tbuckley/cabot-search huggingface dataset:
Abstract 059: COVID-19 And Type II NSTEMI: A Comprehensive Overview
Authors: Sahishnu Patel, Alexis Visotcky, Adam Devine, Vishwajit Kode, Srisha Kotlo, Michael Aljadah, Rodney Sparapani, Jacquelyn P Kulinski
Journal: Circulation (2022)

Introduction: Data on the incidence of type 2 NSTEMI (T2MI) in hospitalized patients with COVID-19 infection has been limited to single-center studies. We propose to define the incidence of T2MI in a national cohort and identify pre-hospital patient characteristics associated with a diagnosis of T2MI in hospitalized patients with COVID-19. We will also examine the impact of T2MI on morbidity and mortality. Methods: We performed a retrospective analysis on data from the American Heart Association COVID-19 Cardiovascular Disease Quality Improvement Registry. This national registry contains data on tens of thousands of patients hospitalized with COVID-19 from at least 122 centers across the United States. From January 2020 through May 2021, there were 709 (2.2%) out of 32,015 patients with a coded diagnosis of T2MI. We performed Wilcoxon tests, chi-squared test, and multivariable logistic regression to (1) identify predictive pre-hospital patient characteristics (Table 1) of T2MI for patients hospitalized with COVID-19 and (2) investigate the impact of T2MI on mortality and morbidity. Results: Patients in the T2MI group were older (71 vs. 63 years, p&lt;0.001), and in forward selection analyses, patients with a diagnosis of T2MI had higher odds of known HTN (OR 1.79 [1.01-3.1], p=0.026) and heart failure (OR 3.46 [2.24-5.34], p&lt;0.001). Increased age, admission troponin, CRP, and d-dimer were also associated with higher odds of T2MI. Hispanic race (OR 0.517 [0.289-0.924], p=0.026) and use of antihyperglycemics (OR 0.562 [0.377-0.836], p=0.005) were both associated with lower odds of T2MI. T2MI led to increased mortality (HR 1.32, [1.17-1.5], P&lt;0.001) and morbidity including cardiac arrest, major bleeding, and stroke. Conclusion: A history of heart failure was the strongest predictor of T2MI in hospitalized COVID19 patients. Patients with a T2MI compared to those without, had significantly higher mortality and morbidity. Limitations include the heterogenous ascertainment of the T2MI diagnosis across sites in this registry.
HOW TO TREAT UNFIT AND FRAIL PATIENTS
Authors: Gordon Cook
Journal: HemaSphere (2022)

Therapeutic options have greatly expanded over recent years defining new standards of care in multiple myeloma (MM). However, MM is a heterogeneous disease as are the patients it affects. As the median age of MM at presentation is 70 years, treating physicians are faced with the quandary of how to efficiently identify frail individuals that may have more difficulty tolerating and recovering from systemic therapy, thus being in need of treatment delivery modifications. Recently developed clinical scoring systems which are able to delineate patients into fit, unfit & frail groupings, with respective differences in PFS and OS in clinical trials have been highlighted. To date these have been proven to be prognostic biomarkers yet not evidence exists as to their potential as predictive biomarkers and thus used in the clinic to direct treatment decisions. Consequentially, such identified limitation have led to a study in the front-line setting using frailty scoring to prospectively adapt therapy (UKMRA Myeloma XIV trial). Dose and delivery modifications may be pertinent to patients with altered performance if we are to attain similar outcomes as with younger patients in the current era of novel agent combinations. The potential exists for improving performance (senolytics, exercise, nutrition) as well as how we measure performance more accurately through establishing digital phenotypes. Such clinical frailty scores may allow for better prediction of toxicity but there is a need for the development of additional, biological-based tools to reflect the processes of accelerated aging and how they impact on tolerance of cancer treatment and survivorship. Identifying specific biologic determinants of frailty may allow physicians to become even more adept at identifying patients at risk of excessive toxicity and provide the opportunity to target these processes therapeutically to help improve tolerability, quality of life and survival outcomes for older patients with cancer. Host response biology (HRB), is the measurable pathophysiological processes resulting from the impact of disease and accelerated aging on an individual’s biological function. Biomarkers of HRB can include end-organ damage parameters, clinical scoring systems of fitness, immune system quantitation (immunosenescence) and serial markers of age-related inflammation (inflammaging). Less fit patients represent a substantial proportion of newly diagnosed patients requiring treatment. Whilst age does not necessarily equate to fitness to tolerate therapy nonetheless age-related inflammation is perhaps the most important physiologic correlate of the age-related frailty syndrome. There is a need to design clinical trial research going forward, cognisant of a number of disease and patient related determinants, realising the mantra that “one size doesn’t fit all” which will inevitably allow us to deliver Better Research, Better Impact.
Abstract 047: Effects Of The Dash Diet On Change In High-Sensitivity Cardiac Troponin I Over Time: Results From The Dash-Sodium Trial
Authors: Matthew J Belanger, Lara C Kovell, Ruth-Alma Turkson-Ocran, Kenneth J Mukamal, Xiaoran Liu, Lawrence J Appel, Edgar R Miller, Frank M Sacks, Robert H Christenson, Heather Rebuck, Alex R Chang, Stephen P Juraschek
Journal: Circulation (2022)

