OBJECTIVE:To evaluate the clinical efficacy and safety of single-dose preoperative systemic glucocorticoids in adults undergoing major gastrointestinal surgery. SUMMARY OF BACKGROUND DATA:Major gastrointestinal surgery induces a systemic inflammatory response that contributes to postoperative morbidity and delayed recovery. Single-dose glucocorticoids attenuate inflammation, but uncertainty remains regarding clinical benefit, safety, and optimal dosing. METHODS:A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials was performed and registered with PROSPERO. Trials comparing a single preoperative systemic glucocorticoid with placebo or no steroid in adult major gastrointestinal surgery were included. Primary outcomes were total postoperative complications and infectious complications. Secondary outcomes included length of stay, anastomotic leak, postoperative day 1 inflammatory markers, and mortality. Random-effects models were used. Dose-stratified analyses were prespecified and exploratory. RESULTS:Eighteen randomized trials, including 3667 patients were analyzed. Preoperative glucocorticoids reduced total postoperative complications (OR 0.69, 95% CI: 0.54-0.89; I²=12%) and infectious complications (OR 0.62, 95% CI: 0.45-0.88; I²=55%). Length of stay was reduced by 1.09 days (95% CI: -1.68 to -0.50). Postoperative day 1 IL-6 was lower with glucocorticoids, while CRP showed no consistent difference. Anastomotic leak and mortality were not increased. Exploratory analyses suggested greater benefit with higher-dose regimens. CONCLUSIONS:Single-dose preoperative systemic glucocorticoids reduce postoperative morbidity, infections, and length of stay after major gastrointestinal surgery, without evidence of increased surgical harm in included trial populations.
OBJECTIVE:To report the expanding application of nonvascularized rectus fascia allotransplantation (NVRF-alloTx) in solid organ transplant (SOT) and non-SOT patients and evaluate its effectiveness, integration, and immunologic response in complex abdominal and thoracic reconstruction. SUMMARY BACKGROUND DATA:Synthetic and biological meshes are limited by infection risk, long-term failure, donor-site morbidity, and high cost. NVRF-alloTx, first applied in intestinal/multivisceral-Tx with a 5.9% herniation rate, offers a simple and promising alternative for challenging defects. METHODS:This prospective single-center study included all consecutive patients undergoing NVRF-alloTx (2020-2025). Patients were divided into 2 groups: (1) reconstruction in SOT patients (simultaneous or elective closure post-SOT) and (2) reconstruction in non-SOT patients, without immunosuppression. NVRF-allografts were procured from deceased donors, preserved at 2°C, and implanted without HLA-matching. Primary endpoints were successful closure, graft failure, and functional outcome. Clinical and radiologic follow-up was performed, with HLA donor-specific antibody (HLA-DSA) testing and histology whenever available. RESULTS:Forty-seven NVRF-Tx procedures were performed in 41 patients using grafts from 48 deceased donors: group 1 (n=17) and group 2 (n=24). In 2 patients (4.9%), the graft did not integrate due to pancreatic leakage and vasopressor therapy. Others resulted in successful functional outcomes. Histology (n=5) showed graft integration through host fibrotic remodeling with neovascularization evident from 1 month after implantation. (De novo) HLA-DSA developed more frequently in non-SOT NVRF recipients than in SOT NVRF recipients. CONCLUSIONS:NVRF-alloTx is a versatile and effective reconstructive option for complex defects in SOT and non-SOT patients, providing an alternative to conventional meshes in challenging clinical scenarios.
