tbuckley/cabot-search huggingface dataset:
Ambient heat and risks of emergency department visits among adults in the United States: time stratified case crossover study
Authors: Shengzhi Sun, Kate R Weinberger, Amruta Nori-Sarma, Keith R Spangler, Yuantong Sun, Francesca Dominici, Gregory A Wellenius
Journal: BMJ (2021)

Abstract Objective To quantify the association between ambient heat and visits to the emergency department (ED) for any cause and for cause specific conditions in the conterminous United States among adults with health insurance. Design Time stratified case crossover analyses with distributed lag non-linear models. Setting US nationwide administrative healthcare claims database. Participants All commercial and Medicare Advantage beneficiaries (74.2 million) aged 18 years and older between May and September 2010 to 2019. Main outcome measures Daily rates of ED visits for any cause, heat related illness, renal disease, cardiovascular disease, respiratory disease, and mental disorders based on discharge diagnosis codes. Results 21 996 670 ED visits were recorded among adults with health insurance living in 2939 US counties. Days of extreme heat—defined as the 95th centile of the local warm season (May through September) temperature distribution (at 34.4°C v 14.9°C national average level)—were associated with a 7.8% (95% confidence interval 7.3% to 8.2%) excess relative risk of ED visits for any cause, 66.3% (60.2% to 72.7%) for heat related illness, 30.4% (23.4% to 37.8%) for renal disease, and 7.9% (5.2% to 10.7%) for mental disorders. Days of extreme heat were associated with an excess absolute risk of ED visits for heat related illness of 24.3 (95% confidence interval 22.9 to 25.7) per 100 000 people at risk per day. Heat was not associated with a higher risk of ED visits for cardiovascular or respiratory diseases. Associations were more pronounced among men and in counties in the north east of the US or with a continental climate. Conclusions Among both younger and older adults, days of extreme heat are associated with a higher risk of ED visits for any cause, heat related illness, renal disease, and mental disorders. These results suggest that the adverse health effects of extreme heat are not limited to older adults and carry important implications for the health of adults across the age spectrum.
Abstract 10171: Higher Rates of Major Adverse Cardiac and Cerebrovascular Events in Non-White Patients Among Nationwide Hospitalizations of Young Adults: A Race and Sex-Stratified Analysis
Authors: Sonali Sachdeva, Mounika Binkam, Nibras Yar Khan, Jamila Begum Jabar Ali, Nilay R Bhatt, Pablo Tzorin, Ummul Asfeen, Ankit Vyas, Rupak Desai
Journal: Circulation (2021)

Introduction: Cardiovascular disease rates among young adults have been increasingly affected by racial and gender disparities and detailed evidence regarding these differences and their impact on cardiovascular events in young adults hospitalizations remain unknown. Methods: The National Inpatient Sample (Oct2015-2017) was queried to identify young adult hospitalizations (18-44 years). Socio-demographics, comorbidities, and rates of major adverse cardiac and cerebrovascular events (MACCE: all-cause mortality, AMI, cardiac arrest, and stroke) were retrieved for males and females and with a more granular comparative analysis for different racial subgroups. A p&lt;0.05 was considered statistically significant. Results: Of 19,448,301 (median age 31 years [25-37], 69.1% non-elective) young adult hospitalizations, 315,290 (1.6%) were identified with MACCE. Black patients followed by Hispanics were most likely hospitalized non-electively. Overall, the MACCE rate was higher in males than in females. Among males, MACCE were higher (5.3%) in Asian or Pacific Islanders (API), whereas in females, black patients were affected the most (1.3%) (Fig. 1). Traditional cardiovascular comorbidities were more prevalent in black and Native American patients (among both male/females) followed by Hispanic/API whereas Caucasians had higher rates of drug abuse including smoking and depression (p&lt;0.001) (Table 1). Conclusions: Among young hospitalizations, non-white, male patients were more frequently admitted non-electively and had higher rates of cardiovascular comorbidities that could have translated into higher MACCE. Special emphasis needs to be laid on gender and racial differences for CVD disease prevention and risk factor modification in young adults.
Abstract 12344: Impact of Age on Hospital Outcomes Associated With Percutaneous Left Atrial Appendage Occlusion: Insights From a Nationwide Cohort Sample
Authors: Islam Shatla, Ahmed Elkaryoni, Abdelrhman Abumoawad, Mahmoud El Iskandarani, kevin kennedy, Alan P Wimmer
Journal: Circulation (2021)

