tbuckley/cabot-search huggingface dataset:
Abstract 16669: Left Atrial Function After Closure of Atrial Septal Defect in Adults: Comparison Between Transcatheter Closure and Surgical Closure
Authors: Manatomo Toyono, Shunsuke Yamada, Mieko Aoki-Okazaki, Tsutomu Takahashi
Journal: Circulation (2018)

Introduction: Transcatheter closure is offered as an alternative to surgery for the majority of patients with secundum atrial septal defect (ASD). However, little is known about the effect of a mechanical device on left atrial (LA) function. Hypothesis: Transcatheter closure of secundum ASD preferably preserves LA function compared with surgical closure in adult patients. Methods: We examined adult patients who underwent transcatheter (n = 58) and surgical ASD closure (n = 17) and controls (n = 20). Patients with greater than mild mitral or tricuspid regurgitation and those with a history of atrial fibrillation were not included. All the devices employed were the Amplatzer TM Septal Occluders. LA volumes were measured by the biplane area-length method using 2-dimensional transthoracic echocardiography at the onset of mitral opening (Vmax), the beginning of LA systole (Va) and the onset of mitral closure (Vmin) before and 15 ± 11 months after ASD closure. LA reservoir, conduit and booster pump functions were assessed by (Vmax-Vmin)/Vmax, (Vmax-Va)/Vmax and (Va-Vmin)/Va, respectively. Left ventricular (LV) ejection fraction was obtained to estimate LV systolic function. For the estimation of LV diastolic function, the ratio of transmitral early to late flow velocity (E/A), deceleration time of early mitral flow velocity (DT) and the ratio of systolic to diastolic pulmonary venous flow velocity (S/D) were obtained by conventional Doppler echocardiography. Results: In transcatheter closure, employed device size indexed to body surface area was 12 ± 3 mm/m 2 . Before ASD closure, there was no significant difference in all the LA parameters between the 2 groups, whereas LV ejection fraction was significantly decreased in the surgical group as compared with the transcatheter group. After ASD closure, Vmax index was significantly increased in the surgical group. LV end-diastolic volume index were significantly increased both after transcatheter and surgical ASD closure. After ASD closure, the surgery group showed significantly decreased LA reservoir and conduit functions as compared with the transcatheter group and controls. Conclusions: The transcatheter group, not surgical group, showed preserved LA function at mid-term follow-up after ASD closure.
Serine-threonine kinase ROCK2 regulates germinal center B cell positioning and cholesterol biosynthesis
Authors: Edd Ricker, Yurii Chinenov, Tania Pannellini, Danny Flores-Castro, Chao Ye, Sanjay Gupta, Michela Manni, James K. Liao, Alessandra B. Pernis
Journal: Journal of Clinical Investigation (2020)

Germinal center (GC) responses require B cells to respond to a dynamic set of intercellular and microenvironmental signals that instruct B cell positioning, differentiation, and metabolic reprogramming. RHO-associated coiled-coil–containing protein kinase 2 (ROCK2), a serine-threonine kinase that can be therapeutically targeted by ROCK inhibitors or statins, is a key downstream effector of RHOA GTPases. Although RHOA-mediated pathways are emerging as critical regulators of GC responses, the role of ROCK2 in B cells is unknown. Here, we found that ROCK2 was activated in response to key T cell signals like CD40 and IL-21 and that it regulated GC formation and maintenance. RNA-Seq analyses revealed that ROCK2 controlled a unique transcriptional program in GC B cells that promoted optimal GC polarization and cholesterol biosynthesis. ROCK2 regulated this program by restraining AKT activation and subsequently enhancing FOXO1 activity. ATAC-Seq (assay for transposase-accessible chromatin with high-throughput sequencing) and biochemical analyses revealed that the effects of ROCK2 on cholesterol biosynthesis were instead mediated via a novel mechanism. ROCK2 directly phosphorylated interferon regulatory factor 8 (IRF8), a crucial mediator of GC responses, and promoted its interaction with sterol regulatory element–binding transcription factor 2 (SREBP2) at key regulatory regions controlling the expression of cholesterol biosynthetic enzymes, resulting in optimal recruitment of SREBP2 at these sites. These findings thus uncover ROCK2 as a multifaceted and therapeutically targetable regulator of GC responses.
The impact of carcinoma in situ at the ductal stump on long-term outcomes in patients who underwent surgical resection for extrahepatic cholangiocarcinoma
Authors: Tomohiko Ikehara, Akira Shimizu, Akira Kobayashi, Tsuyoshi Notake, Kentaro Hukushima, Hikaru Hayashi, Kouya Yasukawa, Yuji Soejima
Journal: International Journal of Surgery (2020)
Prognostic Significance of Long-term HbA1c Variability for All-Cause Mortality in the ACCORD Trial
Authors: Chang-Sheng Sheng, Jingyan Tian, Ya Miao, Yi Cheng, Yulin Yang, Peter D. Reaven, Zachary T. Bloomgarden, Guang Ning
Journal: Diabetes Care (2020)

