Hospital Curry Cabral

Kidney transplant rejection presents a clinical challenge, requiring an accurate and timely diagnosis. While kidney graft biopsy remains the gold standard, its inherent limitations motivate the need for noninvasive diagnosis. This review comprehensively examines emerging non-invasive biomarkers for the monitoring of kidney allograft, specifically donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), chemokines, and DNA methylation patterns. We review their underlying biological principles and discuss their diagnostic accuracy, clinical applications, and limitations in the current available evidence. Donor-derived cfDNA, a promising predictor of allograft injury, shows particular utility in detecting antibody-mediated rejection (ABMR), lacking however for standardization concerning its cutoff. Gene expression profiling provides insights into immune responses, with various gene signatures developed for detecting subclinical and acute rejection. MicroRNAs and long non-coding RNAs demonstrate potential as tissue-specific biomarkers of injury and rejection, yet face challenges in standardization and clinical translation. Chemokines like urinary CXCL9 and CXCL10 exhibit diagnostic and prognostic value for acute rejection. Furthermore, DNA methylation patterns offer a novel approach to identify cell-specific cfDNA and reflect cell death processes within transplanted organs. The integration of these diverse biomarkers, potentially augmented by artificial intelligence platforms, holds immense promise for improving diagnostic precision, minimizing the need for biopsies, and enabling personalized immunosuppression strategies, which would improve long-term graft survival.

IntroductionThe blockage of the renin-angiotensin-aldosterone and sympathetic nervous systems is fundamental in heart failure (HF) treatment; nonetheless, other mechanisms related to myocardial fibrosis and bioenergetic dysfunction also have a relevant role in the genesis and progression of this syndrome. We aim to stratify the short-term outcome of patients hospitalized with acute decompensated heart failure (ADHF) in New York Heart Association (NYHA) class III or IV based on myocardial fibrosis biomarkers galectin-3 (Gal-3), suppression of tumorigenicity 2 (ST2) and growth differentiation factor15 (GDF-15), and bioenergetic dysfunction markers (absolute iron deficiency and functional iron deficiency). Secondary endpoints were evaluation of short-term prognosis through early HF readmission and all-cause mortality (up to 90 days after hospital discharge), annual heart failure readmission and all-cause mortality, and annual risk for major adverse cardiovascular events (MACE), namely fatal and non-fatal stroke and fatal and non-fatal myocardial infarction, and cardiorenal syndrome. Material and methodsThis cohort prospective observational unicentric study had two arms (left ventricular ejection fraction (LVEF)> 40% and ≤ 40%). A total of 128 participants were included, with 64 per group. Gal-3, ST2, and GDF-15 will be assessed in vitroin serum and plasma, and iron kinetics will be evaluated in plasma. Kaplan-Meier survival estimates will be calculated for each endpoint. A univariate Cox propor­tional hazards model will be performed to achieve hazard ratios and 95% confidence intervals for each variable.ResultsWe expect to establish a relation between high values of fibrosis biomarkers, absolute and functional iron deficiency, and impaired short-term outcome in patients admitted due to ADHF.ConclusionsThis study may yield knowledge regarding the role of myocardial fibrosis and bioenergetic dysfunction in HF short-term prognosis.

Abstract Background and Aims Cytomegalovirus (CMV) infection is the primary infectious complication in kidney transplantation (KT), and it contributes to morbidity and mortality rates. CMV-seropositive solid organ transplant recipients have a relatively lower risk of CMV infection when compared to CMV-seronegative recipients who receive allograft from CMV-seropositive donors. Nonetheless, some patients remain at risk. Our aim was to assess the association between the anti-CMV IgG titer and the risk of post-transplant CMV infection among CMV-seropositive KT recipients. Method We conducted a retrospective single-center study on adult CMV-seropositive KT recipients between January 2018 and June 2023. Clinical characteristics, risk factors, and outcomes were extracted from patient medical records. Patients who received anti-thymocyte globulin as induction therapy were given valganciclovir prophylaxis for 6 months post-transplant. The cumulative incidence of CMV infection was estimated using the Kaplan-Meier method (defined as detection of CMV DNA in plasma regardless of symptoms). We analyzed CMV-IgG as a predictor of CMV infection using Cox proportional hazards model (SPSS). The study was approved by the Institutional Review Board. Results The medical records of a total of 263 KT patients were retrieved, and a total of 27 were CMV-seronegative. A total of 236 CMV-seropositive KT recipients were included, being 66.1% male. Their mean ± SD age was 52.5 ± 11.9 years. Among these, 94% received deceased-donor allograft, of which 8.1% were after circulatory death donors (DCD), and 50.7% were expanded criteria donors. The median [IQR] mismatch was 4 [3.0, 5.0]. Regarding induction therapy, 62.7% of KT recipients received anti-thymocyte globulin. During a mean follow-up of 19.9 months, the cumulative incidence of CMV infection was 61.6% (Fig. 1). Lower titers of pretransplant CMV-IgG were associated with CMV infection (P = 0.031). Conclusion We observed that a lower pretransplant anti-CMV IgG titer is associated with an increased risk of post-transplant CMV infection among CMV-seropositive KT recipients. The universally available test for anti-CMV IgG titer could potentially stratify individuals at risk and target them to receive a more specific preventive strategy.

The World Health Organization identified 13 critical threats to global health for the coming decade, including infectious disease prevention and antimicrobial resistance. Given the ongoing advancements in scientific evidence, it is imperative to discuss the Infectious Diseases training program. The aim of this study was to characterize and explore the respondents' perceptions regarding Infectious Diseases training and the clinical learning environment. A survey was developed to assess the clinical learning environment, targeting residents and young specialists who completed their training within the past five years. The questionnaire received 73 responses, 75.3% from residents. Most respondents agreed with the duration of Internal Medicine (83.5%), Microbiology (76.7%), and General Infectious Diseases (71.2%) rotations, but considered that the Intensive Care rotation should last less than six months. The areas of Infection Control/Antibiotic Stewardship and Immunosuppression/Infectious Risk were suggested as mandatory rotations by 84.9% and 65.8% of participants, respectively. Most respondents (67.1%) considered prolonged Internal Medicine Emergency rotations beyond the first year detrimental. In contrast, 84.6% of ARS Norte participants only performed this activity during the first year, whereas 86.8% of ARS LVT participants continued, at least, until the fourth year. Regarding clinical and scientific output, ARS Norte interns reported, on average, higher numbers of weekly assisted (21.7 vs 17.1) and performed (20.8 vs 17.7) appointments, as well as higher annual participation (3.7 vs 3.1) and presentations (2.8 vs 2.4) in scientific events, published articles (1.1 vs 0.6), and weekly study hours (7.4 vs 4.5), compared with ARS LVT. The main challenges reported were a lack of dedicated study time during working hours, scientific updates, and clinical practice in Internal Medicine Emergency rotations. Regarding the evaluation of the residency program, only 2.7% agreed completely with the current exam model and 1.37% with the current curriculum grid. The majority (64.4%) of participants considered themselves at least satisfied with the specialty. The results suggest a need to review the Infectious Diseases training program, include new areas of specialization, and discuss evaluation models throughout residency. Regional asymmetries were observed in emergency work, clinical and scientific output, which affect the equity and quality of training. Discussion of the Infectious Diseases training program is crucial for adapting the curriculum to current and future challenges.