tbuckley/cabot-search huggingface dataset:
Abstract 14372: Identification of the Genes That Are Involved in Severe Pulmonary Hypertension in Type 2 Diabetic Mice
Authors: Qiuyu Zheng, Atsumi Tsuji-Hosokawa, Jody T Cabrera, Jian Wang, Ayako Makino
Journal: Circulation (2020)

Pulmonary hypertension (PH) is a progressive disease characterized by increased pulmonary vascular resistance. Increasing evidence shows that diabetes increases the risks of PH, and diabetic priming leads to severe PH. However, the molecular mechanism by which preconditioning of diabetes results in severe PH is still unknown. It has been shown that endothelium serves as a key regulator of vascular tone, and endothelial cell dysfunction is implicated in the development of PH and diabetes-related vascular complications. Therefore, we identified the genes that contribute to the development of severe PH in diabetic mice with a focus on endothelial function. We first determined the effect of chronic hypoxia (10% O 2 , 4 weeks) on hemodynamics in type 2 diabetic (T2D) mice. We used inducible T2D mice (generated by high-fat diet and a low-dose streptozotocin injection) and spontaneous T2D mice (TALLYHO/Jng). Diabetic mice exhibited a slight increase in right ventricular systolic pressure (RVSP), and chronic hypoxia led to a further rise in RVSP in both inducible and spontaneous T2D mice. We isolated pulmonary endothelial cells (MPEC) from normoxia-exposed control mice (CN), hypoxia-exposed control mice (CH), normoxia-exposed diabetic mice (DN), and hypoxia-exposed diabetic mice (DH) to examine the levels of 92 genes using real-time PCR. Nighty two genes were selected based on their functions, which are significantly related to endothelial function. We found that 27 genes were significantly changed among 4 groups. We then examined the protein levels of genes that were related to apoptosis and glycolysis. Western Blot data indicated that the protein level of GAPDH was significantly increased in CH and DH compared to CN and DN. In addition, hypoxic exposure in diabetic mice (DH) significantly increased HK2 protein level compare to hypoxia-exposed control mice (CH). These data suggest that precondition of diabetes increases susceptibility to developing PH due partly to altering gene expression of HK2 and Gapdh in MPECs. Since HK2 and GAPDH are a crucial regulator of glycolysis, alteration of glycolysis is expected in hypoxia-exposed diabetic mice. Our study revealed the key molecules which could be used for treating severe PH in diabetes.
Abstract 16391: Systemic Ventricular Dysfunction and Long Term Outcomes in Patients With D-transposition of the Great Arteries (D-TGA), Atrial Switch, and Systemic Right Ventricle Physiology
Authors: Anca Chiriac, Davide Giardi, Samantha Espinosa, Patrick J Fitzgerald, Kamal P Cheema, Goyal Umadat, Julio Perez-Downes, David Hodge, Sabrina D Phillips, Christopher J McLeod
Journal: Circulation (2020)

