Copy number variation of gasdermin D gene is associated with atrial fibrillation-related thromboembolic stroke.

AIMS: Atrial fibrillation (AF) is one of the major causes of ischaemic stroke. In addition to clinical risk evaluated by the CHA2DS2-VASC score, the impact of genetic factors on the risk of AF-related thromboembolic stroke has been largely unknown. We found several copy number variations (CNVs) in novel genes that were associated with thromboembolic stroke risk in our AF patients by genome-wide approach. Among them, the gasdermin D (GSDMD) gene was related to inflammation. We aimed to test whether GSDMD deletion was associated with AF-related stroke. METHODS AND RESULTS: A total of 400 patients with documented non-familial AF were selected, of which 100 patients were diagnosed with ischaemic stroke. The baseline characteristics of age, sex, valvular heart disease, coronary artery disease, heart failure, and CHA2DS2-VASc scores were not statistically different between cases and controls. We found that individuals who carried GSDMD homozygous deletion genotype had a higher risk for ischaemic stroke (odds ratio 2.195; 95% confidence interval, 1.24-3.90; P = 0.007), even adjusted by CHA2DS2-VASc scores. We also validated the association of GSDMD with AF stroke in a large Caucasian population (UK Biobank). CONCLUSION: We found a link between the homozygous deletion of the GSDMD gene and an increased risk of stroke in patients with AF. This may implicate the use of therapy targeting GSDMD in the prevention of ischaemic stroke for AF patients.

Highly efficient generation of sheep with a defined FecBB mutation via adenine base editing.

Base editing has the potential to improve important economic traits in agriculture and can precisely convert single nucleotides in DNA or RNA sequences into minimal double-strand DNA breaks (DSB). Adenine base editors (ABE) have recently emerged as a base editing tool for the conversion of targeted A:T to G:C, but have not yet been used in sheep. ABEmax is one of the latest versions of ABE, which consists of a catalytically-impaired nuclease and a laboratory-evolved DNA-adenosine deaminase. The Booroola fecundity (FecBB) mutation (g.A746G, p.Q249R) in the bone morphogenetic protein receptor 1B (BMPR1B) gene influences fecundity in many sheep breeds. In this study, by using ABEmax we successfully obtained lambs with defined point mutations that result in an amino acid substitution (p.Gln249Arg). The efficiency of the defined point mutations was 75% in newborn lambs, since six lambs were heterozygous at the FecBB mutation site (g.A746G, p.Q249R), and two lambs were wild-type. We did not detect off-target mutations in the eight edited lambs. Here, we report the validation of the first gene-edited sheep generated by ABE and highlight its potential to improve economically important traits in livestock.

Intersphincteric Resection Versus Abdominoperineal Resection for Low Rectal Cancer: A Meta-Analysis.

Background. Abdominoperineal resection (APR) has been the standard surgery for ultra-low rectal cancer for a century. In recent years, intersphincteric resection (ISR) has been increasingly used to avoid the permanent colostomy. Up to now, there is no relevant meta-analysis comparing the clinical efficacy of ISR and APR. This meta-analysis aimed to compare the outcomes of these 2 procedures. Methods. A comprehensive search of online databases was performed on PubMed, EMBASE, and the Cochrane Library to obtain comparative studies of ISR and APR. Then the data from studies that met the inclusion criteria were extracted and analyzed. Results. A total of 12 studies covering 2438 patients were included. No significant differences were found between ISR and APR in gender, body mass index, distance from tumor to anal edge, operative time, and blood loss. In addition, hospital stay (weighted mean differences = -2.98 days; 95% confidence interval [CI] = -3.54 to -2.43; P < .00001) and postoperative morbidity (odds ratio [OR] = 0.76; 95% CI = 0.59 to 0.99; P = .04) were significantly lower in ISR group compared with APR group. However, patients who underwent ISR showed lower pathological T-stage (T3T4%, OR = 0.49; 95% CI = 0.28 to 0.86; P = .01) and lymph node metastasis rate (OR = 0.77; 95% CI = 0.59 to 1.01; P = .06) compared with those who underwent APR. Moreover, oncological outcomes were similar between the 2 groups. Conclusion. ISR may provide a safe alternative to APR, with shorter hospital stays, lower postoperative morbidity, and similar oncological outcomes. Well-designed randomized controlled trials are needed to confirm and update the findings of this analysis.