Introduction: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a proven alternative for thromboembolism prevention in patients with atrial fibrillation (AF) who cannot tolerate long term anticoagulation. The mean age in clinical trials has been less than 75 years. There are limited data on LAAO safety in older patients. Methods: We used the National Inpatient Sample and ICD-10 codes to identify AF patients who underwent LAAO during the years 2016-2018. Patients were grouped by age &lt;75 and ≥ 75 years. We studied baseline characteristics, length of stay, cost, hospital mortality, and other adverse events, including, hematoma, vascular complications, and perforation/tamponade, and stroke/transient ischemic attack in the two groups. Results: Our search criteria identified a total of 6877 patients, of whom 4160 (60.4%) were ≥ 75 years. LAAO increased similarly among patients in both groups (figure1). The average length of stay after LAAO was 1.5 ± 1.9 days for the entire cohort and did not differ for the two groups (p=0.603). Hospitalization costs were $25635.6 ± 12041.5 among patients ≥ 75 years and $26175.6 ± 11768.0 in those &lt; 75 years (P=0.067). There were 10 deaths in patients ≥75 years and 1 death among patients &lt;75 years (p=0.059). Perforation/tamponade was 1.3% among patients ≥75 years vs 0.6% for those &lt;75 years (p=0.008). This difference persisted on multivariate analysis (OR 1.82; 95% CI 1.04-3.17; p=0.036). There was a trend towards higher combined procedure related adverse events (OR 1.46; 95% CI 0.99-2.15; p= 0.059) among patients ≥75 years. There was no difference in the individual components of hematoma, vascular complication, and stroke/TIA between both groups. Conclusions: Percutaneous LAAO was associated with a higher incidence of perforation and tamponade and a concerning trend towards higher in-hospital mortality among older patients. Further clinical investigations are warranted to explore the risk in this vulnerable group.
Abstract 11199: Insulin-Like Growth Factor Binding Protein-4 is Associated with Pulmonary Arterial Hypertension Severity and Survival
Authors: Guillermo Torres-viera, Jun Yang, Megan Griffiths, Stephanie Brandal, Rachel L Damico, Dhananjay Vaidya, Catherine Simpson, Michael Pauciulo, Dunbar D Ivy, Eric D Austin, Paul Hassoun, Allen D Everett
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) results in progressive elevation of pulmonary vascular resistance and right heart failure. Insulin like growth factor binding proteins (IGFBPs) are a family of growth factor modifiers. As increased IGFBP4 expression is associated with vascular proliferation in lung cancer, it may also be associated with PAH severity. Hypothesis: Elevated IGFBP4 is associated with worse disease severity and survival in PAH. Methods: Using enzyme-linked immunosorbent assays (ELISA), we evaluated serum IGFBP4 in a multicenter PAH cohort, the NHLBI PAHBiobank (N=2571), and healthy controls (N=125). Hemodynamic and functional measures were used to assess IGFBP4’s association to PAH severity and survival. Spearman’s rank correlation test and Kruskal Wallis test were used for correlations. IGFBP4 was dichotomized at the median and analyzed by Kaplan-Meier survival and Cox proportional Hazard regression. Results: Serum IGFBP4 levels were significantly elevated (p&lt;0.0001) compared to controls. After adjustment for age and sex, IGFBP4 above mean was associated with a 40 meter shorter six minute walk distance (95%CI, -55 to -25, p=&lt;0.001). In the IPAH subtype only, higher IGFBP4 was associated with higher mean right atrial pressures (2 mmHg; 95%CI, 1.2 to 2.9, p=&lt;0.001), mean pulmonary arterial pressures (2.0 mmHg; 95%CI, 0.09 to 4.0, p=0.041) and pulmonary capillary wedge pressures (0.75mmHg; 95%CI, 0.18 to 1.3, p=0.010). Cox multivariable analysis demonstrated higher serum IGFBP4 as an independent predictor of survival in the overall PAHB cohort (See Figure 1; HR, 3.6; 95% CI, 2.6-5.0), with worse outcomes for CHD-APAH (HR, 9.9; CI, 2.2-45) and IPAH (HR, 5.3; 95% CI, 2.9-9.7). Conclusions: Higher circulating IGFBP4 levels are significantly associated with worse PAH severity and shorter survival. Dysregulation of IGF metabolism/growth axis could play a significant role in PAH cardio-pulmonary pathobiology.
Optimizing Donor Selection for Haploidentical Transplantation Utilizing the Four-Group T Cell Epitope (TCE-4) Algorithm for Prediction of HLA-DPB1 Non-Permissive Mismatches
Authors: Scott R. Solomon, Michael T Aubrey, Xu Zhang, Melhem Solh, Lawrence E Morris, H. Kent Holland, Katelin C Jackson, Brian M Freed, Christina L Roark, Asad Bashey
Journal: Blood (2021)
Abstract 13946: Subclinical Atherosclerosis and Peri-Operative Cardiac Events in Patients Undergoing Peripheral Bypass Surgery
Authors: Swapna Sharma, Abiah Pritchard, Michael Young, Stanislav Henkin
Journal: Circulation (2021)

