeast and Northeast.

8.      Infective dermatitis associated with human T-cell lymphotropic virus type-1, an underdiagnosed disease. Int J Infect Dis. 2024 Aug;145:107058. doi: 10.1016/j.ijid.2024.107058.

Bittencourt AL(1), Farre L(2).

Afiliação:
(1)   Department of Pathology, Prof. Edgard Santos Teaching Hospital, Federal University of Bahia, Salvador, Brazil.
(2)   Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), ONCOBELL, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Spain. Electronic address: lfarre@iconcologia.net.

Resumo: Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.

9.      Anesthesia and perioperative care management in patients with Dengue Fever: considerations and challenges. Braz J Anesthesiol. 2024 Jul-Aug;74(4):844511. doi: 10.1016/j.bjane.2024.844511.

Carvalho LIM(1), Azi LMTA(2), Leal PDC(3), Lorentz MN(4), Diego LADS(5), Schmidt AP(6).

Afiliação:
(1)   Hospital Prontomed, Departamento de Anestesiologia, Teresina, PI, Brazil; Hospital Unimed Primavera, Teresina, PI, Brazil.
(2)   Hospital Universitário Professor Edgard Santos, Departamento de Anestesiologia, Salvador, BA, Brazil; Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil.
(3)   Hospital São Domingos, Departamento de Anestesiologia, São Luís, MA, Brazil; Universidade Federal do Maranhão (UFMA), São Luís, MA, Brazil.
(4)   Hospital Biocor / Rede D'or, Nova Lima, MG, Brazil.
(5)   Universidade Federal Fluminense (UFF), Departamento de Anestesiologia, Rio de Janeiro, RJ, Brazil.
(6)   Hospital de Clínicas de Porto Alegre (HCPA), Serviço de Anestesia e Medicina Perioperatória, Porto Alegre, RS, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Santa Casa de Porto Alegre, Serviço de Anestesia, Porto Alegre, RS, Brazil; Hospital Nossa Senhora da Conceição, Serviço de Anestesia, Porto Alegre, RS, Brazil; Universidade Federal do Rio Grande do Sul (UFRGS), Programa de Pós-graduação em Ciências Pneumológicas, Porto Alegre, RS, Brazil; Universidade Federal do Rio Grande do Sul (UFRGS), Programa de Pós-graduação em Ciências Cirúrgicas, Porto Alegre, RS, Brazil; Faculdade de Medicina da Universidade de São Paulo (FMUSP), Programa de Pós-Graduação em Anestesiologia, Ciências Cirúrgicas e Medicina Perioperatória, São Paulo, SP, Brazil.

Sem resumo

10.      Validation of the HIV/AIDS-Targeted Quality of Life (HAT-QOL) for Evaluation of Health-related Quality of Life in People Living with HIV/AIDS in Brazil. AIDS Behav. 2024 Dec;28(12):4188-4198. doi: 10.1007/s10461-024-04496-8.

Valdelamar-Jiménez JR(1)(2), Narváez Betancur MB(2), Brites C(1)(2), Lins-Kusterer L(3)(4)(5)

Afiliação:
(1)   Graduate Program in Medicine and Health, School of Medicine, Federal University of Bahia, Salvador, Brazil.
(2)   LAPI- Infectious Diseases Research Laboratory, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil
(3)   Graduate Program in Medicine and Health, School of Medicine, Federal University of Bahia, Salvador, Brazil.
(4)   LAPI- Infectious Diseases Research Laboratory, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil.

Resumo: HIV/AIDS-Targeted Quality of Life (HAT-QOL) is an instrument for evaluating health-related quality of life (HRQOL) in people living with HIV (PLWHIV). This has been adapted into Brazilian Portuguese, but its dimensional structure has not been analyzed. This study evaluated the psychometric properties of the Brazilian Portuguese version of the HAT-QOL, using a sample of 319 PLWHIV in Salvador, Brazil. The study performed Exploratory Factor Analysis (EFA) to assess the HAT-QOL dimensional structure. The analysis used a polychoric correlation matrix, Robust Diagonally Weighted Least Squares (RDWLS) as an extraction method, Parallel Analysis for factor retention, robust promin as oblique rotation, and Generalized H-index (G-H) for construct replicability of each factor. Model adequacy was assessed using the Root Mean Square Error of Approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI). Concurrent validity was evaluated with the 36-item Short Form Health Survey, version 2 (SF-36v2). EFA identified a HAT-QOL six-factor solution: Financial Worries, Sexual Function, Medication Concerns, Life Satisfaction, Health Worries, and Overall Function. This solution showed high G-H indexes, concurrent validity, and satisfactory adequacy indexes (X2 = 231.345, df = 291, p < 0,001; RMSEA = 0.001, CFI = 0.999, TLI = 1.028). HIV Mastery, Disclosure Worries, and Provider Trust domains were not retained in EFA and did not have evidence of concurrent validity. This study proposed a HAT-QOL six-factor model for measuring HRQOL in the Brazilian PLWHIV. Future research could help identify another latent construct from not-included domains.

11.      Efficacy of sodium nitroprusside in the treatment of drug-naive subjects in first episode psychosis - An open label study. Schizophr Res. 2024 Jul;269:114-115. doi: 10.1016/j.schres.2024.05.010.

Adelino MPM(1), Nunes MV(2), Nunes MFQ(2), Quarantini LC(3), Hallak JEC(4), Lacerda ALT(5).

Afiliação:
(1)   LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo, São Paulo, Brazil; CNS Unit, BR Trials, São Paulo, Brazil.
(2)   LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo, São Paulo, Brazil; CNS Unit, BR Trials, São Paulo, Brazil.
(3)   Hospital Universitário Professor Edgard Santos, Serviço de Psiquiatria, Universidade Federal da Bahia, Brazil; Laboratório de Neuropsicofarmacologia, Universidade Federal da Bahia, Salvador, Brazil; Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Brazil.
(4)   Department of Neuroscience and Behavior, University of São Paulo, Ribeirão Preto, Brazil; National Institute of Science and Technology in Translational Medicine, CNPq/FAPESP/CAPES, Brazil; PRODAF - Programa de Transtornos Afetivos (Mood Disorders Unit), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
(5)   LiNC - Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo, São Paulo, Brazil; CNS Unit, BR Trials, São Paulo, Brazil; National Institute of Science and Technology in Translational Medicine, CNPq/FAPESP/CAPES, Brazil; PRODAF - Programa de Transtornos Afetivos (Mood Disorders Unit), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.

Sem resumo

12.      Rotational flap versus long plantar flap for transmetatarsal amputation closure following revascularization. J Vasc Surg Cases Innov Tech. 2024 Nov 27;11(2):101696. doi: 10.1016/j.jvscit.2024.101696.

Prado Dos Santos V(1), de Mello Ferreira L(2), Queiroz AB(2), Silveira Alves CA(2).

Afiliação:
(1)   Faculdade de Medicina da Bahia, Federal University of Bahia, Salvador, Bahia, Brazil.
(2)   Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Bahia, Brazil.

Resumo: The integrity of the plantar flap is important for transmetatarsal amputation (TMA) classic closure. However, in ischemic wounds, the plantar flap can be compromised, making the TMA coverage difficult. The aim of this study was to compare the outcomes of rotational vs long plantar flaps for transmetatarsal amputation closure in patients with dysvascular partial foot amputations. METHODS: We conducted an observational study including revascularized patients with established forefoot gangrene who required TMA. The coverage was performed by classical long plantar flap or rotational flap due to the lack of adequate plantar skin. Seventeen patients were included in the study. TMA was performed after lower limb revascularization in all cases. We compared the wound healing and functional outcomes of the two groups (rotational vs long plantar flap). RESULTS: The mean age of the sample was 66.5 years (±8.3 years). Eight cases (47%) had open surgical bypass, and nine (53%) had endovascular procedures. Eight cases of rotational flaps (7 medial plantar rotational flaps) and nine classical long plantar flaps were analyzed. Our results demonstrated an overall healing rate of 77% in the sample. There was no significant difference between the surgical techniques evaluated. The healing percentage for the rotational flap group was 75% (6 cases) and 78% (7 cases) for the classical long plantar flap closure (P = .6). CONCLUSIONS: Rotational flap provides a feasible alternative to classical long plantar flap for TMA coverage, showing a satisfactory healing rate for dysvascular foot following revascularization.

13.      Heparan sulfate in cerebrospinal fluid as a biomarker to assess disease severity and for treatment monitoring in patients with Mucopolysaccharidosis Type II: a position statement. Orphanet J Rare Dis. 2024 Nov 26;19(1):436. doi: 10.1186/s13023-024-03463-9.

Giugliani R(1)(2), de Siqueira ACM(3), Santos ES(4), Leão EKEA(5), Carvalho
GDS(6), Santos MLSF(7), Raskin S(8), Martins AM(9).

Afiliação:
(1)   Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brasil.
(2)   Dasa Genômica, Casa dos Raros, Porto Alegre, Brazil. rgiugliani@hcpa.edu.br.
(3)   Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil.
(4)   Universidade Federal de Sergipe, Lagarto, Brazil.
(5)   Hospital Universitário Professor Edgard Santos, Salvador, Brazil.
(6)   Centro de Referência em Doenças Raras, Hospital de Apoio de Brasília, Brasília, Brazil.
(7)   Hospital Pequeno Príncipe, Curitiba, Brazil.
(8)   Centro de Aconselhamento e Laboratório Genetika, Curitiba, Brazil.
(9)   Centro de Referência em Erros Inatos do Metabolismo, Universidade Federal de São Paulo, São Paulo, Brazil.

Resumo: Patients with mucopolysaccharidosis type II (MPS II) can present with a severe neuronopathic phenotype or an attenuated non-neuronopathic phenotype. In the light of the recent development of drugs that cross the blood-brain barrier for treatment of neurologic MPS II symptoms, it is critical to define biomarkers that objectively differentiate phenotypes and monitor therapeutic outcomes of advanced treatments. In December 2023, a panel of Brazilian experts discussed the potential of quantifying heparan sulfate (HS) in the cerebrospinal fluid (CSF) as a biomarker for assessing neurological impairment in patients with MPS II, as well as the potential of the molecule as an objective parameter for therapeutic monitoring. Based on scientific evidence, the experts concluded that HS in CSF is predominantly derived from the brain and reflects neurological impairment in patients with MPS II. CSF HS levels may help differentiate between neuronopathic and non-neuronopathic forms of MPS II, with preliminary observations suggesting a potential threshold around 4,000 ng/mL when HS quantification is performed using the same method described in clinical studies of pabinafusp alfa. According to the authors, monitoring HS levels in CSF can serve as an objective parameter for assessing the effectiveness of treatment with drugs that cross the blood-brain barrier. The recommended timing of HS evaluations in CSF of patients with the severe phenotype is: (i) before treatment; (ii) six months after starting treatment; and (iii) two years after starting treatment. The same monitoring scheme is recommended for patients with the attenuated MPS II phenotype, however, after two years of treatment, the physician may elect to perform regular neurocognitive evaluations instead of measuring HS in CSF. Lastly, the authors reinforced the importance of evaluating adherence to treatment, including interruptions, to provide a more meaningful assessment of the treatment's real-world impact and to determine the ideal timing of CSF collection for therapeutic monitoring.

14.      Clinicogenetic characterization of cerebrotendinous xanthomatosis in Brazil. Clin Genet. 2024 Dec;106(6):721-732. doi: 10.1111/cge.14602.

Fussiger H(1), Lima PLGSB(2), Souza PVS(3), Freua F(4)(5), Husny ASE(6), Leão EKEA(7), ...

Afiliação:
(1)   Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
(2)   Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil.
(3)   Neurometabolic Unit, Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, Brazil.
(4)   Clinics Hospital, Faculty of Medicine, University of Sao Paulo, São Paulo, Brazil.
(5)   Neurology Department, Beneficência Portuguesa Hospital, São Paulo, Brazil.
(6)   Hospital Universitário Bettina Ferro de Souza, Universidade Federal do Pará, Belém, Brazil.
(7)   University Hospital Complex Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.