Glove single-port laparoscopy-assisted transanal total mesorectal excision for low rectal cancer: a preliminary report.

PURPOSE: Glove single-port laparoscopy-assisted transanal total mesorectal excision (TaTME) has been successfully carried out in our medical center. The purpose of this study is to evaluate the feasibility of this emerging operation. METHODS: This technique was performed by self-made glove single-port laparoscopic platform to radically resect low rectal cancer. Short-term postoperative results, including complications, length of hospital stay, and follow-up results were collected and analyzed statistically. RESULTS: There are five consecutive patients (three males, two females) who underwent this surgery and included in this study. The mean distance from the tumor to the anal verge was 4.8 cm (range 4.0-6.0). The surgery was completed in all cases, and the rectal tumor was removed successfully without conversion; circumferential margins of all the excised specimens were negative. The mean time of operation was 338.00 min (range 280-400). The average number of lymph node dissection was 12.20. The average postoperative hospital stay was 8.60 days. During the follow-up (14.80 ± 1.92 months), all preventive ileostomies were successfully closed in about 3 months after the surgery, all patients had satisfactory anal function, and no tumor recurrence was found. CONCLUSION: Glove single-port laparoscopy-assisted TaTME has a significant effect in specific patients with low rectal cancer, with rapid recovery and high safety. Prospective randomized studies involving more case counts and long-term follow-up results, especially oncologic outcomes, are needed to validate this technique.

A Randomized Control Trial of Preoperative Oral Antibiotics as Adjunct Therapy to Systemic Antibiotics for Preventing Surgical Site Infection in Clean Contaminated, Contaminated, and Dirty Type of Colorectal Surgeries.

BACKGROUND: Preoperative bowel preparation with or without oral antibiotics is controversial in terms of postoperative surgical site infections. OBJECTIVE: This study aimed to evaluate the efficacy of oral antibiotics as adjunct therapy to systemic antibiotics with mechanical bowel preparation for preventing surgical site infections in clean contaminated, contaminated, and dirty colorectal procedures. DESIGN: This was a single-center, prospective randomized study. SETTING: This study was conducted at the General Surgery Department at Jinling Hospital, Nanjing University, China, from July 15, 2014 to January 20, 2016. PATIENTS: Patients aged ≥18 years scheduled for abdominal surgery with clean-contaminated, contaminated, and dirty wounds were selected. INTERVENTIONS: Patients were randomly assigned to receive preoperative mechanical bowel preparation or mechanical bowel preparation with oral antibiotics. MAIN OUTCOMES: The primary outcome was the rate of surgical site infections. The secondary outcomes were extra-abdominal complications, duration of postoperative ileus, and readmission rate. RESULTS: Ninety-five patients were allocated to each group. Eight and 26 surgical site infections (8.42% vs 27.3 %, p = 0.004) occurred in the mechanical bowel preparation with oral antibiotics and mechanical bowel preparation groups. Thirteen extra-abdominal complications were reported: 6 in the mechanical bowel preparation with oral antibiotics group and 7 in the mechanical bowel preparation group (6.3% vs 7.3%, p = 0.77). Postoperative ileus duration did not differ between groups (p = 0.23). There were 4 readmissions in the mechanical bowel preparation group and none in the mechanical bowel preparation with oral antibiotics group (p = 0.04). On multivariable analysis, blood loss ≥500 mL (OR, 5.1; 95% CI, 1.27-20.4; p = 0.02), ASA score ≥3 (OR, 3.9; 95% CI, 1.2-12.5; p = 0.01), contaminated types (OR, 3.6; 95% CI, 1.5-8.6; p = 0.01), and administration of preoperative oral antibiotics (OR, 0.20; 95% CI, 0.06-0.60; p = 0.005) independently affected the incidence of surgical site infections. LIMITATIONS: This was a single-center study. CONCLUSION: Preoperative oral antibiotics, as adjunct therapy to systemic antibiotics and mechanical bowel preparation, significantly reduced surgical site infections and minimized the readmission rates in clean contaminated, contaminated, and dirty types of colorectal surgery. See Video Abstract at http://links.lww.com/DCR/A437.

