An improved mouse model of sepsis based on intraperitoneal injections of the enriched culture of cecum slurry.

AIM: Sepsis is a life-threatening clinical syndrome comprising multiorgan dysfunctions caused by a disproportionate body immune response. There are several animal sepsis models which are based on cecum ligation, cecal puncture, and cecum slurry injection. The major limitation of all current sepsis models is the high variability owing to the variable degree of ligation, puncture and inconsistent microbial composition used for sepsis initiation. The primary objective of this work is to demonstrate the feasibility of a standardized method for sepsis development. MATERIALS AND METHODS: The cecal slurry bacterial culture was developed and preserved in glycerol stocks. Antibiotics aztreonam and vancomycin were used for generating several defined, enriched cecal slurry bacterial cultures. Mice survival was assessed until 48 hrs post injection, and the tissue samples were collected after 10 hrs from sepsis initiation. KEY FINDINGS: The results indicate that increasing polymicrobial load resulted in lower survival rates and was associated with the higher number of infiltrating immune cells and necrosis. H&E (haematoxylin & eosin) staining & serum markers revealed that septic mice exhibited increased inflammation and significant damage to the liver and kidneys. The defined Gram-negative and Gram-positive specific cecal slurry bacterial cultures were developed and their efficiency in inducing sepsis was characterized. SIGNIFICANCE: Enriched cecal slurry bacterial cultures can be stored in glycerol stocks at -80 °C. This has an ethical advantage of avoiding unnecessary animal euthanasia for each experiment and provides a standardization capability of sepsis development.

Effects of high ligation plus endovenous laser therapy in patients with varicosis of great saphenous vein and type 2 diabetes.

To analyze the effects of high ligation plus endovenous laser therapy on intraoperative blood loss, postoperative visual analogue scale (VAS) score, and complications in patients with varicosis of great saphenous vein and type 2 diabetes. About 61 patients with varicosis of great saphenous vein and type 2 diabetes treated at our hospital were included. About 32 patients (37 affected limbs) receiving conventional surgery were included in control group, while 29 patients (34 affected limbs) receiving high ligation plus endovenous laser therapy were included in study group. The intraoperative blood loss, operation time, length of postoperative hospital stay, postoperative VAS scores, blood glucose levels, Venous Clinical Severity Score (VCSS), and incidence of complications were compared between the two groups. Compared with the control group, there were less intraoperative blood loss (P < .05), shorter operation time (P < .05), and shorter length of postoperative hospital stay in the study group (P < .05). Besides, there was also lower VAS scores at different time points after surgery in the study group than in the control group (P < .05). Blood glucose levels were decreased in both groups after surgery (P < .05). Moreover, VCSS was decreased in either group at 3 months after surgery (P < .05). Blood glucose levels of patients in the study group were lower than those of the control group after surgery (P < .05). The VCSS was also lower in the study group at 3 months after surgery than in the control group (P < .05). High ligation with endovenous laser therapy for varicosis of great saphenous vein in patients with type 2 diabetes was safe and feasible.

Predictors of recurrence and long-term patient reported outcomes following surgical repair of anal fistula, a retrospective analysis.

PURPOSE: Surgery for anal fistulas can result in devastating complications, including reoperations and fecal incontinence. There is limited contemporary evidence comparing outcomes since the adoption of the ligation of intersphincteric fistula tract procedure into mainstream practice. The purpose of this study is to compare recurrence rates and long-term outcomes of anal fistula following repair. METHODS: Data was collected from the electronic medical records or patient reported outcomes from patients aged 18 or older with a primary or recurrent cryptoglandular anal fistula. Primary outcome was recurrence defined as the identification of at least one fistula os or a high clinical suspicion of anal fistula. Secondary outcomes included fecal incontinence and postoperative quality of life. RESULTS: A total of 171 patients underwent definitive surgical repairs for their anal fistula. So 66.5% had a simple fistula, and 33.5% had a complex fistula. Of the 171 patients, 12.5% had a recurrence. The recurrence rates were 5.9% for simple fistula and 25.4% for complex fistula. Predictors of recurrence included diabetes mellitus, history of anorectal abscess, complex fistula, and sphincter sparing surgery. LIFT or plug/biologic procedures were both associated with a 50% or greater recurrence rate. No significant differences were found in fecal incontinence or associated quality of life between sphincter sparing or non-sphincter sparing surgical resections. CONCLUSION: The study provides insights into the long-term outcomes of surgical repair for anal fistula. We demonstrate that sphincter sparing operations are associated with increased recurrence, meanwhile, non-sphincter sparing surgeries did not increase the risk of fecal incontinence or worsen quality of life.

