tbuckley/cabot-search huggingface dataset:
Abstract 14688: Relative Blood Volume Change After Single Doses of a Loop Diuretic to Assess Volume Status: A Patient Level Meta-analysis
Authors: Shantum Misra, brian P lucas
Journal: Circulation (2020)

Background: In patients with congestive heart failure administration of an intravenous diuretic results in increased urine production and, depending on the volume status, an immediate change in relative blood volume (RBV). Changes in RBV are already applied clinically to monitor fluid removal and better guide diuresis in patients who undergo peripheral ultrafiltration. Using individual level patient data, we explored whether it is possible to measure changes in RBV after a single intravenous dose of loop diuretic through the measurement of serial hematocrit values. Based on normally occurring variation in volume-stable patients, the smallest change in RBV that would be detectable by routine serial hematocrits ranges from 6.4% to 8.6%. Methods and Results: Electronic databases were queried for articles that contained predefined MeSH terms in order to identify all studies in which patients received intravenous diuretics. The 764 studies that met our entry criteria were systematically reviewed and manually screened. We then conducted a meta-analysis from 14 studies that provided individual, patient-level data from at least 2 time points: just before and within 3 hours of administration of an intravenous loop diuretic. We found that among a total of 240 patients, RBV decreased by 11% (95% CI 10 to 12%) at 2 hours after an intravenous loop diuretic was given (Figure); there was no significant difference in this finding based on whether or not patients had heart failure. Conclusion: We found that anticipated RBV change with single doses of intravenous loop diuretics exceeds the smallest detectable change in RBV that can be obtained by serial hematocrits. This implies that routine hematocrits can be used to track RBV change across serial doses of intravenous loop diuretics, potentially providing a target for a dry interstitium in acute heart failure.
Protein Prenylation Drives Discrete Signaling Programs for the Differentiation and Maintenance of Effector Treg Cells
Authors: Wei Su, Nicole M. Chapman, Jun Wei, Hu Zeng, Yogesh Dhungana, Hao Shi, Jordy Saravia, Peipei Zhou, Lingyun Long, Sherri Rankin, Anil KC, Peter Vogel, Hongbo Chi
Journal: Cell Metabolism (2020)
The Role of Bariatric Surgery in Prevention of Kidney Disease Progression in Moderately Obese Patients With Type 2 Diabetes
Authors: Ben Rees, Maria Digby, Saba Balasubramanian
Journal: JAMA Surgery (2020)

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Association of Hospital-Level Intensive Care Unit Use and Outcomes in Older Patients With Isolated Rib Fractures
Authors: Jessica A. Bowman, Miriam Nuño, Gregory J. Jurkovich, Garth H. Utter
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The optimal level of care for older patients with rib fractures as an isolated injury is unknown. <h3>Objectives</h3> To characterize interhospital variability in intensive care unit (ICU) vs non-ICU admission of older patients with isolated rib fractures and to evaluate whether greater hospital-level use of ICU admission is associated with improved outcomes. <h3>Design, Setting, and Participants</h3> This cohort study included trauma patients aged 65 years and older with isolated rib fractures who were admitted to US trauma centers participating in the National Trauma Data Bank between January 1, 2015, and December 31, 2016. Patients were excluded if they had other significant injuries, were intubated or had assisted respirations in the emergency department (ED), or had a Glasgow Coma Scale (GCS) score of less than 9 in the ED. Hospitals with fewer than 10 eligible patients were excluded. Data analysis was conducted from May 2019 through September 2020. <h3>Exposures</h3> Admission to the ICU. <h3>Main Outcomes and Measures</h3> Composite of unplanned intubation, pneumonia, or death during hospitalization. <h3>Results</h3> Among 23 951 patients (11 066 [46.2%] women; mean [SD] age, 77.0 [7.2] years) at 573 hospitals, the median (interquartile range) proportion of ICU use was 16.7% (7.4%-32.0%), but this varied from a low of 0% to a high of 91.9%. The composite outcome occurred in 787 patients (3.3%), with unplanned intubation in 317 (1.3%), pneumonia in 180 (0.8%), and death in 451 (1.9%). Accounting for the hierarchical nature of the data and adjusting for propensity scores reflecting factors associated with ICU admission, receiving care at a hospital with the greatest ICU use (quartile 4), compared with a hospital with the lowest ICU use, was associated with decreased likelihood of the composite outcome (adjusted odds ratio, 0.71; 95% CI, 0.55-0.92). <h3>Conclusions and Relevance</h3> In this study, admission location of older patients with isolated rib fractures was variable across hospitals, but hospitalization at a center with greater ICU use was associated with improved outcomes. It may be warranted for hospitals with low ICU use to admit more such patients to an ICU.
Systematic Analysis of Intronic miRNAs Reveals Cooperativity within the Multicomponent <i>FTX</i> Locus to Promote Colon Cancer Development
Authors: Zhi Hao Kwok, Bin Zhang, Xiao Hong Chew, Jia Jia Chan, Velda Teh, Henry Yang, Dennis Kappei, Yvonne Tay
Journal: Cancer Research (2021)