...

Resumo: There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.

15.      Dual Antiplatelet Therapy vs Alteplase in Adult Patients with Acute Minor Ischemic Stroke: A Systematic Review and Meta-Analysis. J Thromb Thrombolysis. 2024 Aug;57(6):929-935. doi: 10.1007/s11239-024-02994-z.

Viana P(1), Relvas JH(2), Cabral TDD(3), Persson JE(4), Menegaz de Almeida A(5), Persson M(6), Marques MVO(7), Oliveira-Filho J(8).

Afiliação:
(1)   Universidade Do Extremo Sul Catarinense, Departamento de Medicina, Criciuma, Santa Catarina, Brazil.
(2)   Conjunto Hospitalar Do Mandaqui, Departamento de Clínica Médica, São Paulo, São Paulo, Brazil.
(3)   Faculdade de Medicina Souza Marques, Departamento de Medicina, Rio de Janeiro, Rio de Janeiro, Brazil.
(4)   Universidade Do Extremo Sul Catarinense, Departamento de Medicina, Criciuma, Santa Catarina, Brazil.
(5)   Universidade Federal Do Mato Grosso, Departamento de Medicina, Sinop, Mato Grosso, Brazil.
(6)   Universidade Federal de Pelotas, Departamento de Medicina, Pelotas, Rio Grande Do Sul, Brazil.
(7)   Faculdade de Medicina da Universidade de São Paulo, Departamento de Medicina, São Paulo, São Paulo, Brazil.
(8)   Hospital Universitário Professor Edgar Santos, Departamento de Neurologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.


Resumo: The efficacy and safety of dual antiplatelet therapy (DAPT) relative to intravenous (IV) alteplase in patients with acute minor ischemic stroke are insufficiently established. Therefore, we aimed to perform a meta-analysis to compare DAPT with IV alteplase in patients with acute minor stroke. MEDLINE, Embase, and Cochrane were searched for studies comparing DAPT with IV alteplase in patients with minor stroke. Functional and safety outcomes in 90 days were analyzed. Statistical analysis was performed using Rstudio 4.3.1. Subanalyses were performed restricted to non-disabling minor strokes and NIHSS score ≤ 3. PROSPERO (CRD42023440986). We included five studies with a total of 6,340 patients, of whom 4,050 (63.9%) received DAPT. The follow-up period for all included studies was 90 days. There was no significant difference for individual outcomes of mRS 0-1 (OR 1.26; 95% CI 0.85-1.89; p = 0.25), mRS 0-2 (OR 0.99; 95% CI 0.69-1.43; p = 0.97), or all-cause mortality (OR 0.80; 95% CI 0.20-3.13; p = 0.75) between groups. Symptomatic intracranial hemorrhage (sICH) was significantly lower (OR 0.11; 95% CI 0.003-0.36; p < 0.001) in patients treated with DAPT compared with IV alteplase. In terms of mRS 0-1 and mRS 0-2, we found no significant difference in both subgroup analyses. We found no statistically significant difference between DAPT and IV alteplase regarding functional outcome (mRS scores of 0-1 and 0-2) or all-cause mortality at 90 days in patients with minor ischemic stroke. Additionally, DAPT was associated with a significantly lower rate of sICH.

16.      Beneficial Bacteria in the Gut Microbiota May Lead to Improved Metabolic and Immunological Status in Chronic Obstructive Pulmonary Disease. Med Sci (Basel). 2024 Aug 16;12(3):41. doi: 10.3390/medsci12030041.

Passos FC(1), Oliveira LMG(1), Jesus FR(2), Zanette DL(3), Neto OLL(1), Neves MCLC(4), Lemos ACM(4), Baccan GC(1).

Afiliação:
(1)   Departamento de Bioquímica e Biofísica, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador 40170-110, Bahia, Brazil.
(2)   Maternidade Climério de Oliveira (MCO/EBSERH), Universidade Federal da Bahia, Salvador 40055-150, Bahia, Brazil.
(3)   Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Paraná, Brazil.
(4)   Unidade do Sistema Respiratório, Ambulatório Professor Francisco Magalhães Neto, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110-200, Bahia, Brazil.

Resumo: The progression of chronic obstructive pulmonary disease (COPD) is characterized by functional changes in the airways. The lung-gut axis and gut microbiota (GM) have been linked to the pathophysiology of airway diseases. Regarding COPD, studies have shown that GM alterations could be related the stages of this disease. However, the relationship between GM and clinical, biochemical and immunological parameters in patients with COPD are not well understood. The aim of this study was to compare the relative abundance of specific groups of beneficial gut bacteria between COPD patients and healthy controls (CTLs) in order to evaluate relationships with metabolic and inflammatory markers in COPD. METHODS: We included 16 stable COPD patients and 16 healthy volunteer CTLs. The relative abundances of Bifidobacterium spp. (Bf) and Akkermansia muciniphila (Akk) bacteria and the Bacteroidetes and Firmicutes phyla were assessed by qPCR. Pulmonary function was evaluated by spirometry, biochemical parameters by colorimetric methods and plasma cytokine levels by cytometric bead array analysis. RESULTS: The Firmicutes/Bacteroides ratio was related to emergency hospital visits and six-minute walk test (6MWT) results. Furthermore, the relative abundance of Bf was associated with plasma concentrations of glucose, triglycerides, HDL-C and IL-10. In addition, Firmicutes levels and the Firmicutes/Bacteroidetes ratio were associated with the IL-12/IL-10 ratio, while Akk abundance was linked to IL-12 levels. CONCLUSIONS: The present findings suggest that the abundance of beneficial bacteria in the GM could influence clinical presentation and immunoregulation in COPD.

17.      Arketamine: a scoping review of its use in humans. Eur Arch Psychiatry Clin Neurosci. 2024 Dec 16. doi: 10.1007/s00406-024-01945-2.

Leal GC(1)(2), Lima-Araújo I(1), Roiter DG(1), Caliman-Fontes AT(1)(2), Mello RP(1)(2), Kapczinski F(3), Lacerda ALT(4), Quarantini LC(5)(6).

Afiliação:
(1)   Laboratório de Neuropsicofarmacologia (LANP), Psychiatry Service, Hospital Universitário Professor Edgard Santos, Serviço de Psiquiatria, Universidade Federal da Bahia;
(2)   Faculdade de Medicina da Bahia, Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(3)   Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
(4)   Programa de Transtornos Afetivos (Mood Disorders Unit), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, State of São Paulo, Brazil.
(5)   Laboratório de Neuropsicofarmacologia (LANP), Psychiatry Service, Hospital Universitário Professor Edgard Santos, Serviço de Psiquiatria, Universidade Federal da Bahia, Rua Dr. Augusto Viana, s/n-Canela, Salvador, Bahia, 40110-060, Brazil.
(6)   Faculdade de Medicina da Bahia, Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

Resumo: Arketamine (R-ketamine), an enantiomer of ketamine, has historically been less studied than esketamine (S-ketamine) and the racemic mixture. Recent preclinical studies suggest that arketamine may offer prolonged antidepressant effects and a superior safety profile. This scoping review aims to assess and synthesise existing literature on the clinical use of arketamine in humans. This review follows the PRISMA for Scoping Reviews guidelines, with a comprehensive search conducted in PubMed, Embase, ClinicalTrials.gov, and the WHO International Clinical Trials Registry. Eligible studies included those reporting the administration of arketamine to humans. Data were extracted and synthesised descriptively. A total of 20 studies involving 410 subjects were included. Arketamine was primarily investigated for pain management and depression. While early evidence suggests arketamine may be effective in reducing pain, most studies were small and conducted in non-clinical settings. In psychiatry, trials indicate potential antidepressant effects, but results are inconsistent, and some studies remain unpublished. A consistent observation across most studies is arketamine's favourable safety profile, showing lower incidences of dissociative and psychotomimetic effects compared to esketamine and racemic ketamine. Arketamine may have a role in pain management and psychiatry, with a favourable safety profile compared to other forms of ketamine. However, the small scale of many studies limits the generalizability of findings, and results in depression trials are mixed. Larger, well-designed studies, possibly with higher doses, are needed to determine its therapeutic potential and establish its place in clinical practice.

18.      A Systematical Review on ART Use in HTLV Infection: Clinical, Virological, and Immunological Outcomes. Pathogens. 2024 Aug 27;13(9):721. doi: 10.3390/pathogens13090721.

Fernandez T(1)(2), Marconi C(1)(2), Montaño-Castellón I(1)(2), Deminco F(1)(2), Brites C(1)(2).

Afiliação:
(1)   Laboratório de Pesquisa em Infectologia (LAPI), Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador 40110-060, Brazil.
(2)   Programa de Pós Graduação em Medicina e Saúde (PPgMS), Federal University of Bahia, Salvador 40110-060, Brazil.

Resumo: Human T-cell lymphotropic virus (HTLV) infection affects over ten million eople worldwide, but there is no effective treatment so far. This review describes the virological, immunological, and clinical outcomes of antiretroviral therapy (ART) in people with HTLV infection. This systematic review followed PRISMA reporting guidelines and was registered in PROSPERO: CRD42022350076. The Newcastle-Ottawa Scale, adapted for cross-sectional studies, and Rob-2 were used to assess the methodological quality of these studies. Systematic searches were conducted in the Medline (PubMed), Scopus (Elsevier), Cochrane Library, and Web of Science (Clarivate Analytics) databases. We retrieved data from eight methodologically diverse articles on treatment of patients infected by HTLV-1 or HTLV-2 alone, or coinfected by HIV-1, who received Raltegravir, Tenofovir, amivudine, or Zidovudine. The proviral load decreased in three out of seven studies over 4 to 48 weeks of antiretroviral use. Cellular immune response (CD4, CD8, CD25, CD69, and CD71 cells) was evaluated in six studies. While no significant clinical improvement was observed, all studies reported clinical stability during treatment. Despite the demonstrated antiviral activity of ART, in vitro, clinical improvement was not proven. Most studies showed disease stability during ART use, suggesting potential clinical benefits. There is a need of larger, well-controlled trials to define the role of ART in the treatment of HTLV infection.

19.      Tirofiban vs. aspirin in patients with acute ischemic stroke: A meta-analysis of randomized clinical trials. Clin Neurol Neurosurg. 2024 Dec;247:108626. doi: 10.1016/j.clineuro.2024.108626.

de Oliveira MPR(1), Sandes PHF(2), de Souza DCR(2), Piñeiro GTO(2), Medrado-Nunes GS(2), Dos Santos NSSF(2), Oliveira-Filho J(3).

Afiliação:
(1)   Federal University of Bahia, Salvador, Bahia, Brazil.
(2)   Federal University of Bahia, Salvador, Bahia, Brazil.
(3)   Department of Neurology, Hospital Universitário Professor Edgar Santos, Salvador, Bahia, Brazil.