OBJECTIVE:To evaluate procedural maturation, donor-site morbidity, and midterm durability of posterior rectus sheath flap for hiatal augmentation (PoRSHA) within an IDEAL Phase 2b framework. BACKGROUND:Large paraesophageal hernia repair remains limited by high recurrence rates associated with structural weakness of the diaphragmatic crura. Existing reinforcement strategies remain limited by inconsistent long-term durability. PoRSHA, a vascularized autologous tissue technique developed for complex hiatal repair, previously demonstrated early feasibility and promising early outcomes in IDEAL Phase 2a evaluation. METHODS:This prospective single-center IDEAL Phase 2b study included 104 consecutive patients undergoing PoRSHA between 2021 and 2026. The analytic cohort consisted of patients with primary type III/IV (n=71) and recurrent paraesophageal hernias (n=23). Radiologic recurrence (>2 cm) was assessed using Kaplan-Meier analysis to account for variable imaging follow-up. Secondary outcomes included symptomatic recurrence requiring reoperation, postoperative dysphagia, and donor-site morbidity. RESULTS:Estimated radiologic recurrence in the overall analytic cohort was 1.4% at 12 months and 13.8% at 24 months (95% CI, 5.7%-31.3%), remaining stable at 18.1% through 48 months. After exclusion of the procedural maturation phase (n=16), estimated radiologic recurrence improved to 9.2% at both 24 months and 36 months (95% CI, 2.9%-27.4%), with no additional recurrences during follow-up. Recurrences were small and did not result in reoperation. Donor-site morbidity was infrequent. CONCLUSIONS:Following procedural maturation, PoRSHA demonstrated favorable midterm durability with limited donor-site morbidity. These findings support continued multicenter evaluation of vascularized autologous tissue augmentation for complex paraesophageal hernia repair.
OBJECTIVE:To evaluate the use and impact of current surgical guidelines for chronic pancreatitis (CP) across Europe. SUMMARY BACKGROUND DATA:Current guidelines recommend morphology-based surgery for CP, but international studies evaluating their use and impact are lacking. METHODS:Post hoc analysis of the prospective multicenter ESCOPA study, including patients undergoing surgery for symptomatic CP at 22 centers in 13 countries (June 2021-November 2022), with 6-month follow-up. Patients were stratified by morphologic subtype: "isolated dilated main pancreatic duct (MPD)," "isolated enlarged pancreatic head (PH)," "combined dilated MPD and enlarged PH," and "small duct disease." Treatment was based on the European HaPanEU and International IAP-APA-JPS-EPC guidelines. Primary outcomes were 90-day major morbidity, mortality, and pain relief at 6 months. Practice variation was assessed, including a case-based survey. RESULTS:Overall, 207 patients were included following surgery for CP, with 1.4% 90-day mortality and 72.6% pain relief. The surgical approach varied widely by morphologic subtype: duodenum-preserving pancreatic head resections (DPPHR) were most common for "combined dilated MPD and enlarged PH" (46.8%, P=0.016); whereas formal pancreatectomy predominated for "isolated dilated MPD" (63.3%, P=0.040) and "small duct disease" (66.0%, P=0.004). Guideline-concordant surgery (66%) was not associated with improved rates of major morbidity (12.9% vs. 18.8%, P=0.387), mortality (1.6% vs. 1.6%, P>0.999), or pain relief (75.3% vs. 66.7%, P=0.468). Outcomes were also comparable between drainage/parenchyma-preserving surgery and formal pancreatectomy. Survey findings confirmed practice variation, including the use of formal and V-shaped pancreatectomy for small duct disease. CONCLUSION:The substantial variation in surgical practice for CP across Europe highlights the need for unified guidelines with clear recommendations, particularly regarding formal and V-shaped pancreatectomy.
Objective: To evaluate the clinical efficacy and safety of single-dose preoperative systemic glucocorticoids in adults undergoing major gastrointestinal surgery. Summary of Background Data: Major gastrointestinal surgery induces a systemic inflammatory response that contributes to postoperative morbidity and delayed recovery. Single-dose glucocorticoids attenuate inflammation, but uncertainty remains regarding clinical benefit, safety, and optimal dosing. Methods: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials was performed and registered with PROSPERO. Trials comparing a single preoperative systemic glucocorticoid with placebo or no steroid in adult major gastrointestinal surgery were included. Primary outcomes were total postoperative complications and infectious complications. Secondary outcomes included length of stay, anastomotic leak, postoperative day 1 inflammatory markers, and mortality. Random-effects models were used. Dose-stratified analyses were prespecified and exploratory. Results: Eighteen randomized trials, including 3667 patients were analyzed. Preoperative glucocorticoids reduced total postoperative complications (OR 0.69, 95% CI: 0.54–0.89; I²=12%) and infectious complications (OR 0.62, 95% CI: 0.45–0.88; I²=55%). Length of stay was reduced by 1.09 days (95% CI: −1.68 to −0.50). Postoperative day 1 IL-6 was lower with glucocorticoids, while CRP showed no consistent difference. Anastomotic leak and mortality were not increased. Exploratory analyses suggested greater benefit with higher-dose regimens. Conclusions: Single-dose preoperative systemic glucocorticoids reduce postoperative morbidity, infections, and length of stay after major gastrointestinal surgery, without evidence of increased surgical harm in included trial populations.