Golden bifid treatment regulates gut microbiota and serum metabolites to improve myocardial dysfunction in cecal ligation and puncture-induced sepsis mice.

Myocardial damage is a major consequence and a significant contributor to death in cases of sepsis, a severe infection characterized by a distinct inflammatory response and a potential threat to the patient's life. Recently, the effects of intestinal microbiota and serum metabolites on sepsis have garnered increasing attention. Herein, the effects of golden bifid treatment upon cecal ligation and puncture (CLP)-induced sepsis in mice as a model for myocardial dysfunction were explored. Our results demonstrated that golden bifid treatment partially improved myocardial dysfunction and apoptosis, cardiac inflammation and oxidative stress, and intestinal mucosal permeability and barrier dysfunction in CLP-induced sepsis mice. The intestinal microbiota diversity and abundance were also altered within sepsis mice and improved by golden bifid treatment. Mucispirillum schaedleri, Acinetobacter baumannii and Lactobacullus intestinalis were significantly correlated with heart damage markers, inflammatory factors, or oxidative stress indicators. Serum differential metabolite levels were also significantly correlated with these parameters. Altogether, golden bifid treatment might be an underlying approach for treating sepsis-induced myocardial dysfunction and highlight the underlying effect of intestinal microbiota and serum metabolites on the pathogenesis and treatment of sepsis-triggered myocardial dysfunction.

Evaluation of the efficacy and safety of endoscopic band ligation in the treatment of bleeding from mild to moderate gastric varices type 1.

BACKGROUND: According to practice guidelines, endoscopic band ligation (EBL) and endoscopic tissue adhesive injection (TAI) are recommended for treating bleeding from esophagogastric varices. However, EBL and TAI are known to cause serious complications, such as hemorrhage from dislodged ligature rings caused by EBL and hemorrhage from operation-related ulcers resulting from TAI. However, the optimal therapy for mild to moderate type 1 gastric variceal hemorrhage (GOV1) has not been determined. Therefore, the aim of this study was to discover an individualized treatment for mild to moderate GOV1. AIM: To compare the efficacy, safety and costs of EBL and TAI for the treatment of mild and moderate GOV1. METHODS: A clinical analysis of the data retrieved from patients with mild or moderate GOV1 gastric varices who were treated under endoscopy was also conducted. Patients were allocated to an EBL group or an endoscopic TAI group. The differences in the incidence of varicose relief, operative time, operation success rate, mortality rate within 6 wk, rebleeding rate, 6-wk operation-related ulcer healing rate, complication rate and average operation cost were compared between the two groups of patients. RESULTS: The total effective rate of the two treatments was similar, but the efficacy of EBL (66.7%) was markedly better than that of TAI (39.2%) (P < 0.05). The operation success rate in both groups was 100%, and the 6-wk mortality rate in both groups was 0%. The average operative time (26 min) in the EBL group was significantly shorter than that in the TAI group (46 min) (P < 0.01). The rate of delayed postoperative rebleeding in the EBL group was significantly lower than that in the TAI group (11.8% vs 45.1%) (P < 0.01). At 6 wk after the operation, the healing rate of operation-related ulcers in the EBL group was 80.4%, which was significantly greater than that in the TAI group (35.3%) (P < 0.01). The incidence of postoperative complications in the two groups was similar. The average cost and other related economic factors were greater for the EBL than for the TAI (P < 0.01). CONCLUSION: For mild to moderate GOV1, patients with EBL had a greater one-time varix eradication rate, a greater 6-wk operation-related ulcer healing rate, a lower delayed rebleeding rate and a lower cost than patients with TAI.

