How can the knowledge of probiotics and their mechanisms of action be translated into clinical practice when treating patients with diverticular disease and acute diverticulitis? Changes in microbiota composition have been observed in patients who were developing acute diverticulitis, with a reduction of taxa with anti-inflammatory activity, such as Clostridium cluster IV, Lactobacilli and Bacteroides. Recent observations supported that a dysbiosis characterised by decreased presence of anti-inflammatory bacterial species might be linked to mucosal inflammation, and a vicious cycle results from a mucosal inflammation driving dysbiosis at the same time. An alteration in gut microbiota can lead to an altered activation of nerve fibres, and subsequent neuronal and muscular dysfunction, thus favoring abdominal symptoms’ development. The possible role of dysbiosis and mucosal inflammation in leading to dysmotility is linked, in turn, to bacterial translocation from the lumen of the diverticulum to perivisceral area. There, a possible activation of Toll-like receptors has been described, with a subsequent inflammatory reaction at the level of the perivisceral tissues. Being aware that bacterial colonisation of diverticula is involved in the pathogenesis of acute diverticulitis, the rationale for the potential role of probiotics in the treatment of this disease becomes clearer. For this review, articles were identified using the electronic PubMed database through a comprehensive search conducted by combining key terms such as “gut microbiota”, “probiotics and gut disease”, “probiotics and acute diverticulitis”, “probiotics and diverticular disease”, “probiotics mechanism of action”. However, the amount of data present on this matter is not sufficient to draw robust conclusions on the efficacy of probiotics for symptoms’ management in diverticular disease.
Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise.
Intensive Care Unit-Acquired Weakness (ICU-AW) is a common and severe complication in critically ill patients, characterized by profound and often prolonged muscle weakness. The complexity of its diagnosis and management requires a multidimensional approach that integrates clinical, electrophysiological, and imaging tools. This review focuses on the challenges in diagnosing ICU-AW, emphasizing the limitations of traditional methods such as manual muscle testing and electrophysiological studies, and highlights the emerging role of neuromuscular ultrasound (NMUS) as a promising, non-invasive diagnostic aid. Despite its utility, no gold standard exists for NMUS, making it an evolving area of research. The pathophysiological basis of ICU-AW involves multiple mechanisms, including critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and muscle atrophy due to disuse. Understanding these underlying mechanisms is crucial for advancing diagnostic strategies and informing therapeutic interventions. Recent insights into the molecular and cellular pathways involved, such as the role of oxidative stress, mitochondrial dysfunction, and the ubiquitin-proteasome system, have opened new avenues for targeted therapies. Management of ICU-AW remains challenging as no specific treatment has been proven fully effective. Current strategies focus on early mobilization, minimizing sedation, and optimizing nutritional support. Emerging therapies targeting molecular pathways involved in muscle degradation are under investigation, highlighting the potential to translate pathophysiological understanding into therapeutic innovations. This review underscores the need for ongoing research to establish standardized diagnostic protocols and develop targeted treatments for ICU-AW.
Background: This study aims to evaluate the prognostic role of serum PCT in older patients with suspect sepsis or infective diagnosis in the Emergency Department (ED) with a particular focus on the clinical consequences and characteristics due to frailty status. Methods: This is a observational retrospective study conducted in the ED of a teaching hospital. We identified all consecutive patients aged ≥ 80 years admitted to the ED and subsequently hospitalized for clinical suspicion of infection. Inclusion criteria were: age ≥ 80 years and clinical suspicion of infection; availability of a PCT determination obtained < 24 h since ED access; and Clinical Frailty Scale (CFS) determination. Study endpoints were the diagnostic accuracy of PCT for all-cause in-hospital death, infective diagnosis at discharge, and bloodstream infection. Diagnostic accuracy was calculated via ROC analysis and compared in the patients with severe frailty, measured by CFS > 6, and patients with low or moderate frailty (CFS 1–6). A multivariate analysis was performed to calculate the adjusted odds of raised PCT values for the study endpoints. Results: In total, 1459 adults ≥ 80 years with a clinical suspicion of infection were included in the study cohort. The median age of the sample was 85 years (82–89), with 718 (49.2%) males. The multivariate models revealed that, after adjusting for significant covariates, the PCT values at ED admission were significantly associated with higher odds of infective diagnosis only in the fit/moderately frail group (Odds Ratio [95% CI] 1.04 [1.01–1.08], p 0.009) and not in very frail patients (Odds Ratio [95% CI] 1.02 [0.99–1.06], p 0.130). Similarly, PCT values were significantly associated with higher odds of in-hospital death in the fit/moderately frail group (Odds Ratio [95% CI] 1.01 [1.00–1.02], p 0.047), but not in the very frail ones (Odds Ratio [95% CI] 1.00 [0.98–1.02], p 0.948). Conversely, the PCT values were confirmed to be a good independent predictor of bloodstream infection in both the fit/moderately frail group (Odds Ratio [95% CI] 1.06 [1.04–1.08], p < 0.001) and the very frail group (Odds Ratio [95% CI] 1.05 [1.03–1.07], p < 0.001). Conclusions: The PCT values at ED admission do not predict infective diagnosis, nor are associated with higher odds of in-hospital death. Still, in frail older adults, the PCT values in ED could be a useful predictor of bloodstream infection.
Waterhouse-Friderichsen syndrome is a rare disease characterized by bleeding into the adrenal glands, and its symptoms may vary from non-specific abdominal pain to multi-organ failure. Commonly related to a variety of infectious diseases among which sepsis from Neisseria meningitidis is the most frequent, many other etiologies have been described, and in some rare cases, even no apparent cause can be identified. We report a rare case of an idiopathic bilateral adrenal hemorrhage in a 70-year-old male who presented to our emergency department with non-specific abdominal pain. Ultrasonography Scan (US) and Computed Tomography (CT) findings were crucial for making an early diagnosis, which resulted in a short hospitalization time and, eventually, a complete recovery of the adrenal function. After discharge, Magnetic Resonance Imaging (MRI) was also performed, providing a more complete ensemble of multimodality imaging findings that can be associated with this rare syndrome.
Intensive Care Unit-Acquired Weakness (ICU-AW) is a common and severe complication in critically ill patients, characterized by profound and often prolonged muscle weakness. The complexity of its diagnosis and management requires a multidimensional approach that integrates clinical, electrophysiological, and imaging tools. This review focuses on the challenges in diagnosing ICU-AW, emphasizing the limitations of traditional methods such as manual muscle testing and electrophysiological studies, and highlights the emerging role of neuromuscular ultrasound (NMUS) as a promising, non-invasive diagnostic aid. Despite its utility, no gold standard exists for NMUS, making it an evolving area of research. The pathophysiological basis of ICU-AW involves multiple mechanisms, including critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and muscle atrophy due to disuse. Understanding these underlying mechanisms is crucial for advancing diagnostic strategies and informing therapeutic interventions. Recent insights into the molecular and cellular pathways involved, such as the role of oxidative stress, mitochondrial dysfunction, and the ubiquitin-proteasome system, have opened new avenues for targeted therapies. Management of ICU-AW remains challenging, as no specific treatment has been proven fully effective. Current strategies focus on early mobilization, minimizing sedation, and optimizing nutritional support. Emerging therapies targeting molecular pathways involved in muscle degradation are under investigation, highlighting the potential to translate pathophysiological understanding into therapeutic innovations. This review underscores the need for ongoing research to establish standardized diagnostic protocols and develop targeted treatments for ICU-AW.