Background: The DASH (Dietary Approaches to Stop Hypertension) diet has been shown to reduce high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of subclinical cardiac injury. However, the time course of the DASH diet’s effects on this biomarker has not been determined. Hypothesis: The DASH diet lowers hs-cTnI within 4 weeks and the effects gradually increase over time. Methods: We analyzed data from the DASH-Sodium trial, a randomized controlled feeding study of healthy adults with systolic blood pressure 120 to 159 mm Hg and diastolic blood pressure 80 to 95 mm Hg. Participants were randomly assigned to the DASH diet or a typical American diet (control). Within each arm of the study, participants were assigned three sodium levels, in random order, changed every 4 weeks. Hs-cTnI was measured from serum collected at baseline and at 4, 8, and 12 weeks of feeding. Energy intake was adjusted to maintain body weight throughout the trial. Results: Of the 411 participants included in the final analysis, their mean age was 48 years, 56% were women, and 56% were Black. The mean baseline systolic/diastolic blood pressure was 135/86 mm Hg. Compared with baseline, the control diet did not have a significant effect on hs-cTnI at any of the measured time points. In contrast, the DASH diet reduced hs-cTnI by 0.18 ng/l (95% CI: -0.32, -0.04) at 4 weeks, 0.14 ng/l (95% CI: -0.29, 0.00) at 8 weeks, and 0.33 ng/l (95% CI: -0.48, -0.18) at 12 weeks ( Figure ; P -trend = 0.025). The %-difference in mean change from baseline of hs-cTnI for DASH vs. control was -13.30% (95% CI: -25.34, 0.69), -10.47% (95% CI: -23.08, 4.21), and -17.78% (95% CI: -29.51, -4.09) at 4, 8, and 12 weeks, respectively. Conclusions: The DASH diet reduced hs-cTnI within 4 weeks of feeding with greater diet effects occurring at 12 weeks of feeding. These results suggest that the DASH diet has both early and cumulative effects on subclinical cardiac injury.
Testicular Cancer in the Cisplatin Era: Causes of Death and Mortality Rates in a Population-Based Cohort
Authors: Ragnhild Hellesnes, Tor Åge Myklebust, Sophie D. Fosså, Roy M. Bremnes, Ása Karlsdottir, Øivind Kvammen, Torgrim Tandstad, Tom Wilsgaard, Helene F. S. Negaard, Hege S. Haugnes
Journal: Journal of Clinical Oncology (2021)

