To compare the peri-operative outcomes between the minimally-invasive surgery (MIS) and open surgery for the resection of perirenal tumors larger than 7 cm. This retrospective single-center study included 46 patients who underwent resection of retroperitoneal perirenal tumors larger than 7 cm between April 2009 and March 2025. Patients were stratified into MIS (laparoscopic or robot-assisted; n = 26) and open surgery (n = 20) groups. Demographic, peri-operative, and pathological variables were collected and analyzed. Subgroup analyses were further performed in patients with tumors larger than 10 cm. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for peri-operative blood transfusion, complications, and postoperative hospital stay. Baseline characteristics were comparable except for tumor size, which was significantly larger in the open surgery group (13.36 ± 5.49 vs. 9.43 ± 2.31 cm, P = 0.006). MIS was associated with lower estimated blood loss (90.00 vs. 350.00 mL, P < 0.001), and shorter postoperative hospital stays (9.00 ± 3.83 vs.5.23 ± 1.31 days, P < 0.001). Similar results were observed in the subgroup of patients with tumors larger than 10 cm. Adjacent organ resection was more frequent in the open group (65.00% vs. 34.60%, P = 0.041). Overall complication rate was similar (65.00% vs. 46.20%, P = 0.203), but all three major complications (Clavien-Dindo grade ≥ III) occurred in the open group. On multivariate analysis, surgical method (open or MIS) was identified as an independent predictor of postoperative hospital stay (OR 0.074, P < 0.001), while adjacent organ resection was the only independent risk factor for peri-operative complications (OR 8.481, P = 0.005). Both MIS and open surgery are safe and effective selection for patients with perirenal tumors larger than 7 cm. MIS may offer faster recovery and less blood loss, while open surgery remains necessary for large tumors. Multicenter prospective studies with extended follow-up are needed to validate these findings.
To evaluate whether the addition of epidural analgesia to general anesthesia is associated with improved early postoperative ICU recovery in patients undergoing elective open abdominal aortic aneurysm (AAA) repair. Prospective, single-center observational cohort study. Tertiary care university-affiliated vascular surgery center. Sixty adult patients undergoing elective open AAA repair between August 2024 and July 2025. Patients received either general anesthesia alone (GA group, n = 30) or combined general anesthesia with epidural analgesia as part of a multimodal analgesic strategy (GA+EA group, n = 30), based on anesthesiologist clinical judgment and patient-specific factors. The primary outcome was early postoperative ICU recovery, assessed by postoperative mechanical ventilation time and ICU length of stay. Secondary outcomes included perioperative opioid consumption and intraoperative hemodynamic parameters (vasopressor requirements and fluid administration). The GA+EA group demonstrated significantly shorter postoperative mechanical ventilation time (1.5 ± 1.0 vs 5.0 ± 2.0 hours, p = 0.00000008) and ICU length of stay (1.0 ± 0.5 vs 2.0 ± 0.9 days, p = 0.000003). Additionally, patients in the GA+EA group required lower intraoperative opioid doses (fentanyl 3.5 ± 1.0 vs 8.5 ± 1.6 μg/kg, p = 2.63 × 10-19 ) and reduced 24-hour postoperative morphine consumption ( 2 ± 4 vs 18 ± 6 mg, p = 1.30 × 10-16 ). Mean intraoperative MAP, heart rate, the proportion of patients with MAP <60 mmHg, and norepinephrine requirement did not differ significantly between groups. Intraoperative crystalloid administration was lower in the GA+EA group, while colloid use, blood loss, cell-saver volumes, and transfusion requirements were comparable. This exploratory, hypothesis-generating study found that epidural-based multimodal analgesia was associated with improved early postoperative ICU recovery following open AAA repair, particularly through earlier extubation and shorter ICU stay. Integration of neuraxial techniques within multimodal perioperative care pathways may represent a feasible strategy to optimize recovery in high-risk vascular surgery.