Introduction: Patients with D-TGA palliated with atrial switch operations have the morphologic right ventricle in the systemic position. There is increased risk of atrial arrhythmias and systemic right ventricle (SRV) failure. We sought to analyze the long term outcomes of these patients. Methods: All patients with D-TGA and SRV followed in the Adult Congenital Heart Disease Clinic of a large tertiary care institution were reviewed. A comprehensive retrospective analysis of the medical record was performed, including consult notes, ECGs, echocardiograms and electrophysiology reports. Results: A total of 154 patients (63% male) aged 29±11 years were followed for a mean of 10±9 years (range 0-51). During follow-up, 3 patients underwent cardiac transplantation and 15 died; 5 had sudden death, 2 had cardiogenic shock, 5 had non-cardiac death (i.e., infective endocarditis, sepsis) and 3 had unknown causes of death. Heart failure symptoms were present in 53(34%) patients. Severe SRV systolic dysfunction occurred in 37(24%) patients, with a mean EF of 23±5.5%; moderate SRV dysfunction occurred in 67(44%) patients, mean EF 35±4%. Sinus node dysfunction was present in 75(49%) patients, complete AV block in 9(5%) patients, and a pacemaker placed in 60(39%) patients, with cardiac resynchronization therapy in 5. Atrial arrhythmias occurred in 94(61%) patients and ablations were performed in 47(31%) patients. An ICD was implanted in 37 patients; 5 patients had appropriate shocks, but 7 had inappropriate shocks due to atrial arrhythmias. Age (HR 1.07, p=001), heart failure symptoms (HR 4.9, p= 0.007), severe SRV enlargement (HR 3.7, p=0.03), severe systolic dysfunction (HR 5.4, p=0.003), severe systemic AV valve regurgitation (HR 5.2, p=0.002) and a QRS duration&gt; 122ms (HR 3.7, p=0.02) were significant predictors of mortality. The 15 year probability of sudden death was 3.2%(95% CI 0-6.9%). Conclusions: Atrial arrhythmias are common after atrial switch operations secondary to atriotomy scars. Further studies will need to determine whether restoration of sinus rhythm or cardiac synchrony may prevent further deterioration of the systemic right ventricle. Severe SRV dysfunction and prolonged QRS duration &gt;122ms were significantly correlated with mortality.
Pooled testing for SARS-CoV-2 could provide the solution to UK’s testing strategy
Authors: Jonathan Ball, Alan McNally
Journal: BMJ (2020)

<h3>Objectives</h3> Recent cellular work in TDP-43 models of ALS convincingly demonstrated the importance of somatostatin interneuronal circuits in mediating corticomotoneuronal hyperexcitability, previously indirectly measured by short interval intracortical inhibition (SICI). Somatostatin interneurons reside in layers 2–3 of the primary motor cortex, with their output projecting directly onto and modulating pyramidal tract neurons. These circuits can be non-invasively interrogated using TMS. As such, the present study developed a novel threshold tracking TMS technique of this excitatory output, termed short interval intracortical facilitation (or SICF), and postulated that it would be increased in ALS patients when compared with healthy controls. <h3>Methods</h3> Threshold tracking TMS techniques assessed the function of somatostatin excitatory interneurons in 15 ALS patients. Short interval intracortical facilitation was measured by setting the subthreshold conditioning stimulus to 95% of resting motor with interstimulus intervals (ISI) between 1-5 ms. The TMS findings were compared with a cohort of 25 healthy controls. <h3>Results</h3> Short interval intracortical facilitation was significantly increased in ALS patients when compared with controls with Z=2.291 and p&lt;0.05 (mean SICF Ave ALS=−17.23% (+/−2.68) and controls=−10.39% (+/−1.52)). The rise in short interval intracortical facilitation was accompanied by a reduction of SICI (mean ALS SICI Ave=3.13% (+/-1.45) and Controls=13.23% (+/-1.37)) with Z=4.302 and p&lt;0.05. <h3>Conclusions</h3> The present study has established that cortical hyperexcitabilty in ALS is mediated through a combination of reduced inhibition (implying dysfunction of inhibitory circuits) combined with increased activity of the excitatory cortical networks. Strategies aimed at modulating the imbalance in cortical inhibition-excitation axis may prove therapeutically useful.
Abstract 13626: Human Leukocyte Antigen A*30 is Associated With Congenital Heart Disease
Authors: Horacio G Carvajal, Fei Wan, Anoop K Brar, Chang Liu, Pirooz Eghtesady
Journal: Circulation (2020)