Using complete information regarding testicular cancer (TC) treatment burden, this study aimed to investigate cause-specific non-TC mortality with impact on previous treatment with platinum-based chemotherapy (PBCT) or radiotherapy (RT).Overall, 5,707 men identified by the Cancer Registry of Norway diagnosed with TC from 1980 to 2009 were included in this population-based cohort study. By linking data with the Norwegian Cause of Death Registry, standardized mortality ratios (SMRs), absolute excess risks (AERs; [(observed number of deaths - expected number of deaths)/person-years of observation] ×10,000), and adjusted hazard ratios (HRs) were calculated.Median follow-up was 18.7 years, during which non-TC death was registered for 665 (12%) men. Overall excess non-TC mortality was 23% (SMR, 1.23; 95% CI, 1.14 to 1.33; AER, 11.14) compared with the general population, with increased risks after PBCT (SMR, 1.23; 95% CI, 1.07 to 1.43; AER, 7.68) and RT (SMR, 1.28; 95% CI, 1.15 to 1.43; AER, 19.55). The highest non-TC mortality was observed in those < 20 years at TC diagnosis (SMR, 2.27; 95% CI, 1.32 to 3.90; AER, 14.42). The most important cause of death was non-TC second cancer with an overall SMR of 1.53 (95% CI, 1.35 to 1.73; AER, 7.94), with increased risks after PBCT and RT. Overall noncancer mortality was increased by 15% (SMR, 1.15; 95% CI, 1.04 to 1.27; AER, 4.71). Excess suicides appeared after PBCT (SMR, 1.65; 95% CI, 1.01 to 2.69; AER, 1.39). Compared with surgery, increased non-TC mortality appeared after 3 (HR, 1.47; 95% CI, 0.91 to 2.39), 4 (HR, 1.41; 95% CI, 1.01 to 1.99), and more than four (HR, 2.04; 95% CI, 1.25 to 3.35) cisplatin-based chemotherapy cycles after > 10 years of follow-up.TC treatment with PBCT or RT is associated with a significant excess risk of non-TC mortality, and increased risks emerged after more than two cisplatin-based chemotherapy cycles after > 10 years of follow-up.
APOL1 risk variants in kidney transplantation: a modulation of immune cell function
Authors: Andrew F. Malone
Journal: Journal of Clinical Investigation (2021)

APOL1 G1 and G2 variants are established risk factors for nondiabetic kidney disease. The presence of two APOL1 risk variants in donor kidneys negatively impacts kidney allograft survival. Because of evolutionary pressure, the APOL1 risk variants have become common in people from Africa and in those with recent African ancestry. APOL1 risk variant proteins are expressed in kidney cells and can cause toxicity to these cells. In this issue of the JCI, Zhang, Sun, and colleagues show that recipient APOL1 risk variants negatively affect kidney allograft survival and T cell-mediated rejection rates, independent of donor APOL1 genotype or recipient ancestry. The authors provide evidence that APOL1 risk variants play an immunomodulatory role in T cells and NK cells in the setting of kidney transplantation. These findings have important clinical implications that require further investigation.
Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar
Authors: Hiam Chemaitelly, Patrick Tang, Mohammad R Hasan, Sawsan AlMukdad, Hadi M Yassine, Fatiha M Benslimane, Hebah A Al Khatib, Peter Coyle, Houssein H Ayoub, Zaina Al Kanaani, Einas Al Kuwari, Andrew Jeremijenko, Anvar H Kaleeckal, Ali N Latif, Riyazuddin M Shaik, Hanan F Abdul Rahim, Gheyath K Nasrallah, Mohamed G Al Kuwari, Hamad E Al Romaihi, Adeel A Butt, Mohamed H Al-Thani, Abdullatif Al Khal, Roberto Bertollini, Laith J Abu-Raddad
Journal: New England Journal of Medicine (2021)

BackgroundWaning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer–BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear.MethodsWe used a matched test-negative, case–control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021.ResultsEstimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months.ConclusionsBNT162b2-induced protection against SARS-CoV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine–Qatar and others.)
Impaired Humoral and Cellular Responses to COVID-19 Vaccine in Heart and Lung Transplant Recipients
Authors: Vicky Gerovasili, Anand Shah, Aran Singanayagam, Peter M. George, Raymond Njafuh, Maria Prendecki, Martin Carby, Michelle Willicombe, Peter Kelleher, Anna Reed
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

To the Editor: Solid organ transplant recipients are at high risk from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with reported mortality rates of up to 39%, with emerging data demonstrating impaired humoral responses to vaccination (1, 2).Sparse data exist examining T-cell immunity (3-6).The calcineurin inhibitors, tacrolimus and cyclosporin, specifically inhibit T-cell activity.We hypothesized that highly immunosuppressed cardiothoracic transplant recipients (HICTTR) on triple immunosuppression are at an immunological disadvantage and are unlikely to produce robust humoral or cellular immune responses to the SARS-CoV-2 vaccination.
Clonal Hematopoiesis Is Associated with Increased Risk of Progression of Asymptomatic Waldenström Macroglobulinemia
Authors: Sabrin Tahri, Tarek H Mouhieddine, Robert A. Redd, Luisa Maria Lampe, Katarina Nillson, Nang Kham Su, Habib El-Khoury, Amin H Nassar, Elio Adib, Govind Bindra, Sarah Abou Alaiwi, Lorenzo Trippa, David P. Steensma, Jorge J. Castillo, Steven P. Treon, Irene M. Ghobrial, Adam S. Sperling
Journal: Blood (2021)
COVID-19 and social inequalities: a complex and dynamic interaction
Authors: Catherine Quantin, Pascale Tubert-Bitter
Journal: The Lancet Public Health (2022)

