Heitor Siffert Pereira de Souza

Objective: The aim of this study was to investigate the cell‐mediated immune response to SARS‐CoV‐2 vaccination in patients with inflammatory bowel disease (IBD) and its relationship with IgG antibodies. Methods: This cross‐sectional observational study included 138 consecutive patients (1:1 ratio of Crohn′s disease and ulcerative colitis). The patients were divided into three therapeutic groups: nonimmunosuppressed, corticosteroid or azathioprine users, and biological agent users. Blood samples were analyzed for IgG antibodies against the SARS‐CoV‐2 spike protein and for the antigen‐specific levels of several cytokines. Results: The study demonstrated that all cytokines increased significantly after stimulation with the SARS‐CoV‐2 spike protein, except for IL‐4 and IL‐17 in patients taking biologicals. Patients not on immunosuppressants had higher levels of TNF‐ α , IL‐6, and IL‐10 than the other groups. There was no correlation between antibody titers and cytokine levels, except for interferon gamma (IFN‐ γ ), which showed a positive correlation. Conclusion: This study suggests that immunosuppression may affect cellular immunity without compromising humoral immunity. The decreased production of IL‐6, IL‐10, and TNF α in immunosuppressed patients could explain the reduced adverse outcomes from SARS‐CoV‐2 infection observed in this group in previous research.

Background: The effectiveness of anti ‐ H. pylori treatment diminishes with therapy failure, making regional performance understanding crucial. Objective: To evaluate the effectiveness of empirical therapy in second‐line and subsequent treatments in Brazil. Methods: A multicenter, prospective, noninterventional registry assessed H. pylori management outcomes by Brazilian gastroenterologists (Hp‐BrazilRe, Hp‐ WorldReg 's partner). Data were registered at e‐ CRF AEG ‐ ReCap from March 2022 to October 2024 and analyzed via modified intention‐to‐treat ( mITT ) methodology. Data were subject to quality review. Results: 572 patients (mean age 52 years, 64% women) were included. The primary treatment indications were dyspepsia (64%) and gastroduodenal ulcer (9.2%). Among them, 67% underwent second‐line therapy, while 33% received third‐line or subsequent treatments. Proton‐pump inhibitors ( PPIs ) were administered at low (40%), standard (10%), and high doses (24%), with vonoprazan used in 26% of cases. The overall eradication rate for second‐line treatment was 74%, with the most common regimen being triple therapy ( PPI + amoxicillin + levofloxacin), achieving 73% eradication for 14 days and 57% for 10 days. Adding bismuth to the 14‐day regimen increased effectiveness to 100% ( p = 0.016). In third‐line therapy, a regimen of PPI ‐bismuth‐tetracycline‐metronidazole yielded an 87% cure rate. The fourth‐line dual therapy with amoxicillin‐vonoprazan achieved 100% eradication, while bismuth‐quadruple therapy showed similar results. Dual therapy with vonoprazan and amoxicillin was also effective in fifth‐line treatments, achieving 100% effectiveness. Mild adverse events occurred in 23% of patients, with nausea being the most common (14%), and compliance was 99%. Conclusion: In Brazil, the overall effectiveness of second‐line therapy was suboptimal (< 90%); however, the combination of bismuth‐amoxicillin‐levofloxacin prescribed for 14 days reported successful cure rates. In the third‐line, the classical bismuth‐quadruple therapy with metronidazole‐tetracycline provided acceptable results (87%). Alternatively, dual therapy with vonoprazan and amoxicillin and rifabutin‐based bismuth‐quadruple therapy showed promising results in third‐ and fifth‐line rescue treatment.

Background/Objectives: The Brazilian Unified Health System was established in 1988 as a public health system with principles of universality, equity, and integrality. One of Brazil’s main strategies to strengthen universal healthcare is the Family Health Strategy (FHS), a primary health care policy established in 1994 and fully incorporated in the country in 2006. This study aims to describe the time trends of FHS coverage in Brazil and its states from 2008 to 2023 and to correlate this coverage with the states’ Human Development Index (HDI). Methods: Data on the number of FHS teams, population, and HDI during the period were collected for each Brazilian state in the Brazilian Ministry of Health’s public-access databases. Prais–Winsten regression was used to conduct a time series analysis for each state and country. The annual percentage change (APC) was used to describe time trends in time series. Linear regression was used to identify a correlation between HDI and FHS coverage across states. Results: The FHS coverage in the country increased from 66.81% to 84.66% from 2009 to 2023. Disparities in coverage between regions are evident throughout the entire study period. The Northeast region (NE) exhibited higher FHS coverage but lower APC rates compared to other regions. Results suggest a negative correlation between HDI and FHS coverage in all Brazilian states for 2009, 2012, 2015, 2018, 2021, and 2023. Conclusions: The FHS coverage increased in Brazil and its states during the period. The highest coverages were found in states from the North (N) and NE regions, and the lowest were in the Southeast region. Nine federative units achieved full coverage (100%) and maintained it afterward, with seven from the N and NE. A negative correlation was found between FHS and HDI, suggesting that the expansion of FHS effectively targets vulnerable populations.

