Clinical studies demonstrated a correlation between sleep dysfunction and intestinal diseases. However, the detailed interactions and underlying mechanisms linking sleep disruption to intestinal microenvironment remain poorly understood. We employed the Curling Prevention by Water (CPW) paradigm to establish a mouse model of sleep deprivation (SD) for durations ranging from 0 to 96 h. The dynamic changes in the intestinal microenvironment were systematically profiled using multi-omics approaches, including metagenomic sequencing, untargeted metabolomics and RNA sequencing. The causal role of microbial dysbiosis and the underlying mechanisms were further investigated using germ-free mice, fecal microbiota transplantation (FMT), flow cytometry, and targeted intervention. The intestinal microenvironment was highly sensitive to SD. Distinct microbial communities and metabolite profiles were observed among brief SD (< 24 h of SD), prolonged SD (24–96 h of SD) and control. Brief SD triggered a self-regulatory response of the gut microbiota, characterized by an increase in certain beneficial bacteria (e.g., Parabacteroides goldsteinii). In contrast, prolonged SD shaped a pro-inflammatory microbial structure, characterized by reduced Akkermansia muciniphila and enriched Pseudomonadota. Multi-omics analysis revealed that SD significantly inhibited microbial bile acid metabolism, particularly taurodeoxycholic acid (TDCA), and impaired intestinal barrier function while suppressing the intestinal immune response to bacteria antigens. Mechanistically, SD exacerbated intestinal barrier damage by inhibiting the TDCA/group 3 innate lymphoid cells (ILC3)/IL-22 axis. Supplementation with TDCA effectively restored ILC3 function, IL-22 production, and barrier integrity in SD mice. Furthermore, FMT from patients with sleep dysfunction significantly disturbed intestinal microenvironment and increased serum cortisol by regulating gut microbiota and inhibiting TDCA/ILC3/IL-22 axis. This study dynamically delineates how SD disrupts intestinal homeostasis by reshaping the gut microbiota and suppressing the TDCA/ILC3/IL-22 axis. These findings provide novel mechanistic insights and identify potential therapeutic targets for sleep dysfunction-associated intestinal complications.
BACKGROUND Perineal small bowel fistula (PSF) is a highly debilitating complication of radical pelvic malignancy resections. It is typically driven by empty pelvis syndrome (EPS) and chronic adhesive disease. Current therapeutic guidelines lack standardization. AIM To evaluate an etiology-driven surgical algorithm, where procedures are chosen based on the underlying mechanism, aiming to improve closure rates. METHODS Retrospective cohort analysis was performed on 28 consecutive patients who underwent definitive repair for complex PSF. Patients were stratified into two surgical groups based on etiology: Group 1 (n = 15) underwent modified pelvic floor reconstruction for structural defects or EPS; group 2 (n = 13) underwent internal intestinal plication for extensive adhesions or tumor recurrence. Overall survival was calculated from the date of definitive surgery to the last follow-up or death. RESULTS The study cohort (mean age 56.6 years) included patients with rectal (35.7%), gynecological (35.7%), and various other pelvic malignancies. There were no significant baseline demographic differences between the groups. A significant correlation was observed between fistula etiology and surgical strategy (P = 0.02). While reconstruction was the exclusive surgical approach for patients with EPS (100%), plication was predominantly utilized for cases of tumor recurrence (66.7%). The overall fistula closure rate was 89.3% (25/28), showing no significant difference between group 1 (86.7%) and group 2 (92.3%; P = 1.0). However, group 2 experienced a significantly longer mean time to postoperative flatus (6.8 days vs 4.2 days; P = 0.002). The median follow-up time for the entire cohort was 34.5 months (range: 9.0-107.0 months). Overall survival was comparable across the two surgical groups (32.0 months vs 37.0 months; P = 0.66). CONCLUSION Managing complex PSFs requires a tailored approach. Employing an etiology-driven strategy, specifically pelvic floor reconstruction for structural voids (EPS) and internal intestinal plication for “frozen” adhesive conditions, achieves > 89% closure rates with acceptable morbidity.
