Citations

Background Perceived social isolation has been shown to have a negative impact on health outcomes, particularly among older adults. However, these relationships have not been fully examined among patients with heart failure. Methods and Results Residents from 11 southeast Minnesota counties with a first‐ever International Classification of Diseases, Ninth Revision ( ICD‐9 ) code 428 for heart failure between January 1, 2013, and March 31, 2015 (N=3867), were prospectively surveyed to measure perceived social isolation. A total of 2003 patients returned the survey (response rate, 52%); 1681 patients completed all questions and were retained for analysis. Among these patients (53% men; mean age, 73 years), ≈19% (n=312) had moderate perceived social isolation and 6% (n=108) had high perceived social isolation. After adjustment, patients reporting moderate perceived social isolation did not have an increased risk of death, hospitalizations, or emergency department visits compared with patients reporting low perceived social isolation; however, patients reporting high perceived social isolation had >3.5 times increased risk of death (hazard ratio, 3.74; 95% confidence interval [ CI ], 1.82–7.70), 68% increased risk of hospitalization (hazard ratio, 1.68; 95% CI , 1.18–2.39), and 57% increased risk of emergency department visits (hazard ratio, 1.57; 95% CI , 1.09–2.27). Compared with patients who self‐reported low perceived social isolation, patients reporting moderate perceived social isolation had a 16% increased risk of outpatient visits (rate ratio, 1.16; 95% CI , 1.03–1.31), whereas those reporting high perceived social isolation had a 26% increased risk (rate ratio, 1.26; 95% CI , 1.04–1.53). Conclusions In patients with heart failure, greater perceived social isolation is associated with an increased risk of death and healthcare use. Assessing perceived social isolation during the clinical encounter with a brief screening tool may help identify patients with heart failure at greater risk of poor outcomes.

Objectives To characterize the individual and combined effects of multimorbidity and functional limitation on healthcare use and mortality in a large, community cohort of individuals with heart failure (HF). Design Prospective cohort study. Setting Eleven southeastern Minnesota counties. Participants Individuals (mean age 74, 54% male) with a first‐ever HF code ( International Classification of Diseases, Ninth Revision code 428 or Tenth Revision code I50) between January 1, 2013 and March 31, 2016 (N=2,692). Measurements Eight activities of daily living measured using a survey on a Likert scale (1=without any difficulty, 5=unable to do; median=8). Participants with a score greater than 8 were categorized as having functional limitation. Multimorbidity was defined as having 2 or more noncardiac comorbidities. Results Twenty‐five percent of participants had neither multimorbidity nor functional limitation, 35% had multimorbidity, 9% had functional limitation, and 31% had both. After adjustment, participants with multimorbidity and functional limitation had greater risks of all outcomes (death: hazard ratio (HR)=4.92, 95% confidence interval (CI)=3.03–8.00; emergency department (ED) visit: HR=3.67, 95% CI=2.94–4.59; hospitalization: HR=3.66, 95% CI=2.85–4.70; outpatient visit: HR=1.73, 95% CI=1.52–1.96) than those with neither. Participants with functional limitation alone had greater risks of death (HR=4.84, 95% CI=2.78–8.43), ED visits (HR=2.35, 95% CI=1.75–3.16), and hospitalizations (HR=2.10, 95% CI=1.52–2.88) but not outpatient visits. Those with multimorbidity alone had similar risks of ED visits and hospitalizations as those with functional limitation alone but were more likely to have outpatient visits (HR=1.50, 95% CI=1.34–1.67). Conclusion Individuals with both multimorbidity and functional limitation have the highest risk of death and healthcare use. Individuals with only functional limitation have similar rates of hospitalizations and ED visits as those with only multimorbidity, underscoring the need to consider both when managing individuals with HF.

Background Ossabaw pigs are unique miniature swine with genetic predisposition to develop metabolic syndrome and coronary atherosclerosis after extended periods receiving atherogenic diets. We have hypothesized that transgenic Ossabaw swine expressing chimp PCSK9 (proprotein convertase subtilisin‐like/kexin type 9) containing the D374Y gain of function would develop familial hypercholesterolemia and coronary artery plaques more rapidly than Landrace swine with the same transgene. Methods and Results Ossabaw and Landrace PCSK9 gain‐of‐function founders were generated by Sleeping Beauty transposition and cloning. Histopathologic findings in the Ossabaw founder animal showed more advanced plaques and higher stenosis than in the Landrace founder, underscoring the Ossabaw genetic predisposition to atherosclerosis. We chose to further characterize the Ossabaw PCSK9 gain‐of‐function animals receiving standard or atherogenic diets in a 6‐month longitudinal study using computed tomography, magnetic resonance (MR) imaging, intravascular ultrasound, and optical coherence tomography, followed by pathological analysis of atherosclerosis focused on the coronary arteries. The Ossabaw model was consistently hypercholesterolemic, with or without dietary challenge, and by 6 months had consistent and diffuse fibrofatty or fibroatheromatous plaques with necrosis, overlying fibrous caps, and calcification in up to 10% of coronary plaques. Conclusions The Ossabaw PCSK9 gain‐of‐function model provides consistent and robust disease development in a time frame that is practical for use in preclinical therapeutic evaluation to drive innovation. Although no animal model perfectly mimics the human condition, this genetic large‐animal model is a novel tool for testing therapeutic interventions in the context of developing and advanced coronary artery disease.