BACKGROUND:Understanding changes in quality of life that occur with colectomy is critical to decision-making in management of recurrent diverticulitis. We hypothesized that patients choosing colectomy at surgical consultation would report better disease-specific quality of life at 1 year than those choosing observation. OBJECTIVE:To investigate the association between colectomy versus observation for recurrent sigmoid diverticulitis and disease-specific quality of life at 1 year. METHODS:We performed a multicenter prospective observational study including patients with recurrent uncomplicated diverticulitis choosing colectomy versus observation at initial consultation. The primary outcome was disease-specific quality of life at 1 year, measured by the Diverticulitis Quality of Life questionnaire total score. RESULTS:A total of 113 patients were enrolled (median age 57; 64% female, 92% white); 42 (37%) chose colectomy at surgical consultation. At enrollment, median lifetime episodes of diverticulitis were similar between groups (colectomy: 5, observation: 4); the colectomy group had a higher rate of hospitalization in the past 5 years (colectomy: 71%, observation: 49%). In an adjusted linear mixed effects model, choosing colectomy was associated with better quality of life by 1.73 points (95% CI: 1.02-2.46) compared with choosing observation. 7 people (17%) who chose colectomy experienced recurrence within 1 year compared with 32 who chose observation (45%). In an adjusted model, choosing colectomy was associated with lower odds of recurrence (aOR 0.16; 95% CI: 0.05-0.48). CONCLUSION:For patients with recurrent sigmoid diverticulitis presenting for surgical consultation, colectomy may offer meaningful improvement in disease-specific quality of life and may be associated with reduced 1-year recurrence rates.
OBJECTIVE:To determine the impact of severity of esophageal anastomotic leak (AL), standardized by ECCG grading, on long-term survival within a contemporary multicenter cohort. SUMMARY BACKGROUND DATA:Historical evidence suggesting AL is associated with increased recurrence and poor survival is limited by heterogeneous definitions and outdated management. This study utilizes the standardized ECCG definition to evaluate the prognostic significance of AL severity under modern perioperative protocols and endoscopic rescue strategies. METHODS:An international multicenter cohort across 17 high-volume European centers. Adult patients with esophageal or junctional cancer treated with neoadjuvant CROSS or FLOT, followed by esophagectomy were included (2018-2023). RESULTS:Out of 2905 patients, 425 (14.6%) developed an AL. AL was associated with a nearly two-fold increase in pulmonary complications (46.8% vs. 26.7%; P<0.001). AL requiring surgical reintervention (type III) was associated with an increased 30- and 90-days mortality rate (7.3% vs. 2.7% and 12.3% vs. 4%, P<0.001) and a significant reduction in median overall survival versus the no leak group (33.9 vs. 69.3; months P<0.001). After multivariable adjustment, type III AL was associated with a greater likelihood of death (HR 1.51; 95% CI: 1.04-2.18; P=0.029). A lower rate of adjuvant therapy administration (33.9% vs. 43.3%; P=0.004) was observe for AL patients. No significant survival deficits were observed for leaks treated conservatively or with no-surgical intervention. CONCLUSIONS:AL requiring surgical reintervention was associated with impaired survival. This relationship identifies a high-risk clinical profile and represents a critical target for future research into strategies for clinical stabilization and risk mitigation.
