Transurachal Catheter for Management of Difficult Catheterization in Anorectal Malformations: A Novel Technique.

BACKGROUND: Urinary tract drainage is necessary to facilitate the maneuver in laparoscopic-assisted anorectoplasty (LAARP). Male patients with Anorectal malformations (ARM) are often encounter difficult catheterization during surgery. OBJECTIVE: We pioneered the urinary catheterization through the urachus in ARM patients and evaluated the efficacy. METHOD: Fourteen ARM patients undergoing urinary catheterization through urachus between September 2015 and September 2023 were reviewed. RESULTS: The median age at the time of surgery was 0.06 months. Nine neonatal patients underwent the one-stage LAARP, while five patients underwent staged procedure. Four ARM patients with rectoprostatic fistula, while ten with rectobulbar fistula. All patients successfully underwent transurachal catheterization. No incidents of catheter blockage, accidental removal, or urinary tract infection symptoms were detected during hospitalization. CONCLUSIONS: Transurachal catheterization is a safe, effective, and cosmetic procedure for ARM patients with difficulty urethral catheterization. LEVEL OF EVIDENCE: IV.

Evaluation of the impact of repeated intravenous phage doses on mammalian host-phage interactions.

Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.IMPORTANCEPhage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes.

Pharmacokinetics and safety evaluation of intravenously administered Pseudomonas phage PA_LZ7 in a mouse model.

IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.

Laparoscopic-assisted anorectoplasty for anorectal malformation with rectobulbar fistula: A two-center comparative study with posterior sagittal anorectoplasty.

Due to the controversy on the feasibility of laparoscopic-assisted anorectoplasty (LAARP) for the treatment of the anorectal malformation (ARM) with rectobulbar fistula (RBF), this study aimed to compare the outcomes of LAARP and posterior sagittal anorectoplasty (PSARP) for ARM with RBF. Demographic data, postoperative complications, and bowel function of RBF patients who underwent LAARP and PSARP at 2 medical centers from 2016-2018 were retrospectively reviewed. Eighty-eight children with RBF were enrolled, including 43 in the LAARP group and 45 in the PSARP group. There were no significant differences in the sacral ratio (P = .222) or sacral agenesis (P = .374). Thirty-seven and 38 patients in the LAARP and PSARP groups were followed up for a median of 4.14 years. The postoperative complications were comparable between the groups (P = .624), with no cases of urethral diverticulum. The urination of all cases was normal and no evidence of cyst formation was found on MCU or MRI during the follow-up period. The incidence of rectal prolapse was similar between the 2 groups (9.3% vs 17.8%, P = .247). The groups had equivalent Bowel Function Score (15.29 ± 2.36 vs 15.58 ± 2.88, P = .645), but the LAARP group had better voluntary bowel movement (94.6% vs 84.2%, P = .148) by Krickenbeck classification. The intermediate-term outcomes of LAARP show that the urethral diverticulum was rare by the intraluminal incision of the fistular and the bowel function was comparable to that of PSARP in ARM with rectobulbar fistula. However, LAARP was associated with smaller perineal wounds.

Risk factors analysis for clinical symptoms of prenatally diagnosed choledochal cysts: a retrospective study.

BACKGROUND: This study aimed to screen the impact factors for clinical symptoms of prenatally diagnosed choledochal cysts (CDCs), to warn about the occurrence of clinical symptoms and the timing of surgery. METHODS: Medical records of patients with prenatally diagnosed CDCs admitted to our hospital from April 2013 to April 2018 were retrospectively reviewed. Fetal hilar or abdominal cysts were found by prenatal ultrasonogram. All patients underwent laparoscopic cyst excision and hepaticojejunostomy in our center. Univariate analysis and multivariate logistic regression analysis were performed to screen the factors related to clinical symptoms intimately. RESULTS: Two hundred eighteen cases were included. One hundred thirty-four patients (134/218, 61.5%) presented clinical symptoms before surgery. The results of univariate analysis showed that patients with clinical symptoms had earlier time of prenatal diagnosis (P = 0.002), higher values of GGT, TBIL, DBIL (P < 0.001, P < 0.001, P < 0.001, respectively) and larger maximum diameter of cyst before surgery (P = 0.012). Multivariate logistic regression analysis suggested that the time of prenatal diagnosis (P = 0.001, OR = 0.898, 95% CI: 0.845 ~ 0.955) and the GGT value within one week of life (P = 0.028, OR = 1.002, 95% CI: 1.000 ~ 1.003) were independent influencing factors for symptoms. CONCLUSIONS: For children with prenatally diagnosed CDCs, approximately 2/3 patients presented noticeable clinical symptoms before surgery. The time of prenatal diagnosis and the GGT value within 1 week of life were independent impact factors for the occurrence of clinical symptoms.

Establishment and validation of a predictive nomogram for the risk of premalignant lesions in children with choledochal cyst.