Post-ligation cardiac syndrome after surgical versus transcatheter closure of patent ductus arteriosus in low body weight premature infants: a multicenter retrospective cohort study.

Transcatheter patent ductus arteriosus (PDA) closure is a safe and effective alternative to surgical ligation in low-body-weight infants. Post-ligation cardiac syndrome (PLCS) is defined as severe hemodynamic and respiratory collapse within 24 h of PDA closure, requiring initiation or an increase of an inotropic agent by > 20% of preligation dosing and an absolute increase of at least 20% in ventilation parameters compared with the preoperative value. Whilst PLCS is routinely observed after surgery, its incidence remains poorly described following transcatheter closure. This study aimed to compare the incidence of PLCS after surgical versus transcatheter closure of PDA in low-body-weight premature infants. Propensity scores were used to compare surgical (N = 78) and transcatheter (N = 76) groups of preterm infants who underwent PDA closure at a procedural weight less than 2000 g in two tertiary institutions between 2009 and 2021. The primary outcome was the incidence of PLCS. Secondary outcomes included overall mortality before discharge, risk factors for PLCS, and post-procedural complications. Procedural success was 100% in both groups. After matching, transcatheter group experienced no PLCS vs 15% in the surgical group (p = 0.012). Furthermore, overall mortality (2% vs 17%; p = 0.03) and major complications (2% vs 23%; p = 0.002) were higher in the surgical group. Surgery (100% vs 47%; p < 0.01), gestation age (25 ± 1 vs 26 ± 2 weeks, p < 0.05) and inotropic support before closure (90% vs 29%; p < 0.001) were associated with PLCS occurrence.          Conclusion: Transcatheter PDA closure may be equally effective but safer than surgical PDA closure in low-body-weight premature infants. What is Known: • Post-ligation cardiac syndrome is a serious and common complication of surgical closure of the ductus arteriosus in preterm infants. • Transcatheter closure of preterm ductus arteriosus is a safe and effective technique that is becoming more and more common worldwide. What is New: • Device closure is safer than surgical ligation for patent ductus arteriosus closure in preterm infants and may be the first-line non-pharmacological therapeutic option in this indication in experienced teams. • Our findings should encourage neonatologists and pediatric cardiologists to start and/or strengthen a durable interventional program for transcatheter PDA closure in premature infants.

Chylopericardium following esophagectomy: a case report and systematic review.

BACKGROUND: Chylopericardium is a rare condition characterized by the accumulation of chyle in the pericardial space. It is most commonly caused by thoracic duct injury. Chylopericardium following esophagectomy is extremely rare but can cause life-threatening complications. This report presents a case of chylopericardium post-esophagectomy, resulting in cardiac tamponade and cardiac arrest. A systematic literature review was also conducted to facilitate the understanding of this rare condition. CASE PRESENTATION: A 41-year-old male was admitted to our hospital with intermediate to highly differentiated squamous cell carcinoma of the mid-thoracic esophagus (clinical T4NxM0). He underwent thoracoscopic-laparoscopic esophagectomy with cervical anastomosis. On postoperative day 1, patient had a cardiac arrest secondary to cardiac tamponade, requiring emergency ultrasound-guided drainage. The drained fluid was initially serous but became chylous after the administration of enteral nutritional emulsion. As a result of significant daily pericardial drainage, patient subsequently underwent thoracic duct ligation. The amount of drainage was substantially reduced post-thoracic duct ligation. Over a period of 2 years and 7 months, patient recovered well and tolerated full oral diet. A comprehensive literature review was conducted and 4 reported cases were identified. Among these cases, three patients developed pericardial tamponade secondary to chylopericardium post-esophagectomy. CONCLUSION: Chylopericardium is a rare but serious complication post-esophagectomy. Prompt echocardiography and thorough pericardial fluid analysis are crucial for diagnosis. Thoracic duct ligation has been shown to be an effective management approach for this condition.

