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Immunogenicity and safety to SARS-Cov-2 vaccination in patients with systemic vasculitis
(2025) Biegelmeyer, Erika; Aguiar, Mariana de Freitas; Ribeiro, Priscila Dias Cardoso; Machado, Ketty Lysie Libardi Lira; Telles, Camila Maria Paiva França; Ribeiro, Sandra Lúcia Euzébio; Sartori, Natália Sarzi; Rezende, Rodrigo Poubel Vieira de; Melo, Ana Karla Guedes de; Cruz, Vitor Alves
Background/objectives: Patients with systemic vasculitis faced the risk of severe COVID-19 and high mortality during the pandemic. Although SARS-CoV-2 vaccination mitigates these outcomes, vaccine hesitancy persists, and data on immunogenicity and safety in vasculitis is still limited. This study aims to assess response to primary and booster doses of SARS-CoV-2 vaccination in systemic vasculitis. Methods: This multicenter cohort study including systemic vasculitis included patients fromSAFER study (Safety and Efficacy ofCOVID-19 Vaccines in Rheumatic Diseases). We evaluated serum IgG levels against the SARS-CoV-2 spike protein receptor-binding domain (IgG anti-RBD) at baseline and 28 days post-vaccination, disease activity scores, new cases of COVID-19 infections, and adverse events. Results: Seventy-three patients with systemic vasculitis were included. Behçet’s disease (n=39), Takayasu arteritis (n=15), and antineutrophil cytoplasmic antibody-associated vasculitis (n=14) were the most common vasculitis forms. The majority of the patients had no comorbidities and were in remission. Seventy patients received one, 65 two, and 60 three vaccine doses. ChAdOx1 nCoV-19 (AstraZeneca/Oxford) (n=36) and CoronaVac (Sinovac) (n=25) were primarily the most common vaccines, while BNT162b2 (Pfizer–BioNTech) was usually the booster vaccine. ChAdOx1 nCoV-19 induced higher IgG anti-RBD than CoronaVac after two doses (p=0.002), but this difference disappeared after the booster dose. No differences in vaccine response were noted between heterologous and homologous regimens or vasculitis types. The new cases of COVID-19 (16.9%), hospitalization (1.5%), and mortality (1.5%) rates were relatively low following vaccination. Disease activity remained stable, and adverse events were mostly mild. Only one severe adverse event was observed. Conclusion: Different SARS-CoV-2 vaccines demonstrated immunogenicity and clinical effectiveness in systemic vasculitis. The three-dose schedule was safe without increasing relapse risk.
Musculoskeletal manifestations in leprosy
(2025) Cruz, Vitor Alves; Tavares, Anna Carolina Faria Moreira Gomes; Araújo, Andréa Monteiro de; Feitosa, Maria Stella Cochrane; Carvalho, Joana Starling de; Gomes, Ciro Martins; Souza, Viviane Angelina de; Mota, Licia Maria Henrique da
Leprosy, a chronic infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis, primarily targets the skin and peripheral nerves, frequently leading to dermatological, neurological, and musculoskeletal complications. This review highlights the spectrum of musculoskeletal manifestations in leprosy, including acute arthritis during Type 2 reactions, chronic arthritis mimicking autoimmune diseases like rheumatoid arthritis, and neuropathic arthropathy. These manifestations underscore the complex interplay of inflammatory and immune mechanisms. Acute arthritis often involves both small and large joints, while chronic forms may present diagnostic challenges due to their resemblance to other inflammatory arthritides. Clinical management centers on multidrug therapy (MDT) for infection control, complemented by immunosuppressive or anti-inflammatory agents for reactional episodes. Recent advancements, such as biologics and synthetic immunosuppressants, have demonstrated efficacy in refractory cases, offering new therapeutic avenues. Heightened clinician awareness is essential for timely diagnosis and integrated management, particularly in endemic regions, to mitigate long-term disabilities and improve patient outcomes.
Brazilian recommendations for the management of tuberculosis infection in immune-mediated inflammatory diseases
(2025) Souza, Viviane Angelina de; Caparroz, Ana Luiza Mendes Amorim; Trevisani, Virginia Fernandes Moça; Tavares, Anna Carolina Faria Moreira Gomes; Melo, Ana Karla Guedes de; Trajman, Anete; Ribeiro, Ana Cristina de Medeiros; Pinheiro, Marcelo de Medeiros; Xavier, Ricardo Machado; Monticielo, Odirlei André; Cruz, Vitor Alves
Background The risk of tuberculosis infection (TBI) and its progression to tuberculosis disease (TBD) among persons with immune-mediated inflammatory diseases (IMID) results from a complex interplay of patient and disease characteristics, immunosuppression level, and the epidemiological context. Brazilian recommendations are unclear about TBI screening and its preventive treatment (TPT) in persons with IMID. Objective To provide a comprehensive and evidence-based guideline for managing TBI in persons with IMID in Brazil. Methods This task force was constituded by 42 specialists with interest in IMID and TBD. A core leadership team (CLT) drafted fourteen clinical questions on the risk of tuberculosis and indications of TPT among persons with IMID who started, or are about to start immunosuppressive drugs. The CLT supervised the systematic reviews and formulated the recommendations. The experts voted using the Delphi Method. Results Nine recommendations were established. More than 80% of panelists voted “agree” and “strongly agree” with all statements. In brief, all persons with IMID starting or about to start immunosuppressive treatment should undergo tuberculin skin testing (TST) or interferon-gamma release assays (IGRAs), a chest imaging test and investigation of contact with active pulmonary or laryngeal TBD. TPT is mandatory for those with any positive result after excluding TBD. Exceptions include individuals with a history of TBD or a past positive TBI infection test. IGRA is preferred only in persons BCG-vaccinated in the past 2 years. Those with inconclusive IGRA results can have the test repeated once, and TPT should be offered if it remains indeterminate. TST or IGRA should be repeated yearly, for three years, when the previous test was negative, when starting or changing to a different class of immunosuppressive drug. Overall, the included studies had a low quality of evidence and high risk of bias. Conclusions These guidelines are meant to improve the management of TBI in IMID. Health professionals must consider the epidemiological risk, host features, the social scenario, the characteristics of the disease, the access to health resources, and the development of an individualized plan for every patient.