Background: Choledochal cyst (CDC) increases the risk (2.5%-30%) of malignancy. Metaplasia and dysplasia have been recognized as premalignant lesions among CDCs. This study aimed to evaluate the risk factors of metaplasia and dysplasia in CDC children. Methods: Two hundred and ten CDC children who underwent cyst excision and Roux-en-Y hepaticojejunostomy at our institution between July 2020 and November 2021 were included and randomly divided into the training set and validation set. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of premalignant lesions in the training set and build a predictive nomogram. The performance and discriminatory abilities of the nomogram were further assessed and validated in the validation set. Results: Of the 210 CDC children, 78 (37.1%) patients developed premalignant lesions. Age (OR, 1.011, 95%CI, 1.000-1.022, P = 0.046), symptoms duration (OR, 1.021, 95%CI, 1.001-1.042, P = 0.036), cyst diameter (OR, 1.737, 95%CI, 1.328-2.273, P < 0.001), recurrent attacks of biliary pancreatitis (OR, 3.653, 95%CI, 1.205-11.076, P = 0.022), and biliary operation history (OR, 5.860, 95%CI, 1.268-27.084, P = 0.024) were identified as independent risk factors. Based on these predictors, a predictive nomogram was generated. The AUC of the nomogram was 0.873 in the training set and 0.793 in the validation set, indicating that it was robust and well calibrated. Conclusions: A novel nomogram to the individualized risk of premalignant lesions in CDC children was successfully built, on the basis of age, symptoms duration, cyst diameter, recurrent attacks of biliary pancreatitis, and biliary operation history. This nomogram, combined with the final pathological results, can help clinicians to develop more efficient follow-up strategies for the high-risk children with CDC.

Prenatal diagnosis at different gestational times and clinical features of choledochal cysts: a single tertiary center report.

PURPOSE: This study aimed to evaluate the effect of prenatal diagnosis at different gestational times on the clinical features of patients with choledochal cysts (CDCs). METHODS: Medical records of patients with prenatally diagnosed CDCs admitted to our hospital (April 2013-April 2018) were retrospectively reviewed. The clinical characteristics and pathological CDC features were analyzed. RESULTS: Two hundred eighteen cases were included. Patients were divided into two groups. Group 1 and group 2 had a prenatal diagnosis at ≤ 27 weeks of gestation (second trimester of gestation, n = 157) and > 27 weeks (third trimester of gestation, n = 61), respectively. The incidence of jaundice and the TBIL, IBIL and GGT levels were higher in Group 1 (P = 0.021, P = 0.029, P = 0.042, P = 0.007, respectively). The maximum cyst diameter at the time of surgery was larger in Group 1 (P = 0.015). An association study showed that the time of prenatal diagnosis was negatively correlated with the maximum cyst diameter both postnatally (r = - 0.223, P = 0.001) and at the time of surgery (r = - 0.268, P < 0.001). CONCLUSION: Unlike patients diagnosed at a late prenatal age, patients diagnosed at an early prenatal age tend to present clinical symptoms (jaundice, manifested as high indirect bilirubin), hepatic function damage, and large cysts at the time of surgery.

Effects of postoperative adjuvant steroid therapy on the outcomes of biliary atresia: A systematic review and updated meta-analysis.

Background: Postoperative adjuvant steroid therapy is regarded as the conventional treatment for patients with biliary atresia (BA) who have undergone Kasai portoenterostomy (KP). However, whether the steroid therapy can improve BA outcomes is controversial. This meta-analysis aimed to evaluate the effects of adjuvant steroid therapy on the surgical prognosis of BA. Methods: We searched related studies published in PubMed, Embase, Web of Science, Cochrane, and the Chinese National Knowledge Infrastructure database up to May 2022. Data on the effect of steroid use on the clinical prognosis of the patients, including the jaundice clearance rate (JCR), native liver survival rate (NLSR) at 6, 12, and 24 months after KP, and the incidence of cholangitis, were extracted. Subgroup analyses based on age at KP, administration method, initial dosage, and steroid type were conducted. Statistical analysis was conducted using Stata/SE 12.0. Results: Eleven articles (a total of 1,032 patients) were included in the present meta-analysis. The results demonstrated that postoperative adjuvant steroid therapy improved JCR at the 6/12/24-month follow-up (RR: 1.35, 95% CI: 1.18-1.55, p < 0.001; RR:1.49, 95% CI, 1.12-1.99, p = 0.006; RR: 1.41, 95% CI: 1.14-1.75, p = 0.002) and improved NLSR at the 24-month follow-up (RR: 1.31, 95% CI: 1.03-1.68, p = 0.028). However, steroids could not significantly improve NLSR at the 6/12-month follow-up (RR: 1.06; 95% CI: 0.98-1.15; p = 0.17; RR: 1.22; 95% CI: 0.97-1.54; p = 0.095), and might not decrease the incidence of postoperative cholangitis (RR: 0.78, 95% CI: 0.60-1.01, p = 0.058). Furthermore, subgroup analyses confirmed that three variables (age at KP, administration method, and initial dosage) could affect the efficacy of steroids in BA patients. Conclusion: Postoperative adjuvant steroid therapy can significantly improve bile flow. The superiority of steroid therapy was more remarkable in patients aged ≤70 days at KP than in those aged >70 days. Additionally, intravenous followed by oral steroid administration method and medium initial dosage seemed to have the more reliable efficiency on bile flow. And patients treated by steroid had better long-term (24-month) native liver survival, but there is no significant effect on short-term native liver survival and postoperative cholangitis. Further studies are warranted.

