Citations

Background and Objectives: Evidence on the relationship between formative assessment engagement and summative assessment outcomes in practicing physicians is sparse. We evaluated the relationship between engagement in the American Board of Family Medicine (ABFM) formative Continuous Knowledge Self-Assessment (CKSA) and performance on high-stakes summative assessments. Methods: This retrospective cohort study included 24,926 ABFM diplomates who completed CKSA modules and summative assessments between 2017 and 2023. We analyzed CKSA engagement metrics—such as the number of quarters completed, time of completion, and self-reported confidence—against performance on summative assessments, measured by z scores. Multivariable regression models controlled for demographic factors and prior assessment performance. Results: The overall cohort summative assessment pass rate during the study period was 90.3%. Greater CKSA engagement was strongly associated with higher summative assessment performance. Diplomates who completed all four CKSA quarters had significantly higher summative assessment z scores than those completing fewer quarters (P<.001). Early CKSA completion and spending more time on low-confidence questions were also positively correlated with both CKSA and summative assessment scores (P<.001). These effects were observed across different levels of prior exam performance. Conclusions: Engagement in formative assessments like CKSA, particularly early and consistent participation and reviewing incorrect or low-confidence questions, is linked to better outcomes on high-stakes assessments. Future research should explore the mechanisms underlying these associations and consider developing an index of engagement to identify physicians at risk of poor performance. Incorporating structured, longitudinal self-assessments like CKSA into certification requirements could enhance continuous learning and improve summative exam readiness.

Abstract Glaucoma is characterized by programmed cell death of retinal ganglion cells (RGCs) after axonal injury. Several studies have shown the cell-intrinsic drivers of RGC degeneration act in a compartment-specific manor. Recently, the transcription factors JUN and DDIT3 were identified as critical hubs regulating RGC somal loss after mechanical axonal injury. It is possible somal DDIT3 and JUN activity initiates axonal degeneration mechanisms in glaucoma. Alternatively, DDIT3 and JUN may act downstream of inciting degenerative mechanisms and only drive RGC somal loss. The MAP2Ks MKK4 and MKK7 control all JNK and JUN activity and can indirectly activate DDIT3. Furthermore, MKK4 and MKK7 have been shown to drive RGC axonal degeneration after mechanical axonal injury. The present work investigated whether JUN and DDIT3, or their upstream activators MKK4 and MKK7, control degeneration of RGC axons and somas after glaucoma-relevant injury. Ddit3 and Jun deletion did not prevent axonal degeneration in ocular hypertensive DBA/2J mice but prevented nearly all RGC somal loss. Despite robust somal survival, Ddit3 and Jun deletion did not preserve RGC somal viability (as assessed by PERG decline and soma shrinkage) in DBA/2J mice or after glaucoma-relevant mechanical axonal injury. In contrast, Mkk4 and Mkk7 deletion significantly lessened degeneration of RGC somas and axons, and preserved somal function and size after axonal injury. In summary, activation of MKK4 and MKK7 appears to be the inciting mechanism governing death of the entire RGC after glaucoma-relevant injury; driving death of the RGC soma (likely through activation of DDIT3 and JUN), decline in somal viability, and axonal degeneration via DDIT3 and JUN-independent mechanisms.

Objective To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA). Methods In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open‐label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months. Results Sixty‐five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo ( P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid‐free remission, relapse severity, prevention of damage, and patient‐reported quality‐of‐life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection. Conclusion In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.

ObjectivesAchalasia is an esophageal motility disorder that impairs quality of life and is often missed (20–50%) on endoscopy. A newly developed computer‐aided detection (CAD) software has shown high accuracy for achalasia diagnosis in preclinical settings. However, its benefit in a clinical setting remains unclear.MethodsBetween February and August 2023, 83 endoscopists from 27 centers assessed 50 randomized endoscopic videos (25 achalasia, 25 nonachalasia) without and with CAD. Endoscopists assessed videos without CAD, then with CAD after 2 months. The primary end‐point was improvement in sensitivity for nonexperienced endoscopists (no endoscopic experience of achalasia). Sensitivity, specificity, and accuracy with and without CAD were compared using the McNemar test.ResultsSensitivity for diagnosing achalasia increased significantly with CAD, rising from 74.2% (95% confidence interval [CI] 72.2–76.0%) to 91.2% (95% CI 89.9–92.4%) for all readers, showing a difference of 17.1% (95% CI 15.1–19.0%). Specifically, sensitivity improved from 66.9% (95% CI 63.6–70.0%) to 91.9% (95% CI 89.9–93.6%) among nonexperienced endoscopists, resulting in a difference of 25.0% (95% CI 21.7–28.4%), and from 79.5% (95% CI 77.1–81.8%) to 90.8% (95% CI 89.0–92.3%) among experienced endoscopists (endoscopic experience of at least one achalasia case), with a difference of 11.3% (95% CI 8.9–13.6%). Accuracy and specificity improved significantly with CAD assistance, regardless of reader's experience.ConclusionCAD improves achalasia detection by 17%, confirming preclinical results. The benefit was higher for nonexperienced endoscopists. CAD assistance may lead to prompt and effective treatment, minimizing the risk of false‐negative diagnosis in clinical practice.Trial registrationThis study was registered in the University Hospital Medical Information Network Clinical Trial Registry (https://www.umin.ac.jp/ctr/) number: UMIN000053047.