Comparison of the immunogenicity and safety among COVID-19 vaccines ChadOx-1, CoronaVac and BNT162b2 in systemic lupus erythematosus (SLE) patients: a prospective cohort
(2025) Ribeiro, Priscila Dias Cardoso; Peixoto, Flavia Maria Matos Melo Campos; Reis Neto, Edgard Torres dos; Pileggi, Gecilmara Cristina Salviato; Bellei, Nancy Cristina Junqueira; Pinheiro, Marcelo de Medeiros; Magalhães, Vanessa de Oliveira; Biegelmeyer, Erika; Trolese, André Gustavo Cunha; Souza, Alexandre Wagner Silva de; Cruz, Vitor Alves
Background The immune response and safety using different COVID-19 vaccine platforms in patients with immune mediated rheumatic diseases is still uncertain. The objective of this study is to compare the immunogenicity and safety after two doses of BNT162b2, CoronaVac and ChadOx-1 in SLE patients. Methods Prospective study including SLE patients who received a primary schedule to COVID-19 vaccination between May and August 2021. Immunogenicity, events supposedly attributable to vaccination or immunization (ESAVI) and disease activity were assessed at baseline and after each vaccine dose. Results 121 SLE patients were included in the cohort, 88 in the immunogenicity analysis and 118 in the safety analysis. The groups were homogenous concerning sex, age, and comorbidities. Seropositivity after two doses of vaccines was similar between CoronaVac (68%), ChadOx1 (80,6%) and BNT162b2 (88%) (p=0.231). However, CoronaVac and ChadOx-1 presented lower titers in comparison with BNT162b2. Regarding ESAVI, the most frequent reported following first and second vaccine doses were, respectively: injection site pain (65.2%/41.1%), headache (50.9%/29.9%) and arthralgia (37.5%/22.5%). Fever and myalgia were more related to ChAdOx1 than CoronaVac (23.3 vs. 5.0%; p=0.025). There was no difference in MEX-SLEDAI between vaccine platforms. No serious ESAVI were reported. Conclusion After two doses, the three COVID-19 vaccine platforms induced a significant increase in antibody titers against SARS-CoV-2. Patients who received BNT162b2 exhibited a higher serological response compared to the other vaccines. All three vaccine platforms demonstrated a favorable safety profile, with no serious ESAVI or worsening of disease activity. Clinical trial Number The study was registered in The Brazilian Registry of Clinical Trials (ReBEC) in 04/14/2021 with code RBR-108fyykd.
Immunogenicity of SARS-CoV-2 vaccination schedules including a booster dose in patients with systemic lupus erythematosus: data from a prospective multicenter study
(2025) Sartori, Natália Sarzi; Machado, Ketty Lysie Libardi Lira; Miyamoto, Samira Tatiyama; Pretti, Flávia Zon; Gouvea, Maria da Penha Gomes; Oliveira, Yasmin Gurtler Pinheiro de; Silva, Vanezia Gonçalves da; Faé, Filipe; Burian, Ana Paula Neves; Lallemand Tapia, Karina Rosemarie; Cruz, Vitor Alves
Objective: To evaluate the humoral response to and impact of SARS-CoV-2 vaccination in patients with systemic lupus erythematosus in a multicenter cohort design. Methods: Data for this analysis were obtained from the Study of Safety, Effectiveness and Duration of Immunity after Vaccination against SARS-CoV-2 in Patients with Immune- Mediated Inflammatory Diseases (SAFER), a prospective, multicenter, phase IV, real-world study conducted across different regions of Brazil from June/2021 to March/2024. Patients aged >18 years with systemic lupus erythematosus (SLE) who received any one of the SARSCoV- 2 vaccines approved by the Brazilian health regulatory agency (CoronaVac [inactivated SARS-CoV-2 vaccine], ChAdOx-1 [AstraZeneca], or BNT162b2 [Pfizer-BioNTech]) were included. Immunogenicity was assessed in pre- and post-vaccination blood samples, and patients were monitored in person and remotely for the occurrence and severity of COVID-19. Results: Two hundred and thirty-five patients with SLE who had completed their vaccination schedules (two doses + booster dose) were included in this study. Most patients were female (89.3%) and had low disease activity or were in remission (72.4%); the majority were also on some form of immunosuppressive therapy (58.1%). One hundred and sixteen patients received two doses of CoronaVac followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, eighty-seven received two doses of ChAdOx1-S (AstraZeneca) followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, and thirty-two received three doses of BNT162b2 (Pfizer-BioNTech) vaccine. Twenty-eight cases of COVID-19, none meeting criteria for severe COVID-19, were recorded in patients with respiratory symptoms after the second dose of a SARS-CoV-2 vaccine. Regarding immunogenicity, an increase in seroconversion rate was observed following consecutive vaccine doses, with no difference between vaccination schedules, reaching 97.57% seropositivity after a booster dose. The geometric mean IgG titers differed between the different vaccination schedules after the first and the second vaccine dose, being lowest for the CoronaVac-based schedule, but titers were similar after the administration of a booster dose. Conclusion: In patients with SLE, SARS-CoV-2 vaccines are immunogenic, inducing a robust humoral response. No severe outcomes associated with death or hospitalization were found in the evaluated patient sample. Complete vaccination schedules including a booster dose induced higher humoral responses than incomplete schedules, especially in patients initially immunized with an inactivated virus vaccine schedule and those with a suboptimal humoral response.
