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Purpose: To highlight spontaneous resolution or improvement of myopic retinoschisis (MR) in actively surveilled patients. Methods: Case series of five patients diagnosed with MR who did not undergo pars plana vitrectomy and were carefully monitored by a single retina specialist. Ocular and medical history were reviewed, and clinical characteristics including visual acuity and the status of the MR were monitored with spectral domain optical coherence tomography (SD-OCT) at each clinic visit. Results: Five patients were identified to have MR without vitreomacular traction, or macular hole formation. Two patients exhibited spontaneous and complete resolution of MR without surgical intervention over an average observation time of 52.5 months. In these cases, a clinical posterior vitreous detachment was documented preceding the resolution of MR over an average time of 26.5 months. Snellen best-corrected visual acuity in these patients improved (Case 1 from 20/50 to 20/40, Case 2 from 20/30 to 20/25). The remaining three patients were monitored for an average of 52 months and showed improvement of MR via OCT imaging. Snellen best-corrected visual acuity either remained stable or improved from baseline (Case 3 stable at 20/30, Case 4 improved from 20/40 to 20/30, and Case 5 stable at 20/20). Conclusion: These findings suggest that conservative management of MR with observation can be considered especially in patients with challenging comorbidities (such as monocular status), and with a clinically identified posterior vitreous detachment without vitreomacular traction.

Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.

BACKGROUND: Global medical education is gradually moving toward more comprehensive implementations of a competency-based education (CBE) model. Elimination of standard time-based training and adoption of time-variable training (competency-based time-variable training [CB-TVT]) is one of the final stages of implementation of CBE. While CB-TVT has been implemented in some programs outside the United States, residency programs in the United States are still exploring this approach to training. The Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Medical Specialties (ABMS) are encouraging member boards and residency review committees to consider innovative ways programs could implement CB-TVT. The goals of this study were to (1) identify potential problems with the implementation of CB-TVT in anesthesiology residency training, (2) rank the importance of the problems and the perceived difficulty of solving them, and (3) develop proposed solutions to the identified problems. METHODS: Study participants were recruited from key stakeholder groups in anesthesiology education, including current or former program directors, department chairs, residents, fellows, American Board of Anesthesiology (ABA) board members, ACGME residency review committee members or ACGME leaders, designated institutional officials, residency program coordinators, clinical operations directors, and leaders of large anesthesiology community practice groups. This study was conducted in 2 phases. In phase 1, survey questionnaires were iteratively distributed to participants to identify problems with the implementation of CB-TVT. Participants were also asked to rank the perceived importance and difficulty of each problem and to identify relevant stakeholder groups that would be responsible for solving each problem. In phase 2, surveys focused on identifying potential solutions for problems identified in phase 1. RESULTS: A total of 36 stakeholders identified 39 potential problems, grouped into 7 major categories, with the implementation of CB-TVT in anesthesiology residency training. Of the 39 problems, 19 (48.7%) were marked as important or very important on a 5-point scale and 12 of 19 (63.2%) of the important problems were marked as difficult or very difficult to solve on a 5-point scale. Stakeholders proposed 165 total solutions to the identified problems. CONCLUSIONS: CB-TVT is a promising educational model for anesthesiology residency, which potentially results in learner flexibility, individualization of curricula, and utilization of competencies to determine learner advancement. Because of the potential problems with the implementation of CB-TVT, it is important for future pilot implementations of CB-TVT to document realized problems, efficacy of solutions, and effects on educational outcomes to justify the burden of implementing CB-TVT.

ImportanceSyncope is the most powerful predictor for subsequent life-threatening events (LTEs) in patients with congenital long QT syndrome (LQTS). Whether distinct syncope triggers are associated with differential subsequent risk of LTEs is unknown.ObjectiveTo evaluate the association between adrenergic (AD)– and nonadrenergic (non–AD)-triggered syncopal events and the risk of subsequent LTEs in patients with LQT types 1 to 3 (LQT1-3).Design, Setting, and ParticipantsThis retrospective cohort study included data from 5 international LQTS registries (Rochester, New York; the Mayo Clinic, Rochester, Minnesota; Israel, the Netherlands, and Japan). The study population comprised 2938 patients with genetically confirmed LQT1, LQT2, or LQT3 stemming from a single LQTS-causative variant. Patients were enrolled from July 1979 to July 2021.ExposuresSyncope by AD and non-AD triggers.Main Outcomes and MeasuresThe primary end point was the first occurrence of an LTE. Multivariate Cox regression was used to determine the association of AD- or non–AD-triggered syncope on the risk of subsequent LTE by genotype. Separate analysis was performed in patients with β-blockers.ResultsA total of 2938 patients were included (mean [SD] age at enrollment, 29 [7] years; 1645 [56%] female). In 1331 patients with LQT1, a first syncope occurred in 365 (27%) and was induced mostly with AD triggers (243 [67%]). Syncope preceded 43 subsequent LTEs (68%). Syncopal episodes associated with AD triggers were associated with the highest risk of subsequent LTE (hazard ratio [HR], 7.61; 95% CI, 4.18-14.20; P < .001), whereas the risk associated with syncopal events due to non-AD triggers was statistically nonsignificant (HR, 1.50; 95% CI, 0.21-4.77; P = .97). In 1106 patients with LQT2, a first syncope occurred in 283 (26%) and was associated with AD and non-AD triggers in 106 (37%) and 177 (63%), respectively. Syncope preceded 55 LTEs (56%). Both AD- and non–AD-triggered syncope were associated with a greater than 3-fold increased risk of subsequent LTE (HR, 3.07; 95% CI, 1.66-5.67; P ≤ .001 and HR, 3.45, 95% CI, 1.96-6.06; P ≤ .001, respectively). In contrast, in 501 patients with LQT3, LTE was preceded by a syncopal episode in 7 (12%). In patients with LQT1 and LQT2, treatment with β-blockers following a syncopal event was associated with a significant reduction in the risk of subsequent LTEs. The rate of breakthrough events during treatment with β-blockers was significantly higher among those treated with selective agents vs nonselective agents.Conclusion and RelevanceIn this study, trigger-specific syncope in LQTS patients was associated with differential risk of subsequent LTE and response to β-blocker therapy.