Effectiveness of antibiotic prophylaxis for acute esophageal variceal bleeding in patients with band ligation: A large observational study.

BACKGROUND: Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis. The current standard treatment is endoscopic variceal ligation (EVL), and Western guidelines recommend antibiotic prophylaxis following hemostasis. However, given the improvements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria, there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis. AIM: To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL. METHODS: We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals. Patients were divided into the prophylaxis group (received antibiotics on admission or the next day) and the non-prophylaxis group (did not receive antibiotics within one day of admission). The primary outcome was composed of 6-wk mortality, 4-wk rebleeding, and 4-wk spontaneous bacterial peritonitis (SBP). The secondary outcomes were each individual result and in-hospital mortality. A logistic regression with inverse probability of treatment weighting was used. A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures, while sensitivity analyses for antibiotic type and duration were also performed. RESULTS: Among 980 patients, 790 were included (prophylaxis: 232, non-prophylaxis: 558). Most patients were males under the age of 65 years with a median Child-Pugh score of 8. The composite primary outcomes occurred in 11.2% of patients in the prophylaxis group and 9.5% in the non-prophylaxis group. No significant differences in outcomes were observed between the groups (adjusted odds ratio, 1.11; 95% confidence interval, 0.61-1.99; P = 0.74). Individual outcomes such as 6-wk mortality, 4-wk rebleeding, 4-wk onset of SBP, and in-hospital mortality were not significantly different between the groups. The primary outcome did not differ between the Child-Pugh subgroups. Similar results were observed in the sensitivity analyses. CONCLUSION: No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study. Global reassessment of routine antibiotic prophylaxis is imperative.

[The association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices].

Objective: To investigate the association between portal vein thrombosis and rebleeding after non-urgent endoscopic treatment of esophagogastric varices. Methods: The cirrhotic patients with esophagogastric varices diagnosed in the People's Hospital of Zhengzhou University from January 2017 to March 2023 were retrospectively collected. The patients were divided into thrombotic group and non-thrombotic group according to the presence or absence of portal vein thrombosis. The failure rate of endoscopic treatment and rebleeding rate in different periods were compared between the two groups. Receiver operating characteristic (ROC) curve was used to select the best cutoff value of gastric varicose diameter that affected total rebleeding during follow-up in both groups. The influencing factors of rebleeding within 12 and 36 months in both groups were analyzed, and the influencing factors of rebleeding within 36 months in thrombus group were further analyzed. Results: A total of 106 patients were enrolled, including 53 patients in the thrombotic group [male 37, female 16, aged 18-78 (54±13) years] and 53 patients in the non-thrombotic group [male 37, female 16, aged 27-83 (55±12) years]. The follow-up time of the two groups were (20±15) and (25±15) months, respectively. The total rebleeding rate in the thrombotic group was higher than that in the non-thrombotic group [30.2% (16/53) vs 13.2% (7/53), P˂0.05]. The rebleeding rates within 6, 12, 24 and 36 months in the thrombotic group were higher than those in the non-thrombotic group [18.9% (10/53) vs 5.7% (3/53), 18.9% (10/53) vs 5.7% (3/53), 28.3% (15/53) vs 9.4% (5/53), 30.2% (16/53) vs 11.3% (6/53), all P˂0.05]. The best cut-off value of the diameter of gastric varices that affects the total rebleeding in the two groups was 10.4 mm (10 mm was selected as the best cut-off value for the convenience of practical clinical application). Hemoglobin ˂ 85 g/L (HR=0.202, 95%CI: 0.043-0.953, P=0.043), 10 mm ˂ the diameter of GV ≤ 15 mm (HR=5.321, 95%CI: 1.161-24.390, P=0.031) and endoscopic variceal ligation combined with endoscopic tissue adhesive injection (EVL+ETAI) (HR=7.172, 95%CI: 1.910-26.930, P=0.004) were the risk factors for the first gastroesophageal variceal rebleeding within 12 months after non-urgent endoscopic treatment. EVL+ETAI (HR=3.811, 95%CI: 1.441-10.084, P=0.007) and portal vein thrombosis (HR=4.026, 95%CI: 1.483-10.932, P=0.006) were the risk factors for the first gastroesophageal variceal rebleeding within 36 months after non-urgent endoscopic treatment. The study found that, 10 mm ˂ the diameter of GV ≤ 15 mm (HR=7.503, 95%CI: 1.568-35.890, P=0.012) was the risk factor for rebleeding within 36 months in the thrombotic group. Conclusion: Portal vein thrombosis is a risk factor for rebleeding after non-urgent endoscopic treatment of esophagogastric varices.

Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

Intractable chylous leak after radical esophagectomy treated with radiotherapy.

Postoperative chylous leak after esophagectomy is a rare but potentially life-threatening complication that results in hypovolemia, electrolyte imbalance, malnutrition, and immunologic deficiency. However, the management of postoperative chylous leak remains controversial. Following a diagnosis of esophageal cancer, a 64-year-old man was treated by video-assisted thoracoscopic esophagectomy, laparoscopic gastric tube formation, prophylactically thoracic duct ligation, and reconstruction with esophagogastrostomy at the neck level. Massive postoperative drainage from the thorax and abdomen did not initially meet the diagnostic criteria for chylothorax, which was ultimately diagnosed 3 weeks after the operation. Despite various treatments including total parenteral nutrition, octreotide and midodrine, reoperation (thoracic duct ligation and mechanical pleurodesis), and thoracic duct embolization, the chylous leak persisted. Finally, low-dose radiation therapy was administered with a daily dose of 2 Gy and completed at a total dose of 14 Gy. After this, the amount of pleural effusion gradually decreased over 2 weeks, and the last drainage tube was removed. The patient was alive and well at 60 months postoperatively. Herein, we describe a patient with intractable chylous leak after esophagectomy, which persisted despite conservative treatment, thoracic duct ligation, and embolization, but was finally successfully treated with radiotherapy.

Predicting the risk of early bleeding following endoscopic variceal ligation in cirrhotic patients with computed tomography.

BACKGROUND: Life-threatening bleeding following endoscopic variceal ligation (EVL) in patients with cirrhosis rarely can occur. The present study aimed to evaluate the performance of computed tomography (CT) in predicting the risk of early bleeding following EVL in cirrhotic patients. METHODS: We retrospectively investigated 285 cirrhotic patients who had undergone EVL. EVL was performed for prophylaxis or acute variceal bleeding. The patients were classified into 2 groups: early bleeding (< 14 days after EVL) and non-early bleeding. We compared baseline characteristics including CT findings between the patient groups. RESULTS: Among the 285 patients who underwent EVL treatment, 19 patients (6.7%) experienced early bleeding. On average, these bleeding occurred 9.3 ± 3.5 days after the EVL, with a range of 3 to 13 days. Patients who experience early bleeding had a higher six-week bleeding-related mortality rate compared to those in the non-early bleeding group (31.6% vs. 10.2%; p = 0.014). There was a correlation between the grade of esophageal varix observed during endoscopy and the diameter of esophageal varix observed on CT (p < 0.001). The diameter of esophageal varix on CT was identified as the only significant predictive factor for early bleeding (p = 0.005). CONCLUSION: A larger esophageal varix diameter observed on CT is associated with an increased risk of early bleeding after EVL treatment. Early identification of this high-risk group can provide a change of treatment strategies to improve patient outcomes.

Mitochondrial transplantation attenuates traumatic neuropathic pain, neuroinflammation, and apoptosis in rats with nerve root ligation.