Intraoperative hypotension is associated with adverse postoperative outcomes. This pilot randomized controlled trial evaluated whether hemodynamic-guided management using continuous noninvasive finger-cuff blood pressure monitoring reduces intraoperative hypotension compared with standard intermittent oscillometric monitoring in patients undergoing open thoracic surgery. Pilot randomized controlled trial. Single tertiary university hospital. Forty adult patients undergoing elective open thoracic surgery under general anesthesia. Patients were randomized to either hemodynamic-guided management using continuous finger-cuff blood pressure monitoring with the Hypotension Prediction Index and waveform-derived parameters (protocolized intervention) or standard care using intermittent oscillometric blood pressure monitoring. The primary outcome was the time-weighted average (TWA) of mean arterial pressure (MAP) <65 mmHg. The TWA of hypotension was significantly lower in the finger-cuff group compared with the oscillometric group (median [interquartile range], 0 [0-0] v 0.11 [0-0.40]; p = 0.001). The incidence and duration of hypotensive episodes were also reduced. Fewer patients in the hemodynamic-guided group required vasopressor therapy, primarily ephedrine, than in the oscillometric group (35% v 80%; p = 0.004). No significant differences were observed in postoperative serum creatinine or cognitive outcomes, and no cases of acute kidney injury or postoperative delirium occurred. In this pilot randomized trial, hemodynamic-guided management using continuous noninvasive finger-cuff monitoring was associated with reduced intraoperative hypotension and vasopressor use compared with intermittent oscillometric monitoring. These findings support the feasibility and potential benefit of continuous noninvasive hemodynamic monitoring; however, larger studies are required to confirm clinical outcome benefits.
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Early-life stress (ELS) sensitizes individuals to subsequent stressors to increase lifetime risk for psychiatric disorders. Within the nucleus accumbens (NAc) - a key limbic and reward-associated brain region - ELS sensitizes both cellular and transcriptional response to later stress, which are programmed by enduring epigenetic changes. Among the histone modifications persistently enriched by ELS in NAc is H3K4me1, which is associated with open chromatin and epigenetic priming of genomic enhancers. Here, we sought to determine whether H3K4me1 enrichment in NAc was sufficient to prime cellular and behavioral responses to adult stress. Viral-mediated overexpression of the histone H3 monomethyltransferase Setd7 in juvenile NAc of male and female mice induced persistent chromatin changes and predominately opened chromatin at long-range cis-regulatory elements predicted to enhance immediate early-genes and transcriptional regulators of mesolimbic development and synaptic activity. These epigenetic changes altered physiological properties of D2-type medium spiny neurons in NAc to resemble neurons of stressed mice, without significantly altering D1-type neurons. Finally, juvenile - but not adult - Setd7 overexpression and H3K4me1 enrichment in NAc enhanced behavioral sensitivity to future stress. Together, these data indicate that altered postnatal chromatin development in NAc by H3K4me1 enrichment is sufficient to prime long-lasting transcriptional, physiological, and behavioral stress sensitivity.Significance Statement Early-life stress enriches for H3K4me1 in the nucleus accumbens, which is sufficient to open chromatin, alter medium spiny neuron physiological properties, and prime behavioral response to future stress. This work links multiple levels of analysis and provides neurobiological evidence that altered maturation of the juvenile epigenome encodes long-lasting stress sensitivity.
Anesthesiologists play a critical role in healthcare system, yet the overall working conditions of anesthesiologists in China remain unclear. This study aimed to conduct a comprehensive national assessment of this workforce. An open nationwide, cross-sectional, non-probability sampling survey focusing on working conditions, clinical practice and career challenges of anesthesiologists across China was conducted by Chinese Society of Anesthesiology from June 2022 to February 2023. The questionnaire was distributed via WeChat online platform to anesthesiology practitioners across all healthcare tiers and diverse regions of mainland China. Data were analyzed and visualized using R software. Logistic regression analysis was conducted to identify factors associated with resignation intention. A total of 30,255 participants from 5,808 medical institutions were included in the analysis, with females accounting for 47.28%. Overall, 16.29% of participants reported resignation intention. Regression analyses identified significant associations between resignation intention and service years, weekly work hours, daily anesthesia caseload, annual income, sleep quality, smoking, alcohol, and exercise frequency. A majority (62.72%) participants reported weekly meaningful work accomplishment, while 50.4% reported weekly work overload, and 30.1% experienced weekly work-induced exhaustion. In addition, 82.12% of participants never treated patients with indifference. Overall, 56.27% reported job satisfaction. Chinese anesthesiologists exhibited high self-reported clinical quality and efficacy, with low rate of adverse events (2.99%). Medical disputes (7.44%) and physical violence (4.91%) were rare, while 35.32% reported experiencing verbal violence from patients. The primary barrier to professional title promotion was paper publication (62.81%). Despite demonstrating high clinical quality and professional fulfillment, Chinese anesthesiologists face substantial challenges including heavy workloads, occupational burnout, and career advancement barriers. These findings provide critical insights for targeted interventions and inform evidence-based policy-making to ensure a sustainable, high-quality anesthesia workforce in China.
