The incidence of common bile duct injuries following laparoscopic cholecystectomy (LC) remains three times higher than that following open surgery despite numerous attempts to decrease intraoperative incidents by employing better training, superior surgical instruments, imaging techniques, or strategic concepts. This paper is a narrative review which discusses from a contextual point of view the need to standardise the surgical approach in difficult laparoscopic cholecystectomies, the main strategic operative concepts and techniques, complementary visualisation aids for the delineation of anatomical landmarks, and the importance of cognitive maps and algorithms in performing safer LC. Extensive research was carried out in the PubMed, Web of Science, and Elsevier databases using the terms ”difficult cholecystectomy”, ”bile duct injuries”, ”safe cholecystectomy”, and ”laparoscopy in acute cholecystitis”. The key content and findings of this research suggest there is high intersocietal variation in approaching and performing LC, in the use of visualisation aids, and in the application of safety concepts. Limited papers offer guidelines based on robust data and a timid recognition of the human factors and ergonomic concepts in improving the outcomes associated with difficult cholecystectomies. This paper highlights the most relevant recommendations for dealing with difficult laparoscopic cholecystectomies.

The prediction of severity in acute calculous cholecystitis (AC) is important in therapeutic management to ensure an early recovery and prevent adverse postoperative events. We analyzed the value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammatory index (SII) to predict advanced inflammation, the risk for conversion, and postoperative complications in AC. Advanced AC was considered the cases with empyema, gangrene, perforation of the gallbladder, abscesses, or difficulties in achieving the critical view of safety. A 3-year retrospective was performed on 235 patients admitted in emergency care for AC. The NLR was superior to the PLR and SII in predicting advanced inflammation and risk for conversion. The best predictive value was found to be at an NLR “cut-off” value of >4.19, with a sensitivity of 85.5% and a specificity of 66.9% (AUC = 0.824). The NLR, SII, and TG 13/18 correlate well with postoperative complications of Clavien–Dindo grade IV (p < 0.001 for all variables) and sepsis. For predicting early postoperative sepsis, TG 13/18 grading >2 and NLR > 8.54 show the best predicting power (AUC = 0.931; AUC = 0.888, respectively), although not significantly higher than that of the PLR and SII. The NLR is a useful biomarker in assessing the severity of inflammation in AC. The SII and PLR may be useful in the prediction of systemic inflammatory response.

Laparoscopic cholecystectomy (LC) is the gold standard treatment in acute cholecystitis. However, one in six cases is expected to be difficult due to intense inflammation and suspected adherence to and involvement of adjacent important structures, which may predispose patients to higher risk of vascular and biliary injuries. In this study, we aimed to identify the preoperative parameters with predictive value for surgical difficulties. A retrospective study of 255 patients with acute cholecystitis admitted in emergency was performed between 2019 and 2023. Patients in the difficult laparoscopic cholecystectomy (DLC) group experienced more complications compared to the normal LC group (33.3% vs. 15.3%, p < 0.001). Age (p = 0.009), male sex (p = 0.03), diabetes (p = 0.02), delayed presentation (p = 0.03), fever (p = 0.004), and a positive Murphy sign (p = 0.007) were more frequently encountered in the DLC group. Total leukocytes, neutrophils, and the neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the DLC group (p < 0.001, p = 0.001, p = 0.001 respectively). The Tongyoo score (AUC ROC of 0.856) and a multivariate model based on serum fibrinogen, thickness of the gallbladder wall, and transverse diameter of the gallbladder (AUC ROC of 0.802) showed a superior predictive power when compared to independent parameters. The predictive factors for DLC should be assessed preoperatively to optimize the therapeutic decision.