Introduction: Coronary artery disease (CAD) is associated with a higher risk of peri-operative adverse events after vascular surgery. Subclinical CAD, defined as presence of coronary calcium, has not been established as a risk factor for adverse events after vascular surgery. Hypothesis: We sought to describe the epidemiology and peri-operative outcomes in patients with subclinical coronary atherosclerosis (SCA) undergoing supra- and infra-inguinal peripheral bypass. Methods: Using the Vascular Quality Initiative, we identified patients at a single institution undergoing supra- and infra-inguinal peripheral bypass surgery (2009-2020). Retrospective chart review was performed to identify chest computed tomography (CT) within one year prior to revascularization; imaging was reviewed for presence of coronary calcifications, a marker of SCA. Individuals were stratified by: no atherosclerosis, SCA, and CAD. Comorbidities and peri-operative outcomes were compared among groups with the chi-square or ANOVA, as appropriate. Results: Of 1018 patients undergoing peripheral bypass surgery, 199 (20%) had a CT available. SCA was noted in 96 patients (48%) while 72 (36%) had known CAD. Patients with SCA had similar comorbidities to patients with CAD (Table) but were less likely to be on a pre-operative beta-blocker or P2Y12 inhibitor. The incidence of postoperative myocardial infarction and congestive heart failure was similar in patients with SCA (13% and 9%, respectively) as those with CAD (10%, 6% respectively), compared to those without atherosclerosis (3% and 0, respectively). Conclusions: SCA is common in patients undergoing peripheral bypass surgery and is associated with a risk of peri-operative myocardial infarction or congestive heart failure similar to occult CAD. Aggressive secondary prevention measures should be considered in patients with polyvascular disease, including subclinical CAD.
Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts
Authors: Raffaele Marfella, Nunzia D'Onofrio, Maria Consiglia Trotta, Celestino Sardu, Lucia Scisciola, Cristiano Amarelli, Maria Luisa Balestrieri, Vincenzo Grimaldi, Gelsomina Mansueto, Salvatore Esposito, Michele D'Amico, Paolo Golino, Giuseppe Signoriello, Marisa De Feo, Ciro Maiello, Claudio Napoli, Giuseppe Paolisso
Journal: Metabolism (2021)

The pathogenesis of experimental diabetic cardiomyopathy may involve the activator protein 1 (AP-1) member, JunD. Using non-diabetic heart transplant (HTX) in recipients with diabetes, we examined the effects of the diabetic milieu (hyperglycemia and insulin resistance) on cardiac JunD expression over 12 months. Because sodium/glucose cotransporter-2 inhibitors (SGLT2i) significantly reverse high glucose-induced AP-1 binding in the proximal tubular cell, we investigated JunD expression in a subgroup of type 2 diabetic recipients receiving SGLT2i treatment.We evaluated 77 first HTX recipients (40 and 37 patients with and without diabetes, respectively). Among the recipients with diabetes, 17 (45.9%) were receiving SGLT2i treatment. HTX recipients underwent standard clinical evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsy). In the biopsy samples, we evaluated JunD, insulin receptor substrates 1 and 2 (IRS1 and IRS2), peroxisome proliferator-activated receptor-γ (PPAR-γ), and ceramide levels using real-time polymerase chain reaction and immunofluorescence. The biopsy evaluations in this study were performed at 1-4 weeks (basal), 5-12 weeks (intermediate), and up to 48 weeks (final, end of 12-month follow-up) after HTX.There was a significant early and progressive increase in the cardiac expression of JunD/PPAR-γ and ceramide levels, along with a significant decrease in IRS1 and IRS2 in recipients with diabetes but not in those without diabetes. These molecular changes were blunted in patients with diabetes receiving SGLT2i treatment.Early pathogenesis in human diabetic cardiomyopathy is associated with JunD/PPAR-γ overexpression and lipid accumulation following HTX in recipients with diabetes. Remarkably, this phenomenon was reduced by concomitant therapy with SGLT2i, which acted directly on diabetic hearts.
Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study.
Authors: Benedikt Fritzsching, Marco Contoli, Celeste Porsbjerg, Sarah Buchs, Julie Rask Larsen, Lisa Elliott, Mercedes Romano Rodriguez, Nick Freemantle
Journal: The Lancet Regional Health - Europe (2021)

Allergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs).
Abstract 10045: Higher Morbidity, Mortality and Healthcare Resource Utilization in Admissions for Congestive Heart Failure with Concomitant Aspiration Pneumonia: National Inpatient Sample Analysis
Authors: Akhil Jain, Rishabh Jindal, Charu Agarwal, Gaurav Mudgal, Vivek Joseph Varughese, Athul Raj Raju, Geethu Jnaneswaran, Zainab J Gandhi, Rupak Desai
Journal: Circulation (2021)

Introduction: Data on the burden of congestive heart failure (CHF) in aspiration pneumonia (AP) patients is sparse. Our aim is to study the burden, morbidity and outcomes of CHF on AP patients. Methods: We queried the National Inpatient Sample (2015 October-2017) to identify admissions for AP in patients with CHF vs without CHF using relevant ICD-codes. Primary outcomes reported were all-cause mortality and pulmonary morbidity. Secondary outcomes included patient disposition, LOS and utilization of hospital resources. Results: We included 14,38,034 aspiration pneumonia (AP) hospitalizations amongst which 3,33,975 had associated CHF (23.2%). AP-CHF cohort often included older (79 [68-87]), white (74.8% vs 72.6%), male (54.7% vs 45.3%) patients admitted non-electively with Medicare insurance at Urban teaching facilities compared to AP only cohort (p&lt;0.001) (Table 1) . AP-CHF cohort was more often associated with valvular disease, pulmonary circulation disease, peripheral vascular disease, chronic pulmonary disease, hypertension (secondary/complicated), diabetes mellitus, hyperlipidemia and obesity compared to AP-only cohort. AP-CHF cohort had lower rates of alcohol abuse, drug abuse and smoking. AP- CHF cohort had higher adjusted odds of all-cause mortality (aOR 1.14 95% CI 1.13-1.15, p&lt;0.001), ARDS (aOR 2.27), respiratory failure (aOR 1.77), severe sepsis with septic shock (aOR 1.34) and requirement of respiratory support (aOR 1.40) compared to AP only cohort. AP-CHF cohort was more often discharged to short-term or intermediate facility and had longer stay with higher hospital charges compared to AP only cohort. Conclusion: Based on our analysis it can be concluded that nearly one-fourth of AP hospitalizations have concomitant CHF and that is associated with higher morbidity, mortality and complications ultimately leading to higher hospital resource utilization.
Abstract 10086: Cardiac Intravital Microscopy Enables Quantitative Mapping of Capillary-Level Blood Flow in the Murine Heart
Authors: Yirong Zhou, Kevin R King, Aaron D Aguirre
Journal: Circulation (2021)

Introduction: Coronary microvascular disease (CMD) is increasingly appreciated as a contributor to adverse cardiovascular outcomes, but underlying mechanisms of CMD remain poorly understood. Investigation of CMD in animal models is limited by a lack of techniques to quantify flow in the heart. We assessed the hypothesis that intravital microscopy (IVM) can enable in vivo imaging of red blood cell (RBC) flow profiles in the coronary microcirculation at cellular resolution. Methods: C57BL/6 mice (n=20) were used to develop cardiac IVM protocols. Cardiomyocyte membrane staining was achieved using intravenous injection of a voltage dye (di-2-anepeq). RBC labeling was done by ex-vivo staining of cells with Ter119 followed by transfusion. IVM was performed through a thoracotomy with animals anesthetized and ventilated. Confocal and two-photon microscopy was done using a custom tissue stabilizer and an Olympus FV1000MPE microscope synchronized to physiologic signals using custom hardware and software and cardiac pacing protocols. Images were analyzed in MATLAB to extract myocyte contractile properties, capillary diameter, and capillary flow properties. Results: Using cardiac and respiratory gating, images with cellular resolution could be measured in the beating heart at all phases of the cardiac cycle. This enabled quantification of cardiomyocyte contractile function and capillary diameter and widefield imaging by stitching of several images (Fig. 1A). Tracking of RBCs over serial images allowed quantification of RBC velocity across multiple capillaries simultaneously (Fig. 1B). Conclusion: Cardiac IVM can provide quantification of cardiac function and blood flow at the single cell scale and will provide an exciting tool for investigating CMD in models of heart disease.
Abstract 6983: Real-World Evaluation of In-Hospital Mortality and Vascular Complications in Patients Receiving Impella Support in a Community Based Health Care System
Authors: Arvind Kalyan Sundaram, Samantha Crissinger, Erin Vanenkevort, Sreelakshmi Kandadai, Stephen J Voyce
Journal: Circulation (2021)

