tbuckley/cabot-search huggingface dataset:
Abstract 16013: Evidence for Improvement in NYHA Class and Freedom From Hospitalization in Bariatric Surgery Patients With an Established Diagnosis of Heart Failure
Authors: Michael W Foster, Sara E Badenhausen, Colleen Tewksbury, Noel N Williams, J Eduardo Rame, Kristoffel Dumon
Journal: Circulation (2020)

Introduction: Heart failure patients with severe obesity endure significant morbidity and frequent hospitalizations. Bariatric surgery is proven to provide durable weight loss for those with severe obesity, but the clinical impact and safety of these procedures among patients with heart failure has not been well-demonstrated. Methods: We conducted a medical record query of patients who have a previous diagnosis of heart failure (HFpEF and HFrEF) and underwent subsequent Roux-En-Y gastric bypass or laparoscopic sleeve gastrectomy at a high-volume metabolic and bariatric surgery center. We compared clinical, demographic, and echocardiographic data captured just prior to the bariatric procedure to the most recent data available in the medical record for each patient. Results: There were 50 patients (88% had HFpEF) included in this study. Time from HF diagnosis to most recent follow-up ranged from 0.2 to 20.3 years (median 6.7 years) and there was no recorded mortality. The median time from HF diagnosis to surgery was 2.3 years and median time from surgery to recent follow-up was 2.9 years. Post-operative median decrease in BMI was 8.8 kg/m 2 , HF hospitalizations were 0.4 per patient year (PPY) to 0.15 PPY, p=0.008, and median NYHA Class was II pre-op and I post-op, p=0.048). LVEF, LVESD, and LVEDD were not significantly changed post-operatively (Table 1). Conclusion: Weight loss following bariatric surgery for patients with HF led to improvements in NYHA Class, fewer hospitalizations for HF, and was not associated with perioperative mortality. It is reasonable to consider bariatric surgery for this patient population, but further prospective investigation is warranted.
Developing Translational Research of iPS Cell-Derived Cardiac Progenitor Cell-Sheet Transplantation for Treating Advanced Cardiac Failure
Authors: Fukushima Satsuki, Miyagawa Shigeru, Saito Atsuhiro, Higuchi Takahiro, Kawamura Masashi, Sakaguchi Taichi, Sawa Yoshiki
Journal: Circulation (2012)
Abstract 15734: Left Atrial Reservoir Strain as a Novel Prognostic Marker in Biopsy-proven Light-chain Amyloidosis
Authors: Peter Huntjens, Kathleen Zhang, Yuko Soyama, Maria Karmpalioti, Daniel Lenihan, John Gorcsan
Journal: Circulation (2020)

Introduction: Light chain cardiac amyloidosis (AL) has a variable but usually poor prognosis. Left ventricular (LV) function measures including LV strain imaging for global longitudinal strain (GLS) have shown clinically prognostic value in AL. However, the utility of novel left atrial (LA) strain imaging and its associations with LV disease remains unclear. Hypothesis: LA strain is of additive prognostic value to GLS in AL. Methods: We included 99 consecutive patients with AL. Cardiac amyloidosis either confirmed by endocardial biopsy (25%) or by non-cardiac tissue biopsy and imaging data supportive of cardiac amyloidosis. Peak LA reservoir strain was calculated as an average of peak longitudinal strain from apical 2- and 4-chamber views. GLS and apical sparing ratio were assessed using the 3 standard apical views. All-cause mortality was tracked over a median of 5 years. Results: Echocardiographic GLS and peak longitudinal LA strain were feasible in 96 (97%) and 86 (87%) of patients, respectively. There were 48 AL patients who died during follow-up. Patients with low GLS (GLS &lt; median; 10.3% absolute values) had worse prognosis than patients with high GLS group (p&lt;0.001). Although peak longitudinal LA strain was correlated with GLS (R=0.65 p&lt;0.001), peak longitudinal LA strain had additive prognostic value. AL patients with low GLS and low Peak LA strain (&lt;13.4%) had a 8.3-fold increase in mortality risk in comparison to patients with high GLS (95% confidence interval: 3.84-18.03; p&lt;0.001). Multivariable analysis showed peak longitudinal LA strain was significantly and independently associated with survival after adjusting for clinical and echocardiographic covariates (p&lt;0.01). Conclusions: Peak longitudinal LA strain was additive to LV GLS in predicting prognosis in patients with biopsy confirmed AL amyloidosis. LA strain imaging has potential clinical utility in patients with AL cardiac amyloidosis.
Abstract 13385: Protective Effect of Beta3-Adrenergic Receptor Deficiency on Diabetic Cardiomyopathy: Reversal of Type 2 Diabetes-Induced Contrast Changes of Cardiac SERCA 2a and Inducible Nitric Oxide Synthase
Authors: Heng Jie Cheng, Xiaoqiang Sun, Jing Cao, Zhe Chen, Yixi Liu, David Zhao, Dalane Kitzman, Che Cheng
Journal: Circulation (2020)