A 50-year-old HIV-positive woman, nonadherent to antiretroviral therapy, developed asthenia, weight loss, and lymphadenopathy after restarting treatment. Imaging revealed adenopathies and a breast nodule, with biopsies confirming Paracoccidioides brasiliensis. Despite initial therapy failure (trimethoprim-sulfamethoxazole), liposomal amphotericin, corticosteroids, and a regimen change led to partial improvement until a psoas abscess required drainage, ultimately stabilizing her condition.

Disease tolerance is a defensive strategy that limits tissue damage during infection. Macrophage migration inhibitory factor (MIF)-deficient mice ( Mif ^-/- ) are protected in different models of infection and intestinal inflammation due to unclear disease tolerance mechanisms, whereas low disease-tolerant Il10 ^-/- mice develop microbiota-dependent spontaneous gut inflammation. Here, we examined whether IL-10 is required for the phenotype seen in Mif ^-/- mice and, conversely, the contribution of MIF during IL-10 deficiency. While breeding for double-deficient Mif ^-/- Il10 ^-/- mice, we unexpectedly observed that Il10 ^-/- individuals died within days after co-housing with Mif ^-/- mice. We found that healthy Mif ^-/- hosts endure a highly diverse, unique and dysbiotic-like microbiota composition, including antibiotic-resistant Enterobacteriaceae species, which were sufficient to cause acute and lethal Th1-driven colitis in Il10 ^-/- recipients. The disease was characterized by increased frequencies of IFNγ ⁺ cells and neutrophils within colonic lamina propria. Mif ^-/- Il10 ^-/- mice died prematurely, and survivors developed communicable disease, - indicating that lack of IL-10 is a dominant trait. These findings suggest that tolerant individuals harbor a gut microbiota enriched in pathogens/pathobionts, which can trigger disease in susceptible hosts.

Colorectal cancer CRC remains one of the leading causes of cancer-related deaths worldwide, with chronic intestinal inflammation identified as a major risk factor. Notably, the tumor suppressor TP53 undergoes mutation at higher rates and earlier stages during human inflammation-driven colon tumorigenesis than in sporadic cases. We investigated whether deleting Trp53 affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice. We examined azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis in wild-type Trp53 (+/+), heterozygous (+/−), and knockout (−/−) mice. Trp53−/− mice showed increased sensitivity to DSS colitis and earlier accelerated tumorigenesis with 100% incidence. All groups could develop invasive tumors, but knockouts displayed the most aggressive features. Unlike wild-type CRC, knockouts selectively showed increased populations of Lgr5+ colon cancer stem-like cells. Trp53 loss also boosted laminin, possibly facilitating the disruption of the tumor border. This study highlights how Trp53 deletion promotes the perfect storm of inflammation and stemness, driving colon cancer progression. Trp53 deletion dramatically shortened AOM/DSS latency and improved tumor induction efficiency, offering an excellent inflammation-driven CRC model.

Aberrant signaling through damage-associated molecular patterns (DAMPs) has been linked to several health disorders, attracting considerable research interest over the last decade. Adenosine triphosphate (ATP), a key extracellular DAMP, activates the purinergic receptor P2X7, which acts as a danger sensor in immune cells and is implicated in distinct biological functions, including cell death, production of pro-inflammatory cytokines, and defense against microorganisms. In addition to driving inflammation mediated by immune and non-immune cells, the persistent release of endogenous DAMPs, including ATP, has been shown to result in epigenetic modifications. In intestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), consequent amplification of the inflammatory response and the resulting epigenetic reprogramming may impact the development of pathological changes associated with specific disease phenotypes. P2X7 is overexpressed in the gut mucosa of patients with IBD, whereas the P2X7 blockade prevents the development of chemically induced experimental colitis. Recent data suggest a role for P2X7 in determining gut microbiota composition. Regulatory mechanisms downstream of the P2X7 receptor, combined with signals from dysbiotic microbiota, trigger intracellular signaling pathways and inflammasomes, intensify inflammation, and foster colitis-associated CRC development. Preliminary studies targeting the ATP−P2X7 pathway have shown favorable therapeutic effects in human IBD and experimental colitis.