Resumo: Antiplatelet therapy is recommended as the standard treatment for patients with acute ischemic stroke (AIS) who, for several reasons, did not receive thrombolysis or thrombectomy. However, whether tirofiban or aspirin provides greater benefits for these patients remains unclear. Therefore, we aimed to perform a meta-analysis comparing the functional outcomes and hemorrhagic risks associated with tirofiban and aspirin in the management of AIS.METHODS: We searched PubMed, EMBASE, Web of Science, and Cochrane Library for studies comparing tirofiban to aspirin in patients with AIS who did not receive thrombolysis or thrombectomy until September 2024. Outcomes were modified Rankin Scale (mRS) and mortality at 90 days, symptomatic intracranial hemorrhage, and any bleeding events. Statistical analysis was performed using the R Studio (version 2024.04.1+748). RESULTS: We included 3 randomized controlled trials with a total of 1959 patients, of whom 996 (50.8 %) were in the tirofiban group. Excellent (mRS 0-1) functional outcome (RR 1.25, 95 % CI: 1.05-1.49; I2 = 70 %) and favorable (mRS 0-2) functional outcome at 90 days (RR 1.09, 95 % CI: 1.01-1.16; I2 = 35 %) were significantly higher in tirofiban compared to aspirin. Furthermore, tirofiban showed no difference in mortality (RR 0.77, 95 % CI: 0.24-2.53; I2 = 56 %), or symptomatic intracranial hemorrhage (RR 3.42, 95 % CI: 0.27-43.30; I2 = 38 %). However, any bleeding event (RR 1.75, 95 % CI: 1.25-2.45; I2 = 0 %) was more common in the tirofiban group. Lastly, the meta-regression analysis showed that the outcomes were not influenced by the initial NIHSS of the included studies (p  0.05). CONCLUSION: Tirofiban is associated with better functional outcomes at 90 days, with no difference in mortality. Additionally, despite being associated with higher bleeding events, there is no difference in symptomatic intracranial hemorrhage. Therefore, our results suggest that tirofiban is a promising alternative to aspirin.

20.      Immunogenicity and safety of beta variant COVID-19 vaccine AZD2816 and AZD1222 (ChAdOx1 nCoV-19) as primary-series vaccination for previously unvaccinated adults in Brazil, South Africa, Poland, and the UK: a randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study. Lancet Microbe. 2024 Aug;5(8):100863. doi: 10.1016/S2666-5247(24)00078-8

Costa Clemens SA(1), Jepson B(2), Bhorat QE(3), Ahmad A(4), Akhund T(4), Aley PK(5), Bansal H(2), Bibi S(5), Kelly EJ(6), Khan M(7), Lambe T(8), Lombaard JJ(9), Matthews S(10), Pipolo Milan E(11), Olsson U(12), Ramasamy MN(13), Moura de Oliveira Paiva MS(14), Seegobin S(10), Shoemaker K(2), Szylak A(15), Villafana T(16), Pollard AJ(5), Green JA(17); AZD2816 Study Group.

Collaborators: de Oliveira Paiva HD(14), Smith CC(18), Brites C(19), Sprinz E(20), Vasconcellos E(21), Badal-Faesen S(22), Koen A(23), Burgess L(24), Engelbrecht J(25), Vekemans J(26), Kobielusz-Gembala I(27), Jones C(28), Hirsch I(28), Aksyuk A(29), Wilkins D(29), Stanely AM(29), Petropoulos CJ(30), Wrin T(30), Rugieri S(31), Bennet JA(32), Greffrath J(33), Sorio GL(34), Mantyka J(35). 

Afiliação:
(1)   Department of Paediatrics, University of Oxford, Oxford, UK; Institute for Global Health, Siena University, Siena, Italy.
(2)   Biometrics, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
(3)   Soweto Clinical Trials Centre, Soweto, Gauteng, South Africa.
...
(19) Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
...

Resumo: AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated. METHODS: In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed. FINDINGS: Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2. INTERPRETATION: Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants.

21.      Ketamine for catatonia: A novel treatment for an old clinical challenge? A systematic review of the evidence. Schizophr Res. 2024 Sep;271:355-370. doi: 10.1016/j.schres.2024.07.055.

Caliman-Fontes AT(1), Vieira F(1), Leal GC(1), Carneiro BA(1), Quarantini-Alvim Y(2), Andrade TV(1), Mello RP(1), Gadelha A(3), Lacerda ALT(4), Quarantini LC(5).

Afiliação:
(1)   Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
(2)   Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
(3)   Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
(4)   Programa de Transtornos Afetivos, Universidade Federal de São Paulo, São Paulo, Brazil.
(5)   Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil; Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.

Resumo: Catatonia, documented since the 19th century, remains a significant challenge in terms of recognition and treatment. Over the last two decades, ketamine has brought new perspectives to psychiatry, sparking widespread interest. Concurrently, catatonia has attracted heightened scientific attention. Preliminary evidence suggests the therapeutic potential of ketamine for catatonia. METHODS: We systematically searched Medline/PubMed, Embase, PsycINFO, Lilacs, and Cochrane Library databases, as well as Google Scholar, for studies with ketamine or its enantiomers as intervention for catatonia, with no restrictions to underlying diagnosis, date, language, or study design. RESULTS: Twenty articles were included, encompassing a total of 25 catatonic patients receiving ketamine or esketamine. Predominantly female (61.9 %), with a mean age of 44.4 years, patients mostly exhibited manifestations compatible with the retarded subtype of catatonia. Mood disorders were the most prevalent underlying diagnoses. Ketamine was primarily administered intravenously over a 40-minute period and in multiple-dosing schemes. Mean response and remission rates of catatonic manifestations for the whole sample were 80 % and 44 %, respectively, with no reports of worsening catatonic features or psychotic symptoms. Only one patient discontinued treatment due to intolerable dissociative effects. CONCLUSION: Challenging the conventional contraindication of ketamine in psychotic disorders, current evidence highlights its potential efficacy, particularly in treating catatonia. Pending further research, we advocate reevaluating this contraindication, as it may offer a promising therapeutic option, especially for challenging cases. Preliminary evidence suggests potentially greater benefits for catatonic patients with underlying mood disorders compared to primary psychotic disorders.

22.      Mass Spectrometry-Based Metabolomics Reveals a Salivary Signature for Low-Severity COVID-19. Int J Mol Sci. 2024 Nov 6;25(22):11899. doi: 10.3390/ijms252211899.

Lopes de Lima I(1)(2), Ap Rosini Silva A(3), Brites C(4), Angelo da Silva Miyaguti N(3), Raposo Passos Mansoldo F(5), Vaz Nunes S(4), Henrique Godoy Sanches P(3), Regiani Cataldi T(6), Pais de Carvalho C(1)(2), Reis da Silva A(1)(2), Ribeiro da Rosa J(3), Magalhães Borges M(1)(2), Vilarindo Oliveira W(1)(2), Canevari TC(1), Beatriz Vermelho A(5), Nogueira Eberlin M(1)(2), M Porcari A(3).

Afiliação:
(1)   PPGEMN, School of Engineering, Mackenzie Presbyterian University, São Paulo 01302-907, SP, Brazil.
(2)   MackGraphe-Mackenzie Institute for Research in Graphene and Nanotechnologies, Mackenzie Presbyterian Institute, São Paulo 01302-907, SP, Brazil.
(3)   MS4Life Laboratory of Mass Spectrometry, Health Sciences Postgraduate Program, São Francisco University-USF, Bragança Paulista 12916-900, SP, Brazil.
(4)   (4)LAPI-Laboratory of Research in Infectology, University Hospital Professor Edgard Santos (HUPES), Federal University of Bahia (UFBA), Salvador 40110-060, BA, Brazil.
(5)   (5)BIOINOVAR-Biotechnology Laboratories, Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, RJ, Brazil.
(6)   (6)Department of Genetics, Luiz de Queiroz College of Agriculture, University of São Paulo (USP/ESALQ), Piracicaba 13418-900, SP, Brazil.

Resumo: Omics approaches were extensively applied during the coronavirus disease 2019 (COVID-19) pandemic to understand the disease, identify biomarkers with diagnostic and prognostic value, and discover new molecular targets for medications. COVID-19 continues to challenge the healthcare system as the virus mutates, becoming more transmissible or adept at evading the immune system, causing resurgent epidemic waves over the last few years. In this study, we used saliva from volunteers who were negative and positive for COVID-19 when Omicron and its variants became dominant. We applied a direct solid-phase extraction approach followed by non-target metabolomics analysis to identify potential salivary signatures of hospital-recruited volunteers to establish a model for COVID-19 screening. Our model, which aimed to differentiate COVID-19-positive individuals from controls in a hospital setting, was based on 39 compounds and achieved high sensitivity (85%/100%), specificity (82%/84%), and accuracy (84%/92%) in training and validation sets, respectively. The salivary diagnostic signatures were mainly composed of amino acids and lipids and were related to a heightened innate immune antiviral response and an attenuated inflammatory profile. The higher abundance of thyrotropin-releasing hormone in the COVID-19 positive group highlighted the endocrine imbalance in low-severity disease, as first reported here, underscoring the need for further studies in this area.

23.      The urine protein/creatinine ratio as a reliable indicator of 24-h urine protein excretion across different levels of renal function and proteinuria: the TUNARI prospective study. BMC Nephrol. 2024 Nov 21;25(1):418. doi: 10.1186/s12882-024-03804-7.

Gutiérrez-Peredo GB(1)(2)(3)(4), Montaño-Castellón I(5)(6)(7), Gutiérrez-Peredo AJ(5)(6)(8), Lopes MB(5)(6)(9)(10), Tapioca FPM(11), Guimaraes MGM(11), Montaño-Castellón S(12), Guedes SA(11), da Costa FPM(11), Mattoso RJC(11), Filho JCBO(5), Norris KC(13), de Almeida ARP(5)(6)(14), Lopes AA(5)(6)(10)(14).

Afiliação:
(1)   Professor Edgard Santos Hospital University, Federal University of Bahia, Rua Doutor Augusto Viana - Canela, Salvador, BA, 40110-060, Brazil.
(2)   Master and Doctoral Graduate Program in Medicine and Health, Federal University of Bahia, Rua Doutor Augusto Viana - Canela, Salvador, BA, 40110-060, Brazil.
(3)   Ana Nery Hospital, Federal University of Bahia, Rua Saldanha Marinho, s/n - Caixa D'agua, Salvador, BA, 40301-155, Brazil.
(4)   Faculty of Medicine Aurelio Melean, Universidad Mayor de San Simón, Cochabamba, CBBA, Bolivia.
(5)   Professor Edgard Santos Hospital University, Federal University of Bahia, Rua Doutor Augusto Viana - Canela, Salvador, BA, 40110-060, Brazil.
(6)   Master and Doctoral Graduate Program in Medicine and Health, Federal University of Bahia, Rua Doutor Augusto Viana - Canela, Salvador, BA, 40110-060, Brazil.
(7)   Faculty of Medicine Aurelio Melean, Universidad Mayor de San Simón, Cochabamba, CBBA, Bolivia.
(8)   Faculty of Medicine, Universidad Privada Abierta Latinoamericana, Cochabamba, CBBA, Bolivia.
(9)   Arbor Research Collaborative for Health, Ann Arbor, MI, USA.
(10) Unit of Clinical Epidemiology and Evidence-Based Medicine, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, BA, Brazil.
(11)  Ana Nery Hospital, Federal University of Bahia, Rua Saldanha Marinho, s/n - Caixa D'agua, Salvador, BA, 40301-155, Brazil.
(12) Faculty of Medicine, Universidad de Aquino Bolivia (UDABOL), Cochabamba, CBBA, Bolivia.
(13) Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
(14) Department of Internal Medicine, School of Medicine, Federal University of Bahia, Salvador, BA, Brazil.