The Tianhe Procedure is a functional sphincter-preserving surgical approach developed for patients with rectal cancer following radiotherapy. This technique involves proximal extended resection of the colon beyond the pelvic cavity, followed by anastomosis of the non-irradiated proximal colon to the distal rectum or anal canal. This strategy aims to reduce the incidence of anastomotic complications and postoperative bowel dysfunction. However, there is currently a lack of standardized practice guidelines for implementing the Tianhe Procedure in China. Therefore, the Chinese Radiation Intestinal Injury Research Group, the Colorectal Surgery Group of Surgery Branch of the Chinese Medical Association, the Anorectal Branch of Chinese Medical Doctor Association, the Colorectal Cancer Committee of the Chinese Medical Doctor Association, the Colorectal Cancer Committee of China Anti-cancer Association, and the Gastrointestinal Surgical Branch of Guangdong Medical Doctor Association have jointly convened a panel of national experts to discuss and establish this standardized surgical procedure. This standard, based on the latest evidence from literature, research advancements, and expert experience, focuses on key aspects of the Tianhe Procedure, including its precise definition, indications, critical procedural steps, postoperative complications, and functional rehabilitation strategies. It aims to promote standardized implementation and broader clinical adoption of this innovative surgical technique.
Objective:The aim of this study was to construct a preoperative ultrasound prediction model, and compare its diagnostic performance with the existing sliding sign to predict the severity of abdominal adhesions in order to reduce the occurrence of intraoperative complications and shorten the duration of surgery. Methods:Between June 2020 and June 2022, 100 patients with a history of abdominal surgery were included in this retrospective study. All participants underwent ultrasound examination of five sites on the anterior abdominal wall before surgery. Eighteen sites were excluded because of surgical stomas, etc. Finally, 482 sites were examined by ultrasound, of which 138 (28.6%) were severe adhesions. Based on the intraoperative findings, the patients were divided into two groups: patients with severe adhesions and patients with non-severe adhesions. Finally, the data of 482 abdominal sites examined were randomly divided into a training cohort (70%) and a validation cohort (30%). The least absolute shrinkage and selection operator (LASSO) regression and multivariate binary logistic regression were used to determine the independent influencing factors, thereby constructing a clinical ultrasound prediction model for severe abdominal adhesions. The sensitivity, specificity, positive and negative predictive value (PPV and NPV) and accuracy of the model were calculated. Prediction models were established, and the area under the receiver operating curve (AUC) between models and compared with sliding sign (MA) using the DeLong test to determine the optimal model. At the same time, intraclass correlation coefficient (ICC) was used to evaluate the inter-observer agreement. Results:The LASSO regression showed that wall syndrome, traction sign, deformation of abdominal organs, two-layer peritoneal bright lines, sliding sign (head-foot direction mobility), and examination site were associated with severe adhesions. Multivariate analysis showed that traction sign, two-layer peritoneal bright lines, head-foot direction mobility and examination site (all P < 0.05) were the independent predictors of severe abdominal adhesion. Based on these predictors, the improved prediction model (referred as MB) was established. It showed that the diagnostic performance of MB was better than MA [AUCMB = 0.943 (95% CI: 0.920-0.967) vs AUCMA = 0.827 (95% CI: 0.920-0.967), P < 0.001] in the training cohort. The results were validated [AUCMB = 0.873 (95% CI: 0.818-0.928) vs AUCMA = 0.803 (95% CI: 0.755-0.851), P = 0.005] in the validation cohort. In the training cohort, the MB improved the specificity (22.5%), PPV (22.6%) and the accuracy (13.6%). In the validation cohort, the MB improved the specificity (19.2%), PPV (10.8%) and the accuracy (6.9%). At the same time, the ICC showed that the ultrasonic parameters had high consistency. Conclusions:In the presence of complex adhesions in the abdominal cavity, the new diagnostic model (MB) significantly improved the diagnostic performance compared with the conventional model (MA). The MB improved the AUC, specificity, PPV, and accuracy. Therefore, this model has the potential to reduce severe intraoperative complications.
