Background and Objectives: Intestinal barrier dysfunction is increasingly recognized as a contributor to inflammatory bowel disease (IBD) pathophysiology. Zonulin, a regulator of epithelial tight-junction permeability, has emerged as a potential non-invasive biomarker; however, its clinical relevance remains uncertain. This study evaluated whether fecal zonulin levels reflect clinical disease activity in inflammatory bowel disease and explored their association with ileal involvement in Crohn’s disease (CD). Materials and Methods: Forty-six consecutive IBD patients (26 CD, 20 UC) were prospectively included. Fecal zonulin was measured using a commercially available ELISA. In this study, the term “fecal zonulin” refers to ELISA-detected zonulin-related proteins. Clinical disease activity was assessed using CDAI for CD and the Mayo score for UC. Standard blood and fecal inflammatory markers were obtained, and subgroup analyses were performed according to disease type and location. Results: Fecal zonulin levels were significantly higher in active IBD compared with remission (106.37 vs. 53.80 ng/mL, p = 0.002). Patients with CD had higher zonulin concentrations than those with UC (91.4 vs. 51.0 ng/mL, p = 0.001). Zonulin showed a moderate positive correlation with fecal calprotectin (r = 0.338; p = 0.021). In multivariable analysis, clinical disease activity remained independently associated with zonulin levels, whereas ileal involvement was no longer statistically significant. Conclusions: Fecal zonulin is associated with disease activity in IBD, suggesting that fecal zonulin-related proteins may represent a potential adjunctive marker of epithelial barrier dysfunction and clinical disease activity in IBD. However, these findings should be considered exploratory and require validation in larger, longitudinal multicenter studies using standardized assays and endoscopic correlation.

Background: Biological therapies have substantially improved clinical outcomes in inflammatory bowel disease (IBD); however, the relationship between long-term biologic therapy, disease remission, and gut microbiome characteristics remains incompletely understood. This pilot study aimed to characterize the taxonomic composition and taxonomically inferred functional microbiome features of patients with IBD receiving long-term biologic therapy and achieving clinical and biological remission at the time of microbiome assessment. Methods: Patients with IBD receiving long-term biologic therapy and achieving clinical and biological remission at the time of microbiome assessment were prospectively enrolled. Gut microbiome composition was assessed using 16S rRNA gene sequencing. Functional microbiome profiling included microbial diversity (Shannon index), fecal pH, Firmicutes/Bacteroidetes ratio, and bacterial groups associated with short-chain fatty acid production, mucin degradation, and lipopolysaccharide (LPS) production. Comparative analyses between disease phenotypes and biologic therapies were performed using non-parametric statistical methods. Results: Fifteen patients with IBD were included, comprising eight patients with ulcerative colitis and seven with Crohn’s disease. Several microbiome features were outside the laboratory-specific reference intervals despite clinical and biological remission at the time of microbiome assessment. Shannon diversity values were below the laboratory-specific reference threshold in 60.0% of patients, while taxa associated with mucin degradation, lactate production, and LPS production were outside the respective reference intervals in 66.7%, 53.3%, and 46.7% of patients. The Firmicutes/Bacteroidetes ratio was outside the reference interval in 46.7% of patients. The gut microbiota was predominantly composed of Firmicutes and Bacteroidetes, with considerable interindividual variability in taxonomic composition and taxonomically inferred functional features. No statistically significant differences were identified between Crohn’s disease and ulcerative colitis or between biologic therapies after false discovery rate correction. Conclusions: Patients with IBD receiving long-term biologic therapy and achieving clinical and biological remission at the time of microbiome assessment exhibited substantial interindividual variability in taxonomic composition and taxonomically inferred functional microbiome features. Several parameters were outside laboratory-specific reference intervals; however, the cross-sectional design and absence of pre-treatment and matched healthy control samples preclude conclusions regarding microbiome restoration or treatment-related effects. These findings support further longitudinal investigation of microbiome characteristics during biologic therapy.

Among the mechanisms involved in disease progression, apoptosis has emerged as a central process contributing to immune dysregulation, lymphocyte depletion, organ dysfunction, and poor clinical outcomes. This review summarizes the current evidence regarding the molecular pathways of apoptosis in sepsis and discusses the potential role of apoptosis-related biomarkers in improving early diagnosis, prognostic stratification, and therapeutic decision-making. The limitations of conventional clinical assessment and currently available biomarkers are highlighted, emphasizing the need for more comprehensive approaches capable of reflecting the temporal evolution of the disease. Recent advances in bioengineering, including biosensors, microfluidic platforms, multi-omics technologies, and continuous physiological monitoring, offer new opportunities for real-time assessment of critically ill patients. Furthermore, artificial intelligence and machine learning provide powerful tools for integrating heterogeneous clinical, physiological, and molecular data into predictive models that support personalized management strategies. The convergence of apoptosis research, bioengineering innovations, and artificial intelligence has the potential to transform sepsis care by enabling earlier recognition of disease progression, more accurate risk stratification, and the development of precision medicine approaches tailored to individual patients.