Introduction: Congenital heart disease (CHD) arises from many etiologies, ranging from genetic to environmental exposures, such as viral infections. The human leukocyte antigens (HLA) play an important role in the immune response to pathogens. HLA has been extensively explored and linked with several diseases; no such investigations, however, have been done in context of CHD. Hypothesis: We sought to identify potential HLA associations with CHD in a large population sample with molecular-based HLA typing. Methods: Available data on race, gender, HLA-A, B, and DRB1 typing (1-field, antigen level) was collected from the 2,349 patients in the United Network for Organ Sharing (UNOS) database undergoing heart transplant due to CHD between 2005 and 2017. These were compared to all 80,893 deceased kidney donors in the same period. Nominal variables were compared with Pearson’s chi-square, and logistic regression was used to compare all HLA antigens between groups, adjusting for race and gender. The false discovery rate was used to control for multiple comparisons, with adjusted p-values &lt;0.05 considered significant. Results: There were 14 HLA-A, 25 HLA-B, and 14 HLA-DRB1 antigens with an overall frequency of 1% or higher. The frequency of HLA-A*30, B*44, and DRB1*08 differed significantly between groups (Table 1). Unconditional regression showed significantly increased odds of CHD in patients with HLA-A*30 and HLA-DRB1*08, as well as significantly lower odds in those with HLA-B*44 (Table 1). The demographics between groups were comparable, with the exception of fewer Caucasians in the cases (CHD 60.7% vs controls 65.6%, p=0.026). When adjusted for race and gender, only HLA-A*30 remained statistically significant. Conclusions: HLA-A*30 appears to be linked with CHD independent of race. Further analyses with detailed CHD diagnoses and high-resolution HLA typing data are needed to explore potential associations between specific cardiac defects and HLA at the allele level.
Refining Assumptions About Specialty Compensation Rates
Authors: Roy Xiao, Vinay K. Rathi
Journal: JAMA Surgery (2020)

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Abstract 14971: Impact of Medicare Diagnosis Code Expansion and Inclusion of Outpatient Data on Risk-adjusted 30-day Mortality and Readmission Rates After Acute Myocardial Infarction
Authors: Lauren Gilstrap, Rishi Wadhera, Andrea Austin, Stephen A Kearing, Karen Joynt Maddox, Robert W Yeh
Journal: Circulation (2020)

Introduction: In January 2011, the Center for Medicare and Medicaid Services increased the number of billing codes allowed per admission from 9 to 25. This caused an artificial increase in comorbidity burdens. Some have argued including outpatient data mitigates this problem. The aim of this study was to explore the impact of diagnosis code expansion, using inpatient and inpatient+outpatient data and evaluate potential solutions for conducting longitudinal studies of 30-day risk-adjusted outcome rates after acute myocardial infarction (AMI). Hypothesis: Limiting diagnosis codes and including outpatient data would produce the most stable estimates of risk-adjusted outcomes over time. Methods: We used 100% Medicare data to create a cohort of beneficiaries with AMI between 2008 and 2013. We used 4 methods to calculate the hierarchical condition categories/patient (HCC/pt) necessary for risk adjustment: 1) inpatient-only data, limited codes after 2011; 2) inpatient-only data, unlimited codes; 3) inpatient+ outpatient data, limited codes; 4) inpatient+outpatient data, unlimited codes. Results: Using inpatient-only data, expanding diagnosis codes increased the average HCC/pt by +0.23 HCC/pt. Using inpatient+outpatient data, the average increase was only +0.11 HCC/pt. (relatively 109% less, Figure A ). Between 2009-2013, AMI mortality was flat while readmissions declined ( Figure B ). For mortality, all 4 methods produced estimates that were, on average, +0.7% higher than unadjusted (raw) rates. For readmission, the closest to unadjusted and most stable over time was inpatient+outpatient data with limited codes. Conclusion: For studies that span January 2011, diagnosis codes should be limited to 9 after 2011 when using inpatient or combined inpatient and outpatient data.
Wernicke's encephalopathy.
Authors: J E Andersson
Journal: BMJ (1979)