BACKGROUND:The impact of preoperative tumor necrosis factor alpha inhibitors on surgical outcomes in Crohn's disease remains controversial, whereas postoperative tumor necrosis factor alpha inhibitors are known to prevent endoscopic recurrence. OBJECTIVE:To evaluate whether preoperative tumor necrosis factor alpha inhibitors reduce the need for staged surgery without increasing complications, and whether postoperative tumor necrosis factor alpha inhibitors decrease endoscopic postoperative recurrence. DESIGN:Retrospective observational cohort study. SETTING:Inflammatory Bowel Disease Surgery Centre, Shanghai Tenth People's Hospital, China. PATIENTS:A total of 202 patients with Crohn's disease undergoing bowel resection (June 2019-June 2024). Follow-up included 143 patients at 6 months and 116 at 1 year. INTERVENTIONS:Preoperative tumor necrosis factor alpha inhibitors (within 12 weeks before surgery) or postoperative tumor necrosis factor alpha inhibitors (initiated more than 2 weeks after surgery) compared with no use of tumor necrosis factor alpha inhibitors. MAIN OUTCOME MEASURES:Staged surgery rate, complications, hospital stay, and endoscopic postoperative recurrence (Rutgeerts score greater than or equal to i2) at 6 months and 1 year. RESULTS:Patients who received reoperative tumor necrosis factor alpha inhibitors had significantly reduced staged surgery compared with inhibitor-naive patients (39.7% vs 60.5%; OR 0.43, p = 0.01). No differences were found in hospital stay, 1-month complications (13.7% vs 14%), or 1-year reoperation rates (9.5% vs 4.1%). Postoperative tumor necrosis factor alpha inhibitors significantly reduced endoscopic recurrence at 6 months (18.7% vs 35.3%; OR 0.42, p = 0.03) and 1 year (22.4% vs 39.7%; OR 0.44, p = 0.05). One-year reoperation complication rates were similar (3.5% vs 8.6%, p = 0.44). LIMITATIONS:Retrospective design; selection bias; single-center study. CONCLUSIONS:Preoperative use of tumor necrosis factor alpha inhibitors reduces the need for staged surgery without increasing complications. Postoperative tumor necrosis factor alpha inhibitors effectively reduce endoscopic recurrence at 6 months and 1 year. Perioperative use appears safe and beneficial for patients with Crohn's disease who require surgery. See Video Abstract . LOS INHIBIDORES DEL FACTOR DE NECROSIS TUMORAL ALFA REDUCEN LA TASA DE CIRUGA POR ETAPAS Y PREVIENEN LA RECURRENCIA ENDOSCPICA POSOPERATORIA EN PACIENTES CON ENFERMEDAD DE CROHN:ANTECEDENTES:El impacto de los inhibidores del factor de necrosis tumoral preoperatorios en los resultados quirúrgicos de la enfermedad de Crohn sigue siendo controvertido, mientras que se sabe que los inhibidores del factor de necrosis tumoral postoperatorios previenen la recurrencia endoscópica.OBJETIVO:Evaluar si los inhibidores del factor de necrosis tumoral preoperatorios reducen la necesidad de cirugía por etapas sin aumentar las complicaciones, y si los inhibidores del factor de necrosis tumoral postoperatorios disminuyen la recurrencia endoscópica postoperatoria.DISEÑO:Estudio de cohorte observacional retrospectivo.ESCENARIO:Centro de Cirugía de la Enfermedad Inflamatoria Intestinal, Décimo Hospital Popular de Shanghái, China.PACIENTES:Un total de 202 pacientes con enfermedad de Crohn sometidos a resección intestinal (junio de 2019 - junio de 2024). El seguimiento incluyó a 143 pacientes a los 6 meses y a 116 al año. INTERVENCIONES: Inhibidores del factor de necrosis tumoral preoperatorios (en las 12 semanas previas a la cirugía) o inhibidores del factor de necrosis tumoral postoperatorios (iniciados más de 2 semanas después de la cirugía) versus pacientes sin tratamiento previo con inhibidores del factor de necrosis tumoral.PRINCIPALES MEDIDAS DE RESULTADOS:Tasa de cirugía por etapas, complicaciones, estancia hospitalaria y recurrencia postoperatoria endoscópica (puntuación de Rutgeerts ≥ i2) a los 6 meses y al año.RESULTADOS:Los inhibidores del factor de necrosis tumoral preoperatorios redujeron significativamente la cirugía por etapas en comparación con los pacientes sin tratamiento previo (39,7 % frente a 60,5 %; odds ratio: 0,43; p = 0,01). No se encontraron diferencias en la estancia hospitalaria, las complicaciones al mes (13,7 % frente a 14 %) ni en las tasas de reintervención al año (9,5 % frente a 4,1 %). Los inhibidores del factor de necrosis tumoral (INF) postoperatorios redujeron significativamente la recurrencia endoscópica a los 6 meses (18,7 % frente a 35,3 %; odds ratio: 0,42; p = 0,03) y al año (22,4 % frente a 39.7 %; odds ratio: 0,44; p = 0,05). Las tasas de complicaciones de la reintervención al año fueron similares (3,5 % frente a 8,6 %, p = 0,44).LIMITACIONES:Diseño retrospectivo; sesgo de selección; estudio unicéntrico.CONCLUSIONES:Los inhibidores del factor de necrosis tumoral (INF) preoperatorios reducen la necesidad de cirugía por etapas sin aumentar las complicaciones. Los INF postoperatorios reducen eficazmente la recurrencia endoscópica a los 6 meses y al año. Su uso perioperatorio parece seguro y beneficioso para los pacientes con enfermedad de Crohn que requieren cirugía. ( AI-generated translation ).
