tbuckley/cabot-search huggingface dataset:
DNA methylation at birth is associated with lung function development until age 26 years
Authors: Nandini Mukherjee, Ryan Arathimos, Su Chen, Parnian Kheirkhah Rahimabad, Luhang Han, Hongmei Zhang, John W. Holloway, Caroline Relton, A. John Henderson, Syed Hasan Arshad, Susan Ewart, Wilfried Karmaus
Journal: European Respiratory Journal (2020)

Little is known about whether DNA methylation (DNAm) of cytosine–phosphate–guanine (CpG) sites at birth predicts patterns of lung function development. We used heel prick DNAm from the F1-generation of Isle of Wight birth cohort (IOWBC-F1) for discovery of CpGs associated with lung function trajectories (forced expiratory volume in 1 s, forced vital capacity, their ratio, and forced expiratory flow at 25–75% of forced vital capacity) over the first 26 years, stratified by sex. We replicated the findings in the Avon Longitudinal Study of Parents and Children (ALSPAC) using cord blood DNAm. Epigenome-wide screening was applied to identify CpGs associated with lung function trajectories in 396 boys and 390 girls of IOWBC-F1. Replication in ALSPAC focussed on lung function at ages 8, 15 and 24 years. Statistically significantly replicated CpGs were investigated for consistency in direction of association between cohorts, stability of DNAm over time in IOWBC-F1, relevant biological processes and for association with gene expression (n=161) in IOWBC F2-generation (IOWBC-F2). Differential DNAm of eight CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6, and WNT11 involved in developmental processes, were significantly associated with lung function in the same direction in IOWBC-F1 and ALSPAC, and showed stable patterns at birth, aged 10 and 18 years between high and low lung function trajectories in IOWBC-F1. CpGs on LHX1 and COL18A1 were linked to gene expression in IOWBC-F2. In two large cohorts, novel DNAm at birth were associated with patterns of lung function in adolescence and early adulthood providing possible targets for preventative interventions against adverse pulmonary function development.
Abstract 13697: Prevalence and Disability Associated With Vitamin D Deficiency Amongst Patients With Cardiovascular and Cerebrovascular Disorders
Authors: Nirmaljot Kaur, Angelina Yogarajah, Chika Nwodika, Rashmi Subhedar, Payu Raval, Salma Yousuf, Chail Shah, Mehwish Martin, Harmandeep Singh, Jigisha Rakholiya, Urvish K Patel
Journal: Circulation (2020)

Introduction: Previous studies had provided evidence that vitamin D deficiency is a strong negative predictor for survival and recovery after severe vascular events but national estimate on disability related burden is not clear. Hypothesis: We evaluate the prevalence of vitamin D deficiency (VDD) amongst patients with cardiovascular disease (CVD) and cerebrovascular disorders (CeVD) and to find out whether or not CVD and CeVD in the presence of VDD increases the disability. Methods: We performed a retrospective analysis of the Nationwide Inpatient Sample data (years 2016-2017) in adults (≥18 years) hospitalizations. We identified patients with secondary diagnosis of VDD and primary diagnosis of CVD (AFib, CHF, IHD, acute MI, and angina) and CeVD (AIS, TIA, ICeH and SAH) using ICD-10-CM codes. We performed a chi-square test and multivariable survey logistic regression to analyze disability of patients with CVD and CeVD in presence of VDD. Disability/loss of function was investigated by APRDRGs severity using 3M Health Information Systems software. (Score 1-4 indicates minor to extreme loss of function) Results: Among 58,259,589 US hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23% and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH and SAH, respectively and 1.82% had VDD. Prevalence of hospitalizations due to CHF (14.66% vs 11.43%), AIS (1.87% vs 1.71%) and TIA (0.4% vs 0.38%) was higher; and IHD (2.62% vs 3.45%), acute MI (1.58% vs 2.16), angina (0.05% vs 0.06%), AFib (1.14% vs 1.28%), ICeH (0.17% vs 0.23%) and SAH (0.05% vs 0.08%) was lower among VDD patients in compare to non-VDD. (p&lt;0.0001) In regression analysis, VDD was associated with higher odds of severe or extreme disability amongst patients hospitalized with AIS (OR:1.1; 95%CI:1.06-1.14), ICeH (1.22; 1.08-1.39), TIA (1.36; 1.25-1.47), IHD (1.37; 1.33-1.41), acute MI (1.44; 1.38-1.49), Afib (1.10; 1.06-1.15), and CHF (1.03; 1.02-1.05) in comparison to without VDD. Conclusions: CVD and CeVD in presence of VDD increase the disability amongst US hospitalizations. Future studies should be planned to evaluate the discharge outcomes as well as the effect of identification and in-hospital management of VDD on improvement of the outcomes.
Response to Comment on Gan et al. Efficacy of Modern Diabetes Treatments DPP-4i, SGLT-2i, and GLP-1RA in White and Asian Patients With Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Diabetes Care 2020;43:1948–1957
Authors: Sushrima Gan, Adem Y. Dawed, Louise A. Donnelly, Anand T.N. Nair, Colin N.A. Palmer, Viswanathan Mohan, Ewan R. Pearson
Journal: Diabetes Care (2020)