Wernicke's encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine (vitamin B1)-deficiency. WE is most commonly seen among patients with alcohol abuse, and thiamine deficiency is here caused by several factors, among others inadequate diet, insufficient gastrointestinal absorption and enzymatic abnormalities. The syndrome, however, is also seen among non-alcoholic, undernourished patients, e.g. certain patients with cancer or AIDS. The diagnosis WE has traditionally been given when the triad of confusion, ataxia and ophthalmoplegia was present. However, it should be recognised, that these three symptoms are not always present at the same time, partly because the mental symptoms often dominate and cloud, possible ocular abnormalities and ataxia. The syndrome is, according to the author's opinion, still underdiagnosed. The treatment of WE, consisting of large doses of intravenous thiamine, is effective and safe, and therefore it is important to be aware of WE among risk-patients, especially among patients with alcohol abuse, and to institute treatment with intravenous thiamine at the slightest suspicion.
Gut microbiome stability and dynamics in healthy donors and patients with non-gastrointestinal cancers
Authors: Allyson L. Byrd, Menghan Liu, Kei E. Fujimura, Svetlana Lyalina, Deepti R. Nagarkar, Bruno Charbit, Jacob Bergstedt, Etienne Patin, Oliver J. Harrison, Lluís Quintana-Murci, Ira Mellman, Darragh Duffy, Matthew L. Albert
Journal: The Journal of Experimental Medicine (2020)

As microbial therapeutics are increasingly being tested in diverse patient populations, it is essential to understand the host and environmental factors influencing the microbiome. Through analysis of 1,359 gut microbiome samples from 946 healthy donors of the Milieu Intérieur cohort, we detail how microbiome composition is associated with host factors, lifestyle parameters, and disease states. Using a genome-based taxonomy, we found biological sex was the strongest driver of community composition. Additionally, bacterial populations shift across decades of life (age 20–69), with Bacteroidota species consistently increased with age while Actinobacteriota species, including Bifidobacterium, decreased. Longitudinal sampling revealed that short-term stability exceeds interindividual differences. By accounting for these factors, we defined global shifts in the microbiomes of patients with non-gastrointestinal tumors compared with healthy donors. Together, these results demonstrated that the microbiome displays predictable variations as a function of sex, age, and disease state. These variations must be considered when designing microbiome-targeted therapies or interpreting differences thought to be linked to pathophysiology or therapeutic response.
Abstract 14064: Left Circumflex Lesion a Great Masquerader: Stemi Mimicking Classic Pericarditis
Authors: Roshan Jha, Qiu Tong, Cameron Hall
Journal: Circulation (2020)

Introduction: Pericarditis and STEMI both present with acute chest pain and ST elevations in the EKG. The pattern of ST-elevation and the nature of chest pain usually aid in clinching the diagnosis but there are exceptions. Case: 34 Y.o male with Hypertension, tobacco abuse presented with abrupt onset central chest tightness, worsening with inspiration, relieved on sitting up. EKG revealed diffuse concave ST elevation in all leads with PR depression, Posterior EKG was negative for posterior wall MI. Troponin was normal on presentation and was mildly elevated to 0.5 ng/ml 6 hours later. The echocardiogram revealed normal ejection fraction, no wall motion changes. He was being managed for acute pericarditis with colchicine and ibuprofen, 20 hours later, he experienced increased chest pain, repeat EKG was unchanged, troponin up-trended to 6 ng/ml, peaked at 20 ng/ml and was taken for an urgent angiogram. Angiogram revealed an occlusion in the mid circumflex artery and angioplasty was done. Following the procedure, the chest pain subsided. Conclusion: A classic presentation of acute pericarditis turned out to be a STEMI with circumflex as the culprit vessel. Vigilance to patient's symptoms and trending of cardiac markers are essential in identifying atypical presentations of STEMI. The circumflex lesion usually has an atypical presentation and should have a low threshold for diagnostic angiogram so as not to miss them.
Hypoxia-Induced Adaptation to Mitral Regurgitation: A Role for KATP Channel Up-Regulation?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Gary D. Lopaschuk, Jagdip S. Jaswal
Journal: Journal of the American College of Cardiology (2012)
Abstract 14142: Revascularization in Very Elderly Patients With Left Ventricular Dysfunction Suffering From Acute Myocardial Infarction
Authors: Derek Phan, Ara ROSTOMIAN, Mingsum Lee, naing a moore, prakash mansukhani, vicken aharonian, Somjot S Brar, Ray Zadegan
Journal: Circulation (2020)