One-stage versus staged laparoscopic-assisted anorectoplasty for high-and intermediate anorectal malformations: Medium-term outcomes from a propensity score matching analysis.

BACKGROUND: The timing of anorectoplasty for anorectal malformations (ARMs) is controversial and essential for long-term bowel function. The advantages of laparoscopy make primary anoplasty possible for neonates. This study aims to report the medium-term results of the one-stage laparoscopic-assisted anorectoplasty (LAARP) and compare them with the staged LAARP. METHODS: This study included 242 boys who underwent LAARP between June 2013 and December 2018 in our center. Forty-five neonatal patients successfully underwent the one-stage LAARP, and the remaining 197 patients who had already undergone colostomy received staged procedures. The complications and bowel function were compared between the two groups after 1:1 propensity score matching (PSM). RESULTS: Before matching, age at assessment and classification were significantly different between the two groups (P < 0.05). After PSM, 42 patients were included in each of the two groups, and the patients were well balanced. The overall occurrence of postoperative complications in the one-stage group was significantly lower than in the staged group (P < 0.05). The median follow-up periods were 55.0 and 54.5 months, respectively. The mean value of BFS was similar in the two groups. After medical management, a second evaluation was conducted to distinguish overflow pseudo-incontinence from patients with no bowel control potential. The functional outcome in the two groups is comparable (P = 0.307). CONCLUSIONS: One-stage LAARP is safe and feasible for neonates with high-and intermediate-type ARMs. Compared with staged LAARP, one-stage LAARP has fewer complications and comparable functional outcomes. The authors recommend these procedures to be performed in dedicated centers with sufficient expertise. LEVEL OF EVIDENCE: Level III.

Dexmedetomidine regulates sevoflurane-induced neurotoxicity through the miR-330-3p/ULK1 axis.

Sevoflurane (Sev), a widely used volatile anesthetic, can cause long-term neurotoxicity and learning and memory impairment. Dexmedetomidine (Dex) has been reported to exhibit neuroprotective effects in numerous neurological disorders. Our work aimed to evaluate the molecular mechanisms of Dex in Sev-induced neurotoxicity. In this study, it was found that Dex mitigated Sev-induced neurotoxicity. Moreover, Sev treatment upregulated the miR-330-3p expression in hippocampus tissues, while this effect was reversed by the Dex treatment. Additionally, microRNA-330-3p (miR-330-3p) inhibition was verified to inhibit cell apoptosis and facilitate mitophagy. ULK1 was confirmed as a downstream target of miR-330-3p and miR-330-3p could negatively regulate ULK1 expression. Finally, the effects of miR-330-3p inhibition on Sev-induced neurotoxicity could be offset by ULK1 knockdown or further intensified by Dex treatment. In summary, our study demonstrated that Dex regulated cell apoptosis and mitophagy in Sev-induced neurotoxicity through the miR-330-3p/ULK1 axis. These findings might provide novel insights into the treatment of Sev-induced neurotoxicity.

Upstream Natural Pulsed Ventilation: A simple measure to control the sulfide and methane production in gravity sewer.

Production of sulfide and methane due to anaerobic biological transformations in sewer pipes causes serious problems to sewer maintenance. For gravity sewers, enhancing ventilation is a practical method that reduces the production of both sulfide and methane. This study aimed to determine the effectiveness of a new method, Upstream Natural Pulsed Ventilation (UNPV), to control sulfide and methane production in gravity sewers. Two lab-scale reactors simulating the gravity sewer pipe with and without ventilation were set up to assess the effectiveness. The results show that compared with the gravity sewer pipe without ventilation, under the UNPV condition, the total sulfide concentration reduced by 39.08% and 58.74%, and the methane concentration reduced by 42.29% and 35.70% in the upstream and downstream sewer pipe, respectively. High-throughput sequencing analysis showed that the UNPV method could inhibit the proliferation of sulfate-reducing bacteria and stimulate the proliferation of sulfur-oxidizing bacteria within the whole sewer pipe. The composition of methanogenic archaea that are responsible for methane production was changed by ventilation. The increased oxidation-reduction potential and organic carbon transportation in wastewater under ventilation may be responsible for the microbial community changes. The findings of this study may provide new insight to reduce sulfide and methane production in gravity sewers.