Traumatic neuropathic pain (TNP) is caused by traumatic damage to the somatosensory system and induces the presentation of allodynia and hyperalgesia. Mitochondrial dysfunction, neuroinflammation, and apoptosis are hallmarks in the pathogenesis of TNP. Recently, mitochondria-based therapy has emerged as a potential therapeutic intervention for diseases related to mitochondrial dysfunction. However, the therapeutic effectiveness of mitochondrial transplantation (MT) on TNP has rarely been investigated. Here, we validated the efficacy of MT in treating TNP. Both in vivo and in vitro TNP models by conducting an L5 spinal nerve ligation in rats and exposing the primary dorsal root ganglion (DRG) neurons to capsaicin, respectively, were applied in this study. The MT was operated by administrating 100 µg of soleus-derived allogeneic mitochondria into the ipsilateral L5 DRG in vivo and the culture medium in vitro. Results showed that the viable transplanted mitochondria migrated into the rats' spinal cord and sciatic nerve. MT alleviated the nerve ligation-induced mechanical and thermal pain hypersensitivity. The nerve ligation-induced glial activation and the expression of pro-inflammatory cytokines and apoptotic markers in the spinal cord were also repressed by MT. Consistently, exogenous mitochondria reversed the capsaicin-induced reduction of mitochondrial membrane potential and expression of pro-inflammatory cytokines and apoptotic markers in the primary DRG neurons in vitro. Our findings suggest that MT mitigates the spinal nerve ligation-induced apoptosis and neuroinflammation, potentially playing a role in providing neuroprotection against TNP.

Laparoscopic Splenectomy and Esophagogastric Devascularization Versus Endoscopic Varices Ligation Plus Laparoscopic Splenectomy in the Treatment of Portal Hypertension.

Background/Aims: To compare laparoscopic splenectomy and esophagogastric devascularization (LSED) with endoscopic variceal ligation (EVL) plus laparoscopic splenectomy (LS) in treating esophagogastric variceal bleeding (EGVB) caused by portal hypertension (PH). Methods: Between January 2015 and May 2022, 87 patients with PH caused by hepatitis B cirrhosis were included in the retrospective study (34 in LSED versus 53 in EVL + LS). Results: The clinical features of both groups were well-matched (P > .05). The EVL+LS group was associated with shorter operation time, lower operative blood loss, faster gastrointestinal (GI) recovery, lower C-reactive protein levels, and shorter hospital stays after operation (P < .05). Operative morbidity was more significant in the LSED group (19 55.9% versus 18 33.9%) (P < .05). On postoperative days 1 and 3, albumin levels were remarkably lower (P < .05) in the LSED group. The mean follow-up was 24.3 months for LSED and 26.5 for EVL+LS. Hematological parameters, hepatic functional status, hepatic hemodynamics, and endoscopy indicated a substantial improvement in both groups (P < .05), but no significant difference was identified (P > .05). There was no discernible difference in the incidence of GI bleeding between the two groups (P > .05). Conclusion: EVL+LS is a safer, simpler, and more minimally invasive treatment of EGVB secondary to PH.

Effects of Milrinone on Neonates after Patent Ductus Arteriosus Ligation: A Retrospective Nationwide Database Study.

INTRODUCTION: Milrinone is administered after patent ductus arteriosus (PDA) ligation to prevent and treat postoperative hemodynamic instability (i.e., postligation cardiac syndrome). We aimed to explore the effectiveness of milrinone on in-hospital outcomes in infants who underwent PDA ligation using a nationwide inpatient database in Japan. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients who received milrinone after PDA ligation (n = 428) in neonatal intensive care units between July 2010 and March 2021 and those who did not (n = 3,392). We conducted a 1:4 propensity score-matched analysis with adjustment for background characteristics (e.g., gestational age, birth weight, comorbidities, preoperative treatments, and hospital background) to compare morbidities (bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity), mortality, total hospitalization costs, and other outcomes. For sensitivity analysis, we performed an overlap propensity score-weighted analysis. RESULTS: In-hospital morbidity, bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis occurred in 58%, 48%, 9.5%, and 7.1% of patients, respectively; the in-hospital mortality was 5.4%. After 1:4 propensity score matching, no significant difference was observed regarding mortality (7.1 vs. 5.7%), in-hospital morbidity (55 vs. 50%), bronchopulmonary dysplasia (44 vs. 41%), intraventricular hemorrhage (7.8 vs. 9.1%), necrotizing enterocolitis (8.5 vs. 8.9%), retinopathy of prematurity (21 vs. 22%), or total hospitalization costs (median: approximately 86,000 vs. 82,000 US dollars) between milrinone users (n = 425) and nonusers (n = 1,698). Sensitivity analyses yielded consistent results. CONCLUSIONS: Milrinone use after PDA ligation was not associated with improved in-hospital outcomes, such as mortality and morbidity.