Impact of SARS-CoV-2 vaccination on disease activity and severity of COVID-19 infection in patients with systemic lupus erythematosus: a multicenter cohort study
(2025) Sartori, Natália Sarzi; Machado, Ketty Lysie Libardi Lira; Miyamoto, Samira Tatiyama; Pretti, Flavia Zon; Gouvea, Maria da Penha Gomes; Oliveira, Yasmin Gurtler Pinheiro de; Silva, Vanezia Gonçalves da; Faé, Filipe; Burian, Ana Paula Neves; Pinheiro, Marcelo de Medeiros; Cruz, Vitor Alves
Objective: To evaluate the humoral response to and impact of SARS-CoV-2 vaccination in patients with systemic lupus erythematosus in a multicenter cohort design. Methods: Data for this analysis were obtained from the Study of Safety, Effectiveness and Duration of Immunity after Vaccination against SARS-CoV-2 in Patients with Immune- Mediated Inflammatory Diseases (SAFER), a prospective, multicenter, phase IV, real-world study conducted across different regions of Brazil from June/2021 to March/2024. Patients aged >18 years with systemic lupus erythematosus (SLE) who received any one of the SARSCoV- 2 vaccines approved by the Brazilian health regulatory agency (CoronaVac [inactivated SARS-CoV-2 vaccine], ChAdOx-1 [AstraZeneca], or BNT162b2 [Pfizer-BioNTech]) were included. Immunogenicity was assessed in pre- and post-vaccination blood samples, and patients were monitored in person and remotely for the occurrence and severity of COVID-19. Results: Two hundred and thirty-five patients with SLE who had completed their vaccination schedules (two doses + booster dose) were included in this study. Most patients were female (89.3%) and had low disease activity or were in remission (72.4%); the majority were also on some form of immunosuppressive therapy (58.1%). One hundred and sixteen patients received two doses of CoronaVac followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, eighty-seven received two doses of ChAdOx1-S (AstraZeneca) followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, and thirty-two received three doses of BNT162b2 (Pfizer-BioNTech) vaccine. Twenty-eight cases of COVID-19, none meeting criteria for severe COVID-19, were recorded in patients with respiratory symptoms after the second dose of a SARS-CoV-2 vaccine. Regarding immunogenicity, an increase in seroconversion rate was observed following consecutive vaccine doses, with no difference between vaccination schedules, reaching 97.57% seropositivity after a booster dose. The geometric mean IgG titers differed between the different vaccination schedules after the first and the second vaccine dose, being lowest for the CoronaVac-based schedule, but titers were similar after the administration of a booster dose. Conclusion: In patients with SLE, SARS-CoV-2 vaccines are immunogenic, inducing a robust humoral response. No severe outcomes associated with death or hospitalization were found in the evaluated patient sample. Complete vaccination schedules including a booster dose induced higher humoral responses than incomplete schedules, especially in patients initially immunized with an inactivated virus vaccine schedule and those with a suboptimal humoral response.
Brazilian Society of Rheumatology – 2025 recommendations on vaccination in immune-mediated rheumatic diseases
(2026) Pileggi, Gecilmara Cristina Salviato; Cruz, Vitor Alves; Ribeiro, Ana Cristina de Medeiros; Melo, Ana Karla Guedes de; Trolese, André Gustavo Cunha; Tavares, Anna Carolina Faria Moreira Gomes; Zerbini, Cristiano Augusto de Freitas; Biegelmeyer, Erika; Peixoto, Flávia Maria Matos Melo Campos; Ferreira, Gilda Aparecida
Background Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk for infections due to both disease-related immune dysregulation and immunosuppressive therapy. Despite the benefits of vaccination, immunization rates in this population remain suboptimal, often due to concerns about safety, efficacy, and their potential for inducing disease flare. Regional-specific guidelines are necessary to address the particular epidemiological issues and aspects of the healthcare systems, especially in countries like Brazil. Objective To provide updated, evidence-based, and nationally relevant recommendations on vaccination in adult patients with IMRD in Brazil, focusing on immunogenicity, safety and disease activity outcomes. Methods A multidisciplinary task force from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of studies addressing eleven clinical questions related to vaccine safety and efficacy in IMRD. Studies were selected using predefined PICO criteria. Risk of bias was assessed using JBI tools, and the certainty of evidence was evaluated with the GRADE approach. Statements were developed and submitted to a Delphi-based voting process; consensus was achieved if ≥80% of the panelists voted “agree” or “strongly agree” for all the statements. Results Eleven recommendations were developed based on a systematic review of the literature, with meta-analyses conducted when appropriate. Inactivated vaccines demonstrated a favorable safety profile, with low flare rates and no significant increase in disease activity, even under immunosuppression. Live attenuated vaccines, including yellow fever, were considered safe when administered according to timing protocols. Immunogenicity may be reduced in patients receiving methotrexate, mycophenolate, corticosteroids, rituximab, and JAK inhibitors, although this does not appear to compromise clinical protection in most cases. Temporary treatment interruption was associated with improved immunogenicity in selected contexts, but without consistent evidence of clinical benefit and with potential risks related to disease control. Specific guidance was provided for influenza and hepatitis B vaccination, as well as for prioritizing vaccination before initiating immunosuppression whenever feasible. Statements also addressed the approach to revaccination and post-vaccination serologic testing. Despite the overall very low to moderate certainty of evidence, most recommendations reached strong consensus (≥80% agreement). Shared decision-making and individualized strategies were emphasized across all scenarios. Conclusion These recommendations offer tailored guidance for improving vaccination strategies in IMRD patients in Brazil. Given the heterogeneity of evidence, clinical decisions should be individualized, considering disease activity, treatment regimen, vaccine availability, and patient preferences. Shared decision-making is essential in all scenarios to enhance vaccine uptake and align preventive care with patient-centered management.