Crohn’s disease (CD) is a chronic non-specific inflammatory bowel disease with an increasing incidence worldwide. Patients with CD are facing elevated risk for mental disorders (MD) than healthy people, and chronic psychological stress is considered to trigger deterioration and relapse of CD. The microbiome-gut-brain axis (MGBA) is recognized as a crucial factor in unraveling this connection. Whereas, so far, few studies have revealed the relationship of the microbiota communities and tryptophan catabolites of the terminal ileum mucosa on gut-brain communication. A total of 52 patients with CD, along with 11 patients with colorectal cancers recruited as controls, were enrolled in this study. The participants completed Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 Questionnaire. The terminal ileal mucosa was collected during surgery. We profiled the microbiota composition of 37 patients and quantified the tryptophan catabolites of 28 patients utilizing 16 S rRNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively. In addition, bioinformatics methods were used to elucidate the interrelationships between psychological states, microbial communities, and tryptophan catabolites. CD patients with MD showed a significant reduction in microbial diversity within the ileal mucosa. Regarding microbial composition, Prevotella was relatively enriched in CD patients with MD, along with lower relative abundances of Akkermansia and Faecalibacterium. Furthermore, significant disparities in the levels of Picolinic acid (PA), Kynurenic acid (KYNA), Nicotinic acid (N-Acid), and Indole-3-carbaldehyde (ICAld) were detected within the ileal mucosa of CD patients comorbid with MD. A pronounced correlation was observed between PA levels and anxiety scale scores. The heightened abundance of Prevotella may be closely associated with altered levels of PA, N-Acid, and KYNA. Alterations in the microbial composition of the terminal ileum may interact with changes in tryptophan metabolism and are associated with MD in patients with CD undergoing surgery.
Crohn’s disease (CD) often necessitates surgical intervention, with temporary stoma creation after intestinal resection (IR) being a crucial decision. This study aimed to construct novel models based on machine learning (ML) to predict temporary stoma formation after IR for CD. Patient data who underwent IR for CD at our center between July 2017 and March 2023 were collected for inclusion in this retrospective study. Eligible CD patients were randomly divided into training and validation cohorts. Feature selection was executed using the least absolute shrinkage and selection operator. We employed three ML algorithms including traditional logistic regression, novel random forest and XG-Boost to create prediction models. The area under the curve (AUC), accuracy, sensitivity, specificity, precision, recall, and F1 score were used to evaluate these models. SHapley Additive exPlanation (SHAP) approach was used to assess feature importance. A total of 252 patients with CD were included in the study, 150 of whom underwent temporary stoma creation after IR. Eight independent predictors emerged as the most valuable features. An AUC between 0.886 and 0.998 was noted among the three ML algorithms. The random forest (RF) algorithms demonstrated the most optimal performance (0.998 in the training cohort and 0.780 in the validation cohort). By employing the SHAP method, we identified the variables that contributed to the model and their correlation with temporary stoma formation after IR for CD. The proposed RF model showed a good predictive ability for identifying patients at high risk for temporary stoma formation after IR for CD, which can assist in surgical decision-making in CD management, provide personalized guidance for temporary stoma formation, and improve patient outcomes.
Background:Massive postoperative gastrointestinal bleeding is a severe postoperative complication of Crohn's disease (CD) with a high mortality rate, and deteriorating patients' recovery. However, there are few related studies, and it lacks effective prevention measures. Therefore, we conducted a multicenter study to explore the risk factors for massive postoperative gastrointestinal bleeding in CD patients. Methods:This study was a multicenter retrospective case-control study. Patients who were diagnosed with CD and underwent gastrointestinal (GI) surgery were enrolled. The control group was matched 1:4 for gender and age. By comparing perioperative medical information between two groups, risk factors were identified through logistic regression analysis. A nomogram was constructed and internal validation was performed by bootstrap resampling. Results:A total of 170 patients were included. Multivariable logistic regression revealed the independent predictors of massive postoperative gastrointestinal bleeding involving the number of previous abdominal surgeries (OR = 2.56, 95% CI = 1.54-4.24), GI bleeding history (OR = 6.17, 95% CI = 1.59-23.97), serum albumin (ALB) (OR = 0.88, 95% CI = 0.81-0.96), and Nutrition Risk Screening 2002 (OR = 1.57, 95% CI = 1.08-2.29). The nomogram achieved an area under the curve (AUC) value of 0.85 (95% CI: 0.76-0.93). In internal validation, the AUC value was 0.976 (95% CI: 0.955-0.997). Calibration curves showed good alignment. DCA demonstrated that the diagnostic model had good clinical efficiency. Conclusion:The risk of massive postoperative gastrointestinal bleeding in CD patients will be increased with a GI bleeding history, more previous abdominal surgeries, higher nutrition risk, and lower ALB level. Our nomogram model is effective and could be a useful tool for prediction.
