Citations

Abstract: Severe hypertriglyceridemia (sHTG) is a critical metabolic disorder that substantially elevates the risk of atherosclerotic vascular disease and acute pancreatitis. Despite its clinical significance, many conventional triglyceride-lowering therapies often fail to adequately reduce triglyceride levels or prevent these life-threatening complications. This unmet need has spurred interest in targeting regulatory proteins involved in triglyceride metabolism, such as apolipoprotein C3, a key inhibitor of lipoprotein lipase activity that promotes triglyceride-rich lipoprotein accumulation. Plozasiran, an investigational small interfering RNA therapy, has emerged as a breakthrough in sHTG management by selectively degrading hepatic APOC3 messenger RNA. Indeed, clinical trials demonstrate this drug's robust efficacy in reducing triglyceride levels, concomitant with reduced non-high-density lipoprotein (HDL) cholesterol and apolipoprotein B—key markers of cardiovascular risk. Notably, the Phase III PALISADE trial in familial chylomicronemia syndrome patients revealed plozasiran's potential to mitigate acute pancreatitis risk by normalizing triglyceride levels with a favorable safety profile. Current guidelines emphasize a multimodal approach to sHTG, combining dietary restriction of fats and simple carbohydrates with pharmacotherapy. However, plozasiran's prolonged dosing interval and mechanism-based action position it as a transformative option, particularly for patients refractory to existing treatments. Although long-term cardiovascular outcome data remain pending, its ability to durably modulate APOC3 expression offers new hope for breaking the cycle of dyslipidemia-driven organ damage. As research progresses, this therapy may redefine standards of care for high-risk populations, bridging a critical gap in preventive cardiology and pancreatology.

Abstract Objective This study was undertaken to examine acute and chronic electroencephalographic (EEG) and seizure characteristics in new onset refractory status epilepticus (NORSE). Methods Multicenter inpatient and follow‐up clinical and EEG data were analyzed using International League Against Epilepsy definitions and American Clinical Neurophysiology Society (ACNS) EEG terminology. Results Forty‐four patients were included from the Yale NORSE/FIRES Biorepository (median age = 29 years, 33 female, 38 cryptogenic). Nine hundred twenty inpatient EEG days were reviewed (median = 13.5 days/patient). Presenting status epilepticus (SE) types included 24 convulsive SE (CSE), five focal–motor (FMSE), and 15 nonconvulsive (NCSE). Of 39 patients with post discharge follow‐up (median = 14.7 months), 61.5% ( n = 24) had seizures and required more antiseizure medications than seizure‐free patients (median = 4 vs. 1, p < .001). Inpatient EEG captured epileptiform discharges in all and periodic discharges in 38 patients. Seizures were captured in 38 patients: 33 electrographic (11 only electrographic) and 27 electroclinical. Total seizure burden ranged 6.5–29 615.0 min (median = 50.7). Seizures fulfilling ACNS EEG criteria for SE were captured in 20 patients; two had CSE and the remainder NCSE with coma, nine of whom also had FMSE. Inpatient seizure days (median = 50.0 vs. 15.5%, p = .004) and seizure burden (median = 42.9 vs. 0 min, p = .009) were higher in the first half of monitored days. Interictal findings were equally present and did not predict postdischarge seizures, whereas electroclinical seizures (90.9% vs. 45.5%, p = .037), seizure burden (median = 116.8 vs. 32.5 min, p = .045), and proportion of seizure days (36.3% vs. 20.0%, p = .037) did. Among 12 patients with follow‐up EEGs (median = 19.6 months post onset), posterior‐dominant rhythm (PDR) returned in nine; five had periodic discharges, and three had seizure captured. Significance Seizures are most commonly convulsive upon presentation and nonconvulsive or clinically subtle throughout the inpatient course in NORSE. Inpatient seizures, but not interictal abnormalities, occur earlier in the inpatient course and presence of electroclinical seizures, seizure burden, and proportion of seizure days but not interictal findings are associated with postdischarge seizures. Although return of PDR reflects neurological recovery, seizure persistence and EEG abnormalities post‐NORSE are common.