Are global definitions enough? Revisiting CDAI and SDAI remission cut-offs in Brazilian rheumatoid arthritis patients
(2026) Pires, Lucas Castro; Pugliesi, Alisson Aliel Vigano; Albuquerque, Cleandro Pires de; Cruz, Vitor Alves; Bertolo, Manoel Barros; Reis, Ana Paula Monteiro Gomides; Giorgi, Rina Dalva Neubarth; Pereira, Leticia Rocha; Radominski, Sebastião Cezar; Pereira, Ivânio Alves
Background Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease in which achieving remission is the most effective strategy to prevent progression and optimize long-term outcomes. The performance of commonly used disease activity indices has not been well validated in the Brazilian RA population. This study aimed to evaluate the agreement between CDAI/SDAI and the revised Boolean 2.0 remission criteria, which served as the reference standard, and to identify the most accurate CDAI and SDAI remission cut-offs in this population. Methods We conducted a cross-sectional analysis of baseline data from a Brazilian Cohort study, which included 840 patients from 11 public hospitals in Brazil. Disease activity was assessed using DAS28-CRP, DAS28-ESR, SDAI, CDAI, and Boolean 1.0/2.0. Agreement was assessed using Cohen’s kappa, and optimal remission cut-offs were determined through ROC curve analysis. Results The study population was predominantly female (89.8%), with a mean age of 57 years and a median disease duration of 12 years. DAS28-CRP showed the highest remission rate (39.2%), whereas Boolean 1.0 showed the lowest (15.1%). Strong agreement was found between Boolean 2.0, and both the SDAI (κ = 0.775) and CDAI (κ = 0.692). ROC analysis revealed that the most accurate remission cut-offs were SDAI ≤ 4.3 and CDAI ≤ 3.9, which increased remission detection by 5.9% and 6.2%, respectively. Conclusion In our cohort, SDAI ≤ 4.3 and CDAI ≤ 3.9 were the values most closely aligned with Boolean 2.0 remission. These adjusted cut-offs may help minimize overtreatment in resource-limited settings. Prospective studies assessing function, radiographic progression, and quality of life are warranted to confirm their validity in the Brazilian population.
Primary and booster COVID-19 vaccination in patients with Sjögren's disease: data from the longitudinal SAFER cohort study
(2025) Lirio, Maressa Barbosa Beloni; Machado, Ketty Lysie Libardi Lira; Martins Filho, Olindo Assis; Miyamoto, Samira Tatiyama; Oliveira, Yasmin Gurtler Pinheiro de; Serrano, Érica Vieira; Mill, José Geraldo; Lallemand Tapia, Karina Rosemarie; Ferreira, Lunara Baptista; Cruz, Vitor Alves
Introduction: The COVID-19 pandemic posed additional challenges for this vulnerable population, such as Sjögren’s disease (SjD), underscoring the need for effective and safe vaccination strategies. Objective: To evaluate the immunogenicity and safety of COVID-19 vaccines in patients with SjD. Methods: This prospective, observational, longitudinal study included SjD patients from the SAFER cohort. Immunogenicity was assessed via antispike IgG (IgG-S) titers using chemiluminescence reported as geometric mean titers (GMT) and fold increase in GMT (FI-GMT). Disease activity was evaluated using the ESSDAI score. Adverse events and COVID-19 infections were also monitored. Assessments were conducted at four time points: pre-first dose (T1), pre-second dose (T2), pre-booster (T3), and four weeks post-booster (T4). Primary vaccination involved ChAdOx1 nCoV-19 or inactivated vaccine (CoronaVac), and boosters were either homologous (ChAdOx1 nCoV- 19) or heterologous (BNT162b2). Results: Among 51 participants (mean age 46 years; 90% female), 41% had comorbidities and 27% (n = 14/51) were highly immunosuppressed. Among those 73% (n = 37/51) under low immunosuppression, n = 8/51 (13%) were not using any medication. At baseline, 11% (n = 4/35) showed moderate/high disease activity, which decreased to 6.5% (n = 2/31) at T4. Primary vaccination was ChAdOx1 in 94% (n = 48/51) and CoronaVac in 6% (n = 3/51); 73% (n = 37/51) received heterologous and 27% (n = 14/51) homologous boosters. COVID-19 infection post-booster occurred in 20% (n = 10/51). Seroconversion rates reached nearly 100% across all medication subgroups except for biologic users, who showed delayed but stable seroconversion by T4. IgG-S titers increased progressively through T4. Primary immunization induced an ascending GMT in both vaccine types. At T4, the GMT was significantly higher in the BNT162b2 group (2148.03 [1452.05–3155.84]; p < 0.001; 95% CI) than in the ChAdOx1 group (324.29 [107.92–974.48]; p < 0.001; 95% CI); the fold-increase in immune response was six times greater with BNT162b2 (5.98 [2.97–12.03]; p = 0.001; 95% CI). Seroconversion was 100% in the heterologous group versus 83% in the homologous group (p > 0.01). Those with prior infection showed significantly higher titers, particularly at T2 and T3 (p < 0.001 for T1–T3). Adverse events were mild and not statistically significant. Multivariate regression confirmed BNT162b2 as an independent factor for higher antibody titers. Conclusion: COVID-19 vaccination in patients with SjD was safe and induced high anti-spike antibody titers and seropositivity. Heterologous boosting, particularly with BNT162b2, demonstrated superior immunogenicity. No association was found between vaccination and SjD disease flares or worsening activity.
