Introduction: Damage control surgery (DCS) is the classic approach to manage severe trauma and has recently also been considered an appropriate approach to the treatment of critically ill patients with severe intra-abdominal sepsis. The purpose of the present review is to evaluate the outcomes following DCS for Hinchey II–IV complicated acute diverticulitis (CAD). Methods: A comprehensive systematic search was undertaken to identify all randomized clinical trials (RCTs) and observational studies, irrespectively of their size, publication status, and language. Adults who have undergone DCS for CAD Hinchey II, III, or IV were included in this review. DCS is compared with the immediate and definitive surgical treatment in the form of HP, colonic resection, and primary anastomosis (RPA) with or without covering stoma or laparoscopic lavage. We searched the following electronic databases: PubMed MEDLINE, Scopus, and ISI Web of Knowledge. The protocol of this systematic review and meta-analysis was published on Prospero (CRD42020144953). Results: Nine studies with 318 patients, undergoing DCS, were included. The presence of septic shock at the presentation in the emergency department was heterogeneous, and the weighted mean rate of septic shock across the studies was shown to be 35.1% [95% CI 8.4 to 78.6%]. The majority of the patients had Hinchey III (68.3%) disease. The remainder had either Hinchey IV (28.9%) or Hinchey II (2.8%). Phase I is similarly described in most of the studies as lavage, limited resection with closed blind colonic ends. In a few studies, resection and anastomosis (9.1%) or suture of the perforation site (0.9%) were performed in phase I of DCS. In those patients who underwent DCS, the most common method of temporary abdominal closure (TAC) was the negative pressure wound therapy (NPWT) (97.8%). The RPA was performed in 62.1% [95% CI 40.8 to 83.3%] and the 22.7% [95% CI 15.1 to 30.3%]: 12.8% during phase I and 87.2% during phase III. A covering ileostomy was performed in 6.9% [95% CI 1.5 to 12.2%]. In patients with RPA, the overall leak was 7.3% [95% CI 4.3 to 10.4%] and the major anastomotic leaks were 4.7% [95% CI 2.0 to 7.4%]; the rate of postoperative mortality was estimated to be 9.2% [95% CI 6.0 to 12.4%]. Conclusions: The present meta-analysis revealed an approximately 62.1% weighted rate of achieving GI continuity with the DCS approach to generalized peritonitis in Hinchey III and IV with major leaks of 4.7% and overall mortality of 9.2%. Despite the promising results, we are aware of the limitations related to the significant heterogeneity of inclusion criteria. Importantly, the low rate of reported septic shock may point toward selection bias. Further studies are needed to evaluate the clinical advantages and cost-effectiveness of the DCS approach.

Circadian rhythms govern cellular metabolism, redox balance, and endocrine signaling in numerous tissues. However, chronic disturbance of these biological rhythms, mediated by modern lifestyle factors including shift work, sleep irregularity, and prolonged light exposure, has been increasingly associated with oxidative stress, metabolic dysregulation, and the pathogenesis of chronic diseases. This review discusses recent mechanistic advances that link circadian misalignment with tissue-specific metabolic reprogramming and impaired proteostasis, focusing on metabolic inflammation and associated pathologies. Emerging work reveals a close interdependence between the circadian clock and proteasome-mediated protein turnover and highlights this interplay’s importance in maintaining redox homeostasis. Furthermore, circadian modulation of the activity of the inflammasome complex is suggested to represent an important, but largely unexplored, risk factor in the pathobiology of both malignancy and metabolic syndrome. Recently, researchers have proposed them as novel endocrine regulators of systemic energy balance and inflammation, with a focus on their circadian regulation. In addition, the emerging domains of chrono-epigenetics and tissue-specific programming of the clock pathways may serve to usher in novel therapies through precision medicine. Moving ahead, circadian-based therapeutic approaches, including time-restricted feeding, chronopharmacology, and metabolic rewiring, have high potential for re-establishing physiological domain homeostasis linked to metabolic inflammation pathologies. Elucidating this reciprocal relationship between circadian biology and cellular stress pathways may one day facilitate the generation of precise interventions aiming to alleviate the health burden associated with circadian disruption.

Obesity and its related disorders, such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), represent a worldwide health challenge, which is driven primarily by the dysfunction of the adipose tissue–gut–liver axis. This article compiles mechanistic and translational data on curcumin and its analogs as multi-organ regulators targeting this axis. Curcumin plays a pleiotropic role by modulating adipogenesis, lipid metabolism, inflammation, fibrosis, and thermogenic remodeling in adipose tissue, tailoring gut microbial diversity, gut barrier integrity, and metabolic endotoxemia. Curcumin in the liver attenuates steatosis, oxidation, and fibrosis by inhibiting lipogenesis, increasing β-oxidation, and modulating the NF-κB and TGF-β signal pathways. These actions result in overall systemic insulin sensitivity and energy balance. On the contrary, the clinical application of curcumin is restricted due to its low solubility, instability, and poor bioavailability. New formulations (nanoparticles/liposomes/micelles) together with structurally enhanced analogs such as tetrahydrocurcumin and monocarbonyl analogs (C66, B2BrBC) exhibited superior pharmacokinetic and tissue-targeting properties in preclinical models. Pilot and randomized clinical trials suggest that curcumin supplementation enhances glucose and lipid metabolism, reduces liver fat content, and modulates inflammatory markers; however, results across studies remain heterogeneous. Large, high-quality multicenter trials using rigorously standardized, bioavailable curcumin formulations are still required to reliably establish the efficacy and safety of curcumin in metabolic diseases. Next steps involve comparing curcumin analogs, conducting multi-omics analyses to understand host–microbiota–organ crosstalk, and determining cooperative approaches with lifestyle and pharmacological interventions. Taken together, curcumin and its next-generation derivatives may offer a novel therapeutic approach to intervene in the adipose tissue–gut–liver axis for the treatment of obesity-related metabolic diseases.