Resumo: The 24-h urine protein (24-hUP) excretion is the gold standard for evaluating proteinuria. This study aimed to evaluate the diagnostic efficacy of protein/creatinine ratio (PCR) for estimating 24-hUP at various levels of renal function and proteinuria levels. METHODS: A cross-sectional study was conducted between December 2021 and December 2023 in Salvador, Bahia-Brazil, as an extension of previously published data from the TUNARI study. The study included 217 samples from 152 patients with various levels of renal function and proteinuria. PCR in isolated samples and 24-hUP were determined conventionally within a 24-h timeframe. Patients were classified into three groups according to the level of renal function (Group 1 = 10 to < 30 mL/min, Group 2 = 30-60 mL/min, and Group 3 = > 60 mL/min) and level of proteinuria (< 0.3 g/day, 0.3-3.5 g/day, and > 3.5 g/day). The data were analyzed using the Spearman correlation (rs), coefficient of determination (r2), Bland-Altman plots and receiver operating characteristic (ROC) curve. Likelihood ratios, positive (LR +), and negative (LR-) were derived from the sensitivity and specificity of PCR. RESULTS: Mean age was 41.5 ± 15.7 years, 61.8% were women, 36.8% Black and 52% Mixed-race. Glomerulopathies constituted 80.3%; 46.1% with lupus nephritis. Of the total urine samples, we observed a high correlation between PCR in the total sample of 24-hUP sample (rs = 0.86, p < 0.001) across different levels of renal function. However, agreement between PCR and 24-hUP was reduced at higher levels of proteinuria. The ROC analysis showed an AUC of 0.95 (95% CI = 0.92, 0.98), sensitivity of 91% and specificity of 86.5% (LR + 6.7; LR- 0.1), with an optimal cut-off of 0.77. These results were similar across renal function levels. Proteinuria ≤ 0.3 g/day showed a high sensitivity of 83.3% and specificity of 90%, with an area under (AUC) of 0.85 (95% CI = 0.71; 0.94). In the 24-hUP range > 0.3-3.5 g/day, the sensitivity was 64.1%, the specificity was 84.6%, and the AUC was 0.76 (95% CI = 0.67; 0.84), PCR detected all cases > 3.5 g/day. CONCLUSIONS: PCR is a suitable measure to be used as an indicator of 24-hUP at different levels of renal function, but may have limitations at higher levels of proteinuria. Analysis of PCR by proteinuria level found that agreement as well as sensitivity decreases at higher levels, but it maintains good specificity and is able to identify nephrotic range proteinuria.

24.      Adherence to infliximab treatment in patients with immune-mediated inflammatory diseases from a referral center in Brazil: a cohort study. BMC Gastroenterol. 2024 Oct 29;24(1):384. doi: 10.1186/s12876-024-03455-w.

Lauton PM(1)(2), Pereira FS(1), Oliveira LB(3), Brauer AMNW(3), de Araújo Costa Beisl Noblat L(1)(2), Santana GO(4), Santos PM(5)(6).

Afiliação:
(1)   Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Brasil.
(2)   (2)Programa de Pós-Graduação em Assistência Farmacêutica em Rede e Associação de Instituições de Ensino Superior, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Brasil.
(3)   Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brasil.
(4)   Departamento de Ciências da Vida, Universidade do Estado da Bahia (UNEB), Salvador, Brasil.
(5)   Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Brasil.
(6)   Programa de Pós-Graduação em Assistência Farmacêutica em Rede e Associação de Instituições de Ensino Superior, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Brasil.

Resumo: Infliximab therapy is effective in controlling symptoms and attaining clinical remission of immune-mediated inflammatory diseases. However, treatment adherence is essential to achieve the therapeutic objective. This study aimed to determine the rate of adherence to infliximab treatment in patients treated at a referral center at a university hospital. METHOD: This ambispective cohort study included patients treated at the Professor Edgard Santos University Hospital (HUPES) referral center of our university hospital between March 2022 and February 2023. Sociodemographic, clinical, and pharmacotherapeutic data were collected from 101 patients through interviews and medical record reviews using a structured form. The adherence rate was defined as the proportion of days covered in a year. Patients who achieved an adherence rate > 80% were considered adherent. RESULTS: The treatment adherence rate was 91.04%. Individuals with inflammatory bowel diseases had a 39.1% higher risk of non-adherence to treatment compared with other patients in our sample (p < 0,05). Most patients achieved remission or control of the underlying disease activity and had good functional capacities. The main reason for absence on the scheduled date was difficulty traveling to the referral center. CONCLUSIONS: Despite the reported difficulties, treatment adherence was observed to be high. As the study was conducted in a reference unit with multidisciplinary care and continuous monitoring for treatment effectiveness, safety, and adherence, welcoming and good communication between professionals and patients may have contributed to the high adherence rate.

25.      Takayasu's arteritis associated with tuberculosis: a retrospective study. Adv Rheumatol. 2024 Nov 11;64(1):84. doi: 10.1186/s42358-024-00424-5.

Souza Pedreira AL(1)(2), de Oliveira Figueiroa MLC(3), Miranda MO(3), de Santana AR(3), Mattos VP(3), da Paz AS(3)(4), Duran CC(3)(4), Santiago MB(3)(4).

Afiliação:
(1)   Hospital Universitário Professor Edgard Santos - Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(2)   Escola Bahiana de Medicina e Saúde Pública, Av. Dom João VI, 275 - Brotas, Salvador, BA, 40290-000, Brazil.
(3)   Hospital Universitário Professor Edgard Santos - Universidade Federal da Bahia, Salvador, Bahia, Brazil.
(4)   Escola Bahiana de Medicina e Saúde Pública, Av. Dom João VI, 275 - Brotas, Salvador, BA, 40290-000, Brazil.

Resumo: Takayasu arteritis (TA) and tuberculosis (TB) share similar histopathological and immunological characteristics. Studies comparing patients with TA with or without active or latent TB infection (LTBI) have revealed some differences in clinical and angiographic profiles. Patient with TA and history of TB exhibited more constitutional symptoms and structural damage to the aorta. This study compared the clinical and radiological features of patients with TA with and without active TB or LTBI.METHODS: We retrospectively analyzed the data of patients with TA at a public tertiary referral outpatient clinic in northeast Brazil from January 2017 to June 2022. Comparisons of clinical features were made according to the presence of TB. RESULTS: Fifty patients met the eligibility criteria, and a association with TB was identified in 20 (40%) patients (active TB in six and LTBI in 14). There was a predominance of females, and the average age of patients was 40 years. Weight loss was more common in patients with TA and TB (p = 0.005). No significant intergroup differences were noted in terms of comorbidities, medications, erythrocyte sedimentation rates, or C-reactive protein levels. Significant differences were found in abdominal aortic involvement (25% of patients with TA and TB vs. 11.4% in subjects with TA without TB; p = 0.013). Dilations and aneurysms were significantly more common in patients with TA and TB (p = 0.009 and p = 0.027, respectively). CONCLUSION: Patients with TA and TB have a higher prevalence of dilatation and aneurysms, most commonly in the abdominal aorta.

26.      Serum glutathione peroxidase is associated with nonalcoholic fatty liver disease in children and adolescents. Nutr Hosp. 2024 Dec 19;41(6):1165-1171. doi: 10.20960/nh.05105.

Santos PQD(1), Rocha R(1), Daltro CHDC(1), Andrade SCS(2), Cotrim HP(3).

Afiliação:
(1)   Department of Nutrition Sciences. Escola de Nutrição. Universidade Federal da Bahia (UFBA).
(2)   Radiology Department. Hospital Universitário Professor Edgard Santos - HUPES.
(3)   Postgraduate Program in Medicine and Health. Faculdade de Medicina da Bahia. Universidade Federal da Bahia (UFBA).

Resumo:
Oxidative stress is an important factor in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). This study aimed to compare the serum levels of malondialdehyde (MDA), glutathione peroxidase (GPx) and antioxidant micronutrients in children and adolescents with and without NAFLD. Methods: a cross-sectional study with patients between 8-18 years old, of both sexes. Diagnosis of NAFLD: presence of steatosis on ultrasound and absence of history of ethanol consumption and other liver diseases. Anthropometric measures, MDA, GPx, Interleukin-6, serum levels of vitamins A, C and E, selenium, zinc, and copper were evaluated. Results: eighty-nine children with mean age of 12 (3) years, 57.3 % female and 24 % with NAFLD were evaluated. Those with NAFLD had more frequent abdominal obesity (high waist-height ratio: 81.0 % x 48.5 %; p = 0.009). After logistic regression NAFLD was associated with high body mass index/age (p-adjusted = 0.021) and with reduced serum GPx (p-adjusted = 0.034). There was a positive correlation between MDA and copper (r = 0.288; p = 0.006), IL-6 (r = 0.357; p = 0.003) and a negative one with vitamin A (r = -0.270; p = 0.011). Conclusions: oxidative stress is present in children with NAFLD and non-invasive markers such as GPx and BMI can be used in clinical practice and help in the early screening of NAFLD.

27.      Alkaline phosphatase and liver fibrosis at diagnosis are associated with deep response to ursodeoxycholic acid in primary biliary cholangitis. Clin Res Hepatol Gastroenterol. 2024 Oct;48(8):102453. doi: 10.1016/j.clinre.2024.10245.

Cançado GGL(1), Fucuta PDS(2), Gomes NMF(3), Couto CA(4), Cançado ELR(5), Terrabuio DRB(5), Villela-Nogueira CA(6), Braga MH(5), Nardelli MJ(4), Faria LC(4), Oliveira EMG(7), Rotman V(6), Oliveira MB(8), Cunha SMCFD(9), ...

Afiliação:
(1)   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.
(2)   Faculdade de Medicina, FACERES, São José do Rio Preto, São Paulo, Brazil; Fukuta Estatística e Metodologia Científica, São José do Rio Preto, São Paulo, Brazil.
(3)   Disciplina de Gastroenterologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
(4)   Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
(5)   Departamento de Gastroenterologia, Faculdade de Medicina da Universidade 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.

...

Resumo:
Primary biliary cholangitis is a chronic and progressive autoimmune liver disease, whose prognosis can be improved by normalizing alkaline phosphatase and bilirubin. While ursodeoxycholic acid (UDCA) is first line standard of care, approximately 40 % of patients exhibit incomplete response. We aimed to identify prognostic markers for deep response to UDCA therapy at presentation. PATIENT AND METHODS: Data from the Brazilian Cholestasis Study Group cohort were analyzed retrospectively. Patients were assessed for deep response, defined as normal alkaline phosphatase and bilirubin, after 1 year of UDCA treatment. Additionally, the performance of the UDCA response score in predicting deep response was evaluated. RESULTS: A total of 297 patients were analyzed, with 57.2 % achieving an adequate response according to the Toronto criteria, while 22.9 % reached deep response. Cirrhosis (OR 0.460; 95 % CI 0.225-0.942; p = 0.034) and elevated baseline alkaline phosphatase levels (OR 0.629; 95 % CI 0.513-0.770; p < 0.001) were associated with reduced odds of deep response. The UDCA response score exhibited moderate discrimination power (AUROC = 0.769) but lacked calibration. CONCLUSIONS: Baseline ALP and liver fibrosis emerge as the most important prognostic factors to predict normalization of alkaline phosphatase and bilirubin after UDCA. The UDCA response score was inadequate for predicting deep response in the Brazilian PBC population.

28.      ELMO2 biallelic pathogenic variants in a patient with gingival hypertrophy and cherubism phenotype: Case report and molecular review. Am J Med Genet A. 2024 Oct;194(10):e63602. doi: 10.1002/ajmg.a.63602.

Perrone E(1)(2), Coelho AVC(1), Virmond LDA(1), Espolaor JGA(1)(2), Filho JBO(1), Nascimento ATBD(1), Matta MCD(1), Meira JGC(3), Cardoso-Júnior LM(4), Andrade ACM(3), Chaves RZT(5), Acosta AX(3)(6).

Afiliação:
(1)   Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.
(2)   Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil.
(3)   Serviço de Genética Médica do Hospital Universitário Professor Edgard Santos (HUPES), Bahia, Brazil.
(4)   Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
(5)   Disciplina de Cirurgia de Cabeça e Pescoço do Hospital de Clínicas da Universidade de São Paulo, São Paulo, Brazil.
(6)   Departamento de Pediatria da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Bahia, Brazil.