COVID-19, in all its dimensions, including incidence, testing, and severity, is known to be associated with social inequalities.1–6 Such inequalities are associated with differential exposure to the virus, greater susceptibility to infection, more frequent comorbidities associated with severe outcomes, and disparate access to care.
Heteroplasmy of Wild-Type Mitochondrial DNA Variants in Mice Causes Metabolic Heart Disease With Pulmonary Hypertension and Frailty
Authors: Ana Victoria Lechuga-Vieco, Ana Latorre-Pellicer, Enrique Calvo, Carlos Torroja, Juan Pellico, Rebeca Acín-Pérez, María Luisa García-Gil, Arnoldo Santos, Navratan Bagwan, Elena Bonzon-Kulichenko, Ricardo Magni, Marina Benito, Raquel Justo-Méndez, Anna Katharina Simon, Fátima Sánchez-Cabo, Jesús Vázquez, Jesús Ruíz-Cabello, José Antonio Enríquez
Journal: Circulation (2022)

In most eukaryotic cells, the mitochondrial DNA (mtDNA) is transmitted uniparentally and present in multiple copies derived from the clonal expansion of maternally inherited mtDNA. All copies are therefore near-identical, or homoplasmic. The presence of >1 mtDNA variant in the same cytoplasm can arise naturally or result from new medical technologies aimed at preventing mitochondrial genetic diseases and improving fertility. The latter is called divergent nonpathologic mtDNA heteroplasmy (DNPH). We hypothesized that DNPH is maladaptive and usually prevented by the cell.We engineered and characterized DNPH mice throughout their lifespan using transcriptomic, metabolomic, biochemical, physiologic, and phenotyping techniques. We focused on in vivo imaging techniques for noninvasive assessment of cardiac and pulmonary energy metabolism.We show that DNPH impairs mitochondrial function, with profound consequences in critical tissues that cannot resolve heteroplasmy, particularly cardiac and skeletal muscle. Progressive metabolic stress in these tissues leads to severe pathology in adulthood, including pulmonary hypertension and heart failure, skeletal muscle wasting, frailty, and premature death. Symptom severity is strongly modulated by the nuclear context.Medical interventions that may generate DNPH should address potential incompatibilities between donor and recipient mtDNA.
Abstract P206: Proteomic And Metabolomic Signatures Of Plasma Triglyceride-related Trait Responses To Regular Exercise
Authors: Jacob L Barber, Guoshuai Cai, Jeremy M Robbins, Prashant Rao, Michael Mi, Sujoy Ghosh, Clary Clish, Daniel H Katz, Robert E Gerszten, Claude Bouchard, Mark A Sarzynski
Journal: Circulation (2022)

