Fundação Bahiana de Infectologia

Background and ObjectivesProgression independent of relapses (PIRA) is a major therapeutic challenge in multiple sclerosis (MS). Nasal anti-CD3 treats animal models of progressive MS by inducing regulatory T cells (Tregs) that suppress CNS inflammation and lessen clinical disease.MethodsTen patients with nonactive secondary progressive MS (naSPMS) that continued to progress on B-cell therapy were treated with nasal anti-CD3 (foralumab) for a minimum of 6 months in an open-label study. Safety monitoring included otolaryngology evaluation and neurologic assessments including Expanded Disability Status Scale (EDSS), MS Functional Composite, Modified Fatigue Impact Scale (MFIS), California Verbal Learning Test, and Low Contract Visual Acuity. MRI and microglial translocator protein (TSPO)-PET imaging with [F-18]PBR06 were conducted. Serum and CSF proteomic biomarkers and single-cell RNA sequencing of blood were performed to evaluate foralumab-induced immunomodulation. The end points of our study were safety, clinical effects, microglial signal, and immune measures.ResultsOur clinical observations were that all patients stabilized on EDSS scores and 3 of 4 patients treated continuously for 12 months had improvement on EDSS. Six of 10 patients had improvement in fatigue on the MFIS scale. There were no treatment-related serious adverse events or severe AEs, and no new T2 lesions were observed on MRI. There was a reduction in TSPO-PET signal over 6 months (p < 0.05). Changes in peripheral blood gene expression occurred as early as 3 months and affected antigen presentation, interferon responses, and regulatory pathways in multiple cell types including FoxP3+ Tregs, CD4+ Tcm cells, CD8+ Tem cells, CD14+ and CD16+ monocytes, and B cells. TGFβ expression was increased across multiple cell subsets.DiscussionThese findings identify a novel, nontoxic immune based therapy for the treatment for PIRA that acts by the induction of a regulatory immune responses and dampens microglial inflammation. Double-blind placebo-controlled trials are warranted to explore nasal foralumab for the treatment of naSPMS.Classification of EvidenceThis study provides Class IV evidence that nasal foralumab in patients with treatment-refractory nonactive SPMS showed stabilization in EDSS, improvement in fatigue scores and improvement in TSPO-PET imaging.

A major barrier to hepatitis C virus (HCV) elimination is the failure to ensure that individuals complete the HCV care cascade after they test positive for HCV RNA and/or antibody. Microelimination programmes support protocols that reengage patients with care/treatment. We describe 18 microelimination programmes aimed at identifying persons who were diagnosed but untreated/not cured and reconnecting them to care. Here, we report the programmes' effectiveness, identify key challenges and suggest best practices for future initiatives. Pooled and individual programme data (available as of 31 January 2024) were assessed. Each programme had a retrospective phase in which medical/laboratory records were searched within a specified date range for patients who were positive for HCV antibody and/or RNA at last testing. In a prospective phase, programmes attempted to reengage these patients with care. Across the 18 programmes worldwide, 82 006 individuals were identified as eligible for follow-up. Overall, 21 235 people were selected for attempted contact, and 5308 were relinked to care. In 17 programmes reporting treatment data, 51% (1513 of 2976) of relinked patients initiated treatment. Four programmes used innovative care models and achieved treatment initiation rates ≥ 80%. Amongst patients with results available, 89% (643 of 722) who initiated treatment achieved HCV cure. Challenges included the inability to contact people and missed appointments. Systematic screening of medical/laboratory records was effective in identifying patients who had been lost to follow-up, and the use of innovative care models, such as test-and-treat or decentralised approaches, resulted in higher treatment numbers.