Hughes-Stovin syndrome (HSS) preliminary diagnostic criteria: a report by the HSS International Study Group (HSSISG)
(2026) Fekry, Yasser Emad El-Din Amin; Gheita, Tamer Atef A.; Ragab, Yasser Mohamed; Hammam, Nevin Hammam Othman; Kindermann, Michael; Ibrahim, Ossama; Fabi, Marianna; Frikha, Faten Hadded; Alhusseiny, Khalid; Tekavec-Trkanjec, Jasna; Cruz, Vitor Alves
Objective Hughes-Stovin syndrome (HSS) is a systemic vasculitis that remains an enigmatic and poorly understood clinical disorder. Despite this, no diagnostic criteria have been established since the disease was initially described in 1959. The objective of this report is to develop preliminary HSS diagnostic criteria proposed by the HSS International Study Group (HSSISG). Methods This international initiative included a systematic literature review of HSS case reports in a global endeavor. A systematic review of MEDLINE, EMBASE, and the Cochrane database identified 112 HSS patients. The selected reports were based on comprehensive case presentations, encompassing demographic characteristics, initial disease presentations, notable symptoms and signs, laboratory findings, radiological investigations, medical lines of treatment or interventional management received, and finally patients’ outcomes. Diagnostic criteria were selected based on their clinical relevance, dominance, and consensus among the HSSISG members. Each criterion was discussed in detail to enhance comprehension and interpretation by physicians. Results Following consensus agreement, one mandatory entry criterion was selected which included pulmonary findings, along with one exclusion criterion regarding ocular aspects. Two major criteria were defined, vascular aspects and coagulation profile, and four minor criteria: mucocutaneous, central nervous system, cardiac, and inflammatory markers. The maximum achievable score is 30, with a suggested definitive diagnosis of HSS with scores 10 or higher, probable HSS with scores of 5–9, and possible HSS for scores 3–4. Scores < 3 are considered nondiagnostic. Conclusion Preliminary HSS diagnostic criteria were proposed after a comprehensive and critical literature review by the HSSISG to offer support for early diagnosis and optimal management.
Elaboração de uma matriz de atividades profissionais confiáveis (APC) para a residência em patologia
(2026) Naghettini, Alessandra Vitorino; Araújo, Luiz Murilo Martins de
Development and validation of entrustable professional activities in pediatric surgery for pediatricians
(2025) Miranda, Rodrigo Pinheiro de Abreu; Pereira, Edna Regina Silva; Santos Neto, Leopoldo Luiz dos
Objective To develop and validate entrustable professional activities (EPAs) for the training of pediatric residents on topics that interface with pediatric surgical areas in the Brazilian context. Methods The study was conducted in two phases. In the first phase, experts were oriented and contextualized, and they were responsible for developing the initial list of EPAs. In the second phase, the Delphi technique was applied in three rounds: the first for consensus, the second for selection according to relevance and agreement, and the third for validation and detailing of the EPAs. Results In the first phase of the study, 9 experts listed 88 EPAs, which were applied in the Delphi method. In the first round of Delphi, the consensus of these experts defined 31 EPAs, with CVI ≥ 0.80, and ICC of 0.893 (95 % CI 0.823–0.945). In the second round, 25 coordinators of Medical Residency Programs selected 17 EPAs by agreement and relevance (CVI ≥ 0.80, and ICC of 0.851–95 % CI 0.753 to 0.924). In the third round, 50 preceptors from all over Brazil validated 14 EPAs with CVI ≥ 0.965 and ICC 0.866 (95 % CI 0.804–0.915), which were organized and detailed into 7 final EPAs. Conclusion Seven pediatric surgery EPAs were developed, consensualized, selected, and validated by experts for the work of pediatricians in Brazil through the Delphi method. The great participation and interest of medical residency preceptors with a wide geographical coverage in Brazil were strong points of this study, and these EPAs can be applied, reviewed, and updated.
