Thymectomy for juvenile myasthenia gravis: a narrative review.

Background and Objective: Thymectomy as a management strategy for juvenile myasthenia gravis (JMG) has been increasingly adopted with the advent of minimally invasive surgical techniques. This review evaluates existing evidence regarding the surgical management of JMG, including the benefits of surgical compared to medical therapy, important considerations when evaluating surgical candidacy and determining optimal timing of intervention. In addition, we provide an overview of the open, thoracoscopic and robotic surgical approaches available for thymectomy and compare the existing data to characterize optimal surgical management. Methods: A thorough literature review was conducted for full length research articles, including systematic reviews, retrospective cohort studies and case series, published between January 2000 and July 2023 regarding open, thoracoscopic or robotic thymectomy for management of JMG. Reference lists of the identified articles were manually searched for additional studies. Evidence was summarized in a narrative fashion with the incorporation of the authors' knowledge gained through clinical experience. Key Content and Findings: Although data specific to JMG are limited to small retrospective cohort studies, available evidence supports equal to greater disease control following thymectomy versus pharmacologic management. Furthermore, outcomes may be optimized when surgery is performed earlier in the disease course, particularly for patients who are post-pubertal with generalized or severe disease and those necessitating high-dose steroid administration thereby limiting its metabolic and growth inhibitory effects. Open transsternal resection is the historic gold-standard; however, as surgeons become more comfortable with thoracoscopic and robotic-assisted thymectomy, an increasing proportion of patients are expected to undergo thymectomy. At present, the data available is unable to support conclusions regarding which surgical approach is superior; however, minimally invasive approaches may be non-inferior while offering superior cosmesis and decreased morbidity. Conclusions: Higher-level investigation through the use of multi-institutional databases and randomized prospective trials is warranted in order to understand which child warrants thymectomy, at what point in their disease course and their development, and which surgical approach will optimize postoperative outcomes.

Exportin-1 functions as an adaptor for transcription factor-mediated docking of chromatin at the nuclear pore complex.

Nuclear pore proteins (Nups) in yeast, flies and mammals physically interact with hundreds or thousands of chromosomal sites, which impacts transcriptional regulation. In budding yeast, transcription factors mediate interaction of Nups with enhancers of highly active genes. To define the molecular basis of this mechanism, we exploited a separation-of-function mutation in the Gcn4 transcription factor that blocks its interaction with the nuclear pore complex (NPC) without altering its DNA binding or activation domains. SILAC mass spectrometry revealed that this mutation reduces the interaction of Gcn4 with the highly conserved nuclear export factor Crm1/Xpo1. Crm1 both interacts with the same sites as Nups genome-wide and is required for Nup2 to interact with the yeast genome. In vivo, Crm1 undergoes extensive and stable interactions with the NPC. In vitro, Crm1 binds to Gcn4 and these proteins form a complex with the nuclear pore protein Nup2. Importantly, the interaction between Crm1 and Gcn4 does not require Ran-GTP, suggesting that it is not through the nuclear export sequence binding site. Finally, Crm1 stimulates DNA binding by Gcn4, supporting a model in which allosteric coupling between Crm1 binding and DNA binding permits docking of transcription factor-bound enhancers at the NPC.

Patient-reported outcomes in 645 patients after laparoscopic fundoplication up to 10 years.

BACKGROUND: Laparoscopic fundoplication is the gold-standard surgical management for gastroesophageal reflux disease. Optimal patient outcomes include resolution of symptoms with minimal postoperative side effects of dysphagia or gas-bloat. This study aims to review outcomes at a single institution up to 10 years after surgery. METHODS: This is a retrospective review of a prospectively maintained quality database. Patients who underwent laparoscopic fundoplication from 2009 to 2021 were included. Transition in surgical practice mid-2017 with incorporation of fundoplication algorithm and impedance planimetry. Patient-reported outcome scores include Reflux Symptom Index, gastroesophageal reflux disease-health-related quality of life, and dysphagia score. Comparisons were made using two-tailed Wilcoxon rank sum tests. RESULTS: Six hundred forty-five patients underwent laparoscopic fundoplication (2009-July 2017 n = 355, July 2017-November 2021 n = 290) from January 2009 to November 2021. Patients had an improvement in patient-reported outcomes and did not worsen from 2 to 10 years after surgery. Comparison of each time period showed that the second time period had fewer gas-bloat symptoms at 2 years (P = .04). Paraesophageal hernia was present in 66% of patients. Preoperative patient-reported outcomes in non-paraesophageal hernia include worse Reflux Symptoms Index (P < .01) and gastroesophageal reflux disease-health-related quality of life (P < .01) than the paraesophageal hernia group. Patient-reported outcomes were similar between the 2 except for worse gas-bloat in non-paraesophageal hernia patients at 2 years (P = .02). Endoscopy was performed in 10.9% (n = 58) of the study population at a median of 16 months, with 1.5% of patients (n = 8) from the entire cohort with abnormal DeMeester Scores. Median (interquartile range) preoperative DeMeester Score of 31 (17-51) decreased to 5 (2-14) at postoperative evaluation. CONCLUSION: This single-institution study reports excellent long-term patient-reported outcomes after laparoscopic fundoplication that persist up to 10 years.

Impedance planimetry (EndoFLIP) measurements persist long term after anti-reflux surgery.

PURPOSE: The functional lumen imaging probe provides objective measurements of the gastroesophageal junction during laparoscopic anti-reflux surgery. There is a lack of data on how functional lumen imaging probe measurements change at follow-up. We aim to describe our institutional experience in performing functional lumen imaging probe during postoperative endoscopy after laparoscopic anti-reflux surgery. METHODS: A prospectively maintained database was queried. Patients who had postoperative endoscopic functional lumen imaging probe measurements between March 2018 and June 2021 were assessed at different time points from their index laparoscopic anti-reflux surgery using paired t test. Standardized quality of life questionnaires were collected for up to 2 years. Group comparisons were made using the Wilcoxon rank-sum test. RESULTS: Fifty-eight patients who underwent laparoscopic anti-reflux surgery (magnetic sphincter augmentation or fundoplication) had postoperative functional lumen imaging probe. Thirty-two intraoperative functional lumen imaging probe values were compared with their postoperative functional lumen imaging probe. Fundoplication values did not differ. Postoperative functional lumen imaging probe distensibility index for magnetic sphincter augmentation patients was decreased (P = .04). Functional lumen imaging probe measurements for all postoperative endoscopies showed that magnetic sphincter augmentation had the lowest distensibility index (P < .01). Dysphagia as a reason for endoscopy had a decrease in distensibility index (P = .03). CONCLUSION: Functional lumen imaging probe measurements after fundoplication persist at long-term follow up while patients may have a tighter gastroesophageal junction after magnetic sphincter augmentation. Functional lumen imaging probe has the potential to assess the success or failure after laparoscopic anti-reflux surgery and optimize patient outcomes.