Approximately half of all miRNA reside within intronic regions and are often cotranscribed with their host genes. However, most studies of intronic miRNA focus on individual miRNA, while conversely most studies of protein-coding and noncoding genes frequently ignore any intron-derived miRNA. We hypothesize that the individual components of such multigenic loci may play cooperative or competing roles in driving disease progression and that examining the combinatorial effect of these components would uncover deeper insights into their functional importance. To address this, we performed systematic analyses of intronic miRNA:host loci in colon cancer. The FTX locus, comprising of a long noncoding RNA FTX and multiple intronic miRNA, was highly upregulated in cancer, and cooperativity within this multicomponent locus promoted cancer growth. FTX interacted with DHX9 and DICER and regulated A-to-I RNA editing and miRNA expression. These results show for the first time that a long noncoding RNA can regulate A-to-I RNA editing, further expanding the functional repertoire of long noncoding RNA. Intronic miR-374b and miR-545 inhibited tumor suppressors PTEN and RIG-I to enhance proto-oncogenic PI3K-AKT signaling. Furthermore, intronic miR-421 may exert an autoregulatory effect on miR-374b and miR-545. Taken together, our data unveil the intricate interplay between intronic miRNA and their host transcripts in the modulation of key signaling pathways and disease progression, adding new perspectives to the functional landscape of multigenic loci. SIGNIFICANCE: This study illustrates the functional relationships between individual components of multigenic loci in regulating cancer progression.See related commentary by Calin, p. 1212.
B 2 ~D 1 段階の前立せんがん患者の監視のための前立せん特異的抗原の診断的重要性
Authors: Killian C S, Yang N, Emrich L J, Vargas F P, Kuriyama M, Wang M C, Papsidero L D, Murphy G P, Chu T M
Journal: Cancer Research (1985)
Reply to Althuwaybi <i>et al.</i>: Hospitalization Outcomes for COVID-19 in Patients with Interstitial Lung Disease: A Potential Role for Aerodigestive Pathophysiology?
Authors: Nazia Chaudhuri, Peter M. George, Michael Kreuter, Maria Molina-Molina, Pilar Rivera-Ortega, Giulia M. Stella, Iain Stewart, Lisa G. Spencer, Athol U. Wells, R. Gisli Jenkins
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Abstract 209: Ketone Bodies Ameliorate Cardiac Function in Heart Failure
Authors: Jessica Gambardella, Marco B. Morelli, Xujun Wang, Gaetano Santulli
Journal: Circulation (2020)