In patients with diabetes and coronary artery disease, coronary artery bypass grafting (CABG) confers a long-term survival advantage over percutaneous coronary intervention (PCI); however, a knowledge gap remains regarding patient-centred outcomes. We therefore compared patient-defined adverse cardiovascular and noncardiovascular events (PACE) after CABG vs PCI in diabetic patients. We conducted a population-based, retrospective cohort study of all diabetic patients who underwent CABG or PCI between October 2008 and December 2018 in Ontario, Canada. The primary outcome was PACE, defined as the composite of severe stroke requiring hospitalization > 14 days or inpatient rehabilitation, ventilator dependence, heart failure hospitalization, long-term care admission, and new-onset dialysis. Secondary outcomes included all-cause mortality and individual PACE components. Overlap weighting using propensity scores was performed to account for baseline differences between groups. Cumulative incidence functions were estimated, and groups were compared using cause-specific hazard models (with death as a competing risk) and Cox proportional hazards models. A total of 58,826 patients (25,751 CABG; 33,075 PCI) were followed for a mean of 4.7 years (standard deviation 3.1; maximum 11.5). Rates of PACE were lower after CABG vs PCI over 1-5 years postintervention (1-year HR 0.88 [95% CI 0.77-1.00]; 5-year HR 0.83 [95% CI 0.71-0.97]). Rates of death were lower after CABG during the first 8 years (30-day HR 0.61 [95% CI 0.50-0.74]; 5-year HR 0.71 [95% CI 0.63-0.80]; 8-year HR 0.82 [95% CI 0.69-0.98]). We observed lower rates of PACE and all-cause mortality in diabetic patients within the first 5 years after CABG, compared to PCI. Findings could be used to inform shared decision-making to achieve outcomes most valued by patients. Chez les patients atteints de diabète et de maladie coro- narienne (MC), le pontage aorto-coronarien (PAC) confère un avantage de survie à long terme par rapport à l'intervention coronarienne percutanée (ICP); cependant, il existe un manque de connaissances concernant les résultats cliniques centrés sur le patient. Nous avons donc comparé les événements indésirables, cardiovasculaires et non cardiovasculaires, définis par les patients (EIDP) après un PAC en comparaison à une ICP, ceci chez les patients diabétiques. Nous avons mené une étude de cohorte rétrospective populationnelle auprès de tous les patients diabétiques ayant subi un PAC ou une ICP entre octobre 2008 et décembre 2018 en Ontario, au Canada. Le critère d'évaluation principal englobait les EIDP, et était défini comme la combinaison d'un accident vasculaire cérébral grave nécessitant une hospitalisation > 14 jours ou une rééducation en milieu hospitalier, une dépendance à la ventilation mécanique, une hospitalisation pour insuffisance cardiaque, une admission en soins de longue durée et une nouvelle dialyse. Les critères d'évaluation secondaires comprenaient la mortalité toutes causes confondues et chacune des composantes individuelles des EIDP. Une pondération par chevauchement utilisant des scores de propension a été appliquée pour tenir compte des différences de base entre les groupes. Les fonctions d'incidence cumulée ont été estimées et les groupes ont été comparés à l'aide de modèles de risque spécifiques à la cause (le décès étant considéré comme un risque concurrent) et de modèles de risques proportionnels de Cox. Au total, 58 826 patients (25 751 PAC; 33 075 ICP) ont été suivis pendant une durée moyenne (avec écart-type) de 4,7 (3,1) ans (maximum de 11,5 ans). Les taux d'EIDP étaient plus faibles après un PAC qu'après une ICP au cours des 1 à 5 années suivant l'intervention (rapport des risques instantanés [RRI] à 1 an 0,88 [intervalle de confiance (CI) à 95 % 0,77-1,00]; RRI à 5 ans 0,83 [IC à 95 % 0,71-0,97]). Les taux de mortalité étaient plus faibles après un PAC au cours des 8 premières années (RRI à 30 jours 0,61 [IC à 95 % 0,50-0,74] ; RRI à 5 ans 0,71 [IC à 95 % 0,63-0,80] ; RRI à 8 ans 0,82 [IC à 95 % 0,69-0,98]). Nous avons observé, chez les patients diabétiques, des taux plus faibles d'EIDP et de mortalité toutes causes confondues au cours des cinq premières années suivant un PAC par rapport à une ICP. Ces résultats pourraient être utilisés pour éclairer la prise de décision partagée afin d'obtenir les résultats cliniques les plus appréciés par les patients.