Resumo:
Ramon syndrome (OMIM #266270) was first described in a patient with cherubism, gingival fibromatosis, epilepsy, intellectual disability, hypertrichosis, and stunted growth. In 2018, Mehawej et al. described a patient with Ramon syndrome in whom a homozygous variant in ELMO2 was identified, suggesting that this gene may be the causative for this syndrome. ELMO2 biallelic pathogenic variants were also described in patients with a primary intraosseous vascular malformation (PIVM; OMIM #606893). These patients presented gingival bleeding and cherubism phenotype. Herein, a patient with gingival hypertrophy, neurodevelopmental delay, and cherubism phenotype with a novel homozygous predicted loss-of-function (LOF) variant in the ELMO2 gene and family recurrence was reported. A surgical approach to treat gingival bleeding and mandible vascular malformation was also described. Furthermore, this study includes a comprehensive literature review of molecular data regarding the ELMO2 gene. All the variants, except one described in the ELMO2, were predicted as LOF, including our patient's variant. There is an overlapping between PIVM, also caused by LOF biallelic variants in the ELMO2 gene, and Ramon syndrome, which can suggest that they are not different entities. However, due to a limited number of cases described with molecular evaluation, it is hard to establish a genotype-phenotype correlation. Our study supports that LOF pathogenic biallelic variants in the ELMO2 gene cause a phenotype that has cherubism and gingival hypertrophy as main characteristics.

29.      The Leishmania Skin Test Predicts Clinic-Immunologic and Therapeutic Outcomes in Cutaneous Leishmaniasis. Pathogens. 2024 Nov 19;13(11):1018. doi: 10.3390/pathogens13111018.

Guimarães LH(1)(2)(3), Zacarias E(4)(5), Nolasco ST(1), Filho AN(4), Lago J(1), Machado PRL(1)(3), Oliveira J(4), Carvalho LP(1)(3)(4), Carvalho A(1)(3)(4), Carvalho EM(1)(3)(4), Arruda S(3)(4)(6).

Afiliação:
(1)   Immunology Service, University Hospital Professor Edgar Santos, Federal University of Bahia, Salvador 40110-160, Bahia, Brazil.
(2)   Health Sciences Center, Santo Antonio de Jesus campus, Federal University of Recôncavo da Bahia, Santo Antônio de Jesus 44574-490, Bahia, Brazil.
(3)   National Institute of Science and Technology of Tropical Diseases (INCT-DT), MCTI CNPq, Salvador 40110-160, Bahia, Brazil.
(4)   Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador 40296-710, Bahia, Brazil.
(5)   Faculty of Pharmacy, Ondina Campus, Federal University of Bahia, Salvador 40170-115, Bahia, Brazil.
(6)   Department of Life Sciences, School of Medicine, Salvador Campus, State University of Bahia, Salvador 41200-105, Bahia, Brazil.

Resumo:
Cutaneous leishmaniasis (CL), caused by Leishmania braziliensis, is closely associated with a severe form of the disease, indicated by a positive Leishmania skin test (LST) that assesses and reflects the presence of immune T cells specific to Leishmania antigens. In this study, we compare the clinical, immunologic, and histopathologic features between Leishmania skin test-positive (LST+) and Leishmania skin test-negative (LST-) in CL. Compared to LST+ patients, LST- patients had larger lesions and had been sicker for longer, presented with more instances of therapeutic failure with meglumine antimonate, (MA) and the healing times were higher than LST+. While granulomas were less frequent and the parasite load was higher in LST-, there were more CD8+ T cells and an enhanced production of Granzyme B in the supernatants of biopsies from LST- subjects. This study shows that in LST-, an impairment in Th1 immune response is associated with a high parasite burden, and the pathology is mediated by CD8+ T cells and the enhanced production of Granzyme B. The abnormalities in the immunologic response in LST- patients lead to a more severe disease with a high rate of failure to therapy.

30.      Common gastrointestinal symptoms in healthy infants receiving goat milk-based formula or cow's milk-based formula: a double-blind, randomized, controlled trial. BMC Pediatr. 2024 Nov 20;24(1):753. doi: 10.1186/s12887-024-05214-y.

Maximino P(1)(2), van Lee L(1), Meijer-Krommenhoek YN(3), van der Zee L(1), da Costa Ribeiro Junior H(4).

Afiliação:
(1)   Ausnutria B.V, Zwolle, The Netherlands.
(2)   PENSI Institute, CENDA (Center of Excellence in Nutrition and Feeding Difficulties), Fundação José Luiz Egydio Setúbal, São Paulo, SP, Brazil.
(3)   Ausnutria B.V, Zwolle, The Netherlands.
(4)   Hospital Professor Edgard Santos, Federal University of Bahia, Salvador, Brazil.

Resumo:
OBJECTIVE: To assess common gastrointestinal symptoms in healthy Brazilian infants receiving goat milk-based formula (GMF) compared to cow's milk-based formula (CMF).
METHODS: We performed a 24-weeks double-blind, randomized, controlled study in Brazil, enrolling healthy infants from 3 to 12 months of age. Primary outcome were the gastrointestinal (GI) symptoms stool consistency, regurgitation frequency and crying duration. Secondary outcomes were growth trajectories and hemoglobin levels. Repeated mixed models were used to compare outcomes variables between GMF and CMF groups, while adjusting for age at baseline. RESULTS: Fifty-six infants were recruited and randomly allocated in the GMF (n = 26) and the CMF (n = 30) group. Scores on all measured GI symptoms were low and similar among the groups throughout intervention period and improved over time. Average age- and sex-adjusted WHO z-scores of weight, length, head circumference, and weight-for-length were all within +/-1 SD and similar between groups, indicating adequate growth. Serum hemoglobin was 11.1 (SD 0.7) g/dL in infants fed GMF and 11.0 (SD 0.8) g/dL in infants fed CMF after the intervention and was similar between groups. CONCLUSION: GMF was well tolerated, safe and supported adequate growth in infants. This was shown by the low occurrence of GI symptoms, adequate blood hemoglobin levels and adequate growth within WHO standards.TRIAL REGISTRATION: The clinical trial was approved by the ethics committee of the Federal University of Bahia under number CAAE06923319.5.0000.5577. The study was retrospectively registered in clinicaltrials.gov on 02/05/2024 under identifier NCT06395571.

31.      Palliative care and COVID-19: acknowledging past mistakes to forge a better future. Front Med (Lausanne). 2024 Jul 25;11:1390057. doi: 10.3389/fmed.2024.1390057.

de Andrade CRM(1), Luz FST(2), de Oliveira NR(3), Kopittke L(4)(5), Santa Rosa LMM(6), ..., de Carvalho RLR(21)(22), de Godoy MF(23), et al.

Afiliação:
(1)   Centro Universitário de Belo Horizonte, UniBH. Av. Professor Mário Werneck, Belo Horizonte, Brazil.
(2)   Hospital Metropolitano Odilon Behrens. R. Formiga, Belo Horizonte, Brazil.
(3)   Hospital Eduardo de Menezes. R. Dr. Cristiano Rezende, Belo Horizonte, Brazil.
(4)   Hospital Nossa Senhora da Conceição. Av. Francisco Trein, Porto Alegre, Brazil.
(5)   Hospital Cristo Redentor. R. Domingos Rubbo, Porto Alegre, Brazil.
(6)   Faculdade Ciências Médicas de Minas Gerais. Al. Ezequiel Dias, Belo Horizonte, Brazil.
...
(21) Hospital Universitário Professor Edgard Santos. R. Augusto Viana, S/N, Salvador, Brazil.
(22) Escola de Enfermagem da Universidade Federal da Bahia. Basílio da Gama, Salvador, Bahia, Brazil.
...

Resumo:
COVID-19 induces complex distress across physical, psychological, and social realms and palliative care (PC) has the potential to mitigate this suffering significantly.OBJECTIVES: To describe the clinical characteristics and outcomes of COVID-19 patients with an indication of PC, compared to patients who had no indication, in different pandemic waves. METHODS: This retrospective multicenter observational cohort included patients from 40 hospitals, admitted from March 2020 to August 2022. Patients who had an indication of palliative care (PC) described in their medical records were included in the palliative care group (PCG), while those who had no such indication in their medical records were allocated to the non-palliative care group (NPCG).RESULTS: Out of 21,158 patients, only 6.7% had indication for PC registered in their medical records. The PCG was older, had a higher frequency of comorbidities, exhibited higher frailty, and had a higher prevalence of clinical complications and mortality (81.4% vs. 17.7%, p < 0.001), when compared to the NPCG. Regarding artificial life support, the PCG had a higher frequency of dialysis (20.4% vs. 10.1%, p < 0.001), invasive mechanical ventilation (48.2% vs. 26.0%, p < 0.001) and admission to the intensive care unit (53.6% vs. 35.4%, p < 0.001). These differences were consistent across all three waves. CONCLUSION: A low proportion of patients received PC. Patients in PCG were more fragile, had more clinical complications, and had a higher mortality. On the contrary to our expectations, they received more artificial life support in all three waves. Taken together, these findings suggest that decisions regarding PC indication were made too late, within a context of end-of-life and therapeutic failure.

32.      Epidemiological characterization of rare diseases in Brazil: A retrospective study of the Brazilian Rare Diseases Network. Orphanet J Rare Dis. 2024 Oct 30;19(1):405. doi: 10.1186/s13023-024-03392-7.

de Oliveira BM(1)(2), Bernardi FA(3), Baiochi JF(4), Neiva MB(5), Artifon M(6), Vergara AA(7), Martins AM(8), Grumach AS(9), Acosta AX(10), Husny ASE(11), de Freitas Rodrigues Ribeiro B(12), Ramos CF(13), Steiner CE(14), et al.; Raras Network Group.

Afiliação:
(1)   Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
(2)   Postgraduation Program in Genetics and Molecular Biology, Federal University of Rio Grande Do Sul, Porto Alegre, RS, Brazil.
(3)   Engineering School of São Carlos, Bioengineering Department, University of São Paulo, São Carlos, SP, Brazil.
(4)   Ribeirão Preto Medical School, University of São Paulo, Ribeirão Prêto, SP, Brazil.
(5)   Institute of Mathematics and Computer Sciences, São Carlos Campus, University of São Paulo, São Carlos, SP, Brazil.
(6)   Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
(7)   Hospital Infantil João Paulo II, Belo Horizonte, MG, Brazil.
(8)   Hospital São Paulo, São Paulo, SP, Brazil.
(9)   Faculdade de Medicina do Centro Universitario FMABC, Santo André, SP, Brazil.
(10) Hospital Universitário Prof. Edgar Santos and Faculdade de Medicina da Bahia da Universidade Federal da Bahia, Salvador, BA, Brazil.
(11) Hospital Universitário Bettina Ferro de Souza, Universidade Federal Do Pará, Belém, PA, Brazil.
(12) Fundação Hospital Estadual do Acre, Rio Branco, AC, Brazil.
(13) Hospital Universitário Prof. Edgar Santos, Salvador, BA, Brazil.
(14) Universidade Estadual de Campinas, Campinas, SP, Brazil.
...

Resumo:
The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. RESULTS: The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. CONCLUSION: This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

33.      Frequency of anti-MOG antibodies in serum and CSF of patients with possible autoimmune encephalitis: Results from a Brazilian multicentric study. Mult Scler Relat Disord. 2024 Dec;92:106171. doi: 10.1016/j.msard.2024.106171.

de Freitas Dias B(1), Toso FF(1), Barreto MESF(1), Dellavance A(2), Thomaz RB(1), Kowacs PA(3), Teive H(4), Spitz M(5), Juliano AFB(6), Rocha LJA(7), Granja VNT(8), Braga-Neto P(9), Nóbrega PR(9), Oliveira-Filho J(10), Dias RM(11), et al.