Additional progestogens are often used in some countries to stop prolonged bleeding in etonogestrel implant users, although no evidence currently supports this practice. To evaluate the efficacy and safety of oral norethisterone acetate, also known as norethindrone acetate, at a dose of 10 mg/day for prolonged bleeding associated with etonogestrel implant use. IMPLANET is a randomized, controlled, blinded, multicenter trial conducted in Brazil. It included etonogestrel implant users aged 18 to 40 years who had been using the implant for at least 40 days and had experienced uterine bleeding for a minimum of 7 consecutive days at enrollment. Participants had no prior diagnosis of abnormal uterine bleeding and underwent a standardized evaluation to exclude a secondary cause for the current prolonged bleeding episode. Participants were block-randomized to receive 10 mg of oral norethisterone acetate or placebo daily until they experienced no bleeding for 2 consecutive days or completed 30 consecutive days of treatment, whichever occurred first. Participants could repeat treatment up to 3 times over 210 days. Participants reported bleeding via daily messages. The primary outcome was the proportion of participants who achieved bleeding cessation after using up to 7 consecutive pills. Secondary outcomes included the proportion of participants who achieved bleeding cessation after using up to 14 pills, treatment days required to stop the first bleeding episode, time to bleeding recurrence after the first treatment, bleeding-free days within the first 30 days, treatment failure (continued bleeding after 30 days of pill use), bleeding days and bleeding-free days after the first 30 days, and safety outcomes. Exploratory outcomes included study participation time and premature discontinuation. A sample size of 86 participants provided 80% power to detect a 30% in bleeding cessation rates after using a maximum of 7 pills. The modified intention-to-treat analysis included participants who received at least one dose of the randomized treatment and had a negative chlamydia/gonorrhea screen postrandomization. We used Chi-square and Wilcoxon tests for comparisons. The primary outcome was additionally analyzed using a multiple log-binomial regression to adjust for baseline imbalances (age, employment status, and marital status), with adjusted risk difference and 95% confidence intervals. Between September 2020 and May 2023, 114 participants were enrolled, 99 were randomized, and 90 (45 per group) were included in the modified intention-to-treat. Baseline characteristics were similar except for age, employment, and marital status. The norethisterone acetate group had a significantly higher percentage of participants who achieved bleeding cessation after using up to 7 pills than the placebo group (86.7% vs 48.9%, P<.001), even after adjusting for baseline imbalances (adjusted risk difference, 35.6% [95% confidence interval, 17.1%-54.0%], P<.001). Bleeding cessation using up to 14 pills was higher (91.1% vs 64.4%; P=.002) and treatment failure was lower (2.2% vs 17.8%; P=.03) in the norethisterone acetate group than in the placebo group, with fewer median treatment days to stop bleeding in the norethisterone acetate group (3.0 vs 5.0 days; P=.01). Compared to placebo, the norethisterone acetate group had a shorter time to bleeding recurrence (5.0 vs 10.5 days; P=.008), more bleeding-free days in the first 30 days (21.0 vs 13.0 days; P=.007), longer trial participation (159.9 vs 127.2 days; P <.001), and a lower discontinuation rate (33.3%; P=.09). Short-term use of 10 mg/day norethisterone acetate effectively and safely stopped prolonged bleeding in etonogestrel implant users. However, it does not prevent bleeding recurrence.

Chronic liver disease (CLD) has been reported in long-term survivors of gastrointestinal (GI) cancers treated with irinotecan- and/or oxaliplatin-based chemotherapy. This study aims to investigate the frequency and clinical consequences of CLD in GI cancer patients treated with chemotherapy and its potential impact on survival. We retrospectively reviewed patients with GI cancers treated at AMO Oncology Clinic from 2017 to 2022. CLD evaluation was performed in patients without prior liver disease who survived ≥ 12months after chemotherapy. Diagnosis was based on imaging findings of cirrhosis or portal hypertension (PH), histologic evidence of advanced fibrosis, or esophagogastric varices on endoscopy. A total of 328 patients (165 males; mean age 64 ± 13years) were included. Most had colorectal cancer (58%) and TNM stage III or IV disease (69.6%). They received a median of 15.5 (8-28) chemotherapy cycles, mainly with oxaliplatin (86%), 5-fluorouracil (76%), irinotecan (49%), and capecitabine (43%). After a mean follow-up of 30.5 (21-49) months, CLD was identified in 47 patients (14.3%). Overall survival did not differ significantly between those with and without CLD (77.0 [51-102] vs. 85.7 [69-102] months, p = 0.385). CLD was associated with a greater number of chemotherapy agents (4 vs. 3, p = 0.002), cycles (21 vs. 13, p = 0.005), and exposure to 5-FU (89% vs. 73%, p = 0.02) and irinotecan (66% vs. 46%, p = 0.01). Among patients with GI cancer receiving chemotherapy, CLD was relatively frequent but no difference in survival was observed. As PH complications may occur, screening for CLD should be recommended for long-term survivors.