Crohn's disease (CD), a type of inflammatory bowel disease (IBD), is a chronic disorder involving any part of the gastrointestinal tract. Ileocecal resection may serve as a more effective treatment option for early CD. However, the potential relationship and mechanisms between the ileocecum and remission induction of CD are still elusive. In this study, we conducted 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) on 68 terminal ileal mucosa and mesentery samples from 34 patients with CD. The results showed an improvement in the microbial health of the ileal mucosa and mesentery in patients with CD after ileocecal resection. In addition, specific spatial alterations in microbiota and metabolites were observed before and after surgery. Furthermore, differentially expressed metabolites in the ileal mucosa and mesentery were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The findings of this study support the therapeutic value of ileocecal resection in CD from a multi-omics perspective and may guide the clinical translation of microbiome-based strategies for precise treatment of CD.
[Objectives] To investigate the clinical effectiveness of laparoscopic surgical techniques in the treatment of patients with radiation-induced intestinal fistula. [Methods] The clinical data of 14 patients with radiation-induced intestinal fistula who underwent laparoscopic surgical techniques at the Center for Difficult and Complicated Abdominal Surgery, Tenth People’s Hospital of Tongji University from January 2020 to December 2024 were retrospectively analyzed. The basic information about the patients, surgical-related conditions, and postoperative follow-up conditions (follow-up through telephone or outpatient visits) were recorded. [Results] Among the 14 patients, the primary tumor diagnoses included 8 cases of cervical cancer, 2 cases of prostate cancer, and 4 cases of rectal cancer; the intestinal fistula diagnoses included 7 cases of recto-vaginal fistula, 2 cases of vesico-rectal fistula, 1 case of vesico-sigmoid fistula, 1 case of recto-vaginal fistula combined with vesico-rectal fistula, 1 case of rectal fistula, 1 case of small intestine-vaginal fistula, and 1 case of small intestine-presacral fistula; the number of previous surgeries ranged from 2 to 4. In this radiation-induced intestinal fistula surgery: all patients underwent laparoscopic exploration, among whom 6 patients underwent totally laparoscopic surgery, and 8 patients were converted to open surgery after laparoscopic exploration and partial adhesion lysis to complete other surgical procedures; the operative time ranged from 2 to 7 hours; the hospital stay ranged from 5 to 34 days. One patient underwent emergency surgery due to severe intra-abdominal infection and died of disseminated intravascular coagulation on the 10th day after surgery; one patient had an anastomotic leakage 1 month after surgery, underwent ileostomy, and had the ileostomy reversed 6 months later; the remaining 12 patients had good postoperative recovery and showed good food intake and defecation during the 3-month postoperative follow-up. [Conclusion] Based on emphasizing the perioperative management of patients with radiation-induced intestinal fistula, optimizing the methods of preoperative localization and Trocar layout strategy, and with the implementation by an experienced surgical team, the overall safety and feasibility of laparoscopic surgical techniques for radiation-induced intestinal fistula are good.
Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.