Abstract Classically described repairs for helical rim defects include granulation, linear closure, wedge repair, full-thickness skin grafts, helical rim advancement flaps, and two-stage interpolation flaps. The bilateral bidirectional O to Z rotation flap (O to Z flap) is commonly used for large defects on the scalp. The purpose of this study is to examine the clinical and cosmetic outcomes of O to Z flap repairs to the helical rim. The flap was created by incising above and below the defect along the helical rim on opposite sides of the defect to the depth of the perichondrium. Back cuts were performed to facilitate movement along with extensive undermining. The bilateral flaps were rotated into the defect from either end meeting in the defect middle and sutured into place with a running 5–0 FAG. In total, 50 O to Z flap repairs for helical rim defects following Mohs micrographic surgery were performed. Defect depths ranged from subcutaneous fat to through cartilage. The defect size ranged from 0.9 × 0.7 cm to 2.5 × 1.4 cm. The flap repair size ranged from 1.5 × 1.2 cm to 5.1 × 2.1 cm (average size 5.1 cm2). The median follow-up was 6 weeks (range 2 weeks to 2 years). Complications were as follows: 4% (2 of 50) of cases had bleeding requiring intervention, 16% (8 of 50) of cases had partial superficial flap necrosis, and 22% (11 of 50) of cases had mild persistent tenderness at 6 weeks. Cosmetic outcomes were graded on a scale of poor, acceptable, good or excellent. Overall, 78% (39 of 50) were rated good to excellent, 20% (10 of 50) were rated acceptable, and 2% (1 of 50) were rated poor, but did not require revision. The O to Z flap is a reliable repair for helical rim defects. Flap downsides include persistent cartilage tenderness and risk of minor flap necrosis.

Leucine-rich glioma-inactivated-1 (LGI1) IgG-associated autoimmune encephalitis typically presents with faciobrachial dystonic seizures, hyponatremia, and temporal lobe MRI abnormalities. However, the clinical spectrum of LGI1 IgG-associated AE extends beyond these classical features, with reports of diverse seizure semiologies and atypical presentations challenging traditional diagnostic paradigms. This study reports a male in his late 60s presenting with recurrent episodes of right foot cramping and electric shock-like pain, progressing to generalized tonic-clonic seizures. Initial workup suggested chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but LGI1 IgG antibodies were subsequently detected. Despite treatment with intravenous immunoglobulin (IVIG), the seizures persisted. This case highlights the heterogeneity in LGI1 encephalitis presentations. The patient’s proprioceptive-induced reflex seizures represent a rare manifestation of the disease. Treatment with rituximab, a B-cell depleting therapy, resulted in significant improvement, suggesting its potential effectiveness in LGI1 encephalitis with a resistant seizure course. The case also emphasizes the intricate interplay between the mesial temporal lobe, basal ganglia, and frontal regions in LGI1 encephalitis pathophysiology.

Introduction: Advance care planning (ACP) supports goal-concordant care but remains underused nationally. In resident clinics, limited continuity, short visits, and lack of standardized workflows create barriers to ACP integration. In our Community Internal Medicine resident clinic, ACP discussion was documented in 2.5% of annual physicals, and 19.6% of paneled patients had an advance directive (AD) on file. We aimed to increase ACP documentation from 2.5% to 12.5% within 1 year without increasing perceived resident workflow burden. Methods: We conducted a resident-led quality improvement project using Lean Six Sigma methodology. Three interventions were implemented sequentially: nursing distribution of ACP brochures, an electronic medical record DotPhrase to prompt and document ACP discussions, and targeted patient portal outreach to patients without an AD before annual visits. The primary outcome was documented ACP discussion during annual physicals. Secondary outcomes included AD uploads and ACP consult referrals. The balancing measure was resident-perceived workflow burden. Charts were reviewed over 5-week periods at baseline (n = 118) and after each implementation phase (n = 132, 158, 129). Results: ACP documentation increased from 2.5% at baseline to 12.2%, 17.1%, and 24.0% across sequential phases (χ 2 (3) = 24.74, P < 0.0001). Pairwise comparisons versus baseline were significant (all P ≤ 0.005). AD upload rate increased from 1.7 to 6.0 per month, and ACP consult referrals increased from 0.0% to 10.9%. Mean perceived workflow burden decreased from 4.9 to 3.0. Conclusion: Workflow-embedded interventions improved ACP documentation, AD uploads, and ACP referrals without increasing perceived resident burden.