Background: We have shown that diabetes (DM)-induced cardiac dysfunction and β-adrenergic desensitization were prevented in β 3 -adrenergic receptor (AR) knockout (β 3 KO) mice. However, the molecular mechanism is unclear. We hypothesize that reversal of type 2 (T2) DM-induced alterations of cardiac SR Ca 2+ -ATPase (SERCA2a) and inducible nitric oxide synthase (iNOS) by β 3 KO may play a key role for the protective effect. Methods: LV myocyte protein levels of β 1 - and β 3 -AR, SERCA2a and iNOS, myocyte contractile and [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses to isoproterenol (ISO, 10 -8 M) were compared in 4 groups (n=6) female mice: 2 Vehicle controls wild-type (CWT) and Cβ 3 KO; and 2 T2DM of T2WT and T2β 3 KO.T2 was induced by fed high-fat diet (HFD) for 14 weeks (W), but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. for 5 days). Results: Mice-treated with HFD plus STZ had high blood glucose (~350 to 380 mg/dl). Versus CWT, T2WT myocytes had significantly decreased protein levels of SERCA2a (0.18 vs 0.29), and β 1 -AR (0.35 vs 0.49), but increased iNOS (0.25 vs 0.15) and β 3 -AR (0.25 vs 0.14) with reduced cell contraction (dL/dt max ) (72.7 vs 140.9 μm/s), relaxation (dR/dt max ) (50.9 vs 117.3 μm/s) and [Ca 2+ ] iT (0.16 vs 0.22). Moreover, in T2WT myocytes, ISO caused significantly less increases in dL/dt max (37% vs 59%), dR/dt max (30% vs 53%) and [Ca 2+ ] iT (19% vs 30%). Versus CWT, T2β 3 KO did not alter basal myocyte contraction and relaxation and response to ISO stimulation, but had significantly increased protein levels of SERCA2a (0.38 vs 0.29). T2β 3 KO prevented DM-caused increase in iNOS (T2β 3 KO: 0.16 vs CWT: 0.15) and decrease in β 1 -AR (0.46 vs 0.49). Versus T2β 3 KO, Cβ 3 KO mice had similar alterations. Importantly, in contrast to T2WT, in T2β 3 KO myocytes, the increased SERCA2a and reduced iNOS correlated with normal basal cell contraction and relaxation with preserved ISO-stimulated inotropic response. ISO caused similar increases in dL/dt max (60% vs 59%), dR/dt max (51% vs 53%) and [Ca 2+ ] iT (32% vs 30%). Conclusions: β 3 KO prevents T2DM-caused downregulation of cardiac β 1 -ARs and reverses increased iNOS and decreased SERCA2a, leading to the preservation of myocyte function, [Ca 2+ ] iT , and β-adrenergic reserve. Thus, β 3 -AR may provide a new target for DCM.
Potential use of new cooling technologies during Tokyo 2020 Olympics and associated ethical dilemmas
Authors: Borja Muniz-Pardos, Konstantinos Angeloudis, Fergus M Guppy, Kumpei Tanisawa, Yuri Hosokawa, Garrett Ash, Wolfgang Schobersberger, Andrew Grundstein, Victor Bargoria, Gerald O Lwande, James H Ombaka, Emin Ergen, Fumihiro Yamasawa, Sebastien Racinais, Douglas J Casa, Yannis P Pitsiladis
Journal: British Journal of Sports Medicine (2021)