Pembrolizumab plus weekly paclitaxel in platinum-resistant recurrent ovarian cancer (ENGOT-ov65/KEYNOTE-B96): a multicentre, randomised, double-blind, phase 3 study
(2026) Colombo, Nicoletta N.; Zsiros, Emese; Parma, Gabriella Maria; Rulli, Eliana; Sebastianelli, Alexandra; Bidziński, Mariusz; Gallardo Garrido, Carlos Andrés; Matanes, Emad; Kosei, Hasegawa; Köse, Fatih; Freitas Junior, Ruffo de
Background Epithelial ovarian cancer frequently recurs and becomes resistant to platinum chemotherapy. We investigated whether adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, improves progression-free survival and overall survival compared with weekly paclitaxel, with or without bevacizumab, in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens. Methods ENGOT-ov65/KEYNOTE-B96 is a randomised, double-blind, phase 3 study conducted at 187 gynaecologic oncology centres in 25 countries in the Americas, Asia, Europe, and Oceania. Adults (≥18 years) with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who received one to two previous systemic therapies including at least one platinum regimen and who progressed 6 months or less after the last platinum regimen, were eligible. Participants were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle or intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle; intravenous bevacizumab 10 mg/kg every 2 weeks was permitted per investigator. Randomisation was stratified by planned bevacizumab use, region, and PD-L1 combined positive score (CPS). The primary endpoint was investigator-assessed progression-free survival per RECIST version 1.1; the key secondary endpoint was overall survival. Results from two interim analyses and the final analysis are included in this Article. This study is registered with ClinicalTrials.gov, NCT05116189, and is now completed. Findings Between Dec 13, 2021, and July 3, 2023, 643 female participants were randomly assigned; 322 to pembrolizumab plus paclitaxel and 321 to placebo plus paclitaxel. At the first interim analysis, pembrolizumab plus paclitaxel significantly improved progression-free survival versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8·3 months vs 7·2 months; hazard ratio [HR] 0·72; 95% CI 0·58–0·89; p=0·0014 α=0·012]) and overall populations (median 8·3 months vs 6·4 months; HR 0·70, 95% CI 0·58–0·84; p<0·0001, [α=0·0023]), meeting the prespecified criteria for confirmatory efficacy. At the second interim analysis, overall survival was significantly improved in the PD-L1 CPS 1 or higher population (median 18·2 months vs 14·0 months; HR 0·76, 95% CI 0·61–0·94; p=0·0053, [α=0·0083]). At the final analysis, overall survival was significantly improved in the overall population (median 17·7 months vs 14·0 months; HR 0·82, 95% CI 0·69–0·97; p=0·011 [α=0·024]). Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. The most common treatment-related adverse events (any grade) included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group (colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation) and in five participants (2%) in the placebo plus paclitaxel group (cardiac failure, intestinal perforation [in two participants], and large-intestine perforation [in two participants]). Interpretation Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens, supporting this regimen as a new treatment option for this population. Funding
Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial
(2026) Dent , Rebecca Alexandra; Shao, Zhimin; Schmid, Peter; Cortes Castán, Javier; Cescon, David W.; Saj, Shigehira; Jung, Kyung Hae; Bachelot , Thomas; Wang, Shouman; Murillo Ramirez, Emilio; Freitas Junior, Ruffo de
Background Prognosis is poor and treatment options are limited for patients with previously untreated, advanced triple-negative breast cancer (TNBC), especially for those who are not candidates for immunotherapy. Patients and methods In the randomised, open-label, phase III TROPION-Breast02 trial, patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option were randomised 1:1 to datopotamab deruxtecan (Dato-DXd; 6 mg/kg intravenously every 3 weeks) or investigator’s choice of chemotherapy. Randomisation was stratified by geographic location, disease-free interval and programmed cell death ligand-1 status. Dual primary endpoints were progression-free survival (PFS; blinded independent central review per Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival (OS). Efficacy analyses were performed in the intention-to-treat population. Safety analyses included all patients who received ≥1 dose of study treatment. Results Between 16 May 2022 and 11 June 2024, 644 patients were randomised to Dato-DXd (n = 323) or chemotherapy (n = 321). Median PFS was 10.8 months (95% confidence interval [CI] 8.6–13.0) with Dato-DXd and 5.6 months (95% CI 5.0–7.0) with chemotherapy (hazard ratio 0.57 [99% CI 0.44–0.73]; P < 0.0001). Median OS was 23·7 months (95% CI 19.8–25.6) and 18.7 months (95% CI 16.0–21.8) with Dato-DXd and chemotherapy, respectively (hazard ratio 0.79 [95.01% CI 0.64–0.98]; P = 0.029). Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, and TRAEs led to treatment discontinuation in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm. Conclusions Dato-DXd demonstrated significantly improved PFS and OS versus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. Safety was consistent with the known profile for Dato-DXd.
Determinants of delayed postoperative radiation therapy in breast cancer patients undergoing neoadjuvant chemotherapy: A subanalysis of the AMAZONA III prospective cohort
(2026) Prestes, Júlio César; Arruda, Gustavo Viani; Gouveia, André Guimarães; Silva, Maurício Fraga da; Moraes, Fabio Ynoe de; Rosa, Daniela Dornelles; Barrios, Carlos Henrique Escosteguy; Werutsky, Gustavo; Bines, Jose; Silva, Eduardo Henrique Cronemberger Costa e; Freitas Junior, Ruffo de
Background Delays in starting postoperative radiation therapy (PORT) in breast cancer patients may be associated with poorer clinical outcomes. This analysis aimed to identify factors contributing to delayed PORT in patients with breast cancer who underwent neoadjuvant chemotherapy followed by surgery and PORT in a Brazilian cohort. Methods Participants were categorized based on the interval from surgery to the initiation of PORT into two groups: ≤ 8 weeks and > 8 weeks. Socioeconomic and clinicopathological factors were analyzed for associations with delayed PORT. Univariable and multivariable regressions were performed. Results Factors significantly associated with delayed PORT included low educational level (RR: 1.50; 95 % CI: 1.05–2.14; p = 0.0276), public health insurance (RR: 3.29; 95 % CI: 1.76–6.12; p = 0.0002) and having a Luminal A or Luminal B-HER2-negative subtype (RR: 1.92; 95 % CI: 1.14–3.23; p = 0.0153) compared to the Triple Negative subtype. The absence of adjuvant endocrine therapy was associated with a lower risk of delayed PORT (RR: 0.67; 95 % CI: 0.46–0.99; p = 0.0338). In the multivariate analysis, public health insurance remained the sole independent predictor of delayed PORT (RR: 2.98; 95 % CI: 1.60–5.55; p = 0.0006). Conclusion In this cohort, reliance on public health insurance emerged as the primary independent predictor of delayed initiation of PORT in breast cancer patients who received neoadjuvant chemotherapy. Lower educational levels and household income also contributed to delays, highlighting disparities within the healthcare system. Addressing these barriers is essential for improving timely access to PORT and potentially enhancing clinical outcomes in this population.
