In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of Schwann cell development are ...known, the signaling pathways that control myelination are incompletely understood. In this study, we show that Gpr126 is essential for myelination and other aspects of peripheral nerve development in mammals. A mutation in Gpr126 causes a severe congenital hypomyelinating peripheral neuropathy in mice, and expression of differentiated Schwann cell markers, including Pou3f1, Egr2, myelin protein zero and myelin basic protein, is reduced. Ultrastructural studies of Gpr126-/- mice showed that axonal sorting by Schwann cells is delayed, Remak bundles (non-myelinating Schwann cells associated with small caliber axons) are not observed, and Schwann cells are ultimately arrested at the promyelinating stage. Additionally, ectopic perineurial fibroblasts form aberrant fascicles throughout the endoneurium of the mutant sciatic nerve. This analysis shows that Gpr126 is required for Schwann cell myelination in mammals, and defines new roles for Gpr126 in axonal sorting, formation of mature non-myelinating Schwann cells and organization of the perineurium.
The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. However, regulation of hair bundle arrangements has not been fully understood. Recently, defects in ...hair bundle arrangement were reported in postnatal Dishevelled-associating protein (ccdc88c, alias Daple)-deficient mice. In the present study, we found that adult Daple
mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In adult Daple
mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical role of Daple in hair bundle arrangement through the orchestration of apical microtubule distribution, and thereby in hearing, especially at high frequencies.
Background
Native liver survival after laparoscopic Kasai portoenterostomy (Lap-PE) for biliary atresia (BA) is controversial. We examined whether a jaundice-free native liver survival rate is ...comparable between conventional Kasai portoenterostomy (Open-PE) and Lap-PE. Then, the impact of the two types of PE on subsequent living-donor liver transplantation (LTx) was addressed in this study.
Methods
The jaundice-free rate in 1- and 2-year-old patients who underwent Open-PE and Lap-PE from January 2006 to December 2017 was investigated. Additionally, perioperative data (duration from the start of surgery to the completion of hepatectomy and others) of patients aged 2 years or younger who underwent LTx after either Open-PE or Lap-PE from 2006 to 2017 were evaluated.
Results
Thirty-one (67%) out of 46 Open-PE patients and 23 (77%) out of 30 Lap-PE patients showed native liver survival with jaundice-free status at 1 year of age (
p
= 0.384); 29 (63%) out of 46 Open-PE patients and 19 (70%) out of 27 Lap-PE patients showed native liver survival with jaundice-free status at 2 years of age (
p
= 0.524); there were no significant differences. Additionally, there were 37 LTx cases after PE within 2 years of birth, including 29 Open-PE and 8 Lap-PE cases. The patients in the Lap-PE group had fewer adhesions and significantly shorter durations of surgery up to the completion of the recipient’s hepatectomy and durations of post-LTx hospital stay compared to the Open-PE group. There were no differences in blood loss or duration of stay in intensive care unit between the Lap-PE and Open-PE groups.
Conclusions
Jaundice-free native liver survival rate has been comparable between Open-PE and Lap-PE. Lap-PE resulted in fewer adhesions, contributing to better outcomes of subsequent LTx compared to Open-PE.
Urine is a complex liquid containing numerous small molecular metabolites. The ability to non-invasively test for cancer biomarkers in urine is especially beneficial for screening child patients. ...This study attempted to identify neuroblastoma biomarkers by comprehensively analysing urinary metabolite samples from children. A total of 87 urine samples were collected from 54 participants (15 children with neuroblastoma and 39 without cancer) and used to perform a comprehensive analysis. Urine metabolites were extracted using liquid chromatography/mass spectrometry and analysed by Metabolon, Inc. Biomarker candidates were extracted using the Wilcoxon rank sum test, random forest method (RF), and orthogonal partial least squares discriminant analysis (OPLS-DA). RF identified three important metabolic pathways in 15 samples from children with neuroblastoma. One metabolite was selected from each of the three identified pathways and combined to create a biomarker candidate (3-MTS, CTN, and COR) that represented each of the three pathways; using this candidate, all 15 cases were accurately distinguishable from the control group. Two cases in which known biomarkers were negative tested positive using this new biomarker. Furthermore, the predictive value did not decrease in cases with a low therapeutic effect. This approach could be effectively applied to identify biomarkers for other cancer types.
Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the ...pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin βA. We demonstrate that activin A, a homodimer of inhibin βA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin βA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.
Purpose
One of the main causes of stricture at hepaticojejunostomy site after surgery for congenital biliary dilatation is inflammation or infection associated with bile leak. The aim of this study ...was to determine the risk factors and outcomes of bile leak after laparoscopic surgery.
Methods
We retrospectively reviewed the demographics and outcomes of patients who underwent laparoscopic surgery for congenital biliary dilatation between September 2013 and December 2019. Data from patients with bile leak were compared to data from patients without bile leak.
Results
Fourteen of 78 patients had bile leak. Hepatic duct diameter at anastomosis was the only risk factor of bile leak. Patients with the diameter ≤ 10 mm had higher incidence of bile leak than in patients with the diameter > 10 mm (
P
= 0.0023). Among them, bile leak occurred more frequently in patients operated on by non-qualified surgeons based on the Japan Society for Endoscopic Surgery endoscopic surgical skill qualification system than by qualified surgeons (
P
= 0.027). However, none of the patients with bile leak developed anastomotic stricture afterwards.