Afiliação:
(1)   Instituto do Cérebro, Hospital Israelita Albert Einstein, São Paulo, Brazil.
(2)   Research and Development Division, Fleury Group, São Paulo, Brazil.
(3)   Instituto de Neurologia de Curitiba, Curitiba, Brazil.
(4)   Serviço de Neurologia, Departamento de Clínica Médica, Hospital das Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
(5)   Hospital Universitário Pedro Ernesto da Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil.
(6)   Hospital Universitário Presidente Dutra, São Luís do Maranhão, Brazil.
(7)   Hospital Universitário Professor Alberto Antunes da Faculdade de Medicina da Universidade Federal de Alagoas, EBSERH, Maceió, Brazil.(8)   Departamento de Neurologia Infantil, Unidade de Emergência Doutor Armando Lages, Maceió, Brazil.
(9)   Division of Neurology, Department of Clinical Medicine, Universidade Federal do Ceará, Fortaleza, Brazil.
(10) Hospital Universitário Professor Edgard Santos, Salvador, Brazil.
(11)  Instituto Hospital de Base do Distrito Federal, Brasília, Brazil.
...

Resumo:
MOGAD encephalitis and ADEM share several clinical features with autoimmune encephalitis (AE) associated with antineuronal antibodies (ANeA); nonetheless, treatment and prognosis differ. Anti-MOG antibodies (abs) are not routinely tested in possible AE, and epidemiological studies on MOGAD encephalitis are scarce. OBJECTIVES: To determine the frequency of anti-MOG abs in the serum and CSF in a cohort of possible AE and to compare the clinical characteristics of MOGAD patients and those with seropositive AE. METHODS: 481 patients with possible AE from the Brazilian Autoimmune Encephalitis Network underwent tissue-based assay and cell-based assay (CBA) for ANeA. Anti-MOG abs were assessed in serum and CSF with in-house CBA. Clinical and laboratory characteristics of MOGAD and seropositive AE patients were compared. RESULTS: Of the 481 patients, 87 (18 %) had ANeA, and 17 (3.5 %) had anti-MOG abs. Three AE patients with anti-MOG abs and ANeA were excluded from further analysis. Anti-MOG abs were detected in 4 (1.2 %) of the 328 adults and 10 (6.5 %) of the 153 children. Of the 14 patients with MOGAD, nine had ADEM (mostly children), and five had encephalitis (including three adults). Only one patient with ADEM had anti-MOG abs exclusively in CSF. All patients with MOGAD encephalitis were seropositive for anti-MOG abs, and three had normal brain MRI. Patients with MOGAD had fewer behavioral changes (MOGAD 21 % x AE 96 %, p ≤ 0.0001) and movement disorders (MOGAD 42 % x AE 81 %, p = 0.0017) and more demyelinating symptoms, such as myelitis and optic neuritis (MOGAD 14 % x AE 0 %, p = 0.013). CONCLUSION: Approximately 3.5 % of patients with possible AE harbor anti-MOG abs, and 0.9 % of the adults had MOGAD encephalitis. Anti-MOG abs were more frequent than other ANeAs regularly tested in AE. We provide evidence that MOGAD is a differential diagnosis in possible AE, even in adult patients with normal brain MRI, and that serum anti-MOG should be considered as an add-on diagnostic tool in AE among adults and pediatric patients.

34.      A critical perspective on institutional violence against hospitalized children: Testimonies by health professionals and family members. Nurs Inq. 2024 Oct;31(4):e12665. doi: 10.1111/nin.12665.

Santos ACPO(1), de Camargo CL(2), Vargas MAO(3), de Araujo CNV(1), Whitaker MCO(2), Zilli F(4), Martins RD(2), Gomes NP(2).

Afiliação:
(1)   Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil.
(2)   School of Nursing, Federal University of Bahia, Salvador, Brazil.
(3)   Department of Nursing, Federal University of Santa Catarina, Florianópolis, Brazil.
(4)   Federal University of Santa Catarina, R. Delfino Conti, S/N - Trindade, Florianópolis, SC, Brazil.

The purpose of this study is to understand institutional violence (IV) in the relationships between health professionals, hospitalized children, and family members. This is a qualitative study developed at the pediatric inpatient unit of a university hospital in the city of Salvador, Bahia, Brazil. The research participants consisted of 39 health professionals who specialized in pediatrics and 10 family members of hospitalized children. Semi-structured interviews were the method used for data collection. Using discourse analysis as a basis and taking a Foucauldian perspective, the researchers observed that the expressions of IV could be traced to abusive power relations within the system. We found four discursive forms within the data set: communication problems as IV, violence through inattention and neglect, violence as an action and consequent materialization on the body, and psychological violence as a submission mechanism. Based on these findings, we argue that professionals, managers, the scientific community, and users might be able to better guarantee the safety of children by recognizing IV and effectively intervening in it.

35.      A critical perspective on institutional violence against hospitalized children: Testimonies by health professionals and family members. Sci Rep. 2024 Dec 3;14(1):30134. doi: 10.1038/s41598-024-81763-7.

Sridhar S(1)(2), Tonto PB(1)(2), Lumkong L(1)(2), Netto EM(3), Brites C(3), Wang WK(4), Herrera BB(5)(6).

Afiliação:
(1)   Rutgers Global Health Institute, Rutgers University, New Brunswick, NJ, USA.
(2)   Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases, and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
(3)   School of Medicine, LAPI-Laboratório de Pesquisa em Infectologia- Hospital Universitário Professor Edgard Santos, Federal University of Bahia/EBSERH, Salvador, Brazil.
(4)   Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA.
(5)   Rutgers Global Health Institute, Rutgers University, New Brunswick, NJ, USA.
(6)   Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases, and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.

Resumo:
Chikungunya (CHIKV), o'nyong-nyong (ONNV), and Mayaro (MAYV) viruses are transmitted by mosquitoes and known to cause a debilitating arthritogenic syndrome. These alphaviruses have emerged and re-emerged, leading to outbreaks in tropical and subtropical regions of Asia, South America, and Africa. Despite their prevalence, there persists a critical gap in the availability of sensitive and virus-specific point-of-care (POC) diagnostics. Traditional immunoglobulin-based tests such as enzyme-linked immunosorbent assay (ELISA) often yield cross-reactive results due to the close genetic relationship between these viruses. Molecular diagnostics such as quantitative polymerase chain reaction (qPCR) offer high sensitivity but are limited by the need for specialized laboratory equipment. Recombinase polymerase amplification (RPA), an isothermal amplification method, is a promising alternative to qPCR, providing rapid results with minimal equipment requirements. Here, we report the development and validation of three virus-specific RT-RPA-based rapid tests for CHIKV, ONNV, and MAYV. These tests demonstrated both speed and sensitivity, capable of detecting 10-100 viral copies within 20 min of amplification, without exhibiting cross-reactivity. Furthermore, we evaluated the clinical potential of these tests using serum and tissue samples from CHIKV, ONNV, and MAYV-infected mice, as well as CHIKV-infected human patients. We demonstrate that the RPA amplicons derived from the patient samples can be sequenced, enabling cost-effective molecular epidemiological studies. Our findings highlight the significance of these rapid and specific diagnostics in improving the early detection and management of these arboviral infections, particularly in resource-limited settings.

36.      Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes - a multicentric observational study. Front Immunol. 2024 Oct 8;15:1422349. doi: 10.3389/fimmu.2024.1422349.

de Almeida IM(1), Tosta BR(1), Pena LDC(1), Silva HDS(1), Reis-Goes FS(2), Silva NN(2), Cruz JVA(1), Silva MDA(1), de Araújo JF(1), Rodrigues JL(1), Oliveira G(3), Figueiredo RG(4), Vaz SN(5), Montaño-Castellón I(5), Santana D(5), Torres A(2), Beltrão FEL(6), Carneiro VL(7), Campos GS(8), Brites C(5), Fortuna V(2), Figueiredo CA(1), Trindade SC(2)(4), Ramos HE(9), Costa RDS(1).

Afiliação:
(1)   Laboratório de Imunofarmacologia e Biologia Molecular, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
(2)   Laboratório de Imunologia e Biologia Molecular, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
(3)   Laboratório de Análises Clínicas, Instituto Couto Maia, Salvador, Brazil.
(4)   Universidade Estadual de Feira de Santana, Feira de Santana, Brazil.
(5)   Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
(6)   Hospital Universitário Lauro Wanderley, Universidade Federal da Paraíba, João Pessoa, Brazil.
(7)   Departamento de Ciências da Vida, Universidade do Estado da Bahia, Salvador, Brazil.
(8)   Laboratório de Virologia, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
(9)   Programa de Pós-Graduação em Processos Interativos de Órgãos e Sistema, Instituto de Saúde e Ciência, Universidade Federal da Bahia, Salvador, Brazil.

Resumo:
The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes. METHODS: Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants. RESULTS: The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. DISCUSSION: Our findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

37.      Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial. Nat Commun. 2024 Nov 12;15(1):9785. doi: 10.1038/s41467-024-53727-y.

Carpp LN(#)(1), Hyrien O(#)(1)(2), Fong Y(#)(1)(2), Benkeser D(3), Roels S(4), Stieh DJ(5)(6), Van Dromme I(4), Van Roey GA(5), Kenny A(7)(8)(9), Huang Y(1)(2)(7), Carone M(7), McDermott AB(10)(11), Houchens CR(12), Martins K(12), Jayashankar L(12), Castellino F(12),..., Brites C*, et al. Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team; United States Government (USG)/CoVPN Biostatistics Team.

Afiliação:
(1)   Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
(2)   Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
(3)   Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
(4)   Johnson & Johnson Innovative Medicine, Beerse, Belgium.
(5)   Janssen Vaccines and Prevention, Leiden, the Netherlands.
(6)   Vaccine Company Inc., South San Francisco, CA, USA.
(7)   Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA.
(8)   Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
(9)   Duke Global Health Institute, Duke University, Durham, NC, USA.
(10)  Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
...
*Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.

Sem resumo

38.      Dimensions of the COVID-19 pandemic: prevalence of common mental disorders in "invisible" health workers and their association with occupational stressors. Rev Bras Epidemiol. 2024 Jul 29;27:e240039. doi: 10.1590/1980-549720240039.

Maturino MM(1)(2), Sousa CC(3), Moraes LGDS(1), Souza DS(1), Freitas MYGS(4), Araújo TM(1).

Afiliação:
(1)   Universidade Estadual de Feira de Santana, Epidemiology Center - Feira de Santana (BA), Brazil.
(2)   Bahia State Secretariat of Health, Eastern Regional Health Center - Salvador (BA), Brazil.
(3)   Hospital Universitário Professor Edgar Santos - Salvador (BA), Brazil.
(4)   Universidade Estadual de Feira de Santana, Integrated Public Health Research Center, Health Surveillance Research and Extension Center - Feira de Santana, Bahia, Brazil.

Resumo:
To evaluate the association between occupational stressors and common mental disorders (CMD) among "invisible" health workers in the context of the COVID-19 pandemic. METHOD: Cross-sectional study including a probabilistic sample of 1,014 health workers from three municipalities in Bahia. CMDs were assessed using the SRQ-20. The Effort-Reward Imbalance (ERI) scale and the Demand-Control Model assessed occupational stressors. Descriptive, bivariate, and multiple analysis to evaluate the association between the variables of interest. RESULTS: The global prevalence of CMD was 39.9%; it was higher among CHA/EDCA (47.2%), followed by management and surveillance staff (38.6%), technicians (35.4%), and support/maintenance/cleaning staff (29.9%). The association between occupational stressors and CMD varied among occupations: 1. Excessive work commitment (EWC), effort-reward imbalance (ERI), and psychological demand were associated with CMD among support/maintenance/cleaning workers; 2. EWC and ERI were associated with CMD among CHA/EDCA; 3. EWC, ERI, and low control over work were associated with CMD among technicians; 4. Among management and surveillance workers, only ERI remained associated with CMD. CONCLUSIONS: Occupational stressors played a relevant role in mental illness, with variation between occupational strata, demanding attention, monitoring, and control.

39.      Health care Systems as Determinants of Outcomes in Multiple Myeloma: Final Results from the Latin American MYLACRE Study. Blood Adv. 2024 Dec 10:bloodadvances.2024013838. doi: 10.1182/bloodadvances.2024013838.