Lipid-derived and lipid-related microbial metabolites form a functional interface between the gut microbiota, intestinal barrier integrity, mucosal immunity, hepatic metabolism, and systemic immunometabolic homeostasis. At the gut-liver axis, these molecules should not be regarded as passive end-products of microbial metabolism, but as compartment-sensitive signals whose biological effects depend on site of production, mucosal exposure, epithelial utilization, portal delivery, hepatic handling, receptor distribution, and inflammatory context. This narrative review examines five major metabolite classes: short-chain fatty acids, including branched-chain fatty acids; microbially transformed bile acids; bacterial sphingolipids; PUFA-derived or microbially modulated lipid mediators; and choline-, carnitine-, and phospholipid-derived co-metabolites such as trimethylamine N-oxide. We discuss how these pathways regulate tight-junction architecture, epithelial energy metabolism, mucus-associated defense, antimicrobial programs, innate and adaptive immune-cell signaling, bile-acid receptor networks, and portal inflammatory exposure. The evidence is most mature for classical short-chain fatty acids and bile-acid signaling, emerging but mechanistically compelling for bacterial sphingolipids and PUFA-derived mediators, context-dependent for TMAO, and still limited for aging-specific and sarcopenia-related extrapolations. Across classes, translation is constrained by incomplete causal inference, preclinical predominance, heterogeneous human evidence, inconsistent metabolomic and lipidomic standardization, and the non-equivalence of fecal concentrations, mucosal exposure, portal delivery, and systemic availability. Future studies should move beyond single-metabolite associations toward longitudinal, multi-compartment, mechanism-informed models integrating targeted metabolomics/lipidomics, permeability markers, immune phenotyping, liver and cardiometabolic endpoints, and functional outcomes relevant to frailty and sarcopenia.
Intensive care physicians are uniquely positioned to understand the benefits and burdens of life-prolonging treatments. This study aimed to examine the personal end-of-life preferences of intensive care physicians when facing a hypothetical incurable terminal illness and to evaluate the role of palliative care within these preferences. In this descriptive cross-sectional study, a 17-item survey instrument (12 close-ended and 5 open-ended questions) was administered electronically to anesthesiology and reanimation specialists working in public and private hospitals in Istanbul. Quantitative data were analyzed using descriptive statistics, while qualitative responses were evaluated through thematic analysis. Content validity of the questionnaire was assessed using established content validity index methodology. A total of 296 physicians participated (response rate: 28.8%). The mean age was 43.79 ± 7.54 years, and the mean duration of specialist practice was 12.34 ± 9.44 years. Refusal rates for aggressive life-prolonging interventions exceeded 70% across most modalities, with the highest refusal observed for cardiopulmonary resuscitation (88.5%). Only 0.7% of respondents indicated a preference to spend the end of life in a palliative care unit. Among physicians who had previously made end-of-life decisions for first-degree relatives, only 1.3% reported utilization of palliative care services. Intensive care physicians strongly favor comfort-focused and palliative-oriented approaches for themselves at the end of life. However, the extremely low preference for palliative care units highlights a substantial gap between personal values and the current healthcare system. Strengthening palliative care integration, education, and policy frameworks is urgently needed.