Compliance with Brazilian Law 12.732: assessing breast cancer treatment delays across different therapeutic modalities (2017-2022)
(2025) Antonini, Marcelo; Freitas, Sofia Naiara Barboza; Mattar, Andre; Pinheiro, Denise Joffily Pereira da Costa; Campos, Rodrigo Caires; Felix, Leticia Xavier; Ferraro, Odair; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Brenelli, Fabricio Palermo; Freitas Junior, Ruffo de
Introduction: Breast cancer (BC) is the most common cancer among women in Brazil and worldwide, followed by non-melanoma skin cancer. Law No. 12,732, of November 22, 2012, stipulates that cancer treatment should begin within 60 days of the anatomopathological diagnosis. However, the time to start treatment is still variable in Brazil. Methods: A cross-sectional observational ecological study was conducted using data on breast cancer in Brazil between 2017 and 2022, obtained from the DATASUS-SISCAN database. Patients with a diagnosis of breast cancer (ICD C50), the federative unit (UF) of residence, and the treatment modality were considered. Five-time intervals were defined for the start of treatment. The χ² and Z tests of two proportions were used, considering a 95% confidence interval (p<0.05). Results: Of the 243,277 evaluated cases, the highest frequency of patients was in the interval of more than 120 days to start treatment (25.5%). Surgery as a modality had a predominance of treatment initiation within 30 days in Brazil and in all regions, with the Northeast and South presenting 63.3% and 66.9% of patients starting treatment within 30 days, respectively. The chemotherapy modality had a greater distribution of patients in the interval of 31 to 60 days in the Northeast (26.1%) and in the South (26.3%), with the remaining regions predominantly showing intervals of more than 120 days. For radiation therapy, the predominance of treatment was after 120 days from diagnosis in all segments. Conclusion: Most patients waited more than 120 days to start breast cancer treatment. Surgical treatment had the shortest waiting time, while radiation therapy showed the longest intervals. For chemotherapy, the time until initiation was variable. In the trend analysis, a decrease in the time to start treatment was evident.
Prevalence of actionable pharmacogenomic variants in Brazilian patients with cancer
(2026) Schuch, Jaqueline Bohrer; Botton, Mariana Rodrigues; Baumont, Angélica Cerveira de; Curzel, Giovana Dallaio; Cadore, Nathan Araujo; Bordignon, Cláudia; Rosa, Mahira de Oliveira Lopes da; Vasconcellos, Vitor Fiorin de; Barros, Lilian Arruda do Rêgo; Souza, Cristiano de Pádua; Barra, Williams Fernandes; Freitas Junior, Ruffo de
Introduction: Pharmacogenomic (PGx) variants can influence drug efficacy and safety, yet their prevalence in Latin American populations with cancer is underexplored. Our aim is to characterize the frequency and phenotypic distribution of actionable pharmacogenes in Brazilian patients with metastatic prostate cancer (MPC) and Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer (BC).Methods: This analysis included 452 patients (259 BC, 193 MPC) from a multicenter study across 19 Brazilian sites. Exome sequencing was performed, and PGx variants were analyzed using the Pharmacogenomics Clinical Annotation Tool (PharmCAT) following the Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines. Genotypes, star alleles, and predicted phenotypes were reported for 15 clinically relevant pharmacogenes.Results: Actionable PGx phenotypes were detected in 99.33% of participants. The decreased-function ABCG2 rs2231142 T allele occurred at 8.96%, and the VKORC1 rs9923231 T allele at 32.63%. In SLCO1B1, normal function predominated (63.11%), with 21.11% exhibiting decreased function. Normal metabolizer phenotypes were most frequent in CYP2C19 (45.35%), CYP2C9 (70.51%), and CYP3A4 (94.62%), whereas CYP2B6 was dominated by intermediate metabolizers (43.02%) and CYP3A5 by poor/intermediate metabolizers (93.79%). Normal diplotypes predominated in thiopurine-related genes (NUDT15: 92.92%; TPMT: 88.72%), although nonfunctional alleles were observed. In UGT1A1, decreased-function alleles accounted for approximately 37% of participants. Clinically relevant DPYD and RYR1 variants were rare (<2.0%).Conclusion: Nearly all Brazilian patients with cancer carried at least one actionable PGx variant, highlighting the potential impact of PGx-guided therapy in oncology. These results underscore the value of integrating pharmacogenomic strategies into clinical practice in Brazil.
Is axillary surgery still justified in DCIS diagnosed via vacuum-assisted biopsy?