Objective Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) can be monophasic or relapsing, with early relapse being a feature. However, the relevance of early relapse on longer‐term relapse risk is unknown. Here, we investigate whether early relapses increase longer‐term relapse risk in patients with MOGAD. Methods A retrospective analysis of 289 adult‐ and pediatric‐onset patients with MOGAD followed for at least 2 years in 6 specialized referral centers. “Early relapses” were defined as attacks within the first 12 months from onset, with “very early relapses” defined within 30 to 90 days from onset and “delayed early relapses” defined within 90 to 365 days. “Long‐term relapses” were defined as relapses beyond 12 months. Cox regression modeling and Kaplan–Meier survival analysis were used to estimate the long‐term relapse risk and rate. Results Sixty‐seven patients (23.2%) had early relapses with a median number of 1 event. Univariate analysis revealed an elevated risk for long‐term relapses if any “early relapses” were present (hazard ratio [HR] = 2.11, p < 0.001), whether occurring during the first 3 months (HR = 2.70, p < 0.001) or the remaining 9 months (HR = 1.88, p = 0.001), with similar results yielded in the multivariate analysis. In children with onset below aged 12 years, only delayed early relapses were associated with an increased risk of long‐term relapses (HR = 2.64, p = 0.026). Interpretation The presence of very early relapses and delayed early relapses within 12 months of onset in patients with MOGAD increases the risk of long‐term relapsing disease, whereas a relapse within 90 days appears not to indicate a chronic inflammatory process in young pediatric‐onset disease. ANN NEUROL 2023;94:508–517

Background: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn’s disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. Study: Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. Results: Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. Conclusions: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Background The Woven EndoBridge (WEB) has been specifically developed to manage wide neck bifurcation intracranial aneurysms. A wide range of aneurysm occlusion rates and device-related complications are reported in different papers, and a lack of collective evidence in this regard. Objective To clarify the long-term efficacy and safety outcomes of intracranial aneurysm treatment with WEB devices. Methods A systematic literature search was performed on PubMed, Scopus, Web of Science, and Embase databases on April 25, 2023. Considering the eligibility criteria, all the studies reporting the outcomes of the intracranial aneurysm treatment with WEB device at 1 and/or more than 1 year were included. Data elements of interest were extracted and analyzed using R software version 4.2.1. Results Twenty-seven articles were included. Complete occlusion rate was 56.85%, 67.10%, and 56.34% at one year, beyond one year, and at/beyond two years of follow-up, respectively. Adequate occlusion rate was 87.11% at one year, 91.16% beyond one year, and 88.87% at/beyond two years of follow-up. WEB compression and aneurysm recurrence rates increased from 17.62% and 0.58% at one year to 42.59% and 18.99% beyond one year of follow-up, respectively. An increase in retreatment rate from 3.45% at one year to 7.15% beyond one year of follow-up was found. Conclusion The current study supports the long-term efficacy of WEB devices for the treatment of intracranial aneurysms. However, an increase in WEB compression, aneurysm recurrence, and retreatment rates beyond one year reveals the importance of follow-ups after the first year of WEB placement.

AbstractKidney transplantation is the preferred treatment for individuals with end‐stage kidney disease. From a modeling perspective, our understanding of kidney function trajectories after transplantation remains limited. Current modeling of kidney function post‐transplantation is focused on linear slopes or percent decline and often excludes the highly variable early timepoints post‐transplantation, where kidney function recovers and then stabilizes. Using estimated glomerular filtration rate (eGFR), a well‐known biomarker of kidney function, from an aggregated dataset of 4904 kidney transplant patients including both observational studies and clinical trials, we developed a longitudinal model of kidney function trajectories from time of transplant to 6 years post‐transplant. Our model is a nonlinear, mixed‐effects model built in NONMEM that captured both the recovery phase after kidney transplantation, where the graft recovers function, and the long‐term phase of stabilization and slow decline. Model fit was assessed using diagnostic plots and individual fits. Model performance, assessed via visual predictive checks, suggests accurate model predictions of eGFR at the median and lower 95% quantiles of eGFR, ranges which are of critical clinical importance for assessing loss of kidney function. Various clinically relevant covariates were also explored and found to improve the model. For example, transplant recipients of deceased donors recover function more slowly after transplantation and calcineurin inhibitor use promotes faster long‐term decay. Our work provides a generalizable, nonlinear model of kidney allograft function that will be useful for estimating eGFR up to 6 years post‐transplant in various clinically relevant populations.

Abstract The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of VPS35L, VPS26C and VPS29, together with the CCC complex comprising CCDC22, CCDC93, and COMMD proteins, plays a crucial role in this process. The precise mechanisms underlying Retriever assembly and its interaction with CCC have remained elusive. Here, we present the first high-resolution structure of Retriever determined using cryogenic electron microscopy. The structure reveals a unique assembly mechanism, distinguishing it from its remotely related paralog, Retromer. By combining AlphaFold predictions and biochemical, cellular, and proteomic analyses, we further elucidate the structural organization of the entire Retriever-CCC complex and uncover how cancer-associated mutations disrupt complex formation and impair membrane protein homeostasis. These findings provide a fundamental framework for understanding the biological and pathological implications associated with Retriever-CCC-mediated endosomal recycling.