Emergency laparoscopic cholecystectomy (LC) remains the preferred treatment for acute cholecystitis (AC); however, the prevalence of complications and negative outcomes increases in these emergency surgeries, especially when performed by junior surgeons. Recently, indocyanine green (ICG) fluorescent cholangiography has emerged as a useful technique for achieving adequate visualization of the biliary structures during LC, reducing the incidence of bile duct injury (BDI) and operative time. This study aims to evaluate the surgical outcomes of ICG fluorescent cholangiography during emergency LC performed by junior surgeons. A total of 156 consecutive patients (May 2023  to  December 2025) who underwent LC for AC were included, and all the surgeries were performed by junior surgeons. In total, 78 patients underwent ICG fluorescent cholangiography during LC (ICG group), while the remaining 78 patients underwent conventional LC with white light (non-ICG group). The demographic and clinical characteristics of these patients were retrospectively collected and analyzed, including gender, age, comorbidities, intraoperative BDI, conversion to open surgery, operative time, postoperative complications, postoperative hospital stay duration, and overall hospitalization cost. A multiple linear regression analysis was performed to examine whether ICG use was associated with the surgical outcomes. The demographic characteristics of the ICG and non-ICG groups were similar. The patients in the ICG group had a significantly shorter operative time compared to those in the non-ICG group (65 min vs. 72.5 min, P  =  0.007). There were no significant differences between the groups for the other surgical outcomes, including BDI incidence, rate of conversion to open surgery, incidence of postoperative complications, postoperative hospital stay duration, and hospitalization cost. ICG use was found to be an independent factor associated with decreased operative time in the regression analysis. The utilization of ICG fluorescent cholangiography during emergency LC could help junior surgeons shorten the operative time and may not increase the incidence of perioperative complications.
Introduction Documentation-related tasks, including preparation of informed consent (IC) forms for anesthesia, increase workload and cognitive burden in anesthesiology. This study evaluated the time-saving effect and usability of a semi-automated institution-specific assistant application for anesthesia IC form preparation. Methods We developed a semi-automated Python-based (Python Software Foundation, Wilmington, DE, USA) assistant application using generative AI assistant programming. The application was tailored to our institutional electronic medical record (EMR) workflow and was designed to automatically select relevant checkboxes and insert required text into IC forms for anesthesia. Its time-saving effect and usability were evaluated using a randomized crossover design. Twenty anesthesiologists were randomized into two groups: Group A (n = 10, 50%) prepared IC forms for five mock patients first by manual entry and then using the application, whereas Group B (n = 10, 50%) followed the reverse order. Preparation time was defined as the interval from the start of preparing the first IC form to the completion of the fifth IC form. Usability was assessed using a 5-point Likert scale. Results The mean preparation time was 9.7 (SD 1.7) minutes with the application and 16.0 (SD 2.6) minutes without the application (mean difference, 6.2 minutes; 95% CI, 5.2 to 7.2 minutes; p < 0.001). Use of the application reduced preparation time by approximately 40%. Regarding usability, 11 participants (55%) reported that they "very much wanted to continue using" the application, whereas nine participants (45%) reported that they "wanted to continue using" it. Conclusion The tailored application significantly reduced preparation time compared with manual entry and was well accepted by participants. These findings provide proof-of-concept evidence that generative AI-assisted in-house development may enable clinicians to create institution-specific workflow-support tools for improving documentation efficiency in anesthesiology practice.
Perioperative neurocognitive disorders (POCD) are a class of common complications of central nervous system after general anesthesia and surgery. Sevoflurane (SEV) is a widely used inhalation anesthetic in clinical practice, but the mechanism of SEV-induced neuronal damage has not yet been fully elucidated. This study aimed to investigate the mechanism of SEV-induced neuronal pyroptosis involving upstream stimulatory factor 1 (USF1) and poly (ADP-ribose) polymerase 1 (PARP1). Single-cell RNA sequencing screening on GSE267933 dataset was performed. POCD animal model was established using C57BL/6J mice, and open field test and Y maze test were conducted to assess cognitive function. Cell model was constructed using human cortical neuronal cell line (CP-H120) and mouse hippocampal neuron cells (HT22). Western blot was employed for protein detection. Cell viability was examined using cell counting kit-8. Pyroptosis was evaluated by enzyme-linked immunosorbent assay, lactate dehydrogenase release assay, flow cytometry, and immunofluorescence staining. The binding between USF1 and PARP1 promoter was analyzed by chromatin immunoprecipitation assay, DNA pull-down assay and dual-luciferase reporter assay. Single-cell sequencing analysis on GSE267933 dataset identified that PARP1 was highly expressed in hippocampal neurons after SEV exposure (P < 0.05). PARP1 knockdown improved cognitive dysfunction and pyroptosis in SEV-exposed POCD mice (P < 0.05). PARP1 downregulation inhibited SEV-induced pyroptosis in human neuronal cells (P < 0.05). USF1 served as a transcription factor to promote PARP1 expression (P < 0.05). Silencing USF1 suppressed SEV-induced pyroptosis in human neuronal cells by downregulating PARP1 (P < 0.05). These findings indicated that USF1-mediated upregulation of PARP1 promoted SEV-induced neuronal pyroptosis, suggesting that USF1/PARP1 axis may function as a key regulator in SEV-triggered neuronal damage in POCD.