Hungria VTM(1), Gaiolla RD(2), Galvez K(3), Remaggi G(4), Schutz N(5), Bittencourt RI(6), Maiolino A(7), Quintero-Vega GE(8), Cugliari MS(9), Braga WMT(10), Villarim CC(11), Crusoé EQ(12), et al.

Afiliação:
(1)   Clinica São Germano, São Paulo, Brazil.
(2)   Sao Paulo State University, UNESP, BOTUCATU, Brazil.
(3)   Hospital Pablo Tobon Uribe, Envigado, Antioquia, Colombia.
(4)   FUNDALEU, Buenos Aires, Argentina.
(5)   Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
(6)   Hospital Clinicas de Porto Alegre, Porto Alegre, Brazil.
(7)   Instituto Américas de Ensino, Pesquisa e Inovação, Rio de Janeiro, Brazil.
(8)   Santa Fe de Bogotá Fundation, Bogota, Colombia.
(9)   Instituto de Oncología Angel H. Roffo, BUENOS AIRES, Argentina.
(10)  Hospital São Paulo - Federal University of São Paulo, UNIFESP, São Paulo, Brazil.
(11)  Liga Contra o Câncer, Natal, Brazil.
(12)  Hospital Universitário Professor Edgar Santos (HUPES), Universidade Federal da Bahia; Clinica CEHON Rede D'or Oncologia, Salvador, Brazil.
...

Resumo:
Although systemic therapy for multiple myeloma (MM) has evolved considerably over the past two decades, state-of-the-art treatment is not uniformly available in Latin America. In some countries, disparities between the public and private sectors in clinical presentation, access to novel agents and transplantation are striking, with the public sector lagging. We conducted a multicenter, observational study (NCT03955900) of patients with MM in five Latin American countries (Argentina, Brazil, Colombia, Mexico, and Panama). We enrolled patients aged 18 years or older diagnosed with MM between January 2016 and June 2021, using data collected between May 2019 and June 2022. We categorized institutions as "public" when primarily funded by federal or local government, and "private" when financed mostly or completely by other sources. We analyzed 1029 patients, 1021 of whom could be classified into public (N=339) and private (N=682) institutions. These two groups differed in many respects, with the latter having better baseline prognostic features (including eligibility to transplantation) and receiving combinations of immunomodulatory drugs and proteasome inhibitors, as well as anti-CD38 antibodies, more frequently than patients from public institutions. Among 960 patients with complete data for this analysis, the median overall survival was 44.6 months in public institutions and 53.3 months in private institutions (hazard ratio=0.84; 95% confidence interval, 0.67 to 1.04; P=0.109). Our results indicate diagnostic and therapeutic shortcomings in the management of MM in Latin America, with important gaps in patient profile, treatment patterns and long-term outcomes between public and private institutions.

40.      Morphometric measures and desaturations: Proposal for an index with improved accuracy for obstructive sleep apnea screening. Sleep Med. 2024 Oct;122:258-265. doi: 10.1016/j.sleep.2024.08.010.

Galtieri R(1), Salles C(2), Kushida CA(3), Meira E Cruz M(4), Souza-Machado A(5).

Afiliação:
(1)   Post Graduate Program in Interactive Processes of Organs and Systems, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.
(2)   Professor Edgard Santos University Hospital - Federal University of Bahia, Salvador, Brazil.
(3)   Stanford University School of Medicine, Stanford, USA.
(4)   Sleep Unit, Cardiovascular Center of the University of Lisbon, Lisbon School of Medicine, Lisbon, Portugal.
(5)   Post Graduate Program in Interactive Processes of Organs and Systems, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.

Resumo: To evaluate the sensitivity and specificity of the combined Kushida morphometric model (KMM) and the oxygen desaturation index (ODI) for screening individuals with obstructive sleep apnea. METHODS: Diagnostic test study with adults >18 years, both sexes, polysomnography, body mass index, neck circumference and intraoral measurements. RESULTS: 144 patients were invited; of these, 75 met the exclusion criteria. 55 individuals presented AHI ≥5 ev/h and 14, an AHI <5 ev/h. Three AHI cut-off points were evaluated: AHI ≥5, ≥15, ≥30 ev/h. When adopting the cut-off point of AHI ≥5 ev/h, the KMM showed sensitivity (SE) = 60.0 %, specificity (SP) = 71.4 % and 95 % confidence interval of the area under the curve (95 % CI of AUC) = 0.655; the combination of KMM and ODI (KMM + ODI) revealed SE = 73.0 %, SP = 71.4 % (95 % CI of AUC = 0.779) and the ODI showed SE = 76.4 % and SP = 92.9 % (95 % CI of AUC = 0.815). At the cut-off point of AHI ≥15 ev/h, the KMM presented SE = 64.1 %, SP = 76.7 % (95 % CI of AUC = 0.735); the KMM + ODI showed SE = 82.1 %, SP = 83.3 % (95 % CI of AUC = 0.895); and the ODI presented SE = 76.9 %, SP = 100.0 % (95 % CI of AUC = 0.903). For the cut-off point of AHI ≥30 ev/h, the KMM showed SE = 56.0 %, SP = 77.2 % (95 % CI of AUC = 0.722); the KMM + ODI revealed SE = 92.0 %, SP = 79.5 % (95 % CI of AUC = 0.926); and the ODI showed SE = 92.0 %, SP = 90.9 % (95 % CI of AUC = 0.941). CONCLUSION: The combination of oxygen desaturation index and Kushida morphometric model improved the sensitivity and specificity of this model regardless of obstructive sleep apnea severity suggesting greater effectiveness in risk prediction.

41.      Recurrence of Primary Sclerosing Cholangitis and De Novo Cholangiocarcinoma After Liver Transplantation: Results From the Brazilian Cholestasis Consortium. Clin Transplant. 2024 Oct;38(10):e70002. doi: 10.1111/ctr.70002.

Bittencourt PL(1)(2), Nardelli MJ(3), Barros LL(4), Cançado GGL(3)(5), Cançado ELR(4), Terrabuio DRB(4), Villela-Nogueira CA(6), Ferraz MLG(7), Codes L(1), Rotman V(6), Rocco R(8), Felga GE(8), Dotta DD(4), Martins AS(9), Mendes LSC(10), et al.

Afiliação:
(1)   Hospital Português, Salvador, Brazil.
(2)   Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil.
(3)   Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
(4)   Departamento de Gastroenterologia, Universidade de São Paulo, São Paulo, Brazil.
(5)   Hospital da Polícia Militar de Minas Gerais, Belo Horizonte, Brazil.
(6)   Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
(7)   Universidade Federal de São Paulo, São Paulo, Brazil.
(8)   Hospital Israelita Albert Einsten, São Paulo, Brazil.
(9)   Hospital Universitário Professor Edgard Santos, Salvador, Brazil.
(10)  Hospital de Base do Distrito Federal, Brasília, Brazil.
...

Resumo:
Primary sclerosing cholangitis (PSC) has been shown to recur after liver transplantation (LT). Some studies have identified certain clinical and laboratory variables associated with an increased risk for recurrent PSC (rPSC) in Caucasians. Furthermore, de novo cholangiocarcinoma (CCA) has been reported anecdotally in patients with rPSC. This study aims to assess the prevalence of rPSC, identify its associated risk factors, and investigate the occurrence of de novo CCA in a highly admixed population from Brazil. METHODS: All patients submitted to LT for PSC enrolled in the Brazilian Cholestasis Study Group database were retrospectively reviewed for the occurrence of rPSC and de novo CCA. RESULTS: Ninety-six (58 males, mean age 32 ± 13 years) patients with PSC underwent LT. After 90 (39-154) months of follow-up (FU), rPSC was observed in 29 (30%) subjects. There were no significant associations between rPSC and age, gender, concurrent or de novo inflammatory bowel disease, MELD score at the time of LT or allograft rejection. The only factor associated with an increased risk of disease recurrence was time after LT. Although survival was decreased in patients who developed rPSC, this difference was not significant. Only one female patient developed de novo CCA after rPSC, 11 years after LT. CONCLUSIONS: Recurrent PSC was observed in one-third of PSC LT patients in Brazil and was associated with longer time after LT. Despite its frequency, rPSC was not associated with a higher risk of graft loss or a significant reduction in posttransplant survival.

42.      Zika virus infection and acute transverse myelitis: a comprehensive systematic review. Rev Inst Med Trop Sao Paulo. 2024 Dec 6;66:e66. doi:  10.1590/S1678-9946202466066.

Colognese BA(1), Argollo N(1).

Afiliação:
(1)   Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Salvador, Bahia, Brazil.

Resumo:
The Zika virus (ZIKV) has been associated with several complications, including acute transverse myelitis (ATM), an acute inflammation of the spinal cord, with rapid development of motor, sensory and dysautonomic symptoms. It is a rare disease, and its clinical features, as well as differences in relation to idiopathic ATMs, are still not completely known. The objective of this paper is to review the literature in search of clinical features and complementary exams of ATM post-ZIKV infection, alone or in association with other neurological conditions (mixed diseases), as well as its treatments and prognoses. The search was made on 5 databases, using the PRISMA methodology (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nine articles were selected (total of 20 subjects), which were divided between isolated ATM and mixed neurological syndromes with ATM. The study found a predominance of individuals aged 20 to 30. Among the six subjects in the mixed group, three were over 50 years old. The median prodromal period was 2 days for the mixed diseases group and 7 days for the isolated ATM group. Some individuals in the isolated ATM group exhibited signs of dysautonomia, such as syncope, postural lability, and arrhythmia. The mixed group had a higher incidence of coinfections, with 4 cases compared to 1 case in the isolated ATM group. Over 50% of the individuals had moderate to moderately severe disability. These findings suggest that severe conditions may progress to significant sequelae, highlighting the need for prompt diagnosis and treatment, particularly during endemic periods.

43.      Analysis of the Sensitivity and Specificity of Histopathological Findings for Diagnosing Lupus Nephritis. Diagnostics (Basel). 2024 Nov 27;14(23):2681. doi: 10.3390/diagnostics14232681.

da Luz Neto ER(1)(2), Tavares MB(3), de Melo AGJT(1), Dos-Santos WLC(4), Malheiros DMAC(5), Yu L(1).

Afiliação:
(1)   Division of Nephrology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo 05403-010, SP, Brazil.
(2)   Hospital Ana Nery, Salvador 40320-010, BA, Brazil.
(3)   Division of Nephrology, Hospital Universitário Professor Edgar Santos, Federal University of Bahia, Salvador 40110-060, BA, Brazil.
(4)   Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador 40296-710, BA, Brazil.
(5)   Department of Pathology, University of São Paulo School of Medicine, São Paulo 05403-000, SP, Brazil.

Resumo:
Since the introduction of the SLICC criteria in 2012, biopsy-proven lupus nephritis (LN) has been the only independent diagnostic criterion for systemic lupus erythematosus (SLE). This was reaffirmed by the EULAR/ACR in 2019, emphasizing the importance of renal biopsy in LN. However, the current classification lacks specific histopathological criteria for defining LN. This study describes the histological findings of patients with LN, compares them with those of other glomerular diseases, and evaluates their diagnostic accuracy in a large Latin American population. METHODS: This retrospective cohort included 731 kidney biopsies from two distinct academic centers. The patients were divided into two groups as follows: a LN group and a control group comprising patients with membranous nephropathy, IgA nephropathy, membranoproliferative glomerulonephritis, pauci-immune glomerulonephritis, and proliferative glomerulonephritis. Sensitivity and specificity analyses were conducted for various histopathological features. RESULTS: We identified the following five features strongly correlated with LN: mesangial proliferation, subendothelial deposits, C1q staining ≥1+, dominant IgG, and ≥4 positive immunofluorescence elements. Combined, these features yielded an area under the ROC curve of 0.94 (95% CI: 0.91-0.95). These results were validated in a diverse population. In membranous nephropathy, histological features such as mesangial deposits, C1q positivity, and ≥4 positive immunofluorescence elements effectively distinguished class V LN from non-lupus membranous nephropathy, with an area under the ROC curve of 0.85 (95% CI: 0.76-0.93). CONCLUSIONS: The combination of mesangial proliferation, subendothelial deposits, C1q staining ≥1+, dominant IgG, and ≥4 positive immunofluorescence elements offer good accuracy for diagnosing renal involvement in SLE in a large Latin American population. In the absence of pathognomonic features, combined criteria are valuable diagnostic tools, particularly when other SLE criteria are lacking.