Background: Beta hydroxibutirrate (BHB) is the main ketone body produced during fasting or carbohydrate deprivation as an alternative fuel. Mounting evidence suggests that after myocardial infarction (MI), the mitochondrial impairment and metabolic failure coincide with increased levels and utilization of BHB. However, whether the BHB increase is adaptive or maladaptive in damaged myocardium, has never been evaluated. Aim: Our scope was to explore the effects of BHB on cardiac function after ischemia both in vivo and in vitro . Methods and Results: In cultured cardiomyoblasts, the administration of BHB (3 mMol) reduces the activation of caspase-3 in response to ischemia, as well as the number of tunnel positive nuclei. Specifically, the mitochondrial apoptotic pathway seems affected, as BHB reduces cytochrome-C release induced by ischemia. Mitochondrial structure and interconnections, soundly affected by ischemia, were significantly retained in presence of BHB, as well as mitochondrial membrane potential (assessed via TMRE). The preserved mitochondrial health was further supported by higher levels of PGC1-alpha detected in cells exposed to ischemia plus BHB compared to ischemia alone. To explore the in vivo effects of BHB on ischemia damaged- myocardium, we administrated carbohydrate-null diet ( ketogenic diet , KD) or standard diet-supplemented with BHB, to post-MI mice. Both groups treated with KD and BHB supplemented diet displayed preserved left ventricular ejection fraction respect to untreated infarcted mice. The protective effects of BHB on cardiac phenotype were mirrored by increased levels of PGC1-alpha in the myocardium of treated mice, in terms of protein and transcription levels. Interestingly, in the hearts of mice fed KD and BHB supplemented diet, we observed a marked difference in histone acetylation pattern. Conclusions: BHB protects cardiac cells from apoptotic and mitochondrial damage induced by ischemia. Through its ability to regulate epigenetic modifications, BHB could activate a gene expression program able to support mitochondrial function, thereby representing a powerful therapeutic strategy.
Abstract 14709: Dual Pathology of Severe Aortic Stenosis and Cardiac Amyloidosis: Multi-center Study of Prevalence and Outcome
Authors: Christian Nitsche, Paul Scully, Kush Patel, Andreas Kammerlander, Tim Wollenweber, George Thornton, Francesca Pugliese, Andrew Kelion, Michael Mullen, Marianna Fontana, Philip Hawkins, Leon Menezes, James C Moon, Julia Mascherbauer, Thomas Treibel
Journal: Circulation (2020)

Background: Elderly patients with severe aortic stenosis (AS) are increasingly diagnosed with cardiac amyloidosis (CA). It is unclear whether dual AS-CA has worse outcomes or may even result in futility of transcatheter aortic valve replacement (TAVR). Objective: To identify diagnostic predictors and outcomes of AS-CA compared to lone AS. Methods: Severe AS TAVR referrals at three international sites underwent clinical and laboratory assessment, six-minute walk test, ECG, transthoracic echocardiography with strain analysis, and blinded research 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) prior to intervention. Transthyretin CA (ATTR) was diagnosed by bone scintigraphy, unremarkable serum/urine free light chain assessment; light-chain CA (AL) was diagnosis by endomyocardial biopsy. All-cause mortality was captured from national registries. Results: 408 patients (age 83.4±6.5 years, 49.8% male) were recruited. DPD bone scintigraphy was positive in 11.6% (n=47, Grade-1 3.7%[15]) Grade-2/3 7.9%[32]). Positivity was associated with QRS duration (OR 2.5, 95%CI 1.1-5.5, p=0.02), voltage/mass-ratio (OR 0.4, 95%CI 0.2-0.9, p=0.02), history of carpal tunnel syndrome (OR 1.6, 95%CI 1.1-2.3, p=0.02). An additional two cases had biopsy proven AL-CA. Heart Team decision (blinded to bone scintigraphy) resulted in TAVR in 333 (81.6%), surgical aortic valve replacement in 10 (2.5%) and medical management in 65 (15.9%). After a median of 1.7 years, 22.9% of patients had died. AS-CA had a worse 1-year mortality than lone AS (24.5 vs 13.9%, p=0.045, Figure 1A), but there was no difference post valve intervention (p=0.7), which improved outcomes in both lone AS and AS-CA compared to medical management (Figure 1B+C). Discussion: Dual pathology of AS-CA is common in elderly AS patients. AS-CA is prognostically slightly worse than lone AS, but not if treated by valve intervention. Based on this data, TAVR should not be witheld in AS-CA.
Abstract 13609: Predictors of Treatment of Hospitalized Patients With Atrial Fibrillation in the US
Authors: Steven B Deitelzweig, Amol D Dhamane, Manuela Di Fusco, Cristina Russ, Lisa Rosenblatt, Melissa Lingohr-Smith, Jay Lin
Journal: Circulation (2020)