OBJECTIVE:To report real-world data on hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP) in liver transplantation (LT). SUMMARY BACKGROUND DATA:Real-world comparisons between HOPE and NMP are limited and methodologically challenging due to heterogeneity in donor and recipient risk profiles and regional differences in practice patterns. METHODS:This international cohort study analyzed consecutive NMP-preserved LTs performed at 15 predominantly North American centers between 2021 and 2025. Outcomes were compared with the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Risk-adjusted analyses were performed, stratified by graft type and risk category. Imbalances in baseline characteristics were addressed using entropy balancing. RESULTS:A total of 954 NMP-treated and 1202 HOPE-treated grafts were analyzed, revealing substantial differences in donor risk. Extended-criteria DBD grafts accounted for 30% versus 64%, and futile DCD grafts for 10% versus 30%, in the NMP and HOPE cohorts, respectively. In the NMP cohort, death-censored graft survival at 1, 2, and 3 years exceeded 96% for DBD grafts and 94% for DCD grafts. Comparable outcomes were observed in the HOPE cohort, with 93% survival in DBD and 87% in DCD grafts at up to 3 years, despite significantly higher donor risk in the HOPE-DCD cohort. After risk adjustment, death-censored graft survival remained similar between both modalities across graft types and risk categories. CONCLUSIONS:Real-world data on HOPE-treated and NMP-treated LT demonstrate excellent outcomes. Nevertheless, compared with HOPE, further high-quality evidence and longer preservation time is needed to substantiate the clinical benefits of NMP in high-risk grafts.
Objective: RESTORE II compared in an RCT the impact of a 12-week multidisciplinary rehabilitation program versus standard care (SC) on cardiorespiratory fitness and physical function in patients postupper gastrointestinal (UGI) oncologic surgery. Summary of Background Data: The value of multidisciplinary cancer rehabilitation in UGI cancer survivorship is unclear, with limited high-quality data. Methods: Disease-free patients, ≥3 months post-UGI cancer resection were randomized to SC or RESTORE (physiotherapy-led aerobic and resistance exercise, dietary counselling, and psychosocial support). The primary endpoint was cardiorespiratory fitness (VO 2 peak). Secondary endpoints included body composition (anthropometry and bioimpedance analysis), muscle strength (hand grip strength and leg-press 1-repetition maximum), functional performance (Short Physical Performance Battery), physical activity (accelerometery), and health-related quality of life (EORTC-QLQ-C30). Assessments were conducted at baseline (T0), postintervention (T1), and 3-month follow-up (T2). Results: Eighty-eight participants were randomized to SC (n=44) or RESTORE (n=44). Median age was 67.5 (range: 43–86) years, n=60 (68.2%) male, and median time postsurgery was 33 (range: 3.5–145) months. VO₂peak remained stable in the SC group. Estimated interaction effects for time × group indicate that the mean increases in VO₂peak were greater for RESTORE relative to SC from baseline to T1, by a mean of 1.5 mL/min/kg (95% CI: 0.52–2.48; P -value=0.003), and from baseline to T2 by a mean of 1.23 mL/min/kg (95% CI: 0.18–2.27; P -value=0.02). Secondary endpoints remained stable across treatment arms with no significant differences observed. Conclusion: RESTORE II provides Level I evidence that cardiorespiratory fitness can be targeted and improved in survivors of UGI cancer surgery.
Objective: To report real-world data on hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP) in liver transplantation (LT). Summary Background Data: Real-world comparisons between HOPE and NMP are limited and methodologically challenging due to heterogeneity in donor and recipient risk profiles and regional differences in practice patterns. Methods: This international cohort study analyzed consecutive NMP-preserved LTs performed at 15 predominantly North American centers between 2021 and 2025. Outcomes were compared with the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Risk-adjusted analyses were performed, stratified by graft type and risk category. Imbalances in baseline characteristics were addressed using entropy balancing. Results: A total of 954 NMP-treated and 1202 HOPE-treated grafts were analyzed, revealing substantial differences in donor risk. Extended-criteria DBD grafts accounted for 30% versus 64%, and futile DCD grafts for 10% versus 30%, in the NMP and HOPE cohorts, respectively. In the NMP cohort, death-censored graft survival at 1, 2, and 3 years exceeded 96% for DBD grafts and 94% for DCD grafts. Comparable outcomes were observed in the HOPE cohort, with 93% survival in DBD and 87% in DCD grafts at up to 3 years, despite significantly higher donor risk in the HOPE-DCD cohort. After risk adjustment, death-censored graft survival remained similar between both modalities across graft types and risk categories. Conclusions: Real-world data on HOPE-treated and NMP-treated LT demonstrate excellent outcomes. Nevertheless, compared with HOPE, further high-quality evidence and longer preservation time is needed to substantiate the clinical benefits of NMP in high-risk grafts.