Risk factors of surgical site infections in patients with Crohn's disease complicated with gastrointestinal fistula.

PURPOSE: Surgical site infection (SSI) is the most common complication following surgical procedures. This study aimed to determine risk factors associated with SSI in patients with Crohn's disease (CD) complicated with gastrointestinal fistula. METHODS: This was a retrospective review of patients who underwent surgical resection in gastrointestinal fistula patients with CD between January 2013 and January 2015, identified from a prospectively maintained gastrointestinal fistula database. Demographic information, preoperative medication, intraoperative findings, and postoperative outcome data were collected. Univariate and multivariate analysis was carried out to assess possible risk factors for SSI. RESULTS: A total of 118 patients were identified, of whom 75.4% were men, the average age of the patients was 34.1 years, and the average body mass index (BMI) was 18.8 kg/m2. The rate of SSI was 31.4%. On multivariate analysis, preoperative anemia (P = 0.001, OR 7.698, 95% CI 2.273-26.075), preoperative bacteria present in fistula tract (P = 0.029, OR 3.399, 95% CI 1.131-10.220), and preoperative enteral nutrition (EN) <3 months (P < 0.001, OR 11.531, 95% CI 3.086-43.079) were predictors of SSI. Notably, preoperative percutaneous abscess drainage was shown to exert protection against SSI in fistulizing CD (P = 0.037, OR 0.258, 95% CI 0.073-0.920). CONCLUSION: Preoperative anemia, bacteria present in fistula tract, and preoperative EN <3 months significantly increased the risk of postoperative SSI in gastrointestinal fistula complicated with CD. Preoperative identification of these risk factors may assist in risk assessment and then to optimize preoperative preparation and perioperative care.

The Impact of Obesity on the Clinical Course of Inflammatory Bowel Disease: A Meta-Analysis.

BACKGROUND Obesity has been linked with a pro-inflammatory state and the development of inflammatory diseases, including inflammatory bowel disease (IBD). However, there is some controversy regarding whether obesity is associated with an adverse clinical course in patients with IBD. The aim of this meta-analysis was to assess the association between obesity and clinical outcomes in IBD patients. MATERIAL AND METHODS Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched for studies investigating the association between obesity and clinical outcomes in patients with IBD. A meta-analysis was performed using Review Manager software. RESULTS Among the 4,798 articles identified, seven met the inclusion criteria for our meta-analysis. The pooled data revealed that obese patients were significantly less likely to undergo IBD-related surgery, receive hormone therapy, and experience hospitalization compared with non-obese patients. However, no statistically significant difference was observed in perianal disease, anti-TNF use, and immunomodulator use between the two groups. CONCLUSIONS Our meta-analysis indicated that clinical outcomes were significantly different in obese versus non-obese patients with IBD. We found that obesity was associated with a less severe disease course of IBD. Future prospective studies are needed to confirm the relationship between obesity and the clinical course of IBD.

Prediction of procalcitonin for postoperative intraabdominal infections after definitive operation of intestinal fistulae.