Introduction: While a few studies have been conducted that evaluated anticoagulant (AC) treatment of patients with atrial fibrillation (AF) in the outpatient setting, little is known regarding inpatient AC treatment practices. Objective: To identify predictors of AC treatment among patients hospitalized with AF in the US Methods: Patients (≥18 years of age) who had a primary or secondary discharge diagnosis code of AF during a hospitalization (without a diagnosis of venous thromboembolism) were selected from the Premier Hospital database (1/1/2016-9/30/2017). Patients were grouped into 2 study cohorts: 1) Patients who received oral AC (OAC) therapy during hospitalization and 2) Patients who did not receive any AC therapy. Demographics, patient clinical characteristics, and hospital characteristics were examined. A multivariable logistic regression analysis was carried out to evaluate potential predictors of not receiving any AC therapy vs. receiving OACs. Results: Of the patients hospitalized with an AF diagnosis, 65.7% (n=205,438; mean age: 74.4 years; 47.1% female) received OAC therapy and 34.3% (n=107,076; mean age: 75.9 years; 46% female) did not receive any AC therapy. The most common OACs received were warfarin (39.4%) and apixaban (34.2%). Key predictors of a greater likelihood of not receiving any AC therapy vs. receiving OACs were greater comorbidity (Charlson Comorbidity Index [CCI] ≥5 vs. 0 odds ratio [OR]: 1.72; 3-4 vs. 0: 1.32; 1-2 vs. 0: 1.11, all p&lt;0.001) and having had prior bleeding (OR: 1.59, p&lt;0.001). Key predictors of receiving OACs, relative to not receiving any AC therapy, were having a AF diagnosis in the first vs. second position on insurance claims (OR: 0.24, p&lt;0.001), chronic (OR: 0.76, p&lt;0.001) or persistent (OR: 0.61, p&lt;0.001) AF vs. paroxysmal, higher stroke risk (CHA 2 DS 2 -VASc=5 vs. 0 OR: 0.48; 3-4 vs. 0: 0.51; 1-2 vs. 0: 0.58, all p&lt;0.001), and a prior stroke (OR: 0.87, p&lt;0.001). Conclusions: A substantial portion of hospitalized AF patients in the study did not receive any AC therapy, particularly those patients with an AF diagnosis in the second position on insurance claims. The predictors of AC treatment that were identified may be helpful in the clinical decision-making process for patients who are hospitalized with AF.
Abstract 13675: Impact of Antithrombotic Therapy on Clinical Outcomes in Patients With Type B Acute Aortic Syndrome
Authors: Akiko Masumoto, Shuichiro Kaji, Yutaro Miyoshi, Misun Pak, Taiji Okada, Toshiaki Toyota, Yasuhiro Sasaki, Kitae Kim, Takeshi Kitai, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Yutaka Furukawa
Journal: Circulation (2020)

Introduction: In type B acute aortic syndrome (B-AAS), degree of false lumen thrombosis is known to affect clinical outcome. Antithrombotic therapy might have impact on prognosis through affecting false lumen thrombosis.We aimed to assess the impact of antithrombotic therapy on clinical outcomes in patients with B-AAS. Methods: A total of 429 patients with acute B-AAS admitted to our hospital and discharged alive were retrospectively analyzed. The primary outcome was aorta-related adverse events, defined as a composite of aorta-related death, aortic rupture, surgical or endovascular aortic repair and progressive aortic dilation. Results: Of the 429 patients, 72 patients (17 %) were discharged with antithrombotic therapy and 357 (83 %) without antithrombotic therapy. 254 patients (59 %) presented with intramural hematoma with complete thrombosis of false lumen, and 175 (41 %) presented with classic aortic dissection. Reasons for prescription were coronary artery disease (n=25), cerebral ischemia (n=17) and others (n=30). In the antithrombotic group, patients were significantly older than no-antithrombotic group (73 ± 13 vs 67 ± 13 years, P= 0.001) and had more comorbidities such as dyslipidemia (40 % vs 26 %, P= 0.011), diabetes mellitus (22 % vs 11 %, P= 0.007) and coronary artery disease (36 % vs 5 %, P&lt; 0.001). During a mean follow-up of 4.8 ± 5.2 years, 37 patients (51 %) in the antithrombotic group and 98 patients (27 %) in the no-antithrombotic group had a primary outcome event. Event-free survival rate among antithrombotic versus no-antithrombotic group was 36 % vs 73 % at 5 years (P&lt; 0.001). Multivariate Cox regression analysis adjusted for age, sex, comorbidity and medication revealed that antithrombotic therapy was a significant risk factor for aorta-related adverse events (hazard ratio 2.08, 95% confidence interval 1.247-3.463; P= 0.005). Conclusion: In B-AAS, antithrombotic therapy was associated with an increased risk of aorta-related events. For patients with indispensable need of antithrombotic therapy, careful follow-up should be provided.
Abstract 14649: Chloride Channel Calcium-activated-1 Reduces Mouse Abdominal Aortic Aneurysm by Blocking Macrophage Migration Inhibitory Factor Activity in Macrophage Activation
Authors: Tianxiao Liu
Journal: Circulation (2020)

