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In humans, abnormal thickening of the left ventricle of the heart clinically defines hypertrophic cardiomyopathy (HCM), a common inherited cardiovascular disorder that can precede a sudden cardiac death event. The wide range of clinical presentations in HCM obscures genetic variants that may influence an individual's susceptibility to sudden cardiac death. Although exon sequencing of major sarcomere genes can be used to detect high-impact causal mutations, this strategy is successful in only half of patient cases. The incidence of left ventricular hypertrophy (LVH) in a managed research colony of rhesus macaques provides an excellent comparative model in which to explore the genomic etiology of severe HCM and sudden cardiac death. Because no rhesus HCM-associated mutations have been reported, we used a next-generation genotyping assay that targets 7 sarcomeric rhesus genes within 63 genomic sites that are orthologous to human genomic regions known to harbor HCM disease variants. Amplicon sequencing was performed on 52 macaques with confirmed LVH and 42 unrelated, unaffected animals representing both the Indian and Chinese rhesus macaque subspecies. Bias-reduced logistic regression uncovered a risk haplotype in the rhesus MYBPC3 gene, which is frequently disrupted in both human and feline HCM; this haplotype implicates an intronic variant strongly associated with disease in either homozygous or carrier form. Our results highlight that leveraging evolutionary genomic data provides a unique, practical strategy for minimizing population bias in complex disease studies.

Objectives: Target door-to-device (DTD) time for ST-elevation myocardial infarction (STEMI) patients has been 90 minutes, with no distinction between urban and rural hospitals. Rural hospitals have longer DTD times for transferred patients attributed to long transportation times from referring hospitals. Longer DTD times have also been reported during after-hours. The aim of the study was to determine whether DTD times at our rural facility were impacted by arrival method, arrival time period, and season. Design: Retrospective chart review. Setting: Rural tertiary care center in central Wisconsin. Methods: We studied 412 patients presenting with STEMI after initiation of the Rescue One program for rapid triage and transfer from October 2006 through December 2012. They were subdivided by arrival method, arrival time (ON=Monday-Friday, 8 AM-5 PM; OFF=after-hours, weekends, holidays), and season. Median DTD times and proportions below and above 90 minutes were compared. Results: Median DTD time for all groups, which include both directly admitted and transferred patients, was 85 minutes with 60% of patients achieving DTD times below 90 minutes while 30-day mortality was 5.3%. Median DTD time was 67 minutes for the Emergency Department (ED) (n=164), 95 minutes for Transfers (n=204), 68 minutes for Urgent Care (n=22) and 86 minutes for Field (n=22). ED had the highest proportion of patients achieving goal DTD time (81%) compared to Transfers (42%). Patients arriving by ED during OFF hours had a median DTD time 28 minutes longer than during ON hours with 21% fewer patients achieving goal DTD time, attributed to the time required to call in the catheterization team. Seasonal variability was observed due to differences in pre-hospital ambulance transportation times in the Field group. Conclusions: Our data confirm that in a rural facility such as ours, ED patients arriving during afterhours and transferred patients have longer DTD times. Methods are being implemented to shorten the time to assemble the catheterization lab team during after-hours. Better performance will be seen once the first medical contact to device (FTD) time goal of 120 minutes for transferred patients is adopted at our institution. Fibrinolytic therapy should be considered at referring institutions where the FTD time is expected to exceed 120 minutes. [ABSTRACT FROM AUTHOR]

Connective tissue disorders increase the risk of malignancy; conversely, they may manifest as rheumatological paraneoplastic syndromes due to an underlying malignancy. We describe the case of a patient with limited scleroderma whose rapid disease progression coincided with the discovery of a renal tumor. A woman, age 75 years, presented with a 3-month history of progressive difficulty grasping objects, unsteadiness, dyspnea, xerostomia, xerophthalmia, and significant weight loss. She had a 10-year history of gastroesophageal reflux and Raynaud's phenomenon. Pertinent physical examination findings included facial telangiectasias, bibasilar inspiratory rales, sclerodactyly, and absent pinprick and vibratory sensation in her toes. She also had swelling and tenderness in several metacarpophalangeal and interphalangeal joints and in both ankles. A renal mass was demonstrated on abdominal computed tomography. A left partial nephrectomy was performed, confirming an unclassified type of renal cell carcinoma, along with a focal proliferative crescentic pauci-immune glomerulonephritis. Medical therapy with rituximab, pulse methylprednisolone, and prednisone led to improvement in her symptoms. The patient's presentation is consistent with a rapid progression of pre-existing limited scleroderma with the development of new rheumatological symptoms, including vasculitis. We propose that this progression was secondary to paraneoplastic stimulation by the renal cell carcinoma. Clinicians should consider looking for a malignancy in patients with connective tissue disorders who present with a myriad of new symptoms. [ABSTRACT FROM AUTHOR]

Objectives: Target door-to-device (DTD) time for ST-elevation myocardial infarction (STEMI) patients has been 90 minutes, with no distinction between urban and rural hospitals. Rural hospitals have longer DTD times for transferred patients attributed to long transportation times from referring hospitals. Longer DTD times have also been reported during after-hours. The aim of the study was to determine whether DTD times at our rural facility were impacted by arrival method, arrival time period, and season., Design: Retrospective chart review., Setting: Rural tertiary care center in central Wisconsin., Methods: We studied 412 patients presenting with STEMI after initiation of the Rescue One program for rapid triage and transfer from October 2006 through December 2012. They were subdivided by arrival method, arrival time (ON=Monday-Friday, 8 AM-5 PM; OFF=after-hours, weekends, holidays), and season. Median DTD times and proportions below and above 90 minutes were compared., Results: Median DTD time for all groups, which include both directly admitted and transferred patients, was 85 minutes with 60% of patients achieving DTD times below 90 minutes while 30-day mortality was 5.3%. Median DTD time was 67 minutes for the Emergency Department (ED) (n=164), 95 minutes for Transfers (n=204), 68 minutes for Urgent Care (n=22) and 86 minutes for Field (n=22). ED had the highest proportion of patients achieving goal DTD time (81%) compared to Transfers (42%). Patients arriving by ED during OFF hours had a median DTD time 28 minutes longer than during ON hours with 21% fewer patients achieving goal DTD time, attributed to the time required to call in the catheterization team. Seasonal variability was observed due to differences in pre-hospital ambulance transportation times in the Field group., Conclusions: Our data confirm that in a rural facility such as ours, ED patients arriving during after-hours and transferred patients have longer DTD times. Methods are being implemented to shorten the time to assemble the catheterization lab team during after-hours. Better performance will be seen once the first medical contact to device (FTD) time goal of 120 minutes for transferred patients is adopted at our institution. Fibrinolytic therapy should be considered at referring institutions where the FTD time is expected to exceed 120 minutes., (© 2013 Marshfield Clinic.)