ABSTRACTBackgroundLate gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is a well‐established indicator of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). However, its association with electrocardiographic (ECG) abnormalities and the risk of atrial fibrillation (AF) remains uncertain.ObjectivesTo investigate the association between the presence and burden of LGE with ECG characteristics, including precordial voltage, depolarization and repolarization abnormalities, and the incidence of AF in adults with HCM.MethodsWe conducted a retrospective cohort study of 144 adults with HCM with CMR and 12‐lead ECG within 30 days of each other. LGE was quantified as a percentage of LV mass and categorized as absent, < 5%, or ≥ 5%. ECG parameters, including QRS voltage, repolarization abnormalities, and LVH criteria, were analyzed. Incident AF was assessed during a median follow‐up of 6.6 years.ResultsLGE was present in 96 (67%) patients, with 21 (22%) having ≥ 5% LGE. There were no significant differences in precordial voltage between patients with and without LGE across Sokolow‐Lyon, Cornell, and Romhilt‐Estes criteria. However, T‐wave inversion was more common in leads I (41% vs. 19%, p = 0.009), aVL (50% vs. 31%, p = 0.033), and V4 (41% vs. 23%, p = 0.035) in patients with LGE. Patients with ≥ 5% LGE had a significantly lower median LVEF (64% vs. 74%, p = 0.003). Additionally, LGE presence was not associated with an increased risk of incident AF (HR 1.8, 95% CI 0.6–5.3, p = 0.308).ConclusionIn contrast to pediatric HCM, LGE is associated with specific ECG repolarization abnormalities, particularly T‐wave inversion in lateral leads, but does not significantly affect precordial voltage in adults.

Abstract Apathy is a prevalent and persistent neuropsychiatric syndrome across many neurological disorders, significantly impacting both patients and caregivers. We systematically quantified discrepancies between self- and caregiver-reported apathy in 335 patients with a variety of diagnoses, such as frontotemporal dementia (behavioural variant and semantic dementia subtypes), Parkinson’s disease, Parkinson’s disease dementia, dementia with Lewy bodies, Alzheimer’s disease dementia, mild cognitive impairment, small vessel cerebrovascular disease, subjective cognitive decline and autoimmune encephalitis. Using the Apathy Motivation Index (AMI) and its analogous caregiver version (AMI-CG), we found that caregiver-reported apathy consistently exceeded self-reported levels across all conditions. Moreover, self-reported apathy accounted for only 14.1% of the variance in caregiver ratings. This apathy reporting discrepancy was most pronounced in conditions associated with impaired insight, such as behavioural variant frontotemporal dementia, and was significantly correlated with cognitive impairment. Deficits in memory and fluency explained an additional 11.2% of the variance in caregiver-reported apathy. Specifically, executive function deficits (e.g. indexed by fluency) and memory impairments may contribute to behavioural inertia or recall of it. These findings highlight the need to integrate patient and caregiver perspectives in apathy assessments, especially for conditions with prominent cognitive impairment. To improve diagnostic accuracy and deepen our understanding of apathy across neurological disorders, we highlight the need for adapted apathy assessment strategies that account for cognitive impairment particularly in individuals with insight or memory deficits. Understanding the cognitive mechanisms underpinning discordant apathy reporting in dementia might help inform targeted clinical interventions and reduce caregiver burden.

Background: Evaluate survival outcomes of PN compared to RN in patients with T1-2, N0, M0 cRCC. Methods: Patients with cRCC were identified using the National Cancer Database (NCDB). Inclusion criteria included T1-2, N0, M0 disease, treatment with either PN or RN, and a Charleston Deyo co-morbidity score of 0. Patients with missing survival data, advanced staging, or incomplete surgical information were excluded. Propensity score matching was performed to create identical groups with respect to age, sex, and race. Kaplan–Meier survival curves, multinomial logistic regression, and cox proportional hazard models were used for statistical analysis. Results: Of the 476 eligible propensity matched patients, 238 (50.0%) underwent PN and 238 (50.0%) underwent RN. PN was associated with better survival (mean: 186 vs. 170 months, P < 0.05) and lower odds of death (OR = 3.43; 95% CI, 2.05-5.76; P < 0.05). Five- and ten-year survival rates for PN were 95.2% and 91.1%, compared to 87.4% and 76.0% for RN. Patients treated with PN were significantly more likely to come from a higher income quartile and be treated at an academic/research facility. Conclusion: Partial nephrectomy demonstrates superior survival and shorter hospital stays compared to radical nephrectomy in localized cRCC, reinforcing its role as the preferred surgical approach.

Kidney organoids are an increasingly established model of polycystic kidney disease (PKD). Derived from human pluripotent stem cells (hPSCs), organoids may be generated from induced pluripotent stem cells (iPSCs) of patients that bear naturally occurring mutations or from CRISPR mutant hPSCs by virtue of their genetic tractability. PKD is the leading inheritable cause of kidney failure (KF), accounting for ∼5%–10% of the kidney transplant and dialysis needs worldwide. PKD is a disorder of considerable genetic heterogeneity, composed of typical adult-onset autosomal dominant (ADPKD) and fetal-onset autosomal recessive (ARPKD) forms, which share pathomechanisms. Despite advances in our understanding of the genetic and molecular underpinnings of PKD, the limited clinical treatment options have raised concerns regarding the faithfulness of preclinical models. Kidney organoids have emerged as a promising platform to study PKD by mimicking human-specific responses, enabling personalized medicine, and supporting high-throughput screens. Yet, valid criticisms have related to the relative immaturity of kidney organoids for modeling adult-onset forms of PKD, the faithfulness of organoids in modeling the cystic distribution of afflicted patients, and their batch-to-batch variability limiting experimental reproducibility. Here, we summarize a decade of kidney organoid models of PKD, emphasizing their role in advancing translational and therapeutic applications while addressing their limitations and future potential.