Objective: To investigate the potential of integrating muscle and fat compartments into a novel and unified score for outcome prediction in a bicentric European cohort of LT recipients. Background: Body composition (BC) reflects nutritional status and metabolic reserves and influences outcomes after orthotopic liver transplantation (LT). Validated tools for predicting long-term survival after LT remain scarce. Increasing evidence highlights sex-specific disparities in post-transplant outcomes. Study Design: A total of 695 adult patients undergoing LT at Charité–Berlin (n=412, 2010 to 2020; discovery cohort) and University Hospital Aachen (n=283, 2010 to 2018; validation cohort) were included. CT-based BC was assessed at lumbar level 3/4. Muscle mass, quality, and adipose tissue were integrated into the integrative muscle-adipose score (IMAS) and correlated with survival and postoperative morbidity. Results: Median follow-up was 54 (discovery) and 47 months (validation). A total of 31% of recipients were female. IMAS quartiles significantly stratified overall survival in both cohorts ( P <0.01). Low IMAS was independently prognostic of overall survival in both cohorts. Sex-specific IMAS cutoffs were independently prognostic in both sexes (♂︎: HR=1.89, 95% CI: 1.37-2.70, P =0.001; ♀︎: HR=2.04, 95% CI: 1.17-3.55, P =0.012), whereas the BAR score failed to predict long-term survival in female recipients. Across sexes, low IMAS was associated with significantly lower restricted mean survival time at 5 years (♂︎ 43.2 vs. 50.16 mo, P <0.001; ♀︎ 44.2 vs. 51.71 mo, P =0.013) and a higher Comprehensive Complication Index 90 days after LT. Conclusion: The IMAS provides a novel, reproducible sex-sensitive framework for long-term outcome prediction after LT.
Objectives: This national, multicenter retrospective study of 764 adult liver transplantations (LT) in Sweden (2019–2023) employed a data-driven approach to identify the out-of-hours (OOH) high-risk window and evaluate its impact on patient outcomes and health care costs. Summary Background Data: LT logistics often necessitate OOH surgery, but the evidence for an impact on outcomes remains conflicting, partly due to arbitrary window definitions. Methods Using the mathematical principle of permutations and linear regression analysis of 1-hour start-time intervals across 552 temporal windows, we identified the period with the greatest impact on the primary endpoint: the 3-month Comprehensive Complication Index (CCI). Secondary outcomes included intensive care unit length of stay, Clavien-Dindo complications, reoperations, patient and graft survival, and health care costs. Results: The 17:00 to 05:59 window was identified as having the greatest negative impact on CCI. After adjusting for covariates, procedures initiated during this timeframe were associated with significantly higher CCI (β=7.41, 95% CI: 4.27–10.56, P <0.01), increased Clavien-Dindo IIIb and IV complications, 1.16 days longer intensive care unit stay and a higher risk of LT-related reoperations (odds ratio: 1.61, 95% CI: 1.11–2.36). One-year graft and patient survival were comparable between groups. Health care costs were 169.629 SEK (€15,500) higher per patient operated OOH, during the 3-month follow-up. Conclusion: This data-driven analysis identified a high-risk OOH window beginning earlier than previously reported (17:00 vs. traditional nighttime definitions). LT starting in this interval is associated with significantly increased morbidity and health care costs. Further studies are needed to evaluate mitigating strategies to enable daytime transplantation.