We would like to thank Singh et al. (1) for their correspondence, which makes some important points regarding the prescribing of sodium–glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in Asian patients with type 2 diabetes.

We performed a systematic review and meta-analysis to assess the impact of ethnicity on the glucose-lowering efficacy of relatively newer antihyperglycemic agents SGLT-2i, GLP-1RA, and dipeptidyl peptidase 4 inhibitors (DPP-4i) using previously published evidence from randomized clinical trials (2). Careful reading of our article will reveal that we do not compare the drugs, nor do we infer that one drug class is better than another, but …
SAT0180 Do rehabilitation facilities diagnose and treat osteoporosis in hip fracture patients better than acute care hospitals?
Authors: AG Juby, CM De Geus-Wenceslau
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> One in four women and one in eight men over 50 years of age will suffer from osteoporosis. The lifetime prevalence of hip fracture is 18% for women, 6% for men. Mortality within a year of hip fracture is 6–44%. Morbidity is also significant, with many not returning to their premorbid level of function. Proven efficacious pharmacologic therapies are available to treat osteoporosis. <h3>Objectives</h3> The objective of this study was to evaluate the diagnosis and treatment of osteoporosis in seniors after hip fracture both in the acute care hospital and in the rehabilitation facility, and to see if they differ. <h3>Methods</h3> A retrospective chart review on consecutive hip fracture patients (over 65 yrs) admitted to an acute tertiary care referral hospital was carried out. Osteoporosis diagnosis and treatment was recorded. Additional data was collected on osteoporosis investigations including bone densitometry. The patients were then followed up in the rehabilitation facility and the same data collected. The results from the two groups were then compared. <h3>Results</h3> Data was collected on 311 patients in acute care. Average age was 86 years, average length of stay in acute care was 11 days. 18 died and 41 either went straight home or to long term care. Data was unavailable in 26 patients. Therefore 226 were followed up in the rehabilitation facility. Osteoporosis was diagnosed on admission to: acute care in 11.9%; rehabilitation in 9.7% and on discharge from: acute care in 15.4%; and from rehabilitation in 11.2%. Osteoporosis was treated (any treatment) in acute care hospitals in 13% on admission and 9.7% on discharge and in rehabilitation facilities 12.8% and 10.2% respectively. In the majority of cases the treatment was calcium alone, specific osteoporotic drugs were used in &lt;4% in both groups. There was no statistically significant differences between the groups, apart from the use of Vitamin D which was significantly less (p &lt; 0.05) in the rehabilitation group compared to the acute care group. <h3>Conclusion</h3> Rehabilitation facilities are no better than acute care hospitals at diagnosing and pharmacologically treating osteoporosis in seniors after hip fracture. The rate of treatment in both groups is unacceptably low. In spite of their more holistic and multidisciplinary focus the rehabilitation facilities still fared poorly in their approach to this disease. This puts the onus on primary care physicians to provide adequate osteoporosis treatment in this group of patients, otherwise elderly people will continue to be under-managed for this disease.
Abstract 13678: Serum Hepatokine Selenoprotein P is Upregulated by Hepatic Hypoperfusion and Predicts Adverse Prognosis in Heart Failure Patients
Authors: Tomofumi Misaka, Yasuhiro Ichijo, Akiomi YOSHIHISA, Yu Hotsuki, Watanabe Koichiro, Yu Sato, Yusuke KIMISHIMA, Tetsuro Yokokawa, Masayoshi Oikawa, Atsushi Kobayashi, Yasuchika Takeishi
Journal: Circulation (2020)