The environmental conditions during Tokyo Summer Olympics are expected to be comparable to previous years1 with air temperatures and relative humidity in excess of 30°C and >70%, respectively.2 A previous consensus statement highlighted the main considerations for prevention, recognition and treatment of exertional heat illnesses,3 while the impact of extreme heat on athletic performance is examined elsewhere.4 Cooling strategies applied before and during the exercise in the heat have been shown to help athletes better maintain their performances5 by lowering body heat storage and core body temperature.6 The Tokyo Games have also encouraged the development of wearable technologies that could also be used for prevention, diagnosis and real-time monitoring of skin and core temperature and will be trialled during competition in Tokyo 2020. Here, we aim to highlight the potential application of current novel technologies and the associated ethical dilemmas regarding their effectiveness, the use of athlete biodata and predictive algorithms.

Recently, manufacturers have developed new cooling wearables that have the potential to reduce exertional heatstroke (EHS) risk and to reduce the decline in athletic performance in hot environments, with the most novel summarised in table 1. Here, the focus is not on cooling …
Metabolomics in cancer research and emerging applications in clinical oncology
Authors: Daniel R. Schmidt, Rutulkumar Patel, David G. Kirsch, Caroline A. Lewis, Matthew G. Vander Heiden, Jason W. Locasale
Journal: CA A Cancer Journal for Clinicians (2021)

Abstract Cancer has myriad effects on metabolism that include both rewiring of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment, and changes in normal tissue metabolism. With the recognition that fluorodeoxyglucose‐positron emission tomography imaging is an important tool for the management of many cancers, other metabolites in biological samples have been in the spotlight for cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecule metabolites that like other ‐omics technologies can provide critical information about the cancer state that are otherwise not apparent. Here, the authors review how cancer and cancer therapies interact with metabolism at the cellular and systemic levels. An overview of metabolomics is provided with a focus on currently available technologies and how they have been applied in the clinical and translational research setting. The authors also discuss how metabolomics could be further leveraged in the future to improve the management of patients with cancer.
Cost-Effectiveness of Adjuvant Treatment for Ductal Carcinoma In Situ
Authors: Apar Gupta, Sachin R. Jhawar, Mutlay Sayan, Zeinab A. Yehia, Bruce G. Haffty, James B. Yu, Shi-Yi Wang
Journal: Journal of Clinical Oncology (2021)

PURPOSE Ductal carcinoma in situ (DCIS) accounts for 20% of breast cancer cases in the United States and is potentially overtreated, leading to high expenditures and low-value care. We conducted a cost-effectiveness analysis evaluating all adjuvant treatment strategies for DCIS. METHODS A Markov model was created with six competing treatment strategies: observation, tamoxifen (TAM) alone, aromatase inhibitor (AI) alone, radiation treatment (RT) alone, RT + TAM, and RT + AI. Baseline recurrence rates were modeled using the NSABP B17 and RTOG 9804 trials for standard-risk and good-risk DCIS, respectively. Relative risk reductions and adverse event rates for each treatment strategy were derived from meta-analyses of large randomized trials. We used a willingness-to-pay threshold of $100,000 in US dollars/quality-adjusted life-year and a lifetime horizon for two cohorts of women, age 40 and 60 years. Comprehensive sensitivity analyses evaluated the robustness of base-case results. RESULTS RT alone was cost-effective for patients with standard-risk DCIS, and observation was cost-effective for patients with good-risk DCIS, across both age groups. Strategies including TAM or AI resulted in fewer quality-adjusted life-years than observation, because of the prolonged decrement in quality of life outweighing the modest benefit in ipsilateral risk reduction. In sensitivity analysis, RT alone was cost-effective for age 40, good-risk patients when ipsilateral risk reduction matched that of the RTOG 9804 trial, there was minimal increased risk of contralateral breast secondary malignancy, or there was strong patient willingness to pursue RT. CONCLUSION Our findings suggest that cost-effective and clinically optimal treatment strategies are RT alone for standard-risk DCIS and observation for good-risk DCIS, with personalization on the basis of patient age and preference for RT. Hormonal therapy is likely suboptimal for most patients with DCIS.
Abstract 13559: Engineered Three-dimensional Cardiac Tissues Maturated by Dynamic Culture in a Rotating Wall Vessel Bioreactor Remodel the Diseased Heart in the Rat Infarction Model
Authors: Taro Nakazato, Shigeru Miyagawa, Toshimasa Uemura, Li Liu, Junjun Li, Masao Sasai, Akima Harada, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2020)