Conclusion
Although good technical skill is necessary to avoid bile leak in narrow hepatic duct cases (≤ 10 mm), slight bile leak may not result in anastomotic stricture.
The aim of this study was to investigate whether the insertion of an implant into the cochlea is accompanied by a deterioration in otolith function. Cervical and ocular vestibular evoked myogenic ...potentials (cVEMP and oVEMP) and linear vestibulo-ocular reflex (lVOR) during eccentric rotation were assessed before and after cochlear implantation (CI) to evaluate otolith function.
Twelve patients with bilateral severe sensorineural hearing loss who had undergone CI surgery in our hospital between May 2016 and November 2017 were included in this study. cVEMP and oVEMP were assessed using the asymmetry ratio (AR), calculated with the following formula: (peak-to-peak amplitude calculated as the sum of the p13 and n23 amplitudes in the non-operated side) − (that in the operated side)/(that in the non-operated side) + (that in the operated side). The ratio of VOR gain during eccentric rotation against VOR gain during center rotation was used to assess lVOR. For eccentric rotation, patients were rotated while displaced from the axis of rotation. At the same time, linear acceleration stimulated the utricle and induced lVOR. All patients underwent cVEMP and oVEMP tests and center and eccentric rotation tests before and about 30days after CI surgery.
Three patients with absent cVEMP responses before surgery were excluded, leaving pre-surgery cVEMP results for 9/12 patients. In five of these patients, the AR of cVEMP increased after CI, indicating that saccular function, as evaluated by cVEMP, did not deteriorate significantly postoperatively. One patient with an absent oVEMP response before CI was excluded, leaving pre-surgery oVEMP results for 11/12 patients. In 10 of these patients, the AR of oVEMP increased after CI surgery, indicating that utricular function, as evaluated by oVEMP, deteriorated significantly postoperatively. However, because the ratio of VOR gain during eccentric rotation against VOR gain during center rotation did not become worse after CI, utricular function, as evaluated by lVOR, did not deteriorate significantly postoperatively. Symptoms of vertigo became worse after CI in two of the 12 patients.
CI does not cause a deterioration in saccular function, as evaluated by cVEMP. Although CI does cause a deterioration in utricular function in oVEMP tests, this is not consistent in lVOR tests. These results indicate that CI causes a slight deterioration in utricular function that is insufficient to cause vertigo or deterioration of lVOR.
Postoperative chylothorax after surgery for esophageal atresia/tracheoesophageal fistula (TEF) is a rare but serious complication, especially in neonates. This study aimed to identify the thoracic ...duct and ligate chylous leakage sites, using thoracoscopic navigation of an indocyanine-green (ICG)-based near-infrared (NIR) fluorescence imaging system.
From November 2014 to April 2017, thoracoscopic intraoperative ICG-NIR imaging was performed in 10 newborns (11 surgeries) with first TEF operation or with persistent postoperative chylothorax after TEF operation. NIR imaging was performed 1h after an inter-toe injection of ICG. Thoracoscopic ligations against the NIR-detected leakage sites were performed with sutures.
The thoracic duct or lymphatic leakage was directly visualized in each patient. In 8 surgeries with first thoracoscopic TEF operation, one case had suspected minor chylous leakage without postoperative chylothorax. Another case with no chylous leakage at the first operation resulted in chylothorax at postoperative day 11. In three neonates with postoperative chylothorax, leakage points were detected near the ablation site of the azygos vein during the first operation. These points were properly ligated, and postoperative chylous leakage ceased with no adverse events.
Thoracoscopic ICG-NIR imaging encourages the repair of refractory chylothorax and seems reliable.
IV
Background
The indications for and efficacy of revision of portoenterostomy (PE) for biliary atresia (BA) needs to be reassessed in an era of liver transplantation. We therefore reviewed the ...long‐term outcomes following revision of PE.
Methods
This was a retrospective study of the medical records of patients with BA who underwent PE and revision of PE. We investigated the role of revision on outcomes of jaundice‐free native liver survival (approval number: 2015–0094).
Results
Portoenterostomy was performed in 76 patients, among whom 22 underwent revision. Revision for recurrent jaundice was performed for four of 51 patients, who were transiently jaundice free after initial PE, but only one achieved native liver survival. Revision for repeated cholangitis in two patients achieved native liver survival over 10 years. Revision was performed in 16 of the 25 patients in whom initial PE failed; of these, four survived with their native liver (ages 3, 12, 12, and 14 years). The PE revision did not significantly affect liver transplantation duration and survival outcome.
Conclusions
Revision of PE was suitable for repeated cholangitis. Revision for recurrent jaundice, regardless of whether the initial PE was successful, could have a limited but positive effect in preventing long‐term progressive liver failure.
Highlight
Setting out to reassess the indications for and efficacy of revision of Kasai portoenterostomy for biliary atresia in the era of liver transplantation, Shirota and colleagues reviewed the long‐term outcomes following revision. Their results confirm that revision of Kasai portoenterostomy can have a positive effect in preventing progressive liver failure.
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