Introduction: Cardiac and multiple organ network is involved in the pathophysiology of heart failure (HF). Hepatokines, which are produced and secreted from the liver, have regulatory functions in the peripheral tissues. However, the interaction between the heart and liver or clinical relevance of hepakokines in HF remains poorly understood. The present study aimed to elucidate the clinical significance of hepatokine selenoprotein P in HF. Methods and Results: We enrolled 250 participants including 171 hospitalized patients with HF and 79 control subjects. The serum concentration of selenoprotein P was measured by an enzyme-linked immunosorbent assay. We found that the serum selenoprotein P levels in HF patients were significantly higher than those in controls (14.8 ± 7.5 vs. 8.4 ± 4.6 mg/L, P&lt;0.01). Next, the HF patients were categorized into 4 groups based on the hepatic hemodynamics assessed by abdominal-ultrasonography, which determined liver congestion by shear wave elastography (liver-SWE, &gt;1.33 m/s) and liver hypoperfusion by peak systolic velocity of the celiac artery (celiac-PSV, &lt;62.4 cm/s). Selenoprotein P levels were significantly upregulated in patients with liver hypoperfusion compared to patients with liver congestion ( Figure A ). Selenoprotein P was negatively correlated with celiac-PSV (P&lt;0.01), cardiac output (P&lt;0.01), and left ventricular stroke volume (P=0.03), whereas no correlations were observed between selenoprotein P and indices of congestion such as liver-SWE and right atrial pressure. Kaplan-Meier analysis demonstrated that a higher selenoprotein P group showed a lower event-free rate from re-hospitalization due to worsening HF ( Figure B ). Conclusion: Upregulation of liver-derived selenoprotein P was associated with hepatic hypoperfusion, not hepatic congestion, and related to the adverse prognosis in HF. Selenoprotein P may be a novel molecule involved in the cardio-hepatic interaction.
Abstract 14158: Ankle-brachial Index and Risk of Severe Ischemic Leg Outcomes in a Community-based Population: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Amy Paskiewicz, Frances Wang, Chao Yang, Shoshana Ballew, Corey Kalbaugh, Elizabeth Selvin, Maya Salameh, Gerardo M HEISS, Josef Coresh, Kunihiro Matsushita
Journal: Circulation (2020)