Introduction: To completely repair the distressed heart with few myocytes it may be crucial how to construct massive engineered three-dimensional cardiac tissues (E3DCTs) and integrate them to myocardium after transplant. We hypothesized that E3DCTs maturated by dynamic culture could enhance to remodel diseased left ventricle (LV) in the distressed rat heart. Methods: We made E3DCT by seeding 2.0 х 10 6 human induced pluripotent stem cell derived cardiomyocytes on the 6mm х 6mm PLGA fiber sheet. It was cultured in a rotating wall vessel bioreactor for seven days (RWV group) or culture dishes for the control. After in vitro assessment, these tissues were transplanted to myocardial infarction model nude rats, and 4 weeks after transplantation, we evaluated functional recovery and histology. Results: In the RWV group, thickness of E3DCTs were around 400μm, and cardiomyocytes showed mature phenotype evidenced by significantly higher expression of Troponin T (TnT), sarcomeric α actinin (SAA), connexin 43 (Cx43) and myosin heavy chain 7 (MYH7) with upregulation of mammalian target of rapamycin by Western blots (TnT; 2.1±0.2 vs. 1.0±0.2, SAA; 2.0±0.2 vs. 1.0±0.2, Cx 43; 2.0±0.3 vs. 1.0±0.1, MYH7; 2.0±0.2 vs. 1.0±0.2, p&lt;0.05, respectively) (Figure 1A). Moreover, the concentration of angiogenic cytokines was significantly higher in the RWV group. Four weeks after transplantation, the LV ejection fraction was significantly improved in the RWV group than in the control (47±4.9 vs. 38±6.9%, p&lt;0.01). On histological analysis, transplanted E3DCT reached a thickness of 1mm and vascular-like structures were partially observed inside (Figure 1B). In the RWV group, LV remodeling was significantly attenuated and neovascularization was significantly noted (Figure 1C, 1D). Conclusions: E3DCTs maturated by dynamic culture in a RWV bioreactor could remodel the diseased LV in rat infarction model, proposing potent armamentarium for cardiomyogenesis therapy in failed heart.
증례 / Common Variable Immunodeficiency와 병발된 육아종성 간염 1예
Authors: 이한주(Han Chu Lee), 서동진(Dong Jin Suh), 송병철(Byung Cheol Song), 정영화(Young Hwa Chung), 이영상(Yung Sang Lee), 오태훈(Tae Hoon Oh), 이태윤(Tae Yoon Lee), 유은실(Eun Sil Yu)
Journal: Clinical and Molecular Hepatology (2001)

A granuloma is a compact, organized collection of chronic inflammatory cells, predominantly consisting of mature mononuclear phagocytes. Clinical manifestations of hepatic granulomas vary widely from asymptomatic elevation of serum alkaline phosphatase activity to liver cirrhosis. The hepatic granuloma is nonspecific and represents a pathologic reaction induced by any of a number of factors. Although the causes of hepatic granuloma vary considerably according to geographic site, sarcoidosis and tuberculosis are the two leading causes. Here we present a 20-year-old female with a long history of recurrent otitis media, upper respiratory infection, and unexplained hepatosplenomegaly. A diagnosis of common variable immunodeficiency was made, based on the decreased levels of serum immunoglobulins. A liver biopsy revealed chronic granulomatous inflammation, but neither caseous necrosis nor acid-fast bacillus was found. Her liver disease progressed despite a nine-month course of antituberculous medication. Hypogammaglobulinemia should be included in the differential diagnosis of granulomatous liver disease. (Korean J Hepatol 2001;7:95-99)
Effects of Hydrophobicity on Antimicrobial Activity, Selectivity, and Functional Mechanism of Guanidinium‐Functionalized Polymers
Authors: Jason Tan, Yanli Zhao, James L. Hedrick, Yi Yan Yang
Journal: Advanced Healthcare Materials (2021)