Neuroinflammation is recognized as a pivotal pathological process underlying a spectrum of neurological disorders. The exploration of natural flavonoids as therapeutic agents has substantially advanced our understanding of strategies to mitigate neuroinflammatory injury. Accumulating evidence indicates that kaempferol-a dietary flavonoid abundantly present in various fruits and vegetables-exerts potent neuroprotective effects in multiple neurological conditions. Its beneficial actions are mediated through multi-target mechanisms, primarily involving the suppression of microglial activation, modulation of immune cell reactivity, and enhancement of endogenous antioxidant defenses. These mechanisms collectively contribute to reduced production of inflammatory mediators, alleviation of oxidative stress, and inhibition of neuronal apoptosis, thereby counteracting the pathogenesis of various neuroinflammatory diseases. This review summarizes current knowledge on the protective role of kaempferol in the pathogenesis and progression of central nervous system disorders. We further elucidate the underlying molecular and cellular mechanisms, as well as autophagy and oxidative stress. Additionally, potential challenges in clinical translation, such as bioavailability and blood-brain barrier permeability, are discussed to guide future research in this promising field. Elucidating the pleiotropic actions of kaempferol will not only deepen our understanding of its pharmacodynamics but may also open new avenues for the prevention and treatment of neuroinflammatory-related neurological diseases.
Background: Palliative psychiatry as a new subfield of practice focuses on the care of patients with severe, chronic mental diseases. The aim is to improve the quality of life of those affected and alleviate their suffering. The cybernetic approach can be used to achieve these goals. Materials and methods: This narrative study aims to present palliative psychiatry from a cybernetic perspective. To this end, it examines how and whether these concepts are already being used in related fields such as palliative care and general psychiatry. Finally, it discusses the implications of this for palliative psychiatry. The focus is also on schizophrenia and depression. Cybernetic terms were entered along with the terms "schizophrenia" and "depression" in the PubMed and PubPsych databases. In addition, articles and books on psychological terms, such as affect logic, vulnerability, and comorbidity, were used in a snowball system. Results: In recent decades, general psychiatry has dealt with all of the cybernetic terms examined in this study. Palliative psychiatry has only been oriented towards palliative care and has used its cybernetic terms. However, no other cybernetic terms were used. Articles on palliative care for patients with schizophrenia show that palliative psychiatry initially addresses problems that have been known for over ten years. In the case of depression, only studies on palliative care outside the field of psychiatry have been published. Conclusions: The integration of cybernetic concepts could provide palliative psychiatry with a theoretical foundation that goes beyond the previous borrowings from palliative care. This opens up new possibilities for better understanding complex disease progression, especially in schizophrenia and depression, and providing therapeutic support.
Fatigue is characterized as a feeling of exhaustion or lack of energy, is a common symptom of multiple chronic illnesses and interferes with daily activities and quality of life. There is a limited availability of animal models to examine potential underlying mechanisms, ultimately limiting development of potential therapeutic strategies. The primary purpose of this study was to develop a mouse model of persistent fatigue. A secondary purpose was to characterize potential measures of "fatigue-like" behaviors. An exploratory goal was to examine for immune and metabolic changes in the model. We examined voluntary wheel running and open field as measures of physical fatigue, and muscle and paw sensitivity as measures of pain. We also examined immune cell phenotype and plasma metabolite profiles after development of persistent fatigue. Acute stress paired with LPS or saline reduced wheel running compared to LPS alone or stress alone. Animals that received acute stress and LPS, showed a decreased ratio of T-helper to T-cytotoxic cells and reduced fatty acid metabolites 10 days after induction; there were no changes in the other groups. Thus, we characterized two unique methods, each requiring multiple stressors, to induce long-lasting fatigue-like behaviors that were associated with different mechanistic changes.