Background and Objectives: The diverticular disease includes a broad spectrum of different “clinical situations” from diverticulosis to acute diverticulitis (AD), with a full spectrum of severity ranging from self-limiting infection to abscess or fistula formation to free perforation. The present work aimed to assess the burden of complicated diverticulitis through a comparative analysis of the hospitalizations based on the national administrative databases. Materials and Methods: A review of the international and national administrative databases concerning admissions for complicated AD was performed. Results: Ten studies met the inclusion criteria and were included in the analysis. No definition of acute complicated diverticulitis was reported in any study. Complicated AD accounted for approximately 42% and 79% of the hospitalizations. The reported rates of abscess varied between 1% and 10% from all admissions for AD and 5–29% of the cases with complicated AD. An increasing temporal trend was found in one study–from 6% to 10%. The rates of diffuse peritonitis ranged from 1.6% to 10.2% of all hospitalizations and 11% and 47% of the complicated cases and were stable in the time. Conclusions: The available data precluded definitive conclusions because of the significant discrepancy between the included studies. The leading cause was the presence of heterogeneity due to coding inaccuracies in all databases, absence of ICD codes to distinguish the different type of complications, and the lack of coding data about some general conditions such as sepsis, shock, malnutrition, steroid therapy, diabetes, pulmonary, and heart failure.

Background and Objectives: The present study aims to assess the effectiveness and current evidence of the treatment of perirectal bleeding after stapled haemorrhoidopexy. Materials and methods: A systematic literature review was performed that combined the published and the obtained original data after a search of PubMed, Web of Science, and SCOPUS. Results: The present systematic review includes 16 articles with 37 patients. Twelve papers report perirectal and six report intra-abdominal bleeding. Stapled hemorrhoidopexy (SH) was performed in 57% of cases (3 PPH 01 and 15 PPH 03), stapled transanal rectal resection (STARR) in 13%, and for 30% information was not available. The median age was 49 years (±11.43). The sign and symptoms of perirectal bleeding were abdominal pain (43%), pelvic discomfort without rectal bleeding (36%), urinary retention (14%), and external rectal bleeding (21%). The median time to bleeding was 1 day (±1.53 postoperative days), with median hemoglobin at diagnosis 8.8 ± 1.04 g/dL. Unstable hemodynamic was reported in 19%. Computed tomography scan (CT) was the first examination in 77%. Only two cases underwent the abdominal US, but subsequently, a CT scan was also conducted. Non-operative management was performed in 38% (n = 14) with selective arteriography and percutaneous angioembolization in two cases. A surgical treatment was performed in 23 cases—transabdominal surgery (3 colostomies, 1 Hartmann’ procedure, 1 low anterior resection of the rectum, 1 bilateral ligation of internal iliac artery and 1 ligation of vessels located at the rectal wall), transanal surgery (n = 13), a perineal incision in one, and CT-guided paracoccygeal drainage in one. Conclusions: Because of the rarity and lack of experience, no uniform tactic for the treatment of perirectal hematomas exists in the literature. We propose an algorithm similar to the approach in pelvic trauma, based on two main pillars—hemodynamic stability and the finding of contrast CT.

Background and Objective: Klebsiella pneumoniae appears to be a significant problem due to its ability to accumulate antibiotic-resistance genes. After 2013, alarming colistin resistance rates among carbapenem-resistant K. pneumoniae have been reported in the Balkans. The study aims to perform an epidemiological, clinical, and genetic analysis of a local outbreak of COLr CR-Kp. Material and Methods: All carbapenem-resistant and colistin-resistant K. pneumoniae isolates observed among patients in the ICU unit of Military Medical Academy, Sofia, from 1 January to 31 October 2023, were included. The results were analyzed according to the EUCAST criteria. All isolates were screened for blaVIM, blaIMP, blaKPC, blaNDM, and blaOXA-48. Genetic similarity was determined using the Dice coefficient as a similarity measure and the unweighted pair group method with arithmetic mean (UPGMA). mgrB genes and plasmid-mediated colistin resistance determinants (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5) were investigated. Results: There was a total of 379 multidrug-resistant K. pneumoniae isolates, 88% of which were carbapenem-resistant. Of these, there were nine (2.7%) colistin-resistant isolates in six patients. A time and space cluster for five patients was found. Epidemiology typing showed that two isolates belonged to clone A (pts. 1, 5) and the rest to clone B (pts. 2–4) with 69% similarity. Clone A isolates were coproducers of blaNDM-like and blaOXA-48-like and had mgrB-mediated colistin resistance (40%). Clone B isolates had only blaOXA-48-like and intact mgrB genes. All isolates were negative for mcr-1, -2, -3, -4, and -5 genes. Conclusions: The study describes a within-hospital spread of two clones of COLr CR-Kp with a 60% mortality rate. Clone A isolates were coproducers of NDM-like and OXA-48-like enzymes and had mgrB-mediated colistin resistance. Clone B isolates had only OXA-48-like enzymes and intact mgrB genes. No plasmid-mediated resistance was found. The extremely high mortality rate and limited treatment options warrant strict measures to prevent outbreaks.