Introduction: Ankle-brachial index (ABI) ≤ 0.9 is used to define lower-extremity peripheral artery disease (PAD). However, the association between ABI and severe ischemic leg outcomes in the general population has not been investigated. Hypothesis: Lower ABI is independently associated with risk of severe ischemic leg outcomes. Methods: We studied 13,742 ARIC participants (median age 54 [SD 5.75] years, 45% males) without intermittent claudication or a history of revascularization for PAD at baseline (1987-89). We quantified the association of ABI with risk of severe ischemic leg outcomes using Cox regression. ABI was modeled as a restricted cubic spline allowing for potentially non-linear associations. Severe ischemic leg outcomes were ascertained through ICD codes and included critical limb ischemia (CLI) (defined as PAD with rest pain or tissue loss) and ischemic leg amputation (amputations with PAD diagnosis). Results: Over a median of 28 years of follow-up, there were 221 and 129 events of CLI and ischemic leg amputation, respectively. Lower ABI was linearly associated with both CLI and ischemic leg amputation (Figure). With ABI 1.25 as the reference, adjusted hazard ratios of CLI were 2.48 (95% CI 1.15-5.36) at ABI 0.7, 1.97 (1.30-2.99) at ABI 0.9, and 1.73 (1.18-2.54) at ABI 1.0. The corresponding hazard ratios of ischemic leg amputation were 3.57 (1.44-8.81), 2.63 (1.54-4.48), and 2.23 (1.34-3.70), respectively. The association was largely consistent in demographic and clinical subgroups, although the results were less evident in younger and female participants compared to their counterparts. Conclusions: In middle-aged adults without clinical PAD, lower ABI was independently and linearly associated with higher risk of severe ischemic leg outcomes. Our results support the value of ABI as an indicator for leg vascular condition and also indicate that ABI 0.9-1.1 should not be considered normal for ischemic leg prognosis.
The UK needs a sustainable strategy for COVID-19
Authors: Deepti Gurdasani, Laura Bear, Debby Bogaert, Rochelle A Burgess, Reinhard Busse, Roberto Cacciola, Yves Charpak, Tim Colbourn, John Drury, Karl Friston, Valentina Gallo, Lynn R Goldman, Trisha Greenhalgh, Zoë Hyde, Krutika Kuppalli, Maimuna S Majumder, Jose M Martin-Moreno, Martin McKee, Susan Michie, Elias Mossialos, Ali Nouri, Christina Pagel, Dominic Pimenta, Saskia Popescu, Viola Priesemann, Angela L Rasmussen, Stephen Reicher, Walter Ricciardi, Ken Rice, Joshua Silver, Tara C Smith, Clare Wenham, Robert West, Gavin Yamey, Christian Yates, Hisham Ziauddeen
Journal: The Lancet (2020)
MLL4-associated condensates counterbalance Polycomb-mediated nuclear mechanical stress in Kabuki syndrome
Authors: Alessandra Fasciani, Sarah D’Annunzio, Vittoria Poli, Luca Fagnocchi, Sven Beyes, Daniela Michelatti, Francesco Corazza, Laura Antonelli, Francesco Gregoretti, Gennaro Oliva, Romina Belli, Daniele Peroni, Enrico Domenici, Samuel Zambrano, Daniela Intartaglia, Carmine Settembre, Ivan Conte, Claudia Testi, Panagiotis Vergyris, Giancarlo Ruocco, Alessio Zippo
Journal: Nature Genetics (2020)
Early case conferences shorten length of stay in children admitted to hospital with suspected child abuse.
Authors: J Anne S Smith, Daryl Efron
Journal: BMJ (2005)

OBJECTIVE: To compare the outcomes of two models for the management of children admitted to hospital with suspected child abuse: routine early case conferencing versus standard evaluation. METHODS: Between March 2001 and February 2002 professionals from the Royal Children's Hospital, Melbourne, Victoria Police and Child Protection services collaborated on a randomized controlled study involving children admitted to hospital with suspected child abuse. The intervention group (n = 13) received a case conference within 24 h of the child's admission to hospital. The control group (n = 12) were managed according to standard procedures whereby each organization conducted their own evaluation (and a case conference might or might not have been held). Patients were followed for 3 months with data collected from all three professional groups. RESULTS: The process of evaluation, the eventual diagnosis of child abuse and the confidence with which professionals made this diagnosis was not significantly different between the groups. Case conferences were judged to be useful regardless of their timing. Mean length of stay in the intervention group was significantly less than in controls (42.4 h vs 99.7 h, P = 0.01). CONCLUSION: Early case conferences appear to shorten the period of time children spend in hospital when child abuse is suspected. This has significant implications for reducing costs for all organizations involved in the evaluation of suspected child abuse.
Abstract 128: Time for a Change: Use of Doppler Ultrasound for Pulse Checks in Cardiac Arrest Patients
Authors: Allison Cohen, Timmy Li, Lance B Becker, Daniel Rolston, Mathew Nelson, Casey Owens, Miles Gordon
Journal: Circulation (2020)