ABSTRACT Celiac disease (CD) is an autoimmune enteropathy with recognized extraintestinal manifestations. We describe a 55‐year‐old man with long‐standing, well‐controlled CD who developed progressive shortness of breath and cough. Imaging was indeterminate for usual interstitial pneumonia (UIP), and a surgical lung biopsy demonstrated a UIP pattern. Autoimmune serologies were negative, and no alternate etiologies for UIP were identified. With intermittent adherence to a gluten‐free diet and medical management including nintedanib, his disease progressed, ultimately leading to lung transplantation. This case raises the possibility of an association between CD and UIP of uncertain aetiology and should prompt further discussion as the relationship remains unclear. To contextualize this observation, we conducted a systematic review of published case reports evaluating pulmonary manifestations of celiac disease.

Objectives: To summarize the current evidence for radiation therapy (RT) in the prevention and treatment of heterotopic ossification (HO), including patient selection, optimal RT technique, and associated risks. Methods: This multispecialty-led committee includes radiation oncologists, rheumatologists, orthopedic surgeons, and physical medicine/rehabilitation physicians. Using the population, intervention, comparator, outcome, timing and study design (PICOTS) framework, evidence regarding treatment outcomes was assessed using Cochrane and PRISMA methodology. Eligible studies included prospective and retrospective studies published between January 1, 1980, and November 1, 2025, from Embase, Medline, and PubMed databases. Of the 197 articles identified using the search strategy, 83 were selected for inclusion as evidence, including 27 well-designed studies (phase II randomized and phase III), 16 moderately well-designed studies that account for most common biases (matched cohort and phase II studies), 31 studies with design limitations (retrospective reviews), 2 supplemental studies (not useful as primary evidence), and 7 meta-analyses. Additional studies were included to provide context and were not used to guide recommendations. Well-established RAND-UCLA consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options. Results: The results of this analysis demonstrate that in appropriately selected patients, RT is an effective and safe therapy for prophylaxis of HO formation. Conclusions: This systematic review provides consensus guidelines for the use of RT as prophylaxis of HO based on current peer-reviewed evidence in the literature.

Background: Pancreatic resection (Pancreatoduodenectomy, PD, distal pancreatectomy, DP, or total pancreatectomy, TP) is the standard of care for resectable pancreatic adenocarcinoma (PDAC). Despite advances in multimodal therapy, recurrence rates remain high, approaching 80%, and continue to drive poor overall survival. Objective: This review evaluates the burden and clinical significance of localized recurrence in PDAC and critically examines the potential role of intraoperative radiation therapy (IORT) in improving locoregional disease control. Results: Distant recurrence remains the predominant pattern of failure, occurring in 55–75% of patients, most commonly involving the liver, lungs, and peritoneum. However, isolated local recurrence, observed in approximately 17–32% of patients, represents a clinically meaningful subset associated with significant morbidity and potential for subsequent metastatic progression. IORT, delivered as a single high-dose radiation treatment to the tumor bed at the time of surgery, enables precise targeting of areas at highest risk for residual microscopic disease while minimizing radiation exposure to adjacent radiosensitive structures. Retrospective and meta-analytic data, while limited, suggest that IORT is associated with improved local control and modest survival benefit without a significant increase in perioperative morbidity, though interpretation is limited by study heterogeneity and lack of randomized control trials. Conclusion: IORT represents a rational adjunct in the multimodal management of PDAC, particularly for patients at high risk of locoregional failure, including those with borderline resectable or locally advanced disease, nodal involvement, perineural invasion, or concern for margin positivity. Prospective studies are needed to better define optimal patient selection and to clarify the role of IORT in the modern treatment paradigm.