Citations

Background— Ventricular tachycardia and premature ventricular complexes (PVCs) most frequently occur in the context of structural heart disease. However, the burden of idiopathic ventricular arrhythmias (IVA) in the general population is unknown. Methods and Results— We identified incident cases of IVA between 2005 and 2013 from Olmsted County, Minnesota, using the Rochester Epidemiology Project database. For PVC cohorts, we included those with frequent (defined as ≥100 PVC/24 hours) symptomatic PVCs. We defined IVA-associated cardiomyopathy as a drop in ejection fraction of ≥10% from baseline. Between 2005 and 2013, we identified 614 individuals with incident IVA (229 [37.3%] were male; average age was 52.1±17.2 years). Of these, 177 (28.8%) had idiopathic ventricular tachycardia, 408 (66.5%) had symptomatic PVCs, and 29 (4.7%) had IVA-associated cardiomyopathy. The age- and sex-adjusted incidence rates in 2005 to 2007, 2008 to 2010, and 2011 to 2013 were 44.9 per 100 000 (95% confidence interval [CI], 38.0–51.8), 47.6 per 100 000 (95% CI, 40.8–54.5), and 62.0 per 100 000 (95% CI, 54.4–69.6), respectively. In idiopathic ventricular tachycardia, there was an increase in incidence rate with ages ( P <0.001) but not between sexes ( P =0.12). The age-adjusted incidence of symptomatic PVC was higher in females than in males (46.2 per 100 000 [95% CI, 40.9–51.6] versus 20.5 per 100 000 [95% CI, 16.8–24.3]; P <0.001). The small number of individuals with IVA-associated cardiomyopathy precluded any formal testing. Conclusions— The incidence of IVA is increasing. Furthermore, overall incidence increases with age. Although the rate of idiopathic ventricular tachycardia is similar across sexes, women have a higher incidence of symptomatic PVC.

AbstractPatients with light chain amyloidosis (AL) often have delayed diagnosis and present with significant symptomatology; this may result in decreased quality of life (QOL). We prospectively employ a “Hematology Patient Reported Symptom Screen” (HPRSS), which is three questions about fatigue, pain, and QOL, scored 0–10. The aim of this study is to better understand QOL and determine if HPRSS parameters predict for clinical outcomes. From 2009 to 2014, 302 newly diagnosed AL patients were included. Baseline median scores [interquartile range] for fatigue, pain, and QOL were 6 [3,7], 2 [0,5], 5 [3,8], respectively. Median overall survival was 53 months, with 102 (34%) deaths in the first year. There were significant differences in baseline HPRSS between those that lived longer than one year and early death patients in the domains of fatigue (5 [IQR 3, 7] vs. 7 [IQR 5, 8], P < 0.0001) and QOL (6 [IQR 4, 8] vs. 5 [IQR 3, 7], P = 0.006). On univariate analysis fatigue, QOL, physician‐reported performance status, autologous stem cell transplant (ASCT), and Mayo stage were prognostic for survival. On multivariate analysis Mayo stage, ASCT, and baseline fatigue remained independently prognostic. When analyses were restricted to the 125 patients with HPRSS measurements at 12 months, we found that over time QOL scores improved significantly 6 [IQR 3.5, 8] → 7 [IQR 5, 8] (P = 0.01). Asking AL patients to rate their fatigue and QOL has predictive value. Baseline patient reported fatigue is an independent prognostic factor for survival. Survival at one year was associated with significant improvement in QOL.

AbstractPleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy‐number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A‐PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%–60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A‐PXA (93%), BRAF V600E (87%), and wild‐type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses −22 (n = 11), −14 (n = 7), −13 (n = 5). Losses and copy‐neutral loss of heterozygosity were significantly more common in A‐PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy‐number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A‐PXA with areas of distinct low‐ and high‐grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy‐number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy‐number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.