BACKGROUND: Inflammatory biomarkers usually start to rise earlier before the infection becomes clinically evident. This study was designed to evaluate the predictive performance of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) counts in postoperative intraabdominal infections (IAIs) after definitive operation of intestinal fistulae. MATERIAL AND METHODS: We prospectively enrolled a total of 356 consecutive patients who underwent elective digestive tract reconstruction for gastrointestinal fistulae without existing clinical infection. Plasma PCT levels, serum CRP concentration, and WBC counts were assessed preoperatively and on postoperative days (PODs) 1, 3, 5, and 7. The predictive value of each laboratory marker for IAIs was calculated. RESULTS: The occurrence rate of IAIs after elective digestive tract reconstruction for gastrointestinal fistulae in our study was 7.3%. Both PCT levels and WBC counts were significantly higher in patients with IAIs than those in patients without IAIs on POD 1, POD 3, and POD 5, whereas CRP levels differed significantly on POD 3 and POD 5. Receiver-operating characteristics demonstrated that PCT on POD 3 had the highest diagnostic accuracy for IAIs, and the area under the curve reached 0.86, with a sensitivity of 92.0% and specificity of 74.0%. CONCLUSIONS: The value of PCT above 0.98 ng/L on POD 3 and 0.83 ng/L on POD 5 could predict the occurrence of IAIs after definitive operations for intestinal fistulae.

Monocyte subsets and monocyte-platelet aggregates: implications in predicting septic mortality among surgical critical illness patients.

BACKGROUND: Monocyte subsets and monocyte-platelet aggregates (MPAs) play important roles in inflammation. AIM: To evaluate the association between the three human monocyte subsets and their contributions to MPAs and mortality among septic patients. METHODS: Consecutive septic patients were enrolled in. Age- and gender-matched nonseptic patients were recruited as control patients. Monocyte subsets and monocyte-platelet aggregates were determined by flow cytometric analysis. RESULTS: Elevated percentage of MPAs (MPAs%) was associated with an increased risk of mortality. CONCLUSIONS: This study demonstrated increased MPAs% enables the identification of a group of septic patients at high risk of death.

Role of enteral nutrition in nonthyroidal illness syndrome: a retrospective observational study.

BACKGROUND: The nonthyroidal illness syndrome (NTIS) is prevalent among patients with enterocutaneous fistula and is associated with poor outcomes. The present study aimed to explore the role of enteral nutrition (EN) therapy on thyroid function among patients with enterocutaneous fistula and NTIS. METHODS: We conducted a retrospective observational study among patients with enterocutaneous fistula between January 2013 and April 2014. All enrolled patients received EN therapy. Thyroid function and other parameters were measured. RESULTS: After administration of 4 weeks of EN therapy, NTIS was resolved in 66 patients (Group A), while it persisted in 14 patients (Group B). The overall treatment success rate was 82.50 %. There were no significant differences between groups A and B at baseline for all parameters, except for the time from admission to start of EN therapy. The logistic analysis revealed that the time from admission to start of EN therapy was a significant independent indicator for achieving resolution of NTIS in our cohort. CONCLUSIONS: This retrospective observational cohort study demonstrated that EN therapy can aid in the resolution of NTIS among patients with enterocutaneous fistula. These findings confirm the benefit of EN in the treatment of enterocutaneous fistula.

Comparative evaluation of sump drainage by trocar puncture, percutaneous catheter drainage versus operative drainage in the treatment of Intra-abdominal abscesses: a retrospective controlled study.

BACKGROUND: Intra-abdominal and pelvic abscesses are common and result from various illnesses. Percutaneous drainage applies limitedly to well-localized abscesses with appropriate density while surgical drainage usually causes significant physiological disturbance. We herein illustrated an innovative choice "sump drainage with trocar puncture" for the management of intra-abdominal abscesses and compare it with conventional percutaneous and surgical drainage in terms of clinical outcomes and prognosis. METHODS: Medical records of a total of 75 patients with abscesses were retrospectively retrieved and scrutinized. Data consisted of demographics, abscesses characteristics and treatment outcomes including postoperative complication, duration of hospitalization, postoperative recurrence of abscesses, subsequent surgery, ultimate stoma creation and survival rate. All enrolled patients were divided into trocar group (n = 30), percutaneous group (n = 20) and surgical group (n = 25) according to the therapeutic modalities. One-way ANOVA and t-test with Welch's correction were used in continuous variables, and Chi-squared test as well as Fisher's exact test for categorical variables. The cumulative incidence of subsequent surgery and ultimate stoma creation was also indicated by the Kaplan-Meier method and compared by log-rank test. RESULTS: The risk of ultimate stoma creation (p = 0.0069) and duration of postoperative hospitalization (p = 0.0077) were significantly decreased in trocar group compared with the surgical group. Patients receiving trocar puncture also tended to be less likely to have subsequent surgery (p = 0.097). Patients in trocar group displayed a lower rate of postoperative complication than the percutaneous (p = 0.0317) and surgical groups (p = 0.0175). As for Kaplan-Meier analysis, the cumulative incidence of ultimate stoma creation of the patients using sump drainage was also significantly different among three groups during follow-up period (p = 0.011). CONCLUSION: This novel technique "sump drainage by trocar puncture" could produce better clinical outcomes and prognosis than conventional percutaneous drainage and surgical intervention. It might become an optimal choice in the management of intra-abdominal abscesses in the future.