Introduction: Gastrointestinal dysfunction is common in critically ill patients and is associated with increased morbidity and mortality. Plasma citrulline, a non-proteinogenic amino acid synthesized by enterocytes, has been proposed as a biomarker of intestinal function and enterocyte mass. However, the available evidence regarding its clinical significance in critically ill patients remains heterogeneous. This structured narrative review aimed to evaluate the current evidence on plasma citrulline in critical illness, focusing on its association with gastrointestinal dysfunction, disease severity, and clinical outcomes. Methods: A structured narrative review based on a structured literature search was conducted using PubMed and Scopus. Reference lists of included studies and relevant reviews were also screened. Studies evaluating circulating citrulline in adult critically ill patients and reporting gastrointestinal dysfunction, intestinal injury, disease severity, or other relevant clinical outcomes were included. Study selection was performed by two reviewers, and data were analyzed descriptively. Results: Eleven studies met the inclusion criteria, the majority being prospective observational studies. The timing of citrulline measurement, patient populations, analytical methods, and evaluated outcomes varied considerably across studies. Lower circulating citrulline concentrations were frequently associated with gastrointestinal dysfunction or markers of intestinal impairment; however, associations with disease severity, mortality, and other clinical outcomes were inconsistent. Several factors, including renal function, systemic inflammation, and methodological variability, may influence the interpretation of circulating citrulline concentrations. Conclusions: Plasma citrulline may provide complementary information regarding enterocyte function and gastrointestinal dysfunction in critically ill patients. However, current evidence does not support its use as a standalone diagnostic or prognostic biomarker. Further prospective studies using standardized measurement protocols and serial assessment are needed to determine its potential role alongside clinical evaluation and complementary biomarkers.

Cardiogenic shock secondary to acute myocardial infarction complicated by mechanical failure remains associated with high mortality despite advances in cardiac surgery and mechanical circulatory support. We report the case of a 42-year-old patient with posterior papillary muscle rupture leading to severe mitral regurgitation, managed with emergency surgical intervention and extracorporeal membrane oxygenation. The patient, with a history of Type I Bipolar Disorder under long-term lithium therapy and chronic Cannabis use, presented in critical condition with cardiogenic shock (Killip IV), acute pulmonary edema, and ST-segment elevation myocardial infarction in the infero-posterior territory. Coronary angiography revealed right coronary artery occlusion and involvement of an obtuse marginal branch. Emergency mitral valve replacement with a mechanical prosthesis and aortocoronary bypass were performed. Due to failure to wean from cardiopulmonary bypass, central veno-arterial ECMO was initiated. The postoperative course was complicated by hemodynamic instability and recurrent pericardial collections requiring repeated surgical interventions and conversion to peripheral ECMO. Multiorgan dysfunction developed, including hepato-renal failure requiring hemofiltration, neurological injury, respiratory impairment, and neuropsychiatric complications. Despite these challenges, progressive recovery was achieved under intensive multidisciplinary management. This case emphasizes the importance of early surgical correction and tailored ECMO support in managing post-infarction mechanical complications.

Regional anesthesia is widely used in orthopedic surgery because it provides effective postoperative analgesia and reduces opioid requirements. However, increasing attention has been directed toward rebound pain, a phenomenon characterized by the abrupt emergence of severe pain following the resolution of a peripheral nerve block. Although frequently reported, rebound pain remains inconsistently defined, and its true incidence and clinical significance are still debated. Current evidence suggests that rebound pain is a multifactorial phenomenon influenced not only by block resolution itself but also by the transition from regional analgesia to systemic pain management. Variability in postoperative analgesic strategies, timing of rescue analgesia, patient expectations, and surgical factors may substantially affect both its occurrence and perceived severity. Differences in definitions and outcome measures across studies further contribute to the wide variation in reported incidence rates. Available data support several potential mechanisms, including the unmasking of ongoing postoperative nociceptive input after block resolution, inflammatory responses related to surgical tissue injury, and, in some cases, central sensitization. Clinical observations also indicate that inadequate multimodal analgesia and failure to anticipate the analgesic transition period may play a major role in the development of severe rebound pain episodes. Current evidence suggests that proactive analgesic planning, scheduled multimodal analgesia initiated before block resolution, intravenous dexamethasone, and prolonged regional anesthesia techniques may reduce the incidence or severity of rebound pain. However, the reported benefits are not consistent across all studies, and some interventions improved early analgesia or prolonged block duration without reducing rebound pain or opioid consumption. Interpretation remains limited by substantial clinical and methodological heterogeneity. Rebound pain appears to represent a complex interaction between physiological nociceptive processes and modifiable perioperative management factors rather than a simple consequence of peripheral nerve block resolution alone. Greater standardization of definitions and outcome measures is needed to better characterize its incidence, mechanisms, and clinical relevance in orthopedic surgery.