44.      Dietary Adequacy of Individuals with Cardiovascular Disease According to Clinical Guidelines in the Brazilian Cardioprotective Nutritional (BALANCE). Arq Bras Cardiol. 2024 Jul;121(7):e20230705. doi: 10.36660/abc.20230705.

Brito L(1)(2), Sahade V(3), Marcadenti A(4), Torreglosa CR(4), Weber B(5), Bersch-Ferreira ÂC(5), Rodrigues IG(6), Sousa ACS(7), Gomes AB(7), Pinheiro JMF(8), Vasconcelos SML(9), Carlos DMO(10), Figueiredo Neto JA(11), Dantas CF(12), Daltro C(13).

Afiliação:
(1)   Programa de Pós-Graduação em Medicina e Saúde da UFBA - Hospital Universitário Professor Edgard Santos - Universidade Federal da Bahia (UFBA), Salvador, BA - Brasil.
(2)   Empresa Brasileira de Serviços Hospitalares (EBSERH), Salvador, BA - Brasil.
(3)   Universidade Federal da Bahia - Departamento de Nutrição da Escola de Nutrição da UFBA, Salvador, BA - Brasil.
(4)   Instituto de Pesquisa do Hcor, São Paulo, SP - Brasil.
(5)   Real e Benemérita Associação Portuguesa de Beneficência, São Paulo, SP - Brasil.
...

Resumo:
Achieving nutritional goals established by scientific societies is a constant challenge and not always achieved. OBJECTIVE: To investigate the dietary adequacy of individuals with cardiovascular disease (CVD), participants in the Cardioprotective Brazilian Food Program residing in the Northeast region of Brazil, according to the recommendations of the Brazilian Society of Cardiology (SBC). METHODS: Cross-sectional analysis with data from the study implementing the Brazilian Cardioprotective Diet (DICA BR), which evaluated individuals with CVD treated in specialized cardiovascular health centers in eight states in the Northeast region. Food consumption was obtained by 24-hour dietary records and dietary adequacy followed SBC recommendations. Values of p < 0.05 were considered significant. RESULTS: 647 patients were studied, with a mean (standard deviation) age of 63.1 (9.4) years, 50.2% of whom were female. When evaluating food intake, a low adequacy of carbohydrates (52.3%), proteins (70.9%), lipids (38.8%), and fiber  (22.4%) was observed. It was observed that the majority of women consumed a low-protein diet (59.2%) and the elderly had a greater inadequacy in carbohydrate consumption (52.6%). Regarding sodium intake, men had a higher intake (72.9%), while the elderly showed a 13% reduction. Furthermore, it was shown that men ate more fiber (28.1%) and individuals with higher education had a high consumption of saturated fatty acids (70.5%). CONCLUSIONS: Most individuals did not achieve the recommended dietary therapy goals for secondary cardiovascular prevention. The findings of the present study reinforce the need to implement structured strategies to encourage healthy eating habits in these individuals.

45.      Clinical-Epidemiological Profile of Patients With Chronic Obstructive Pulmonary Disease Treated at the Pneumology Outpatient Clinic of a Brazilian University Hospital. C ureus. 2024 Dec 10;16(12):e75451. doi: 10.7759/cureus.75451.

Sarno Filho MV(1)(2), Soares LN(1), Lima Costa Neves MC(3).

Afiliação:
(1)   Internal Medicine, Hospital das Clínicas da Universidade de São Paulo, São Paulo, BRA.
(2)   Medicine, Hospital Universitário Professor Edgard Santos, São Paulo, BRA.
(3)   Internal Medicine, Departamento de Medicina Interna e Apoio Diagnóstico da Faculdade de Medicina da Bahia da Universidade Federal da Bahia, Salvador, BRA.

Resumo:
Background Chronic obstructive pulmonary disease (COPD) is a significant illness that affects many Brazilians. It is a complex and extremely prevalent disease, and thus, understanding the clinical-epidemiological profile of the patients afflicted with this disease is of utmost importance for the adequate management of these patients by multidisciplinary teams. Objective The aim of the study was to describe the clinical and epidemiological profile of COPD patients in a specialized outpatient clinic. Methods This was a cross-sectional study. The sample comprised 198 patients who attended a specialized outpatient clinic in 2018. All variables were collected from the patients' medical records. Results The mean age of the patients was 69.56 ± 8.98 years (CI 95%: 68.30 - 70.82). Of the 198 patients, 115 (58.1%) were male, while 83 (41.9%) were female. Of all patients, 158 (79.8%) were active smokers or former smokers. The mean value for the forced expiratory volume in the first second (FEV1) was 53.35% ± 21.22 of the expected value (CI 95%: 49.76 - 56.94). The mean number of comorbidities presented by the patients was 2.51 ± 1.81 (CI 95%: 2.25 - 2.76) and the average number of drugs the patients were taking for COPD was 2.83 ± 1.24 drugs (IC95%: 2.66 - 3.01). Conclusion This study reveals a complex population, with moderate to severe COPD and a high burden of comorbidities. Thereby, it becomes clear that pulmonologists must consider the COPD patient as a whole due to the high prevalence of factors that can worsen the prognosis in this population.

46.      Evaluation of QuantiFERON-TB Gold for the Diagnosis of Mycobacterium tuberculosis Infection in HTLV-1-Infected Patients. Viruses. 2024 Nov 30;16(12):1873. doi: 10.3390/v16121873. 

Gois LL(1)(2), Carvalho NB(3)(4), Santos FLN(2), Regis-Silva CG(2), Figueiredo TGT(5), Galvão-Castro B(2)(5), Carvalho EM(3)(6), Grassi MFR(2)(5).

Afiliação:
(1)   Departamento de Biointeração, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador 40231-300, Bahia, Brazil.
(2)   Laboratório Avançado de Saúde Pública, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (Fiocruz-BA), Salvador 40296-710, Bahia, Brazil.
(3)   Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador 40110-060, Bahia, Brazil.
(4)   Laboratório de Bacteriologia e Saúde, Instituto de Biologia, Universidade Federal da Bahia, Salvador 40170-110, Bahia, Brazil.
(5)   Escola Bahiana de Medicina e Saúde Pública, Salvador 40290-000, Bahia, Brazil.
(6)   Laboratório de Pesquisa Clínica, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (Fiocruz-BA), Salvador 40296-710, Bahia, Brazil.

Resumo:
Human T-cell leukemia virus type 1 (HTLV-1) is associated with an increased risk of tuberculosis (TB). This study aimed to evaluate the performance of the QuantiFERON-TB Gold (QFT) test for the diagnosis of Mycobacterium tuberculosis (MTB) infection in HTLV-1-infected individuals. HTLV-1-infected participants were divided into four groups: HTLV-1-infected individuals with a history of tuberculosis (HTLV/TB), individuals with positive HTLV and tuberculin skin tests (HTLV/TST+) or negative TST (HTLV/TST-), and HTLV-1-negative individuals with positive TST results (HN/TST+). We compared the diagnostic performance of the QFT assay with that of the TST as a reference and evaluated test sensitivity, specificity, accuracy, likelihood ratio, and diagnostic odds ratio. The results showed a higher frequency of positive TST results and induration diameter ≥10 mm in HTLV-1-infected individuals than in the controls. The QFT test was more frequently positive in the HTLV/TB group than in the other groups, while a combined analysis of HTLV/TB and HTLV/TST+ indicated a QFT sensitivity of 57.5%. No significant differences were found in the other diagnostic performance measures, as QFT test results were in agreement with TST results, particularly in TST-negative individuals. Given the low sensitivity of QFT for LTBI in individuals infected with HTLV-1, the TST may be preferable in regions where both infections are endemic.

47.      Effectiveness of the primary Bacillus Calmette-Guérin vaccine against the risk of Mycobacterium tuberculosis infection and tuberculosis disease: a meta-analysis of individual participant data. Lancet Microbe. 2024 Dec 19:100961. doi: 10.1016/j.lanmic.2024.100961.

Pelzer PT(1), Stuck L(2), Martinez L(3), Richards AS(4), Acuña-Villaorduña C(5), Aronson NE(6), ..., Huerga H(22), Jones-López EC(23), Kritski A(24), Mandalakas AM(25), Mangtani P(16), Martins Netto E(26), et al.

Afiliação:
(1)   Amsterdam University Medical Centres, Amsterdam, Netherlands; KNCV Tuberculosis Foundation, The Hague, Netherlands; London School of Hygiene & Tropical Medicine, London, UK; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.
(2)   Amsterdam University Medical Centres, Amsterdam, Netherlands; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.
(3)   Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA.
(4)   London School of Hygiene & Tropical Medicine, London, UK.
(5)   Boston University Medical Center, Boston, MA, USA.
(6)   Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
...
(22)  Field Epidemiology Department, Epicentre, Paris, France.
(23)  Division of Infectious Diseases, Department of Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
(24)  Programa Acadêmico de Tuberculose, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
(25)  Baylor College of Medicine, Houston, TX, USA; Research Center Borstel, Sülfeld, Germany.
(26)  Faculdade de Medicina da Bahia, Salvador, Brazil; Hospital Universitário Professor Edgard Santos, Salvador, Brazil; Universidade Federal da Bahia, Salvador, Brazil.
...

Resumo:
Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease. METHODS: We conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, M tuberculosis infection test (QuantiFERON IFN-γ release assay [IGRA] and tuberculin skin test [TST]), and tuberculosis incidence. Cohort studies were included only for countries with a mandatory neonatal BCG vaccination policy. Exclusion criteria were previous or current tuberculosis disease, HIV infection, tuberculosis preventive treatment usage, and for household contacts, a positive baseline IGRA or TST test and young children aged 0-2 years; for randomised controlled trials, TST results within 2 years after random assignation were excluded. We contacted the investigators of the identified studies to provide IPD. We compared the protective efficacy of the BCG vaccine against M tuberculosis infection with that against tuberculosis disease using mixed-effects, multivariable proportional hazards modelling, by study type, M tuberculosis infection test (IGRA and TST), cutoff for defining test positivity, age, sex, and latitude. FINDINGS: We identified 79 studies eligible for full screening and of these, IPD datasets from 14 studies were included in our analysis: 11 household contact studies (29 147 participants), two adolescent cohort studies (11 368 participants), and one randomised controlled trial (2963 participants). Among 28 188 participants we found no protection by the BCG vaccine against TST conversion regardless of cutoff in any type of study. Among 1491 household contacts, but not among 5644 adolescents, the BCG vaccine protected against QuantiFERON conversion at the primary cutoff of 0·7 IU/mL or more with the adjusted hazard ratio (0·65, 95% CI 0·51-0·82) being consistent with that for protection against disease (0·68, 0·18-2·59). Protection against QuantiFERON conversion at cutoff of 0·35 IU/mL or more (0·64, 0·51-0·81) was similar. INTERPRETATION: Protection from the BCG vaccination against M tuberculosis infection, measured as QuantiFERON conversion, is inconsistent across different groups. Among groups with recent household exposure, QuantiFERON conversion is consistent with protection against disease and could be evaluated as a proxy for disease in tuberculosis vaccine trials. We found that TST lacks value for prevention in phase 2b proof-of-concept trials.