Exclusive enteral nutritional therapy can relieve inflammatory bowel stricture in Crohn's disease.

GOALS: To examine the efficiency of exclusive enteral nutrition (EEN) in relieving inflammatory bowel stricture in patients with Crohn's disease (CD). BACKGROUND: Patients with CD usually develop bowel strictures due to transmural edema of intestinal wall, which can potentially be managed with conservative medical treatment. Previous studies showed that EEN therapy could induce clinical remission through its anti-inflammation effect. METHODS: We achieved a prospective observational study. CD patients with inflammatory bowel stricture were preliminarily differentiated from a fibrous one, and further treated with EEN therapy for 12 weeks. Demographics and clinical variables were recorded. Nutritional (body mass index, albumin, pre-albumin, transferrin, etc.), inflammatory (C-reactive protein, erythrocyte sedimentation rate, white blood cell, etc.), and radiologic parameters (bowel wall thickness, luminal diameter, and luminal cross-sectional area) were evaluated at baseline, week 4, and week 12, respectively. RESULTS: Between May 2012 and January 2013, 65 patients with CD were preliminarily diagnosed with inflammatory bowel stricture and 6 patients were further excluded. Among the remaining 59 cases, 50 patients (84.7%) finished the whole EEN treatment, whereas the other 9 patients (15.3%) gained progressive bowel obstruction resulting in surgery. Intention-to-treat analyses showed that 48 patients (81.4%) achieved symptomatic remission, 35 patients (53.8%) achieved radiologic remission, and 42 patients (64.6%) achieved clinical remission. Among those patients who complete the whole EEN therapy, inflammatory, nutritional, and radiologic parameters improved significantly compared with baseline. Of note, the average luminal cross-sectional area at the site of stricture increased approximately 331% at week 12 (195.7 ± 18.79 vs. 59.09 ± 10.64 mm, P<0.001). CONCLUSIONS: EEN therapy can effectively relieve inflammatory bowel stricture in CD, which replenishes roles of enteral nutrition in the treatment of CD. Further studies are expected to investigate the underlying mechanisms of this effect in the future.

Development and Validation of a Deep Learning and Radiomics Combined Model for Differentiating Complicated From Uncomplicated Acute Appendicitis.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a deep learning and radiomics combined model for differentiating complicated from uncomplicated acute appendicitis (AA). MATERIALS AND METHODS: This retrospective multicenter study included 1165 adult AA patients (training cohort, 700 patients; validation cohort, 465 patients) with available abdominal pelvic computed tomography (CT) images. The reference standard for complicated/uncomplicated AA was the surgery and pathology records. We developed our combined model with CatBoost based on the selected clinical characteristics, CT visual features, deep learning features, and radiomics features. We externally validated our combined model and compared its performance with that of the conventional combined model, the deep learning radiomics (DLR) model, and the radiologist's visual diagnosis using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of our combined model in distinguishing complicated from uncomplicated AA was 0.816 (95% confidence interval [CI]: 0.785-0.844). In the validation cohort, our combined model showed robust performance across the data from three centers, with AUCs of 0.836 (95% CI: 0.785-0.879), 0.793 (95% CI: 0.695-0.872), and 0.723 (95% CI: 0.632-0.802). In the total validation cohort, our combined model (AUC = 0.799) performed better than the conventional combined model, DLR model, and radiologist's visual diagnosis (AUC = 0.723, 0.755, and 0.679, respectively; all P < 0.05). Decision curve analysis showed that our combined model provided greater net benefit in predicting complicated AA than the other three models. CONCLUSION: Our combined model allows the accurate differentiation of complicated and uncomplicated AA.