Abstract In this study, a series of guanidinium‐functionalized polycarbonate random co‐polymers is prepared from organocatalytic ring‐opening polymerization to investigate the effect of the hydrophobic side chain (ethyl, propyl, isopropyl, benzyl, and hexyl) on their antimicrobial activity and selectivity. Although the polymers exhibit similar minimum inhibitory concentrations, the more hydrophobic polymers exhibit a faster rate of bacteria elimination. At higher percentage content (20 mol%), polymers with more hydrophobic side chains suffer from poor selectivity due to their high hemolytic activity. The highly hydrophobic co‐polymer, containing the hydrophobic hexyl‐functionalized cyclic carbonate, kills bacteria via a membrane‐disruptive mechanism. Micelle formation leads to a lower extent of membrane disruption. This study unravels the effects of hydrophobic side chains on the activities of the polymers and their killing mechanism, providing insights into the design of new antimicrobial polymers.
Abstract 16637: Echocardiographic Screening With Remote Reading as a Tool for Additional Cardiovascular Risk Stratification in Primary Care - Data From the PROVAR+ Study
Authors: Bruno R Nascimento, Maria Do Carmo P Nunes, Craig A SABLE, Kaciane Oliveira, Juliane Franco, Marcia Barbosa, Alison Reese, Leonardo Raso, Sarcha M Paiva, Adriana C Diamantino, Clara Fraga, Frederico Macedo, Domingos Sávio G Ferreira-Filho, Antonio L Ribeiro, Andrea Z Beaton
Journal: Circulation (2020)

Introduction: Morbidity and mortality associated with advanced heart disease (HD) is significant in Brazil. Underserved populations often experience long delays in diagnosis, with long waiting lines for echocardiography (echo). We aimed to evaluate the feasibility of integrating screening echocardiography (echo) with remote interpretation in the Brazilian primary care (PC), and to assess HD prevalence. Methods: In 36 months, 25 healthcare workers at 40 PC units were trained on simplified handheld (GE VSCAN) echo protocols. Screening (SC) groups, including patients aged 17-20, 35-40 and 60-65 years, and patients referred (RF) for clinical indications, in waiting lines, answered a clinical questionnaire and underwent focused echo, interpreted in US and Brazil by telemedicine. Significant HD was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion or wall-motion abnormalities. A study-derived score including clinical variables (sex, body mass, hypertension, coronary disease, heart failure, heart surgery, valve disease and Chagas disease: low (&lt;13%), intermediate (13% - 69%) and high-risk (≥70%)) was applied to predict HD in echo screening. Results: From January 2017 to November 2019, 4425 patients underwent echo; 1338 (30%) in SC group. Mean age was 54±18 years, 63.7% were females; 57.8% had hypertension and 20.1% diabetes. The most frequent symptoms were chest pain (32.3%), dyspnea (32.3%) and palpitations (25.6%). Significant HD was found in 1409 (31.8%) patients, (28.8% in SC vs. 33.2% in RF group, p=0.004). Comparing SC to RF, severe left ventricular dysfunction was observed in 2.6% vs. 3.1%, p=0.45, severe aortic or mitral regurgitation in 1.5% vs. 1.0%, p=0.17. Prevalence was higher in high-risk patients according to the clinical score, compared to intermediate/low risk (45.3% vs. 26.6%, p&lt;0.001). The continuous risk score was strongly associated with HD (odds ratio=25.8, 95% IC 16.5 - 40.4, p&lt;0.001), with area under ROC curve=0.61. Conclusions: Integration of screening echo into PC is feasible in Brazil as a strategy to prioritize cardiovascular care in low income areas through task-shifting. In association with clinical variables, this tool may improve early diagnosis and referrals.
Abstract 12584: Transcription Factor EB Regulates Vascular Smooth Muscle Calcification
Authors: Ryo Ishiwata, Yuji Morimoto
Journal: Circulation (2020)