Introduction: During cardiopulmonary resuscitation, the presence or absence of a pulse is critical in guiding the management of cardiac arrest (CA) patients. Despite the importance placed on palpating a pulse, several reports have shown that providers lack accuracy in determining it the presence via manual palpation. The purpose of this study is to assess the sensitivity, specificity, and accuracy of manual femoral pulse detection as compared to Doppler ultrasound pulse detection in CA patients. Hypothesis: We hypothesize that a Doppler ultrasound obtained pulse will be more accurate than manual palpation for detecting an arterial pulse in patients in CA. Methods: This is a prospective observational study of non-traumatic CA patients that occurred at North Shore University Hospital. During a pulse check, the presence of both a femoral Doppler waveform and manual femoral pulse were recorded simultaneously. These values were compared to the arterial line waveform, which served as the gold standard. During each pulse check, the presence or absence of a pulse was documented, as well as the arterial line measurement. We calculated the sensitivity, specificity, and accuracy of manual palpation and Doppler ultrasound determination of the presence of a pulse. Results: We enrolled a total of 23 patients. The sensitivity of Doppler ultrasound detection of a pulse was 0.82 (95% CI: 0.72, 0.93) with a specificity of 1.00 (95% CI: 1.00, 1.00), and accuracy of 0.88 (95% CI: 0.78, 0.94). The sensitivity and specificity of manual palpation of a pulse was 0.27 (95% CI: 0.15, 0.40) and 0.90 (95% CI: 0.78, 1.00), respectively, with an accuracy of 0.46 (95% CI: 0.34, 0.58). Conclusion: Determining the presence of a pulse in the management of cardiac arrest patients is a critical step in the Advanced Cardiovascular Life Support algorithm. Our preliminary data suggests that Doppler ultrasound has a higher sensitivity and specificity for detecting a pulse in CA patients and highlights the inaccuracy of manual pulse palpation. These preliminary results could lead to a change in the practice of pulse checks, to favor the use of Doppler ultrasound detection. Further data is needed to determine what blood pressure readings correspond to a perfusable rhythm.
Abstract 16397: Presence of Myocardial Injury on Admission is Associated With an Increase in All-cause Mortality in Patients With COVID-19
Authors: Zain Ahmed, Avinainder Singh, Lina Vadlamani, Maxwell Eder, Zaniar Ghazizadeh, Jakob Park, Manan Pareek, Justin Pacor, Chad Gier, Carlos Mena-hurtado, Eric J Velazquez, Nihar R Desai
Journal: Circulation (2020)

Introduction: COVID-19 has emerged as a global health crisis resulting in nearly half a million deaths worldwide to date. Patients with COVID-19 experience significant cardiovascular manifestations including myocardial injury. We sought to determine the risk of myocardial injury within 24 hours of admission on all-cause mortality in patients with COVID-19. Methods: This was a prospective cohort study of patients hospitalized with COVID-19 at a major academic medical center between March 1, 2020-June 1, 2020. The combination of cardiac troponin T (cTnT) elevation (defined as ≥0.01 ng/mL) within 24 hours of admission and an elevated NT-proBNP (defined as &gt;450.0 pg/mL) on admission were used as biomarker surrogates for myocardial injury. Results: There were n = 415 consecutive patients who were hospitalized with COVID-19 with a median age of 68.5 years (IQR 58-81), 44.8% were women, a median BMI of 28.8 (IQR 24.6-35.6), 5.8% of patients had end-stage renal disease on dialysis, 21.6% had a prior diagnosis of coronary artery disease and 21.8% had a prior diagnosis of congestive heart failure. Among patients with at least one positive cTnT level within 24 hours of admission, the median cTnT level was 0.04 ng/mL (IQR 0.01-0.77 ng/mL). Among those with elevated BNP, the median BNP was 1930 pg/mL (IQR 799-5826 pg/mL) on admission. Patients with COVID-19 who had an elevation in both cardiac biomarkers on admission had higher all-cause mortality than patients with COVID-19 who had negative biomarkers (38.2% vs. 7.5%, respectively, p-value &lt; 0.001), with nearly a 5-fold increase in mortality when adjusted for age, gender, BMI and renal dysfunction (adjusted OR 4.9, p-value: 0.003, 95% CI 1.7-13.9, See Figure) Conclusion: Myocardial injury is common in patients with COVID-19 and is associated with a significantly increased risk of death. Cardiac biomarkers on admission can serve as prognostic factors and may guide early management of COVID-19.
Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett’s Esophagus
Authors: D. Chamil Codipilly, Lovekirat Dhaliwal, Meher Oberoi, Parth Gandhi, Michele L. Johnson, Ramona M. Lansing, W. Scott Harmsen, Kenneth K. Wang, Prasad G. Iyer
Journal: Clinical Gastroenterology and Hepatology (2020)
How to Leverage the Medicare Program for a COVID-19 Vaccination Campaign
Authors: Nicole Lurie, Bettina Experton
Journal: JAMA (2020)