Background/Objectives: Our study aimed to identify risk factors for the development of ARDS (acute respiratory distress syndrome) in patients with sepsis resulting from peptic ulcer perforation. Methods: Between January 2018 and December 2025, patients aged 18 years and older who underwent open surgery for peptic ulcer perforation and were diagnosed with sepsis due to intra-abdominal infection related to peptic ulcer perforation during postoperative follow-up or hospitalization were included in the study. Daily ARDS screening was performed within 7 days of sepsis diagnosis. Patients were divided into groups with and without ARDS. Laboratory values were recorded within the first 24 h after sepsis diagnosis, and APACHE II score, SOFA score, NEWS, and SAPS II were calculated based on these values and the patient's clinical condition. Results: The SOFA score showed the highest discriminative ability, with an AUC of 0.710 (95% CI: 0.619-0.794) at a cutoff of 9.0, representing 54.2% sensitivity and 83.1% specificity. Albumin level showed an AUC of 0.654 (95% CI: 0.560-0.748) at a cutoff of 2.40 g/dL; its specificity was high (85.1%), but its sensitivity was relatively low (41.7%). CAR showed moderate predictive performance with an AUC of 0.627 (95% CI: 0.522-0.730) at a cutoff of 61.11, representing 60.4% sensitivity and 72.1% specificity. The combined model demonstrated the best predictive performance with an AUC of 0.727 (95% CI: 0.635-0.820), 70.8% sensitivity, and 72.7% specificity. Conclusions: SOFA score demonstrated the best overall clinical applicability for early ARDS risk stratification, while both SOFA score and APACHE II score showed independent associations with ARDS in separate multivariable models.
The adoption of pure laparoscopic donor right hepatectomy (PLDRH) has been limited by a perceived steep learning curve, traditionally estimated at 60-70 cases. This study evaluates whether "second-generation" laparoscopic surgeons can achieve proficiency more rapidly in a low-volume transplant center using structured training and standardized techniques. We analyzed 29 consecutive, non-selective PLDRH cases performed by a single surgeon. A multimodal CUSUM analysis, incorporating operative time, estimated blood loss, and the Comprehensive Complication Index, was used to define the learning curve, alongside a donor complexity score. Outcomes were compared with a cohort of 21 conventional open donor right hepatectomies. A three-phase learning progression was identified. Competency and proficiency were reached at cases 10 and 20, respectively. Phase 2 (cases 11-20) was characterized by a "second learning curve" as the team encountered more complex anatomical variations within the consecutive cohort. By Phase 3 (cases 21-29), surgical metrics stabilized with zero complications, even as case complexity increased. Compared to CODRH, the PLDRH group achieved similar safety profiles but significantly shorter hospital stays (p < 0.05). PLDRH can be safely implemented in low-volume centers with an accelerated learning curve. For surgeons with prior advanced laparoscopic expertise, institutional proficiency may be achieved within 20 cases. These findings suggest that standardized "second-generation" approaches may broaden the accessibility of laparoscopic donor surgery without compromising safety.
Perioperative neurocognitive disorder (PND) is a frequent postoperative complication in older individuals and is commonly linked to microglial activation. Endoplasmic reticulum (ER) stress has been implicated in neuroinflammation and postoperative cognitive decline; however, whether hippocampal ER stress acts upstream to bias microglia toward a pro-inflammatory M1 phenotype, rather than serving only as a trigger of cytokine cascades, remains insufficiently defined in PND. To determine whether hippocampal ER stress promotes an M1-like microglial shift and amplifies neuroinflammation after anesthesia and surgery. Eighteen-month-old male C57BL/6 mice underwent aseptic tibial fracture surgery under isoflurane anesthesia. Tauroursodeoxycholic acid(TUDCA), a pharmacological ER stress suppressor, was delivered bilaterally into dorsal hippocampal CA1 as a perioperative mechanistic probe. ER ultrastructure in hippocampal cells was examined using transmission electron microscopy (TEM). ER stress related proteins (GRP78, p-PERK, p-eIF2ɑ, p-IRE1ɑ, ATF4, and ATF6) in hippocampus were quantified by Western blotting. Microglial phenotypic signatures were assessed by Western blotting (CD86, iNOS, CD206, ARG-1) and double immunofluorescence (CD86/Iba-1 and CD206/Iba-1). Open-field testing was performed to control for locomotion/anxiety, followed by memory assessments using novel object recognition and Morris water maze starting on postoperative day 3. Anesthesia and surgery induced postoperative cognitive deficits, accompanied by heightened hippocampal inflammatory signaling and a shift toward a pro-inflammatory microglial signature characterized by increased CD86 and iNOS with concomitant reductions in CD206 and ARG-1. In parallel, hippocampal ER stress activation was evident, including ER ultrastructural disruption and increased GRP78 with engagement of PERK/eIF2ɑ/ATF4-, IRE1ɑ-, and ATF6-related pathways. hippocampus-targeted delivery of TUDCA attenuated ER stress activation, mitigated the pro-inflammatory microglial shift (decreasing CD86/iNOS and restoring CD206/ARG-1), reduced inflammatory readouts, and improved postoperative memory performance. These findings support a mechanistic link between hippocampal ER stress and the pro-inflammatory microglia bias linked to postoperative neuroinflammation and cognitive impairment in aged mice.