Introduction: Vascular calcification is a strong predictor of cardiovascular-related mortality. Hyperphosphatemia causes phenotypic switches of vascular smooth muscle cells (VSMCs), leading to medial calcification. Recent studies have suggested that dysfunction of the autophagy-lysosomal pathway in VSMCs is a cause of vascular calcification, but the process through which this pathway fails is elusive. Transcription factor EB (TFEB) is a master regulator of lysosome biogenesis; its function in VSMCs is unknown. Hypothesis: We assessed the hypothesis that the dysfunction of TFEB in VSMCs is a cause of vascular calcification. Methods and Results: We induced vascular calcification in wild type mouse aorta with an ex vivo hyperphosphatemia model . Addition of inorganic phosphate at a 1.7 mmol/L for five days decreased TFEB protein expression (0.23 ± 0.10-fold vs. day0, n = 5-7). Immunohistochemistry and alizarin red staining showed that a decrease in TFEB expression in the tunica media was correlated with the formation of calcification. VSMCs were isolated from rat aorta and were cultured for seven days in vitro . Addition of inorganic phosphate dose-dependently decreased TFEB protein expression both in whole cell lysate and in nuclear fraction (0.07± 0.03-fold vs. control, n = 5 ; 0.01 ± 0.003-fold vs. control, n = 4, respectively) while it rather increased mRNA expression of Tfeb (4.48 ± 0.95-fold, n = 7 vs. control). The Decrease in TFEB protein by inorganic phosphate was correlated with the accumulation of TFEB in the SDS-insoluble fraction, suggesting the formation of protein aggregates. The Knockdown of TFEB in VSMCs by siRNA exacerbated phosphate-induced calcium deposition (2.93 ± 0.85-fold, n = 4 vs. negative siRNA). The addition of inorganic phosphate significantly decreased lysosomal activity determined by LysoTracker dye; and treatment with 20 nmol/L of bafilomycin A, a lysosome inhibitor, further accelerated phosphate-induced calcium deposition (13.6 ± 3.69-fold, n = 7 vs. vehicle). Conclusion: In conclusion, TFEB expression in VSMCs is downregulated at the protein level by hyperphosphatemia. The diminution of functional TFEB predisposes to vascular calcification, presumably through downregulating lysosomal activity.
Abstract 15704: Effectiveness of Continuous Intravenous Infusion of Cyclosporine A for Patients With Intravenous Immunoglobulin-Resistant Kawasaki Disease
Authors: Mitsuru Seki, Takaomi Minami, Tatsuya Anzai, Sadahiro Furui, Shun Suzuki, Tomoyuki Sato, Koichi Kataoka, Takanori Yamagata
Journal: Circulation (2019)

Background: Cyclosporine A (CsA) has been used to treat patients with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD); however, the major administration route of CsA has been oral...
Ferroptosis in infection, inflammation, and immunity
Authors: Xin Chen, Rui Kang, Guido Kroemer, Daolin Tang
Journal: The Journal of Experimental Medicine (2021)

Ferroptosis is a type of regulated necrosis that is triggered by a combination of iron toxicity, lipid peroxidation, and plasma membrane damage. The upstream inducers of ferroptosis can be divided into two categories (biological versus chemical) and activate two major pathways (the extrinsic/transporter versus the intrinsic/enzymatic pathways). Excessive or deficient ferroptotic cell death is implicated in a growing list of physiological and pathophysiological processes, coupled to a dysregulated immune response. This review focuses on new discoveries related to how ferroptotic cells and their spilled contents shape innate and adaptive immunity in health and disease. Understanding the immunological characteristics and activity of ferroptotic death not only illuminates an intersection between cell death and immunity but may also lead to the development of novel treatment approaches for immunopathological diseases.