This study aims to evaluate the effectiveness of student practice in a surgical skills curriculum and their evolution during the process and, therefore, evaluate the relevance of training surgical skills in medical graduation. The study design was prospective observational and analytical, the participants were fourth-year medical students from the Bahiana School of Medical Education and Public Health, and the sample size was 300. The sampling method used was a non-probability sampling method, and data collection was realized through a questionnaire in a QR code with a study overview and a pre-assessment and post-assessment survey link. Data analysis was performed using Microsoft Excel 2021 (Microsoft Corp., Redmond, WA, US). The Shapiro-Wilk test was first conducted to test for normality. Due to the normal distribution of the data, a parametric paired t-test with a 95% confidence interval was used to analyze statistical differences in diagnostic accuracy and knowledge acquisition scores between the pre- and post-assessment and provided the collection of data to assess the impact of a second review moment of surgical skills (SRMSS) for medical students. Perceived readiness to teach improved across all weeks. Pre- and post-assessment scores showed significant increases (p < 0.05), with mean differences ranging from 0.89 to 1.32, the largest change occurring in Week 1 (1.32). Perceived readiness to apply topics in professional life improved across all weeks, with mean differences ranging from 0.52 to 1.32 (p < 0.05). The results show that the SRMSS implemented over the six-week period were effective in enhancing participants' perceived learning, readiness for assessments, readiness to teach, and readiness to apply learned topics in practical or professional contexts.

Hemilaminectomy is a less invasive surgical option than laminectomy for spinal tumors, but which method provides better results remains to be determined. Thus, we aimed to perform a meta-analysis comparing outcomes between the two approaches. We searched PubMed, EMBASE, and Web of Science for studies comparing hemilaminectomy to laminectomy in patients who underwent spinal tumor resection until August 2024. The outcomes were total resection rate, neurological deterioration, postoperative complications, length of stay, operative time, and estimated blood loss. Statistical analysis was performed via R software (version 4.4.1). Heterogeneity was assessed with I2 statistics. We included 12 studies with 1047 patients, of whom 405 (38.7%) underwent hemilaminectomy. The mean age was 56.6 ± 7.5 years. The mean follow-up ranged from 1 to 60 months. Among the tumors, 44.8% were meningiomas, and 57.4% were located in the thoracic spine. With no significant difference between hemilaminectomy and laminectomy in terms of the total resection rate achieved (RR 1.04, 95% CI: 0.98-1.11, I2 = 38%), hemilaminectomy showed lower neurological deterioration (RR 0.53, 95% CI: 0.35-0.81, I2 = 0%) and postoperative complications (RR 0.58, 95% CI: 0.39-0.86, I2 = 12%). Furthermore, the length of stay (MD -2.91 days, 95% CI: -4.98 to -0.85; I2 = 90%), operative time (MD -26.44min, 95% CI: -46.22 to -6.67; I2 = 61%), and estimated blood loss (MD -115.64 mL, 95% CI: -175.68 to -55.60; I2 = 78%) were significantly lower in hemilaminectomy. Hemilaminectomy is associated with lower neurological deterioration, postoperative complications, operation time, length of stay, and estimated blood loss. Therefore, our results might suggest that hemilaminectomy may be a more promising and preferable alternative to laminectomy.

CONTEXT: Physician-scientists occupy a unique and critical position at the intersection of clinical practice and scientific research, yet they are becoming increasingly rare due to systemic challenges, including time constraints, financial disincentives, and insufficient institutional support. This article explores the conceptual and historical differences between physicians, researchers, scientists, and physician-scientists, highlighting their distinct contributions to global health, policy-making, and medical innovation. Historical examples, such as Robert Koch and Virchow Rudolf, exemplify the transformative impact of physician-scientists in advancing medicine. The rise of artificial intelligence (AI) presents new opportunities and challenges for these professionals, as AI can enhance their dual roles in research and patient care. CONCEPTUALIZATION: However, to sustain and grow the physician-scientist workforce, significant changes are needed, including better financial incentives, protected research time, and stronger mentorship programs. Without such support, the future of medical innovation and global health may be jeopardized. This article advocates for a renewed focus on cultivating physician-scientists, emphasizing their indispensable role in bridging the gap between bench and bedside, and ensuring that scientific discoveries translate into tangible improvements in human health and well-being.