Seed and Soil: Consensus Molecular Subgroups (CMS) and Tumor Microenvironment Features Between Primary Lesions and Metastases of Different Organ Sites in Colorectal Cancer.

Purpose: Consensus molecular subtypes (CMS) are mainly used for biological interpretability and clinical stratification of colorectal cancer (CRC) in primary tumors (PT) but few in metastases. The heterogeneity of CMS distribution in metastases and the concordance of CMS between PT and metastases still lack sufficient study. We used CMS to classify CRC metastases and combine it with histopathological analysis to explore differences between PT and distant metastases. Patients and Methods: We obtained gene expression profiles for 942 PT samples from TCGA database (n=376) and GEO database (n=566), as well as 442 metastasis samples from GEO database. Among these, 765 PT samples and 442 metastasis samples were confidently identified with CMS using the "CMS classifier" and enrolled for analysis. Clinicopathological manifestation and CMS classification of CRC metastases were assessed with data from GEO, TCGA, and cBioPortal. Overall, 105 PT-metastasis pairs were extracted from 10 GEO datasets to assess CMS concordance. Tumor microenvironment (TME) features between PT and metastases were analyzed by immune-stromal infiltration with ESTIMATE and xCell algorithms. Finally, TME features were validated with multiplex immunohistochemistry in 27 PT-metastasis pairs we retrospectively collected. Results: Up to 64% of CRC metastases exhibited concordant CMS groups with matched PT, and the TME of metastases was similar to that of PT. For most common distant metastases, liver metastases were predominantly CMS2 and lung and peritoneal metastases were mainly CMS4, highlighting "seed" of tumor cells of different CMS groups had a preference for metastasis to "soil" of specific organs. Compared with PT, cancer-associated fibroblasts (CAF) reduced in liver metastases, CD4+T cells and M2-like macrophages increased in lung metastases, and M2-like macrophages and CAF increased in peritoneal metastases. Conclusion: Our findings underscore the importance of CMS-guided specific organ monitoring and treatment post-primary tumor surgery for patients. Differences in immune-stromal infiltration among different metastases provide targeted therapeutic opportunities for metastatic CRC.

Clinical Efficacy of Intersphincteric Resection for Low Rectal Cancer Compared With Abdominoperineal Resection: A Single-Center Retrospective Study.

BACKGROUND: In recent years, intersphincteric resection (ISR) has been increasingly used to replace abdominoperineal resection (APR) in the surgical treatment of ultra-low rectal cancer. AIM: This study was to compare the clinical efficacy of ISR and APR. METHODS: Between 2012 and 2018, 74 consecutive patients with ultra-low rectal cancer underwent ISR or APR in our medical center. A retrospective comparison of these 2 procedures was performed. RESULTS: A total of 43 patients underwent ISR and 31 underwent APR were included in the study. No significant differences were found between 2 groups in gender, age, BMI, and ASA score. Intersphincteric resection group showed shorter operative time (P = .02) and less blood loss (P = .001). Hospital stays, time to soft diet, and postoperative 30-day complications were not significantly different between the 2 groups. R0 resection achieved 100% in both the groups. As for the long-term outcomes, the survival and recurrence rate were similar between 2 groups. Moreover, the LARS and Wexner score showed that the postoperative anal function after ISR were satisfactory. CONCLUSION: This study suggested that ISR was feasible and safe for selected patients with ultra-low rectal cancer, with clinically superior outcomes in select patients (small tumors/further from the anal verge) and similar oncological outcomes to APR, and the anal functional outcomes after ISR were acceptable.