Background and Objectives: Systemic inflammatory indices have been largely investigated for their potential predictive value in multiple inflammatory, infectious, and oncological diseases; however, their value in colorectal cancer is still a subject of research. This study investigates the dynamics of pre- and postoperative values of NLR, PLR, SII, and MLR in patients with colorectal cancer and their predictive value for early postoperative outcomes. Materials and Methods: A 2-year retrospective cohort study was performed on 200 patients operated for colorectal adenocarcinoma. Systemic inflammatory indices were calculated based on complete blood count preoperatively and on the first and sixth postoperative days. The patients were divided into two groups based on their emergency or elective presentation. The pre- and postoperative values of serum inflammatory biomarkers and their correlations with postoperative outcomes were separately analyzed for the two study subgroups. Results: There were no significant differences in sex distribution, addressability, associated comorbidities, or types of surgery between the two groups. Patients in the emergency group presented higher preoperative and postoperative values of WBC, neutrophils, NLR, and SII compared to elective patients. The postsurgery hospital stays correlated well with pre- and postoperative day one and day six values of NLR (p = 0.001; 0.02; and <0.001), PLR (p < 0.001), SII (p = 0.037; <0.001; <0.001), and MLR (p = 0.002; p = 0.002; <0.001). In a multivariate analysis, reintervention risk was higher for emergency presentation and anemia, and lower in right colon cancer. In the emergency group, a multivariate model including age, MLR PO1, and pTNM stage was predictive for severe postoperative complications (AUC ROC 0.818). First-day postoperative inflammatory indices correlated well with sepsis, with the best predictive value being observed for the first postoperative day NLR (AUC 0.836; sensibility 88.8%; specificity 66.7%) and SII (AUC 0.796; sensitivity 66.6%; specificity 90%). For elective patients, the first postoperative day PLR and anemia were included in a multivariate model to predict Clavien–Dindo complications graded 3 or more (AUC ROC 0.818) and reintervention (AUC ROC 0.796). Conclusions: Easy-to-calculate and inexpensive systemic inflammatory biomarkers could be useful in predicting early postoperative outcomes in colorectal cancer for both elective and emergency surgery.

Background/Objectives: Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. Intravitreal complement inhibitors are an emergent approach in the treatment of AMD, which have had encouraging results. This systematic review analyzes the outcomes and safety of complement inhibitor therapies for GA in AMD cases. Methods: A comprehensive search on the PubMed and Web of Science databases returned 18 studies involving various complement inhibitor agents, with a total of 4272 patients and a mean follow-up of 68.2 ± 20.4 weeks. Results: Most treated patients were white (96.8%) and female (55.8%), with a mean age of 78.3 ± 7.8 years and a mean GA area of 8.0 ± 3.9 mm². There were no differences in visual function change between treated and control participants. The mean GA area change was 2.4 ± 0.7 mm² in treated participants vs. 2.7 ± 0.8 mm² in control groups (p < 0.001). The ocular and systemic side effects were similar to those of intravitreal anti-VEGF. A less-understood effect was that of the onset of choroidal neovascularization (CNV) in 1.1–13% of patients; this effect was found to be more frequent in patients with neovascular AMD in the fellow eye or nonexudative CNV in the study eye at baseline. Conclusions: Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes.

Modern biomedicine frequently contextualizes disease around isolated molecular or organ-specific mechanisms, but numerous chronic diseases, including Alzheimer’s disease, multiple sclerosis, depression, diabetes, and sepsis, share common trajectories of systemic destabilization. An increasing body of evidence indicates that health is not a property of single organs but the emergent property of interdependent feedback networks linking the microbiome, endocannabinoidome, neuroimmune system, and metabolic regulators. We propose the Endocannabinoid–Microbiota–Neuroimmune Super-System (EMN-S) as an evolutionarily conserved conceptual model that describes how these fields of influence reciprocally interact through feedback control. The microbial communities constituting the EMN-S encode environmental and dietary inputs, endocannabinoid signaling serves as an integrative regulator that synchronizes neural and immune activity, and neuroimmune circuits effectuate adaptive behaviors that alter microbiotal and lipid ecosystems. This review formalizes the EMN-S, contending that it is a unitary and cohesive model of physiological resilience, as well as offering a framework for precision feedback therapeutics. We describe how three mechanisms—encoder drift, integrator detuning, and executor overutilization—convert stabilizing negative feedback into runaway feedback cascades that underlie chronic, recurrent, and multisystemic disease. We then specify the EMN-S signature—integrated microbiome, lipidomic, and immune readouts—as an early indicator of resilience collapse and prospective preclinical state. Finally, we recapitulate the potential of AI-driven digital twins to illuminate feedback collapse, predict tipping points, and direct closed-loop intervention and treatments to restore dynamic equilibrium. By anchoring complexity in concrete and measurable feedback principles, the EMN-S shifts focus to investigate pathophysiology as opposed to reductionist lesion models of systemic derangements and embraces a systemic, empirically testable theory of stability.