Human Immunodeficiency Virus (HIV), Human T Lymphotropic Virus (HTLV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection may lead to disease progression or worsen its clinical presentation. Viral coinfections screening during blood donation is critical. To identify risk factors for coinfection among blood donors, we assessed the blood donations at the Fundação de Hematologia e Hemoterapia da Bahia, from 2008 to 2017. We compared serological/molecular evidence of single infection versus two or more viral blood-borne infections-BBI). A multivariable logistic regression model was performed to evaluate independent associations between characteristics of donors with single infection and multiple infection using "non-infection" category as reference. Among 777,446 collected blood donations, 27 358 (3.5%) were reactive, most (n = 26 677, 97.6%) for a single infection and 681 (2.4%) for coinfection. The most frequent coinfections were HBV-HIV (30.6%), HBV-HCV (30.4%), and HBV-HTLV (24.4%). Male sex, lower education, being single, and being a first-time donor were independently associated with both single and coinfections. Nevertheless, the adjusted odds for risk factors of coinfections were much higher than those for single infection. Donors with single and coinfection for BBI shared identical risks, but they were significantly higher for coinfection. Preventive strategies addressing the identified risks can decrease transmission of viral BBI by blood transfusion.

Appendectomy is the treatment of choice for most cases of acute appendicitis, and, considering that the availability of technical variables for closing the appendicular stump raises questions for surgeons, analyzing which closure method provides the best results is necessary. This study aims to compare the variables of operating time, readmission rate, reoperation, and surgical wound infection regarding the endoloop and metallic clip techniques for closing the appendicular stump in laparoscopic appendectomy. Only randomized clinical trials that compared metallic clip and endoloop appendicular stump closing in laparoscopic appendectomy were used. Of these, those that did not fit the PICOT (Patient, Intervention, Comparison, Outcome, and Time) question and inclusion criteria were excluded, with five articles being included for the analysis phase. Five randomized clinical trials were included in the statistical analysis, totaling a population of 344 patients, with 181 patients in the metal clip group. It was observed that the operation time was significantly shorter in the metal clip group (STD -0.81, 95% CI: -1.13, -0.49, p < 0.00001, I² = 50%). To the extent that the reoperation rate (RR 1.27, 95% CI: 0.20, 7.88, p = 0.80, I² = 0%), the readmission rate (RR 0.93, 95% CI: 0.29, 2.91, p = 0.89, I² = 0%), and the surgical wound infection rate (RR 0.87, 95% CI: 0.24, 3.13, p = 0.83, I² = 0%) were statistically similar between the two groups. The findings of this study demonstrate that the closure of the appendicular stump using metal clips in laparoscopic appendectomy is faster, with similar rates of readmission, reoperation, and surgical wound infection between the two groups.

Introduction: Acute‐on‐chronic liver failure (ACLF) is a severe complication of cirrhosis characterized by acute decompensation (AD), organ failure(s), and high mortality.Aims: To investigate the frequency and the clinical course of ACLF in intensive care unit (ICU) patients at different time points, using CLIF‐C and NACSELD criteria as well as to assess their influence on mortality.Methods: Patients admitted with AD with and without ACLF were retrospectively evaluated.Results: 595 patients (443 males, mean age: 66.6 ± 12.0 years) were admitted due to AD (n = 381) or ACLF (n = 214). According to the CLIF‐C criteria, 119 patients (20%) had ACLF Grade I, 63 (10.6%) had ACLF Grade II, and 32 (5.4%) had ACLF Grade III at admission. Using the NACSELD, 155 patients (26.1%) had ACLF at admission. Infection was the main factor associated with ACLF at admission (n = 57; 27%, p = 0.001). In total, 104 (17.5%) patients died during hospitalization. ACLF grade at admission (OR: 4.6; 95% CI: 2.45–8.67; NS: 0.0001), use of vasopressors (OR: 3.83; 95% CI: 1.15–12.7; NS: 0.02), and CLIF‐C ACLF (OR: 1.12; 95% CI: 1.06–1.19; NS: 0.0001) were independently associated with in‐hospital mortality. The improvement in organ dysfunction after 7 days of intensive care was associated with a reduction in the risk of in‐hospital mortality compared to the 3‐day period (OR: 0.098; 95% CI: 0.047–0.204 vs. 0.253; 95% CI: 0.127–0.504; p < 0.00001, respectively).Conclusion: ACLF is associated with significant mortality in ICU patients, the CLIF‐C criteria appear to be more effective for prognostic assessment than NACSELD, and 7 days of intensive care may improve clinical outcomes.