Quantitative composite testing model based on measurement uncertainty and its application for the detection of phthalate esters.

To improve the quantitative detection efficiency of chemical analysis and reduce the detection cost, the sample pass rate was estimated and mathematical statistics were used to calculate the optimal group size (K opt) of the composite testing to save on the maximum workload. A quantitative composite testing model was developed based on chemical analysis measurement uncertainty. Using this model, the maximum allowable number of composited samples (K max) is first calculated using parameters of regulated limits (L), limit of quantification (LOQ), and method measured uncertainty (U rel) to ensure that the sensitivity of the composite testing can meet the limit requirements. Finally, the appropriate composite group size (K a) can be obtained by creating a balance between K opt, K max, and the practical information used for that particular test. Furthermore, based on a constructed model, a practical quantitative composite testing method of 3-10 samples was established for the routine detection of toy phthalates (PAEs). The experimental results showed that the quantitative limits of 7 PAEs were 9.1-41.8 mg/kg, the relative expansion uncertainties were 16.6%-23.2%, and the recovery rates were 91.0%-112.3%, with a relative deviation of less than 10%. All these meet international PAEs standards. Compared with the traditional individual and qualitative composite testing, this model will not decrease the detection sensitivity, but can save up to 17.9%-80.4% of the workload when it is employed in toy PAEs testing with the pass rate of 80%-99%. This quantitative composite testing method will be implemented in the coming revision of ISO 8124-6 toy PAEs standards.

Analysis of abdominal adhesion using the ileostomy model.

Abdominal adhesion occurs commonly in clinical practice, causing unfavorable symptoms and readmission. The ileostomy operation is a common surgical procedure and we utilized this model to evaluate abdominal adhesion. Adhesion grade score was calculated in 35 patients (Cohort 1) and subjected to correlation and receiver operating characteristic analysis. Then 98 consecutive patients (Cohort 2) who underwent ileostomy and ileostomy closure were included into a retrospective study. Logistic regression analysis was performed, and the risk of small bowel obstruction was also assessed. The time of ileostomy closure correlated with adhesion grade score in Cohort 1, justifying its use as an indicator of abdominal adhesion. All patients in Cohort 2 were then divided into the high- and low-adhesion group. A multi-variable logistic regression analysis indicated that type of surgery and peritoneum suture during ileostomy were significant factors affecting the risk of abdominal adhesion. Abdominal adhesion had the trend to prolong the length of stay postoperatively without increasing the risk of bowel obstruction. Nine patients suffered bowel obstruction, and age older than 65 significantly increased the risk. We proposed the ileostomy procedure to be a model of abdominal adhesion, and the operative time of ileostomy closure could be used as an alternative of adhesion score. Type of surgery and peritoneum suture may be risk factors of abdominal adhesion. Older age increased the risk of small bowel obstruction after ileostomy surgery.

Simple transanal total mesorectal resection versus laparoscopic transabdominal total mesorectal resection for the treatment of low rectal cancer: a single-center retrospective case-control study.

Aim: To evaluate the efficacy and safety of simple TaTNE in the treatment of low rectal cancer compared with laparoscopic transabdominal TME. Methods: We collected patients with low rectal cancer admitted to our hospital between January 2019 and November 2021 who received simple TaTME or laparoscopic transabdominal TME. The main outcome was the integrity of the TME specimen. Secondary outcomes were the number of lymph nodes dissected, intraoperative blood loss, operative time, surgical conversion rate, Specimen resection length, circumferential margin (CRM), and distal resection margin (DRM), complication rate. In addition, the Wexner score and LARS score of fecal incontinence were performed in postoperative follow-up. Results: Pathological tissues were successfully resected in all patients. all circumferential margins of the specimen were negative. Specimen resection length was not statistically significant (9.94 ± 2.85 vs. 8.90 ± 2.49, P > 0.05). The incidence of postoperative complications in group A (n = 0) was significantly lower than that in group B (n = 3) (P > 0.05). There was no significant difference in operation time between group A and group B (296 ± 60.36 vs. 305 ± 58.28, P > 0.05). Among the patients with follow-up time less than 1 year, there was no significant difference in Wexner score and LARS score between group A and group B (P > 0.05). However, in patients who were followed up for more than 1 year, the Wexner score in group A (9.25 ± 2.73) was significantly lower than that in group B (17.36 ± 10.95) and was statistically significant (P < 0.05). Conclusion: For radical resection of low rectal cancer, Simple TaTME resection may be as safe and effective as laparoscopic transabdominal TME, and the long-term prognosis may be better.