Stattic ameliorates the cecal ligation and puncture-induced cardiac injury in septic mice via IL-6-gp130-STAT3 signaling pathway.

AIM: Sepsis-induced cardiac dysfunction is the leading cause of higher morbidity and mortality with poor prognosis in septic patients. Our recent previous investigation provides evidence of the hallmarks of signal transducer and activator of transcription3 (STAT3) activation in sepsis and targeting of STAT3 with Stattic, a small-molecule inhibitor of STAT3, has beneficial effects in various septic tissues. We investigated the possible cardioprotective effects of Stattic on cardiac inflammation and dysfunction in mice with cecal ligation and puncture (CLP)-induced sepsis. MAIN METHODS: A polymicrobial sepsis model was induced by CLP in mice and Stattic (25 mg/kg) was intraperitoneally given at one and twelve hours after CLP operation. The cecum was exposed in sham-control mice without CLP. After 18 h of surgery, electrocardiogram (ECG) for anaesthized mice was registered followed by collecting of samples of blood and tissues for bimolecular and histopathological assessments. Myeloperoxidase, a marker of neutrophil infiltration, was assessed immunohistochemically. KEY FINDINGS: CLP profoundly impaired cardiac functions as evidenced by ECG changes in septic mice as well as elevation of cardiac enzymes, and inflammatory markers with myocardial histopathological and immunohistochemical alterations. While, Stattic markedly reversed the CLP-induced cardiac abnormalities and restored the cardiac function by its anti-inflammatory activities. SIGNIFICANCE: Stattic treatment had potential beneficial effects against sepsis-induced cardiac inflammation, dysfunction and damage. Its cardioprotective effects were possibly attributed to its anti-inflammatory activities by targeting STAT3 and downregulation of IL-6 and gp130. Our investigations suggest that Stattic could be a promising target for management of cardiac sepsis and inflammation-related cardiac damage.

A comparative study between high ligation of the inter-sphincteric fistula tract via lateral Approach Versus Fistulotomy and primary sphincteroplasty in High Trans-Sphincteric Fistula-in-Ano: a randomized clinical trial.

BACKGROUND: Trans-sphincteric fistula management is very challenging and everyday new techniques are introduced to reach the safest and the most effective technique. In this study two of the most effective techniques are compared based on their post-operative outcomes. OBJECTIVE: To compare the efficacy of high ligation of the inter-sphincteric fistula tract by lateral approach (modified LIFT) and Fistulotomy and primary sphincteroplasty (FIPS) in the management of high trans-sphincteric fistula regarding their post-operative outcomes in the form of post-operative pain, time of wound healing in weeks, wound infection, incontinence and recurrence within one year. PATIENTS AND METHODS: The current study is single-blind, prospective, randomized, controlled, single-center trial conducted from June 2020 to June 2022 in the colorectal surgical unit of Ain Shams University Hospitals, which included 80 patients presented with high trans-sphincteric perianal fistula 55 (68.75%) males and 25 (31.25%) including a one-year follow-up postoperative. RESULTS: There were 80 patients in our study 40 patients in each group. The mean age of group (I) is 46.65 with standard deviation 6.6. while, in group (II) the mean age is 45.85 with standard deviation 6.07 (p = 0.576). From the included 80 patients 55(68.7%) were males and 25 (31.25%) were females (p = 0.469). Regarding, postoperative wound infection occurred in 2(5%) Patients in group (I) and 7(17.5%) patients in group (II) (p = 0.154). There were no cases of incontinence in group I. However, there were 6(15%) cases of incontinence to gases only scored by Wexner score 3/20 in group II (p = 0.026) and its significant difference between the two techniques. Postoperative pain was assessed for one week duration by the visual analogue score (VAS) from 0 to 10 in which, zero is the least and 10 is the maximum. In group (I) 18(45%) patients scored their pain mild from 1 to 3, 20(50%) patients scored their pain moderate from 4 to 6 and 2(5%) patients scored severe pain from 7 to 9. While, in group (II) 14(35%) patients scored their pain mild from 1 to 3, 22(55%) patients their pain moderate from 4 to 6 and 4(10%) patients scored their pain severe from 7 to 9 (p = 0.275). Recurrence in one-year follow-up occurred in 13(32.5%) patients in group (I) about 7 patients had recurrence in the form of inter-sphincteric fistula and 6 patients in the form of trans-sphincteric fistula. While, in group II recurrence occurred in 1 (2.5%) patient in the form of subcutaneous fistula at the healing site (p = 0.001). CONCLUSION: Fistulotomy and primary sphincteroplasty is an effective and preferred technique for the trans-sphincteric fistula repair with high statistically significant lower incidence of recurrence in one-year follow-up as compared to modified LIFT technique. Although, there is higher incidence regarding incontinence to gases only post-operative. This work recommends fistulotomy and primary sphincter reconstruction procedure in high trans-sphincteric perianal fistulas to be more popular, to be implemented as a corner stone procedure along various and classic operations for such cases as it's easy, feasible.