OBJECTIVE:To compare the safety and effectiveness of the Colovac Anastomosis Protection Device with standard diverting ostomy (DO) following low anterior resection (LAR) for rectal cancer. SUMMARY BACKGROUND DATA:DO is standard of care (SOC) following LAR for rectal cancer but is associated with substantial morbidity. Colovac Device is designed to divert the fecal stream away from the anastomosis intraluminally. METHODS:Three prospective multicenter Colovac trials were pooled and compared with a prospective cohort of patients undergoing LAR with DO for rectal cancer using a propensity score-weighted approach to balance baseline characteristics. The primary safety endpoint for both Colovac and SOC trials was the rate of device-related or stoma-related early major complications by POD10. Secondary endpoints included early anastomotic leak (AL) rates, fecal stream diversion effectiveness, and device migration. RESULTS:Patients were included (Colovac=49, DO=54). By POD10, device- or stoma-related major complications rates were 4.1% (2/49) vs 5.6% (3/54) (P=0.167). All Colovac devices were successfully placed and retrieved with stoma avoidance achieved in 83.7% at POD10. Major complication rates were similar between groups. Rates of AL detected on POD9/10 were comparable between Colovac and control patients (28.6% vs. 20.4%, P=0.102), with total AL rate of 32.6% in Colovac versus 27.8% (P=0.342) in control at POD30. Effective fecal diversion was achieved in 91.7% of Colovac patients, with device migration in 14.3%. CONCLUSIONS:Colovac enabled ostomy avoidance in most patients without increasing major complications or AL, suggesting its role as a potential alternative to DO following LAR for rectal cancer. TRIAL REGISTRATION:SAFE-2019: NCT05180565; SAFE-2: NCT05010850; SAFE-2023: NCT06540807; SH-SOC23: NCT06152276.
OBJECTIVE:RESTORE II compared in an RCT the impact of a 12-week multidisciplinary rehabilitation program versus standard care (SC) on cardiorespiratory fitness and physical function in patients postupper gastrointestinal (UGI) oncologic surgery. SUMMARY OF BACKGROUND DATA:The value of multidisciplinary cancer rehabilitation in UGI cancer survivorship is unclear, with limited high-quality data. METHODS:Disease-free patients, ≥3 months post-UGI cancer resection were randomized to SC or RESTORE (physiotherapy-led aerobic and resistance exercise, dietary counselling, and psychosocial support). The primary endpoint was cardiorespiratory fitness (VO2peak). Secondary endpoints included body composition (anthropometry and bioimpedance analysis), muscle strength (hand grip strength and leg-press 1-repetition maximum), functional performance (Short Physical Performance Battery), physical activity (accelerometery), and health-related quality of life (EORTC-QLQ-C30). Assessments were conducted at baseline (T0), postintervention (T1), and 3-month follow-up (T2). RESULTS:Eighty-eight participants were randomized to SC (n=44) or RESTORE (n=44). Median age was 67.5 (range: 43-86) years, n=60 (68.2%) male, and median time postsurgery was 33 (range: 3.5-145) months. VO₂peak remained stable in the SC group. Estimated interaction effects for time×group indicate that the mean increases in VO₂peak were greater for RESTORE relative to SC from baseline to T1, by a mean of 1.5 mL/min/kg (95% CI: 0.52-2.48; P-value=0.003), and from baseline to T2 by a mean of 1.23 mL/min/kg (95% CI: 0.18-2.27; P-value=0.02). Secondary endpoints remained stable across treatment arms with no significant differences observed. CONCLUSION:RESTORE II provides Level I evidence that cardiorespiratory fitness can be targeted and improved in survivors of UGI cancer surgery.
BACKGROUND AND AIMS:Peritoneal metastases (PMs) represent the most frequent, clinically challenging dissemination pattern in advanced gastric cancer, especially poorly cohesive (PCGC) subtype, and are associated with poor prognosis. We aimed to characterize the transcriptomic landscape of primary gastric tumors (PGTs) and matched PMs to identify differential molecular programs, tumor-microenvironment (TME) features, and potential biomarkers. METHODS:We analyzed 55 FFPE samples from 23 treatment-naïve patients with synchronous peritoneal-only stage IV PCGC and 10 non-neoplastic gastric controls (NNC). RNA sequencing was analyzed using DESeq2 and GSEA, with cell proportions estimated through immune deconvolution (TIMER/xCell). RESULTS:A total of 4279 differentially expressed genes were identified across all groups. CLDN18 expression progressively decreased from NNCs to PGTs and PMs. Direct PGT-PM comparison revealed that PGTs were characterized by cytoskeletal and extracellular-matrix remodeling genes upregulation, mitotic/cell-cycle, NOTCH and apical-junction pathways enrichment, and memory T-cell predominance. Compared with PGTs, PMs showed increased IGF1, IGFN1, NTRK2 and adipogenesis-related transcripts, adipogenesis and MAPK7/11-NTRK2 signaling enrichment, and macrophage-dominant and dendritic-cell-dominant microenvironments. epithelial-mesenchymal transition (EMT), inflammatory pathways, and cancer-associated fibroblasts were shared by both tumor lesions. PMs did not match established TCGA or PCGC subtypes, suggesting a distinct molecular identity. CONCLUSIONS:PMs are characterized by TME remodeling and transcriptional reprogramming. Shared EMT and inflammatory pathways act as bridge linking PGT to PM, consistent with adaptive exploitation of physiological peritoneal programs. Collectively, our findings suggest a transcriptomic framework in which PM can be characterized as a distinct niche-conditioned biological entity and support microenvironment-informed diagnostic and therapeutic strategies.