This Viewpoint proposes that Medicare claims data could inform the rollout of a COVID-19 vaccination program in the US, including notifying beneficiaries of their risk and prioritization and supporting efforts to allocate the vaccine and monitor its uptake, immunogenicity, and safety.
Abstract 12877: Magnesium Deficiency Causes Reversible Metabolic Diastolic and Systolic Cardiomyopathies
Authors: Man Liu, Hong LIU, Feng Feng, An Xie, Cody R Hou, Xiaoxu Zhou, Yang Zhao, Samuel C Dudley
Journal: Circulation (2020)

Introduction: Low circulating magnesium (Mg) level is associated with increased cardiovascular mortality, and conversely, dietary Mg intake is associated with a decreased risk of developing heart failure. Hypothesis: We investigated whether Mg deficiency alone could cause cardiomyopathy. Methods: C57BL/6J mice were fed with a low-Mg diet (low-Mg, 15-30 mg/kg Mg) or a normal diet (nl-Mg, 600 mg/kg Mg) for 6 weeks. To test reversibility, half of the low-Mg mice were fed then with normal diet for another 6 weeks (low→nl-Mg group). Results: Mg deficiency increased mortality, especially in female mice. After 6 weeks of low-Mg diet, surviving mice showed significantly decreased serum Mg (0.9±0.1 vs. 2.8±0.1 mg/dL for nl-Mg) and a reciprocal increase in serum Ca, K, and Na. Low-Mg mice exhibited a decreased cardiac ejection fraction (EF%, 39.8±1.9% vs. 52.0±1.7% of nl-Mg) and impaired relaxation (E/e’: 21.1±1.1 vs. 15.4±0.4 of nl-Mg) in echocardiography. At the cellular level, ATP, Ca transient amplitude, sarcoplasmic reticulum (SR) Ca load, resting sarcomere length, and sarcomere shortening were all decreased significantly in low-Mg hearts and cardiomyocytes. These changes were accompanied by evidence of mitochondrial dysfunction with significantly increased mitochondrial ROS production and mitochondrial membrane depolarization. Mg repletion normalized electrolytes, contraction, relaxation, and cellular changes. The SR Ca pump (SERCA) was decreased, the SR Ca channel RyR2 oxidized, and cardiac myosin binding protein C S-glutathionylated in low-Mg mouse hearts. These changes were normalized with Mg repletion. In vivo , mitoTEMPO treatment during low Mg diet improved the cardiac relaxation and increased cellular ATP levels without improving contraction. Conclusions: Mg deficiency caused a reversible diastolic and systolic cardiomyopathy associated with mitochondrial dysfunction. This cardiomyopathy may explain the relationship of hypomagnesemia and worsening heart failure. Mg intake could reverse these changes, reinforcing the known correlation of increased Mg intake and reduced heart failure symptoms and mortality. In deficiency states, Mg supplementation may represent a novel treatment for systolic and diastolic heart failure.