Introduction: Impella is a peripherally inserted ventricular assist device used for hemodynamic support in patients during high risk percutaneous coronary interventions (PCI) and for management of cardiogenic shock. The aim of our study is to identify the mortality and vascular complications related to Impella placement in a real-world community health care setting. Methods: This is a retrospective observational study of patients who had Impella device implanted for high risk PCI and/or cardiogenic shock at three hospitals in the Geisinger Health Care System from January 2015-March 2020. Results: Ninety-nine patients had devices implanted during this time. One patient was excluded from analysis due to missing data. In hospital mortality rate was 31.6% for the entire group. The mortality rates varied significantly based on the acuity of procedure (p = &lt;.001). In-hospital mortality rates for patients receiving the Impella electively, urgently, emergently, and as a salvage procedure, was 0, 17.1, 46.4 and 65% respectively. The overall rate of vascular complications was 13.1% and was not related to the acuity of procedure (p = .16). Patients with a greater body mass index (BMI) had an increased frequency of vascular complications (OR = 1.89 95%CI: 1.31, 2.47, p &lt; .0001). Although not significantly significant, 14.7% of males had vascular complications compared to 9.7 % of females (p = .49). Conclusions: In-hospital mortality rates of patients with Impella implantation varies significantly based on the acuity of the procedure. Mortality remains high in patients with emergent &amp; salvage procedures. 2. Patients with higher BMI develop more frequent vascular complications. 3. No statistically significant difference in gender related vascular complication rates was found.
Clinicopathologic Characteristic and Natural History of Patients with Non Hereditary, Non Polycythemia Vera (NH/NPV) Persistent Polycythemia
Authors: Omar Mahmood, Hanson Mouanoutoua, Tanjot Saini, Marcel Okura, Mahboub Rahman Noori, Nadia Almasri, Haifaa Abdulhaq, Sani Bukari
Journal: Blood (2021)
TAMI-25. UPREGULATION OF CREATINE METABOLISM BY MYELOID CELLS RESULTS IN GLIOBLASTOMA PROGRESSION
Authors: Aida Rashidi, Alex Cordero, Brandyn Castro, David Hou, Mark Dapash, Peng Zhang, Yu Han, Aurora Lopez-Rosas, Navdeep Chandel, Maciej Lesniak, Catalina Chang, Jason Miska
Journal: Neuro-Oncology (2021)

Abstract Malignant brain tumors are uniquely immunosuppressive, with a predominant infiltration of immunosuppressive tumor-associated myeloid cells (TAMCs) and a deficit in T-cells unrivaled to any other tumor. This unique tumor microenvironment (TME) promotes resistance to both conventional and immune therapies for this disease. The underlying mechanisms by which TAMCs promote glioblastoma (GBM) progression are not fully understood. We found that TAMCs specifically upregulate de-novo creatine metabolism within GBM using unbiased genetic and metabolic screening. This metabolic phenotype was confirmed in human GBM patients by comparing peripheral versus tumor-infiltrating myeloid cells. Examination of de-novo creatine generation using Carbon13 arginine flux revealed that TAMCs, but not tumor-infiltrating CD8+ T-cells, can produce creatine. Furthermore, we demonstrate that TAMCs actively secrete de-novo generated creatine into cell cultures. Examination of the single-cell microenvironment of GBM revealed that malignant cells preferentially express the creatine transporter, indicating that TAMC-derived creatine is taken up by GBM. Notably, SLC6A8 is directly upregulated in the context of hypoxia and suggests that creatine uptake is a mechanism to promote survival under hypoxic stress. Indeed, exogenous creatine supplementation promoted both the migration and survival of multiple glioblastoma cell lines in-vitro. Utilizing an established inhibitor of creatine metabolism, β-Guanidinopropionic acid (β -GPA), we found that β -GPA blocks both the migration and survival of glioma cells under hypoxic stress. Lastly, β -GPA also inhibited creatine secretion by TAMCs, showing that creatine blockade can also influence TAMC metabolic phenotype. In the future, we will examine the importance of creatine metabolism on both immune suppression and tumor progression in-vivo. This work provides novel insights into the role of creatine metabolism in GBM and identifies a unique therapeutic avenue for this devastating disease.