OBJECTIVE:To investigate the potential of integrating muscle and fat compartments into a novel and unified score for outcome prediction in a bicentric European cohort of LT recipients. BACKGROUND:Body composition (BC) reflects nutritional status and metabolic reserves and influences outcomes after orthotopic liver transplantation (LT). Validated tools for predicting long-term survival after LT remain scarce. Increasing evidence highlights sex-specific disparities in post-transplant outcomes. STUDY DESIGN:A total of 695 adult patients undergoing LT at Charité-Berlin (n=412, 2010 to 2020; discovery cohort) and University Hospital Aachen (n=283, 2010 to 2018; validation cohort) were included. CT-based BC was assessed at lumbar level 3/4. Muscle mass, quality, and adipose tissue were integrated into the integrative muscle-adipose score (IMAS) and correlated with survival and postoperative morbidity. RESULTS:Median follow-up was 54 (discovery) and 47 months (validation). A total of 31% of recipients were female. IMAS quartiles significantly stratified overall survival in both cohorts (P<0.01). Low IMAS was independently prognostic of overall survival in both cohorts. Sex-specific IMAS cutoffs were independently prognostic in both sexes (♂︎: HR=1.89, 95% CI: 1.37-2.70, P=0.001; ♀︎: HR=2.04, 95% CI: 1.17-3.55, P=0.012), whereas the BAR score failed to predict long-term survival in female recipients. Across sexes, low IMAS was associated with significantly lower restricted mean survival time at 5 years (♂︎ 43.2 vs. 50.16 mo, P<0.001; ♀︎ 44.2 vs. 51.71 mo, P=0.013) and a higher Comprehensive Complication Index 90 days after LT. CONCLUSION:The IMAS provides a novel, reproducible sex-sensitive framework for long-term outcome prediction after LT.
OBJECTIVE:This study hypothesizes that negative pressure therapy (NPT) reduces wound-healing complications following major amputation. BACKGROUND:Major lower extremity amputation carries a high incidence of incisional complications. NPT reduces these complications in other areas of the body, suggesting a benefit following amputation. METHODS:Patients undergoing above- or below-knee amputation (AKA, BKA) were randomized in this multi-institution study into receiving NPT versus standard dressing. The primary endpoint was any wound complication within 30 days of surgery; secondary endpoints included reoperation, readmission, and length of stay. Post hoc analyses were performed in patients considered high risk for wound complications. RESULTS:The overall 30-day mortality rate was 3.4%. The wound complication rate for the NPT group was 19.4% (n=134) compared with 24% for controls (n=129; RR=0.80; 95% CI: 0.51, 1.26; P=0.339). No significant difference was observed for reoperation (3.7% vs. 8.5%, RR=0.83), readmission (9% vs. 11.6%, RR=0.77), or length of stay (10 vs. 9.3 d, RR=1.1). Post hoc analyses suggested a reduction in complications using NPT in people without diabetes (9.8% vs. 27.6%, RR=0.36), those with end-stage renal disease (ESRD; 23.1% vs. 37.5%, RR=0.66), patients with obesity (18.2% vs. 26.7%, RR=0.65), and those presenting without tissue loss (3.6% vs. 35.5%, RR=0.10). CONCLUSIONS:Wound complications remain a significant problem following major lower extremity amputation, leading to reoperation, readmission, and increased length of stay. NPT does not significantly reduce the overall wound complication rate. Future studies should focus on high-risk subgroups that may benefit from this therapy.