Mitoquinone treatment for the prevention of surgical adhesions via regulation of the NRF2/HO-1 signaling pathway in mice.

BACKGROUND: Postoperative adhesion is a common cause of long-term morbidity after abdominal or pelvic surgery. The development of postoperative adhesion involves oxidative stress, inflammatory response, and collagen deposition mechanisms. Here, we demonstrate that mitoquinone could be useful for the treatment of postoperative adhesion. METHODS: A murine adhesion model was established by induction of peritoneal ischemic buttons. Mice received different doses of mitoquinone via the tail vein. All the ischemic buttons were dissected at 1 day and 7 days after surgery to investigate the effect of mitoquinone in the early and late stage of the adhesion process, respectively. Human peritoneal mesothelial cells were treated with H2O2 to examine the potential mechanisms of mitoquinone in oxidative insult. RESULTS: Postoperative adhesion scores were markedly decreased in mitoquinone-treated mice compared with the control mice. The degree of oxidative stress, inflammatory injury, and collagen deposition were also significantly reduced in the mitoquinone-treated mice. The expression of plasminogen-activating inhibitor, interleukin-1, interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, malondialdehyde, and nitric oxide was decreased, while the expression of tissue-type plasminogen activator, glutathione, superoxide dismutase, and Nrf2 was increased in the peritoneal ischemic buttons after mitoquinone treatment. Cellular reactive oxygen species and the canonical inflammatory pathway were inhibited in mitoquinone-treated human peritoneal mesothelial cells after H2O2 challenge. Mechanistically, mitoquinone was found to enhance the activity of Nrf2 and heme oxygenase-1 and to induce nuclear translocation of Nrf2 in human peritoneal mesothelial cells. CONCLUSION: The mitochondria-targeting antioxidant molecule mitoquinone attenuates postoperative adhesion formation by inhibiting oxidative stress, inflammation, and collagen accumulation, and therefore provides a therapeutic agent for the management of surgical adhesion.

The Effect of Tissue Stromal Vascular Fraction as Compared to Cellular Stromal Vascular Fraction to Treat Anal Sphincter Incontinence.

BACKGROUND: The long-term prognosis of current treatments for anal sphincter incontinence (ASI) is poor. Here, we explored the efficacy of tissue adipose stromal vascular fraction SVF (tSVF) on ASI and compared it to that of cellular SVF (cSVF). We then investigated possible mechanisms. METHODS: Rat cSVF and tSVF were isolated and labeled with DIL. One day after modeling, three groups received phosphate-buffered saline (PBS), cSVF, tSVF, respectively. The control group received nil modeling nor any treatments. The effect was assessed by function test for anal pressure and electromyography, and staining for fiber content, proliferation and differentiation at day 5 and day 10. RESULTS: cSVF injection resulted in faster healing than tSVF. The cSVF group showed significant improvement on anal pressure on day 10. For the electromyography test, cSVF showed significant improvement for the frequencies on day 10, and for the peak values on both time points, while tSVF showed significant improvement for the peak values on day 10. The two SVF both alleviated fibrosis. Immunofluorescence tracing identified differentiation of some injected cells towards myosatellite cells and smooth muscle cells in both SVF groups. For all the tests, the tSVF group tends to have similar or lower effects than the cSVF group with no significant difference. CONCLUSION: cSVF and tSVF are both safe and effective in treating ASI, while the effect of cSVF is slighter higher than tSVF.