(2025) Ramos, Marcellus do Nascimento Moreira; Mattar, André; Zerwes, Felipe Pereira; Cavagna, Felipe Andreotta; Cavagna, Felipe Andreotta; Cavalcante, Francisco Pimentel; Millen, Eduardo Camargo; Brenelli, Fabricio Palermo; Frasson, Antonio Luiz; Madeira, Marcelo; Freitas Junior, Ruffo de; Antonin, Marcelo
Background The role of axillary surgery in ductal carcinoma in situ (DCIS) remains controversial, particularly for cases diagnosed via vacuum-assisted biopsy (VAB), which may reduce “upstage” to invasive disease. This study evaluates the incidence of axillary metastasis and pathologic upstaging in DCIS to identify subgroups where axillary staging can be safely omitted. Methods A retrospective cohort of 494 patients with pure DCIS diagnosed by VAB (2011–2019) was analyzed. Patients were stratified by age, nuclear grade, comedonecrosis, and surgical approach (breast-conserving surgery [BCS] vs. mastectomy). Axillary management included sentinel node biopsy (SNB), axillary dissection (AD), or omission. Multivariate logistic regression identified predictors of axillary surgery and upstaging to invasive carcinoma. Results Most patients underwent BCS (72.7%), with axillary evaluation performed in 35.1% of BCS cases versus 91.9% of mastectomies (p < 0.001). Only 3.8% (19/494) were upstaged to invasive carcinoma, and nodal involvement occurred in 1.2% (3/250) of axillary procedures—all in patients with invasive foci on final pathology. No pure DCIS cases had nodal metastasis. Younger age (< 40 years, p = 0.039), high nuclear grade (grade 3, p = 0.006), and mastectomy (p < 0.001) independently predicted axillary surgery. Comedonecrosis and palpable lesions were associated with higher SNB rates but not nodal positivity. Conclusions Routine axillary surgery is unnecessary in VAB-diagnosed DCIS. Omission of SNB appears safe for patients undergoing BCS without high-risk features (palpability, high grade). Axillary staging may be reserved for mastectomy candidates or those with suspicions imaging of invasive disease.
Pathologic complete response and breast cancer survival post-neoadjuvant chemotherapy: a systematic review and meta-analysis of real-world data
(2025) Antonini, Marcelo; Mattar, André; Pereira, Thais Melo; Oliveira, Ludmilla Lemos; Teixeira, Marina Diógenes; Amorim, Andressa Gonçalves; Ferraro, Odair; Oliveira, Larissa Chrispim de; Ramos, Marcellus do Nascimento Moreira; Cavalcante, Francisco Pimentel; Freitas Junior, Ruffo de
Breast cancer is a leading cause of cancer-related mortality worldwide, and neoadjuvant chemotherapy (NAC) plays a pivotal role in its management by reducing tumor size, enabling breast-conserving surgery, and improving survival outcomes. Achieving pathologic complete response (pCR) is strongly associated with better overall survival (OS) and disease-free survival (DFS), particularly in aggressive subtypes such as triple-negative (TNBC) and HER2-positive breast cancers. This systematic review and meta-analysis evaluated the correlation between pCR, OS, and DFS in breast cancer patients treated with NAC, focusing exclusively on real-world data (RWD). A comprehensive search with PRISMA guidelines of major databases from 1999 to 2024 identified 22 retrospective studies comprising 12,115 patients. Hazard ratios (HRs) and confidence intervals (CIs) were pooled using random-effects models, and heterogeneity was assessed using the I statistic. pCR was achieved in 20.9 % of patients, with higher rates in HER2-positive (44.4 %) and TNBC (31.3 %) subtypes. Achieving pCR was associated with a 30 % improvement in OS (HR: 1.30; 95 % CI: 1.28–1.33) and a 29 % improvement in DFS (HR: 1.29; 95 % CI: 1.24–1.32). Among TNBC patients, pCR correlated with a 51 % increase in DFS (HR: 1.51; 95 % CI: 1.19–1.93). Significant heterogeneity (I
National survey on attitudes of brazilian breast surgeons regarding oncoplastic surgery: success of a training model
(2025) Cavalcante, Francisco Pimentel; Oliveira, Vilmar Marques de; Ziegelmann, Patrícia Klarmann; Brenelli, Fabrício Palermo; Paulinelli, Régis Resende; Garcia, Guilherme Novita; Hassan, Augusto Tufi; Millen, Eduardo Camargo; Zerwes, Felipe Pereira; Mattar, André; Freitas Junior, Ruffo de
Background Historically, breast reconstruction was performed by plastic surgeons. The Brazilian Society of Mastology (SBM) implemented initiatives to improve breast surgeons’ training in oncoplastic techniques; however, the current proportion of surgeons performing these techniques remained unknown. This study aimed to determine the proportion of Brazilian breast surgeons performing oncoplastic surgery, their previous training, the complexity of procedures performed, and factors influencing adoption of techniques. Methods In this survey, a structured questionnaire was sent to all SBM-affiliated breast surgeons between July and December 2023. Outcome proportions were estimated using binomial distribution. Adjusted proportion ratios (aPR) were calculated using robust Poisson regression. Results A 60.2% valid response rate was achieved (n = 1059/1759). Almost half of the respondents performed oncoplastic surgery, with most being young (< 40 years) (aPR: 1.66; 1.31–1.10; p < 0.001), male (aPR: 1.39; 1.22–1.59; p < 0.001), southern residents (aPR: 1.39; 1.18–1.63; p < 0.001), with a specialist degree in breast disease (aPR: 1.19; 1.00–1.42; p < 0.004), primarily trained in general surgery (aPR: 1.32; 1.16–1.51; p < 0.001) and secondarily in breast surgery (aPR: 1.41; 1.08–1.85; p = 0.01), and performing > 100 surgeries/year (aPR: 1.72; 1.49–1.99; p < 0.001). The techniques most commonly mastered were simple displacement (88.7%), therapeutic mammoplasty or contralateral symmetrization (96.4%), reconstruction with implants or tissue expanders (93.6%), extreme oncoplasty (81%), skin- and nipple-sparing (99%) or skin-reducing mastectomy (84.2%), and thoracoabdominal flaps (71.7%). Conclusions A high proportion of Brazilian mastologists perform oncoplastic surgery. These findings provide key insights to further enhance training and improve outcomes.

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