Abstract Objective In recent years, electronic health record systems have been widely implemented in China, making clinical data available electronically. However, little effort has been devoted to making drug information exchangeable among these systems. This study aimed to build a Normalized Chinese Clinical Drug (NCCD) knowledge base, by applying and extending the information model of RxNorm to Chinese clinical drugs. Methods Chinese drugs were collected from 4 major resources—China Food and Drug Administration, China Health Insurance Systems, Hospital Pharmacy Systems, and China Pharmacopoeia—for integration and normalization in NCCD. Chemical drugs were normalized using the information model in RxNorm without much change. Chinese patent drugs (i.e., Chinese herbal extracts), however, were represented using an expanded RxNorm model to incorporate the unique characteristics of these drugs. A hybrid approach combining automated natural language processing technologies and manual review by domain experts was then applied to drug attribute extraction, normalization, and further generation of drug names at different specification levels. Lastly, we reported the statistics of NCCD, as well as the evaluation results using several sets of randomly selected Chinese drugs. Results The current version of NCCD contains 16 976 chemical drugs and 2663 Chinese patent medicines, resulting in 19 639 clinical drugs, 250 267 unique concepts, and 2 602 760 relations. By manual review of 1700 chemical drugs and 250 Chinese patent drugs randomly selected from NCCD (about 10%), we showed that the hybrid approach could achieve an accuracy of 98.60% for drug name extraction and normalization. Using a collection of 500 chemical drugs and 500 Chinese patent drugs from other resources, we showed that NCCD achieved coverages of 97.0% and 90.0% for chemical drugs and Chinese patent drugs, respectively. Conclusion Evaluation results demonstrated the potential to improve interoperability across various electronic drug systems in China.

Key Points HGBL-DH/TH makes up 8% of de novo DLBCL, with HGBL-DH/TH with BCL2 rearrangement being a GCB phenomenon. Restricting FISH testing to tumors with dual protein expression and GCB subtype results in testing <15% of tumors, but missing ∼35% of HGBL-DH/TH.

Abstract Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery. MSC retention in different organs was explored 24 hours, 48 hours, or 2 weeks after injection. Renal volume, perfusion, and oxygenation were studied 2 weeks after injection using magnetic resonance imaging in vivo, and renal inflammation, apoptosis, capillary density, and fibrosis ex vivo. The ab-KIM1 coating had little effect on MSC viability or proliferation. The stenotic kidney showed upregulated KIM1 expression, selective homing, and greater retention of KIM-MSC compared to untreated MSC and compared to other organs. KIM-MSC-injected mice improved renal perfusion and capillary density, and attenuated oxidative damage, apoptosis, and fibrosis compared to mice treated with vehicle or with native MSC. In conclusion, MSC coating with ab-KIM1 increased their retention in the ischemic kidney and enhanced their therapeutic efficacy. This novel method may be useful to selectively target injured kidneys, and supports further development of strategies to enhance cell-based treatment of ischemic kidney injury.

Background Excessive daytime sleepiness ( EDS ), a common symptom among patients with sleep‐disordered breathing, is closely associated with the development of cardiovascular diseases, but its long‐term prognostic value is not completely understood. The aim of this study was to investigate whether EDS would be an independent prognostic factor after myocardial infarction. Methods and Results We prospectively recruited 112 post–myocardial infarction patients. The Epworth Sleepiness Scale was completed before polysomnography, and EDS was defined as a score ≥11. After exclusion of 8 patients who accepted treatment with continuous positive airway pressure, 104 patients were followed up for 48 months. The primary composite end point was major adverse cardiac events. Patients with EDS had higher rates of major adverse cardiac events (48.4% versus 27.4%, χ 2 =5.27, P =0.022) and reinfarction (29.0% versus 5.5%, χ 2 =13.51, P =0.0002) compared with those without EDS . In the Cox proportional hazards model, patients with EDS had 2.15 times (95% confidence interval, 1.08–4.18; P =0.030) higher crude risk of major adverse cardiac events, with prognostic significance persisting after adjusting for age, diabetes mellitus, depression, left ventricular ejection fraction, apnea–hypopnea index, and nocturnal nadir oxygen saturation (hazard ratio: 2.13, 95% confidence interval, 1.04–4.26, P =0.039). Furthermore, among participants with moderate to severe sleep‐disordered breathing, the presence of EDS was associated with higher risk of major adverse cardiac events than those without EDS , after adjusting for age and nadir oxygen saturation (hazard ratio: 3.17, 95% confidence interval, 1.22–7.76, P =0.019). Conclusions EDS may be an independent prognostic factor of adverse outcome in post–myocardial infarction patients with moderate to severe sleep‐disordered breathing. Evaluation of EDS may shed new light on risk stratification and identify treatment responders for this patient population.

AbstractWe conducted a surveillance epidemiology and end results (SEER)‐based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5‐year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de‐novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5‐year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10–1.31, P < 0.001). The median latency period was 60.0 months; the most common 1M among sALL patients were breast (17.9%) and prostate (17.4%). Patients with any 1M were at increased risk of developing sALL (SIR 1.76, 95% CI 1.58–1.95, P < 0.001). Hematological‐1M sites had significantly higher SIRs (hematological‐SIR 7.35; solid‐SIR 1.33; P < 0.001). We observed a significant increase in sALL incidence after a 1M and a significantly worse 5‐year survival with different demographic characteristics from 1ALL. There is a need to define appropriate screening methods for patients surviving their primary cancer.