Introduction: There is limited data on the benefits of revascularization in very elderly patients with left ventricular (LV) dysfunction and coronary artery disease (CAD). Hence, we sought to evaluate the role of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in very elderly patients with LV dysfunction who present with acute myocardial infarction (AMI). Methods: Retrospective study of patients ≥ 80 years old with LV ejection fraction (LVEF) ≤ 40% referred for invasive coronary angiography for AMI at Kaiser Permanente Los Angeles Medical Center between June 2009 and February 2019. Patients were grouped by treatment: PCI, CABG, or medical therapy. Inverse Probability Treatment of Weighting (IPTW) was utilized. Results: A total of 480 patients (average age 84.1±3.3years, 30% female) were analyzed. Of these, 206 (42.9%) underwent PCI and 46 (9.6%) underwent CABG. Compared to medical therapy, those revascularized were less likely to have any chronic total occlusion, prior strokes, diabetes, CAD, peripheral vascular disease, atrial fibrillation, and prior CABG; and more likely to have had prior PCI and higher LVEF. Median follow-up was 24.9 months (interquartile range 7.7-48.7months), After IPTW adjustment, revascularization was associated with a reduction in mortality (Hazard Ratio [HR] 0.72, 95% Confidence Interval [CI] 0.61-0.85) and non-fatal MI (HR 0.58, 95% CI 0.44-0.76). Both PCI and CABG were associated with reduced mortality (PCI: HR 0.75, 95% CI 0.63-0.90; CABG: HR 0.51, 95% CI 0.40-0.66) and non-fatal MI (PCI: HR 0.65, 95% CI 0.49-0.85; CABG: HR 0.28, 95% CI 0.16-0.48). Compared to CABG, there were no differences in mortality (HR 1.27, 95% CI 0.96-1.67), but increased non-fatal MI events (HR 3.81, 95% CI 1.82-8.0) with PCI. Conclusion: In very elderly patients with LV dysfunction, revascularization is superior to medical therapy. There were no differences in mortality between PCI and CABG, but PCI was associated with increased non-fatal MI events.
Race/ethnicity in systemic AL amyloidosis: perspectives on disease and outcome disparities
Authors: Andrew Staron, Lawreen H. Connors, Luke Zheng, Gheorghe Doros, Vaishali Sanchorawala
Journal: Blood Cancer Journal (2020)

Abstract In marked contrast to multiple myeloma, racial/ethnic minorities are underrepresented in publications of systemic light-chain (AL) amyloidosis. The impact of race/ethnicity is therefore lacking in the narrative of this disease. To address this gap, we compared disease characteristics, treatments, and outcomes across racial/ethnic groups in a referred cohort of patients with AL amyloidosis from 1990 to 2020. Among 2416 patients, 14% were minorities. Non-Hispanic Blacks (NHBs) comprised 8% and had higher-risk sociodemographic factors. Hispanics comprised 4% and presented with disproportionately more BU stage IIIb cardiac involvement (27% vs. 4–17%). At onset, minority groups were younger in age by 4–6 years. There was indication of more aggressive disease phenotype among NHBs with higher prevalence of difference between involved and uninvolved free light chains &gt;180 mg/L (39% vs. 22–33%, P = 0.044). Receipt of stem cell transplantation was 30% lower in Hispanics compared to non-Hispanic White (NHWs) on account of sociodemographic and physiologic factors. Although the age/sex-adjusted hazard for death among NHBs was 24% higher relative to NHWs ( P = 0.020), race/ethnicity itself did not impact survival after controlling for disease severity and treatment variables. These findings highlight the complexities of racial/ethnic disparities in AL amyloidosis. Directed efforts by providers and advocacy groups are needed to expand access to testing and effective treatments within underprivileged communities.