Introduction: Elevated plasma triglycerides (TG) are associated with risk of cardiovascular disease and are modifiable through lifestyle interventions such as regular exercise. However, TG responses to regular exercise are characterized by significant inter-individual differences. Hypothesis: We hypothesized that baseline levels of circulating proteins and metabolites are associated with TG response to exercise and can predict exercise-induced changes in plasma TG traits. Methods: We measured circulating proteins (n=4979 proteins) and metabolites (n=300) in 650 Black and White adults of the HERITAGE Family Study who completed 20 weeks of exercise training and had complete data on TG traits. We investigated two TG-related traits that significantly improved with training: fasting TG and large TG-rich lipoprotein particle concentration (LTRLP). The association between baseline analyte values and exercise-induced changes in TG traits were examined using linear mixed models adjusted for age, sex, race, BMI, baseline trait value, and the random effect of family membership. Significance was determined as FDR&lt;0.05. Molecular signatures of TG trait responses were generated via elastic net regression tuned using leave-one-out cross validation. Results: Regular exercise significantly reduced plasma TG (-1.03±1.3 mmol/L, p=0.01) and LTRLP (-0.24±2.2 nmol/L, p= 0.007), with their training-induced changes moderately correlated (r=0.4, p&lt;0.0001). We identified largely distinct panels of baseline analytes associated with changes in TG and LTRLP ( Table 1 ). Similarly, elastic net regression yielded distinct models of 99 analytes for TG and 315 analytes for LTRLP responses to exercise with accuracy of RMSE=1.28 mmol/L for TG and 2.16 nmol/L for the LTRLP model. Conclusions: We identified panels of proteins and metabolites associated with exercise-induced changes in TG traits and demonstrate, within our data, circulating analytes hold promise for predicting the exercise responsiveness of plasma TG-related traits.
Abstract 10039: Rise in Incidence of Takotsubo Syndrome, Associated Comorbidities and Major Adverse Cardiac and Cerebrovascular Events Among Cancer Survivors: A Nationwide Analysis of Two Cohorts a Decade Apart (2007 &amp; 2017)
Authors: Malak Modi, Nilay R Bhatt, Jamila Begum Jabar Ali, Mounika Binkam, Mimoza Isufi, Nibras yar khan, Ummul Asfeen, Zainab J Gandhi, Bansari Kalolia, Rupak Desai
Journal: Circulation (2021)

Introduction: Studies in the last decade have shown an increased prevalence of Takotsubo syndrome (TTS); however, there is limited data on the prevalence and impact of TTS on hospitalizations among cancer survivors. Methods: We identified adult hospitalizations with prior cancer and TTS using National inpatient samples from 2007 &amp; 2017. We then compared the demographics, comorbidities, and in-hospital outcomes between two cohorts 10-years apart. In addition, we also performed multivariable analysis to evaluate the composite outcomes of MACCE (all-cause mortality, cardiac arrest, arrhythmia and stroke) after adjusting for sociodemographic, type of admission, hospital characteristics, comorbidities, current cancer, and prior chemo/radiotherapy. Results: Prevalence of TTS per 100,000 hospitalizations among cancer survivors increased about 8-fold from 23 to 163 (p&lt;0.001) between 2007 and 2017 (Fig. 1a) . There was high prevalence of TTS among Caucasian, elderly and females in both cohorts, female (38 to 261/100,000 hospitalizations) and geriatric cancer survivors (24 to 174/100,000 hospitalizations) showed nearly 7-fold increase in TTS in 2017 vs. 2007 (p&lt;0.001). Traditional cardiovascular risk factors, heart failure, chronic pulmonary disease, depression, renal failure and other neurological disorders also increased in the 2017 cohort vs. 2007 cohort. Along with higher rates of atrial tachyarrhythmias (Fig. 1b) , There was nearly 40% (OR 1.39, 95%CI: 1.06-1.82, p=0.016) higher risk of composite MACCE in the 2017 TTS cohort compared to 2007 cohort among cancer survivors Conclusions: Prevalence of TTS among hospitalized cancer survivors increased 8-fold in 2017 compared to 2007. Despite increased awareness about etiopathogenesis and access to improved diagnostic measures, this analysis of TTS cohorts among cancer survivors showed increasing comorbidities with nearly 40% higher risk of composite MACCE across two cohorts selected a decade apart.
Hepatic Lesion of Mucosa-Associated Lymphoid Tissue Lymphoma Revealed by Al18F-NOTA-FAPI-04 PET/CT
Authors: Ying Kou, Zhiwei Yao, Zhuzhong Cheng
Journal: Clinical Nuclear Medicine (2021)

Abstract A middle-aged man was newly diagnosed with mucosa-associated lymphoid tissue lymphoma with secondary liver involvement. The hepatic lesion was not shown on FDG PET/CT but FAPI (fibroblast-activated protein inhibitor) PET/CT, which revealed abnormal FAPI accumulation. This case demonstrated that FAPI PET/CT might provide value in hepatic mucosa-associated lymphoid tissue lymphoma.
194P Modelling strategies to combine multiple serum tumor biomarkers for early prediction of immunotherapy non-response in non-small cell lung cancer
Authors: F. van Delft, M. Schuurbiers, M. Muller, S. Burgers, H. van Rossum, M. Ijzerman, M. van den Heuvel, H. Koffijberg
Journal: Annals of Oncology (2022)