Aloe-Emodin Ameliorates Cecal Ligation and Puncture-Induced Sepsis.

Sepsis remains a major challenge owing to its severe adverse effects and high mortality, against which specific pharmacological interventions with high efficacy are limited. Mitigation of hyperactive inflammatory responses is a key factor in enhancing the likelihood of survival in patients with sepsis. The Aloe genus has several health benefits, including anti-inflammatory properties. The toxicological implications of aloe-emodin (AE), extracted from various Aloe species, remain uncertain in clinical contexts. However, AE has been shown to inhibit inflammatory responses in lipopolysaccharide-induced mice, indicating its potential as a therapeutic approach for sepsis treatment. Nonetheless, there is a paucity of data regarding the therapeutic benefits of AE in the widely recognized cecal ligation and puncture (CLP)-induced sepsis model, which is commonly used as the gold standard model for sepsis research. This study demonstrates the potential benefits of AE in the treatment of CLP-induced sepsis and investigates its underlying mechanism, along with the efficacy of postoperative AE treatment in mice with CLP-induced sepsis. The results of this study suggest that AE can mitigate sepsis in mice by diminishing systemic inflammation and regulating the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.

Establishing a new model of cancer neuropathic pain in rats.

To guide the treatment of malignant neuropathic pain (MNP) in clinical practice, by inoculating MADB-106 breast cancer cells into the right L4 nerve root in Sprague-Dawley rats, a rat model of MNP was established, providing basic conditions for the study of neuropathic pain and development and application of therapeutic drugs. As the tumor grew over time, it pressed the nerve roots, causing nerve damage. The spinal nerve ligation (SNL) model, which is a neuropathic pain model widely used in rats, was compared with the L4 nerve root SNL model, and histologic examination of the nerve tissue of both models was performed by electron microscopy. In addition to the infiltration and erosion of the L4 nerve by tumor cells, the tumor tissue gradually grew and compressed the L4 nerve roots, resulting in hyperalgesia of the rat's posterior foot on the operative side. Some spontaneous pain phenomena were also observed, such as constant lifting or licking of the posterior foot on the operative side under quiet conditions. Electron microscopy images showed that nerve injury was due to progressive compression by the tumor, cells of which were visualized, but the injury was lighter than that in SNL rats. Imaging showed a paravertebral tumor near the L4 nerve root in the carcinomatous neuropathic pain model rat. These results suggest that progressive compression of the nerve by a malignant tumor leads to nerve damage similar to the behavioral changes associated with chronic compression injury resulting from a loose ligature of the nerve. The cancer neuropathologic pain model at the L4 nerve root was successfully established in Sprague-Dawley rats.