Citations

Background: Fluorescence in situ hybridization (FISH) is recommended as part of multimodality sampling in the evaluation of biliary strictures, but can be false negative in 40%–50% cases. The aim of this study was to comprehensively assess predictors of false-negative FISH in patients with biliary strictures. Methods: Patients undergoing tissue sampling for biliary strictures from October 20 to February 22 were prospectively enrolled (NCT04572711). Procedural factors such as sampling techniques, order, and utilization of combination sampling were recorded. Results of an optimized pancreatobiliary FISH panel with locus-specific probes for 1q21, 7p12, 8q24, and 9p21 were reported per guidelines. Statistical analyses were performed using BlueSky Statistics v.10.3.1, R package v8.81. Results: Of 327 patients, 93 (28.5%) were diagnosed with malignancy. A false-negative pancreatobiliary fluorescence in situ hybridization (PB-FISH) was reported in 40 (43.1%) patients. A history of primary sclerosing cholangitis was associated with lower odds of having a false-negative PB-FISH (aOR=0.38, 95% CI=0.16–0.82, p=0.02), whereas a hilar stricture was associated with a significantly higher false-negative PB-FISH in those with cholangiocarcinoma (aOR=3.2 [1.4–7.9], p=0.009). Dilation of biliary strictures prior to brushing was not associated with a lower rate of false-negative PB-FISH. Conclusions: In this prospective study, hilar strictures were more likely to have false-negative PB-FISH. Dilation of strictures did not affect PB-FISH performance. These results can help guide PB-FISH interpretation.

Background Disease‐causative variants in LMNA ‐encoded lamin A/C cause a genetic cardiomyopathy characterized by atrioventricular block, atrial fibrillation, ventricular arrhythmias, and systolic dysfunction. The influence of LMNA variant type/localization on late gadolinium enhancement (LGE) patterns and clinical outcomes remains unclear. Methods Retrospective analysis of 822 genotype‐positive patients with arrhythmogenic/dilated cardiomyopathy was used to identify those with disease‐causative variants in LMNA . Data on LGE distribution and prevalence of advanced heart failure, thromboembolic and sudden cardiac death/major ventricular arrhythmia events were extracted from the electronic record and analyzed by variant type/localization. Results Among the 72/116 (62%) LMNA variant‐positive patients with cardiac magnetic resonance imaging data, LGE was observed in 40/72 (56%) cases. Most exhibited a nonischemic, midmyocardial or subepicardial pattern (73%), and 6/40 (15%) showed a unique “pseudo‐infarct” transmural pattern, predominantly affecting the apical segments. All 6 patients with this distinct LGE pattern harbored C‐terminal IgD (immunoglobulin‐like domain) variants (p.Arg471His or p.Arg541His). In patients with clinically manifest disease (76/116), those with IgD‐localizing variants had a lower prevalence of atrioventricular block (25% versus 72%, P =0.002) and atrial fibrillation (50% versus 81%, P =0.019) but higher rates of thromboembolic events (42% versus 16%, P =0.038). During a median follow‐up of 37 months, IgD variant presence independently predicted sudden cardiac death/major ventricular arrhythmia (hazard ratio, 2.391 [95% CI, 1.046–5.464]; P =0.039). Conclusions LMNA missense variants localizing to IgD present a distinct apical pseudo‐infarct LGE pattern associated with increased risk of ventricular arrhythmias and thromboembolic events but reduced atrioventricular block and atrial fibrillation. Multicenter studies are warranted to develop variant‐specific risk‐stratification strategies in cardiac laminopathy.

Background There is a global mismatch between the number of adults with congenital heart disease and adult congenital heart disease (ACHD) cardiologists, potentially impacting patient outcomes. This survey explores factors influencing trainees and cardiologists' career choices in ACHD. Methods An online, anonymous global survey on demographics, ACHD as a career choice, encouraging and deterring factors assessed via a 5‐point Likert scale and open‐ended questions on recommending ACHD was distributed through targeted emails and social media. Responses meeting a 75% completion criterion were analyzed using descriptive statistics and thematic analysis. Results Among 811 included responses, most were from women (53.5%), aged 31 to 40 years (48.3%), White individuals (43.3%), non‐Hispanic individuals (85%), from outside the ACHD field (79.0%), and from North America (42.7%). Only 30.9% of non‐ACHD physicians considered specializing in ACHD despite 78.9% recommending it. Encouraging factors included awareness of ACHD significance, mentor influence, and clinical exposure. Key deterrents were inadequate financial incentives, limited job opportunities, and lengthy training. Regional variations showed that longer training duration and lack of compensation incentives were the main deterrents in North America. Suggested solutions included structured training programs, salary improvements, and early ACHD exposure during medical education. Conclusions Less than a third of respondents considered ACHD as a career largely due to inadequate financial incentives, limited job opportunities, and long training duration. Addressing these barriers could enhance recruitment and help meet the growing demands of the ACHD population.

ABSTRACT Iatrogenic spinal accessory nerve (SAN) injuries can occur as complications of posterior triangle of the neck surgery, resulting in lateral scapular winging and a shoulder droop. Rarely has this complication been described after a cosmetic rhytidectomy (face‐lift procedure). Here, we present two cases of iatrogenic SAN injuries that occurred after cosmetic rhytidectomies. The use of electrodiagnostic and ultrasound examinations provides invaluable information to assess peripheral nerve injuries. Electrodiagnostic testing can confirm the presence and severity of the injury, while ultrasound can provide additional anatomical information and direct visualization to confirm the continuity of the nerve and assess muscle denervation changes.

Abstract Background Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM). Methods To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated. Results Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n = 279), 240 (86%) harbored the mutation. A chr7+/chr10− pattern was observed in 103 of 469 (22%) samples. Among samples tested for TERT promoter mutations (n = 143), 32 (22%) harbored the mutation. Progression-free and overall survival of patients with mcPXA were comparable to patients with methylation class IDH-mutant astrocytoma, low grade, but a GBM-like subset (ie, cases with a pre-methylation working diagnosis of GBM) showed shorter survival. Histologic features of high grade, including palisading necrosis and microvascular proliferation, were prognostic in mcPXA. Compared to patients with BRAF p.V600E-altered GBM, patients with mcPXA were younger and had a lower frequency of TERT promoter mutations. Conclusion Tumors in mcPXA share molecular characteristics with histologically defined PXA, and high-grade histologic features can help predict their clinical behavior. The use of an epigenetic classification of PXA reveals that this group of tumors is more common than previously appreciated and warrants in-depth study to identify efficacious therapeutic options.

The indications for immune checkpoint inhibitor (ICI) use in cancer treatment continue to expand. This is attributable to their proven anticancer activity in addition to their tolerability and favorable toxicity profile as compared to conventional chemotherapeutic agents. ICIs work by blocking the inhibitory signals between tumor cells and T-cells, thereby enhancing the T-cell cytotoxic activity to inhibit tumor growth. Because of their immune-stimulating effect, ICIs are linked to adverse renal outcomes in both native and transplanted kidneys. The risk of kidney allograft rejection in the setting of ICI use has been reported to be around 40%, leading to an increased risk of graft loss. In this report, we review the literature examining outcomes in kidney transplant recipients receiving ICIs for various oncologic indications.