AbstractBackgroundCrohn's disease (CD) is a chronic inflammatory disease in the intestinal tract. Mesenteric fat wrapping and thickening, or creeping fat (CrF), is a typical characteristic of CD and it involves lymphangiogenesis and altered lymphatic function. By releasing extracellular vesicles (EVs), adipose tissue‐derived stem cells (ADSCs) can regulate their adjacent cells. However, the regulating roles of ADSC‐EVs in CrF (CrF‐EVs) in CD, especially in modulating lymphatic function and mitigating the progression of mesenteritis and colitis, remains elusive.MethodsTo evaluate the regulative roles of CrF‐EVs on lymphatic functions, in vitro assays were performed using human lymphatic endothelial cells (HLECs). Next, Interleukin 10 knock‐out (Il‐10−/−) mice were used to assess the biological functions of CrF‐EVs in spontaneous mesenteritis and colitis. Moreover, tissue and serum from various cohorts of CD patients were used to determine the prognostic value of miR‐132‐3p.ResultsCrF‐EVs significantly attenuated spontaneous mesenteritis and colitis in Il‐10−/− mice via promoting lymphangiogenesis and lymphatic drainage. Using high‐throughput sequencing, we demonstrated that CrF‐EVs significantly increased HLEC proliferation, migration, tube formation and CCL‐21 production in a miR‐132‐3p/RASA1/ERK1/2 axis‐dependent manner. Accordingly, upregulated miR‐132‐3p was observed in patient CrF, positively correlated with lymphangiogenesis while negatively correlated with inflammatory factors (tumour necrosis factor‐α and IL‐6) level. Moreover, serum miR‐132‐3p demonstrated a positive correlation with disease activity.ConclusionsEVs derived from CrF ADSCs, containing elevated levels of miR‐132‐3p, could promote lymphatic function and restrain inflammation of CD. Our results provide a novel insight into the role of mesenteric lymphatics in CD progression and reveal a new potential therapeutic.Key points Extracellular vesicles (EVs) of creeping fat (CrF) derived adipose stem cells effectively attenuate chronic mesenteritis and colitis in Crohn's disease (CD). The lymphatic vessels play an important role in disease development of CD and their functions are improved by CrF‐EV‐miR‐132‐3p through RASA1/ERK1/2 signaling. MiR‐132‐3p expression is upregulated in CrF and serum of CD patients, and tightly linked with inflammation and disease activity.
Lymphatic abnormalities are essential for pathophysiologic changes of creeping fat (CrF) in Crohn's disease (CD). Anti-tumor necrosis factor (TNF) therapy has been proved to alleviate CrF lesions, however, whether it achieves these by remodeling lymphatics is unknown. CD74 expression was detected in CrF and uninvolved mesentery of CD patients. Lymphatic functions in vitro were evaluated and lymphatic endothelium barrier were checked by transendothelial electrical resistance (TEER) and FITC-Dextran permeability. Protein level of tight junction and signaling pathways were detected by western blotting. CD74 was upregulated in LECs of CrF and positively correlated with TNF-α synthesis. This was suppressed by IFX administration. In vitro, TNF-α stimulated LECs to express CD74 through NF-κB signaling pathway, and this was rescued by IFX. CD74 downregulation suppressed the abilities of LECs in proliferation, migration and tube formation. Interaction of CD74-MIF impaired LECs’ barrier via reducing tight junction proteins in an ERK1/2-dependent manner, which was reversed by CD74 downregulation. Consistently, the CD patients receiving IFX therapy displayed decreased lymphangiogenesis and improved mesenteric lymphatic endothelium barrier, companied with reduced adipocyte size and adipokine levels in CrF. Anti-TNF therapy could modify pathological changes in CrF by alleviating CD74-mediated lymphatic abnormalities.
The Endoscopic Purse-string Suture (EPSS) technique has gained attention for its potential in closing large defects following gastrointestinal procedures. However, its application in fistula closure is not as widely reported. This study aims to evaluate the safety and efficacy of EPSS and naso-jejunal tube feeding in the closure of duodenal cutaneous fistulas and gastric cutaneous fistulas. This single-center retrospective study, conducted from September 2020 to September 2023 at Tongji University in Shanghai, China, examined the outcomes of EPPS and nasojejunal feeding for patients with gastric and duodenal cutaneous fistulas (n = 10). Demographic data, fistula characteristics, procedure technique and outcomes were evaluated. In this study, the average size of a fistula opening was 7.9 ± 4.6 mm. The operations took an average of 25.8 ± 5.6 min. Patients typically needed naso-jejunal tube feeding for a median of 14.0 days, with an interquartile range (IQR) of 7.7–19.0 days. The median duration of hospital stay post-operation was 16.5 days, with an IQR of 7.0–25.0 days. Nine patients were successful in their initial fistula closure using the EPSS technique. The other patient underwent a second EPSS and, ultimately, all patients experienced complete healing and fully recovered. There were no major adverse events reported. EPSS and naso-jejunal tube feeding are a safe and effective treatment option for duodenal and gastric cutaneous fistulas. Larger, prospective studies are needed to validate these findings and establish the long-term safety and efficacy of this approach.
BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.