Introduction: Human chloride channel calcium-activated-1 (CLCA1) protein is a secretory protein that goblet cells from trachea epithelium express abundantly where it participates in hypersecretory lung diseases by mucus overproduction. Studies from CLCA1-deficient mice or CLCA1 blocking agents have however yielded inconsistent conclusions. CLCA1 not only regulates mucin expression, but also participates in innate immune responses by binding to yet unidentified molecules on the inflammatory cells and regulating cytokine and chemokine production. Seeking CLCA1 binding proteins identified CLCA1 expression by endothelial cells (EC), smooth muscle cells (SMC), and macrophages in human and mouse abdominal aortic aneurysms (AAA). Ligation of CLCA1 mediated the actions of macrophage migration inhibitory factor (MIF). Hypothesis: CLCA1 controls AAA growth by regulating MIF activity. Methods and Results: Immunoblots revealed high levels of the 110 and 75-kDa CLCA1 fragments in human abdominal aneurysm lesions, but normal human aortas contained predominantly the 35-kDa carboxyl-terminal fragments. Cultured human EC and SMC contained only the 35-kDa fragment, but human monocyte-derived macrophages contained both the 75 and 35-kDa fragments. Confocal microscopy colocalized CLCA1 and MIF in macrophages from human AAA lesions. CLCA1 immunoprecipitation followed by MIF immunoblot showed that the 35-kDa CLCA1 fragment complexes with MIF in cultured macrophages. Adventitial CaPO 4 -induced AAA in male Clca1 -/- mice demonstrated significantly greater aneurysm diameter, and increased lesion neutrophil and eosinophil content, as well as neutrophil- and eosinophil-associated chemokine (CXCL1, 2, 5, CCR3, and eotaxin-2 and 3) expression than those in wild-type or sham-operated mice. Macrophages cultured from Clca1 -/- bone-marrow showed enhanced MIF activity compared to those from wild-type mice. Conclusions: The 35-kDa CLCA1 fragment reduces formation of experimental AAA by acting as a decoy receptor, sequestering MIF and thus limiting MIF-mediated macrophage activation.
Abstract 16622: Methodological Study for Validation of a Protocol for Behavioral Change in Patients on Warfarin: EmpoderACO
Authors: Hannah Cardoso Barbosa, Adriana Silvina Pagano, Marcus Fernando da Silva Praxedes, Ilka Afonso Reis, Josiane Moreira da Costa, Heloisa de Carvalho Torres, Maria A Martins
Journal: Circulation (2020)

Introduction: To achieve stable control in warfarin therapy is challenging in clinical practice. Patients′ active participation is essential to promote self-care and medication adherence. We sought to build a conceptual map to substantiate the validation of EmpoderACO, in Brazilian Portuguese, a protocol for behavior change for patients on warfarin. Methods: This methodological study involved the development of a conceptual map focused on identifying self-care domains in warfarin users. Its content guided the development and validation of a behavior change protocol which comprised the following steps: definition of instrument objectives; construction and selection of items; construction and measurement of response scales; iv) structuring and assessment of content validity. The content validity was assessed by a committee of judges (CJ) and calculated by content validity coefficient (CVC). We used the software CmapTools (version 6.04, 2020) to build the conceptual map. Ethical approval 65928316.3.0000.5149. Results: Self-care domains in the conceptual map were divided into three categories: understanding and satisfaction with drug therapy; reduction of adverse events; promotion of well-being and healthy habits. The use of the conceptual map allowed the development of the final version of EmpoderACO with 27 items. A total of 34 specialists composed the multiprofessional CJ that analyzed the validity content. The overall average of CVC was ≥0.91, including relevance (0.92), adequacy (0.92) and clarity (0.91). Conclusions: The protocol EmpoderACO may contribute to a global approach of patients on warfarin to improve patient′s understanding of drug therapy, self-care behaviors and design of patient-centered care. The application of empowerment principles may be of particular utility in vulnerable populations living in low- and middle-income countries where warfarin is still widely prescribed for oral anticoagulation. Fig. 1 Conceptual map