ABSTRACTIntroduction: Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. Methods: We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease‐causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. Results: We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult‐onset Pompe disease, myofibrillar myopathy, multi‐minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. Conclusion: We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881–886, 2017

AbstractBackgroundCardiac allograft vasculopathy (CAV) remains an important cause of graft failure after heart transplantation (HT). Although many risk factors for CAV have been identified, there are no clinical prediction models that enable clinicians to determine each recipient's risk of CAV.MethodsWe studied a cohort of 14 328 heart transplant recipients whose data were reported to the International Society for Heart and Lung Transplantation Registry between 2000 and 2010. The cohort was divided into training (75%) and test (25%) sets. Multivariable modeling was performed in the test set using variables available at the time of heart transplant using three methods: (i) stepwise Cox proportional hazard, (ii) regularized Cox proportional hazard, and (iii) Bayesian network.ResultsCardiac allograft vasculopathy developed in 4259 recipients (29.7%) at a median time of 3.0 years after HT. The regularized Cox proportional hazard model yielded the optimal performance and was also the most parsimonious. We deployed this model as an Internet‐based risk calculator application.ConclusionsWe have developed a clinical prediction model for assessing a recipient's risk of CAV using variables available at the time of HT. Application of this model may allow clinicians to determine which recipients will benefit from interventions to reduce the risk of development and progression of CAV.

AbstractThe Fenwal Alyx for collecting double red cell products has two red cell volume collection settings: fixed collection target of 360 ml (180 ml/unit) and a variable target of collecting either 400 or 360 ml (200 or 180 ml/unit), where the machine aims for the higher possible collection target. We retrospectively compared the two collection targets for the RBC content, donor time, technician time, and collection efficiency. We compared 18 fixed (F) target collections to 40 variable (V) target collections. All collections were performed as per the manufacturer's recommendations on Alyx and donors met the manufacturer's eligibility criteria. There was no significant difference in average whole blood processed (F: 963 ml, V: 1,000 ml); donor time (F: 43 min, V: 45 min) or technician time (F: 64 min, V: 64 min). There was a significant difference in unit volume (F: 283 ml, V: 300 ml); grams Hb/unit (F: 53 g, V: 57 g); ml RBC/unit (F: 157 ml, V: 167 ml); and RBC recovery (F: 87.8%, V: 88.9%). The fixed target had a significantly lower frequency of products with ≥51 g Hb (80.6%) than variable target (96.3%) and ≥153 ml RBC/unit (F: 55.6%, V: 96.3%). In conclusion, the variable target efficiently allows collections of products with higher red cell volume and hemoglobin without a significant increase in collection and processing time.

AbstractPrimary CNS lymphoma (PCNSL) is a rare diffuse large B-cell lymphoma originating within the central nervous system. The overall incidence of PCNSL is rising, particularly in the elderly population. Immunosuppression is a strong risk factor, but most patients with this tumor are apparently immunocompetent. Diagnosis of PCNSL can be challenging. Non-invasive or minimally invasive tests such as ophthalmological evaluation and spinal fluid analysis may be useful, but the majority of patients require tumor biopsy for definitive diagnosis. Our knowledge concerning optimum treatment of PCNSL is fragmentary due to paucity of adequately sized trials. Most patients are now initially treated with high-dose-methotrexate-based chemotherapy alone, as the addition of whole-brain radiotherapy at standard doses has not been shown to increase survival and does increase the risk of neurological toxicity. Ongoing trials are addressing issues such as the roles of reduced-dose radiotherapy, the addition of the CD20 antibody rituximab to chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation, and maintenance therapy in the primary management of PCNSL.

AbstractBackgroundThough a rare tumor, sebaceous carcinoma is relatively well‐described in immunocompetent patients, in whom it often occurs in a periorbital distribution where it has an overall poor prognosis with a high metastasis rate. The effect of transplant‐related immunosuppression on the development of sebaceous carcinoma and its outcomes has not been characterized.MethodsWe collected 9 cases from a single institution of patients developing sebaceous carcinoma after solid organ transplantation. We analyzed clinicopathologic features.ResultsWe estimate the prevalence of sebaceous carcinoma post‐solid organ transplantation to be 0.09%. The mean age at diagnosis was 66.1 years (std 7.0 years). The mean time between transplantation and sebaceous carcinoma diagnosis was 7.1 years (std 5.1 years). All tumors occurred in extra‐ocular distribution. Two patients likely had Muir‐Torre syndrome, of whom 1 died from metastatic sebaceous carcinoma. No other patients developed metastatic disease or had disease‐related death. Mohs micrographic surgery and wide local excision were equally effective and there were no recurrences with either procedure.ConclusionsOur study found that sebaceous carcinoma in solid organ transplant recipients occurs in in an extraorbital distribution with only 1 patient developing metastatic disease. Both Mohs micrographic surgery and wide local excision are acceptable treatment modalities for sebaceous carcinoma in transplant recipients.