Gut microbiota has increasingly been shown to exert effects beyond the gastrointestinal tract, some of which are mediated through its metabolites, such as trimethylamine N-oxide (TMAO)—a compound converted by gut bacteria from dietary choline found predominantly in animal products that is associated with cardiovascular disease (CVD). However, a significant gap persists in human clinical trials assessing its potential causal role. This narrative review aims to present the current understanding of the gut microbiome, TMAO, and their relationship with CVD, while proposing future directions that may support the use of TMAO as a biomarker and guide potential interventions to reduce its harmful impact. Both animal and human studies have demonstrated a link between TMAO and CVD, with animal studies also indicating a causal effect—showing increased cardiovascular risk following TMAO administration and reduced risk when TMAO is eliminated. While direct extrapolation from animal models to humans is limited due to biological differences, these findings offer a foundation for the development of well-designed clinical trials in human populations. Although direct approaches to target TMAO—such as trimethylamine (TMA) lyase inhibitors and antisense oligonucleotide (ASO) therapy—have shown promising results in animal studies, they have yet to be investigated in human trials, leaving indirect strategies such as dietary changes and probiotics as the only currently available options.

Introduction: CREST syndrome is a clinical entity associated with systemic sclerosis, which meets at least three of the five clinical features: calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Three of these clinical features (Raynaud’s phenomenon, sclerodactyly and esophageal dysmotility) are often present in classical subsets of SSc: limited and diffuse, and their presence in association does not define CREST syndrome. Calcinosis seems to be less common in SSc and its association with other clinical features is characteristic of CREST syndrome. Therefore, it can be appreciated that calcinosis is the key element of CREST syndrome. Methods: This study included a number of 37 candidates with SSc, diagnosed with the help of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 criteria. Results and Discussions: These three elements (calcinosis, Raynaud’s phenomenon, esophageal dysmotility) were recorded both in the limited subset of SSc, but especially in the subset of diffuse SSc, contrary to the data in the literature. Conclusion: We appreciate that CREST syndrome is a clinical entity that can overlap with both subsets of SSc. Given the divergent views of the authors on the classification of CREST syndrome, future studies may contribute to a reassessment of SSc classification.

Iron deficiency (ID) is a common comorbidity in heart failure (HF), affecting nearly 50% of patients and worsening symptoms, exercise capacity, and prognosis. This review summarizes recent evidence from meta-analyses, clinical trials, and guidelines on the pathophysiology, diagnosis, and treatment of ID in HF. ID in HF results from chronic inflammation, intestinal congestion, and impaired iron metabolism. Diagnosis is based on serum ferritin and transferrin saturation (TSAT) levels. While oral iron therapy has limited efficacy, intravenous iron, particularly ferric carboxymaltose and ferric derisomaltose, improves symptoms and exercise tolerance and reduces hospitalizations. Timely diagnosis and treatment of ID in HF are essential. Intravenous iron is the preferred therapeutic approach, but further research is needed to optimize long-term management.

Systemic sclerosis (SSc) is a chronic inflammatory disease with an autoimmune substrate that affects the skin and a large number of internal organs. The chronic inflammatory process is sustained by a wide range of cytokines and chemokines, which are discharged by inflammatory cells, with fibrosis and nail bed vascular changes (disorganized vasculature architecture with microhemorrhages, megacapillaries and areas without capillaries). Confocal microscopy contributes to the understanding of the molecular mechanism involved in chronic inflammation and mainly targets the field of research. Coherent optical tomography, capillaroscopy, and skin biopsy are useful for the differential diagnosis of SSc with other sclerodermoid syndromes. The immunological profile is a classification criterion for SSc and directs the diagnosis to the two subsets of the disease. Multisystemic damage requires evaluation with the help of a set of investigations specific to each affected organ, such as: diffusing capacity for carbon monoxide, forced vital capacity, 6-minute walk test, high-resolution computed tomography standard and reduced sequential, cardiac ultrasound and right cardiac catheterization. The current possibilities of diagnosis, treatment and monitoring are permanently adapting to new medical discoveries.

Background: Pan-drug-resistant (PDR) Acinetobacterinfections are an escalating ICU threat, demanding both patient-level triage and facility-wide forecasting. Objective: The aim of this study was to build a dual-scale AI framework that (i) predicts PDR status at infection onset and (ii) forecasts hospital-level PDR burden through 2027. Methods: We retrospectively analyzed 270 Acinetobacter infection episodes (2020–2024) with 65 predictors spanning demographics, timelines, infection type, resistance-class flags, and a 25-drug antibiogram. TabTransformer and XGBoost were trained on 2020–2023 episodes (n = 210), evaluated by stratified 5-fold CV, and externally tested on 2024 episodes (n = 60). Metrics included AUROC, AUPRC, accuracy, and recall at 90% specificity; AUROC was optimism-corrected via 0.632 + bootstrap and DeLong-tested for drift. SHAP values quantified feature impact. Weekly PDR incidence was forecast with an attention–LSTM model retrained monthly (200 weekly origins, 4-week horizon) and benchmarked against seasonal-naïve, Prophet, and SARIMA models (MAPE and RMSE). Quarterly projections (TFT-lite) extended forecasts to 2027. Results: The CV AUROC was 0.924 (optimism-corrected 0.874); an ensemble of TabTransformer + XGBoost reached 0.958. The 2024 AUROC fell to 0.586 (p < 0.001), coinciding with a PDR prevalence drop (75→38%) and three covariates with PSIs > 1.0. Isotonic recalibration improved the Brier score from 0.326 to 0.207 and yielded a net benefit equivalent to 26 unnecessary isolation-days averted per 100 ICU admissions at a 0.20 threshold. SHAP highlighted Ampicillin/Sulbactam resistance, unknown acquisition mode, and device-related infection as dominant drivers. The attention–LSTM achieved a median weekly MAE of 0.10 (IQR: 0.028–0.985) vs. 1.00 for the seasonal-naïve rule, outperforming it on 48.5% of weeks and surpassing Prophet and SARIMA (MAPE = 6.2%, RMSE = 0.032). TFT-lite projected a ≥ 25% PDR tipping point in 2025 Q1 with a sustained rise in 2027. Conclusions: The proposed framework delivers explainable patient-level PDR risk scores and competitive 4-week and multi-year incidence forecasts despite temporal drift, supporting antimicrobial stewardship and ICU capacity planning. Shrinkage and bootstrap correction were applied to address the small sample size (EPV = 2.1), which poses an overfitting risk. Continuous recalibration and multi-center validation remain priorities.

Systemic sclerosis (SSc) is a collagenosis with a substrate of chronic inflammation, which is determined by autoimmunity. The pathogenesis of this disease involves microvasculopathy (small vessel pathology) followed by excessive cutaneous and visceral fibrosis. Although acoustic and vestibular impairment is not classified as being a secondary pathology of SSc, several studies have identified cases of SSc that associate hearing loss and especially vertigo and tinnitus. This paper presents data from the medical literature that have identified vestibular and auditory symptoms among patients with SSc, associating the clinical case presentation of a patient suffering from SSc, which is associated with hearing loss. The need for additional studies on larger groups of patients is underlined, in order to clarify the impact of vasculopathy and fibrosis on the acoustic and vestibular analyzer in patients with SSc.