Propofol is widely used in pediatric anesthesia, but it has been implicated in adverse effects on brain development following repeated early-life exposure. Bag3, a co-chaperone protein involved in proteostasis and the neuronal stress response, may play a critical role in regulating synaptic function during early brain maturation. Neonatal mice were treated with propofol on postnatal days 5-7. Hippocampal neurogenesis was assessed via BrdU immunofluorescence. Synaptic proteins (PSD95, SNAP25) and Bag3 expression were measured by Western blotting. Behavioral performance in adolescence was evaluated using open-field, elevated plus-maze, Morris water maze, Y-maze, and T-maze tests. Propofol exposure significantly reduced proliferative activity (BrdU incorporation) in the dentate gyrus and decreased PSD95 and SNAP25 expression in both the cortex and hippocampus. Bag3 expression was markedly upregulated, accompanied by a mild increase in its phosphorylated form. Behaviorally, propofol-treated mice showed anxiety-like behavior and impairments in spatial learning and working memory. These findings suggest that early-life exposure to propofol impairs neurogenesis and synaptic plasticity. This process is temporally associated with the upregulation of stress-responsive co-chaperone BAG3, which precedes the of synaptic protein homeostasis. While causal relationship remains to be established, these findings identifies BAG3 as a candidate correlative marker of anesthetic-induced neurotoxicity and highlights it as a target for future mechanistic studies.
Intensive care units require rapid, high-stakes decision-making. Although artificial intelligence (AI) offers superior predictive accuracy compared with traditional scoring methods, its "black-box" nature remains a barrier to clinical adoption. This scoping review systematically mapped the translational potential and characteristics of explainable artificial intelligence (XAI) strategies in AI/ML-based clinical decision support tools for adult intensive care unit (ICU) settings. Following PRISMA-ScR guidelines, we searched Web of Science, PubMed, Scopus, and EBSCOhost up to January 2026. Translational potential was staged using an ICU-adapted, nine-level Technology Readiness Level (TRL) framework, and explainability strategies were classified as post-hoc or inherently interpretable (glass-box) to assess methodological transparency and clinical readiness. A total of 808 records were identified, of which 29 studies met the inclusion criteria. The findings revealed a marked retrospective predominance (86.2%) and reliance on North American data, predominantly MIMIC (Medical Information Mart for Intensive Care). Tree-based ensembles (82.8%) and post-hoc SHAP explanations (86.2%) were dominant, with proposed clinical utility spanning three domains: therapeutic guidance, resource-allocation optimisation, and user-centric design. Most innovations were standalone, web-based prototypes requiring manual data entry (69.0%, TRL 4-5); a further 10.3% were shared only as open-source code, and only 17.2% reported integration with hospital systems. Only one study claimed clinical maturity (TRL 9), although its validation remained retrospective. Accuracy is no longer the primary bottleneck; the constraint has shifted to "last-mile" integration and external validity. Current XAI relies almost entirely on post-hoc methods that risk an "illusion of clarity", while inherently interpretable, glass-box models remain a rare but promising alternative. Future research should prioritise external validation in independent settings, prospective evaluation of clinical impact, and explicit comparison between post-hoc and interpretable approaches.