OBJECTIVE The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population. RESEARCH DESIGN AND METHODS We studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition from intensive to standard glycemic therapy. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI. RESULTS Compared with the standard therapy group (n = 4,728), the intensive therapy group (n = 4,755) had significantly lower mean HbA1c (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], P &amp;lt; 0.0001) and lower CV, VIM, and ARV (P &amp;lt; 0.0001). In multivariate adjusted analysis, all three HbA1c variability indices were significantly associated with total mortality in all patients as well as in the standard- and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA1c variability indices for all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA1c mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI 1.17–3.61; P &amp;lt; 0.01) only in the intensive-therapy group. CONCLUSIONS Long-term visit-to-visit HbA1c variability was a strong predictor of all-cause mortality. HbA1c VIM combined with HbA1c mean conferred an increased risk for all-cause mortality in the intensive-therapy group.
Potential Legal Liability for Withdrawing or Withholding Ventilators During COVID-19
Authors: I. Glenn Cohen, Andrew M. Crespo, Douglas B. White
Journal: JAMA (2020)

With an anticipated shortage of ventilators for patients with coronavirus disease 2019 (COVID-19), hospitals, physicians, and nurses may have to make an unprecedented decision: should they withdraw or withhold ventilators from some patients and use them for other patients who have a better chance of survival?It is not uncommon for care teams to decide against initiating or continuing mechanical ventilation when such treatment would not achieve a patient's goals or directives.COVID-19 presents a different case: patients who do not receive a ventilator could benefit, perhaps living for many additional years, if they receive short-term mechanical ventilation.Denying patients such treatment, against their wishes, most likely will result in their death, but it will also make this scarce resource available to other patients who are more likely to survive if they receive ventilator support.Recently developed protocols expressly call for the rationing and reallocation of ventilators, in a manner that aims to save the greatest number of lives. 1 These protocols are broadly accepted by medical ethicists. 1,2But ethics aside, there are potential legal ramifications of either withholding or withdrawing a ventilator from a patient who would ordinarily receive such aid in the absence of a public health emergency.In this Viewpoint, we assess the legal risks that physicians, other health care workers, and hospital systems confront in such scenarios and recommend that states explicitly and immediately adopt legal protections for health care workers, modeled on provisions in place in Maryland.
Abstract 105: Utilization of Therapeutic Hypothermia Post Cardiac Arrest and Outcomes in Teaching vs Nonteaching Hospital: A Retrospective Study of Nationwide Inpatient Sample (NIS) Database
Authors: Anil K Jha, Anand M Krishnan, Fangcheng Wu, Kevin Buda
Journal: Circulation (2019)

Introduction: Therapeutic Hypothermia (TH) is a measure to reduce the core body temperature of survivors of cardiac arrest, to further minimize neurological damage caused by severe hypoxia. Clinical trials have shown significant improvement in neurological function among survivors of cardiac arrest received TH. Methods: We conducted a retrospective analysis of the Nationwide Inpatient Sample (HCUP-NIS) 2016 database. Patients admitted with a principal diagnosis of cardiac arrest who underwent TH were identified using the ICD-10 codes. A weighted descriptive analysis was performed to generate national estimates. Group of patients admitted to teaching hospitals were compared to those admitted to non-teaching hospitals. Patients were stratified by age, sex, race, demographic and clinical data including Charlson comorbidity index for these two groups and compared for the primary outcome, in-hospital mortality and secondary outcomes of length of stay (LOS) and total hospitalization charges. Analyses were done using STATA statistical software. Results: In 2016 total 13780 patients met inclusion criteria out of which half were female. Mean age was 64 years. Admissions to teaching hospital were 9285. Total 670 patients received TH, of which 74% were in teaching hospitals. Group who received therapeutic hypothermia, majority were Caucasians (65%) followed by Hispanics (16%) (p=0.30). Patients who received TH were majority Medicare (58.8% vs 49.5%; p=0.75). Southern hospitals had the most admissions in both groups (45.7% and 31.3%); Northeast region had the least non-teaching hospital admissions (8.5%). Total deaths in TH group were 510, 73% were in teaching hospitals. After adjusting for age, sex, race, income, charlson index, hospital location, and bed-size, there was no statistical significant difference in mortality , LOS and total charges between these two groups (p=0.82, p=0.24 and p=0.67 respectively). Interestingly there was 35% increase in adjusted odds for mortality of cardiac arrest patients in teaching hospitals (p=0.005). Conclusions: Among patients admitted with cardiac arrest and undergoing TH there were no significant differences in mortality, LOS or total hospitalization charges between teaching and non-teaching hospitals.
Prescribing systemic steroids for acute respiratory tract infections in United States outpatient settings: A nationwide population-based cohort study
Authors: Kueiyu Joshua Lin, Evan Dvorin, Aaron S. Kesselheim
Journal: PLoS Medicine (2020)

Background Evidence and guidelines do not support use of systemic steroids for acute respiratory tract infections (ARTIs), but such practice appears common. We aim to quantify such use and determine its predictors. Methods and findings We conducted a cohort study based on a large United States national commercial claims database, the IBM MarketScan, to identify patients aged 18–64 years with an ARTI diagnosis (acute bronchitis, sinusitis, pharyngitis, otitis media, allergic rhinitis, influenza, pneumonia, and unspecified upper respiratory infections) recorded in ambulatory visits from 2007 to 2016. We excluded those with systemic steroid use in the prior year and an extensive list of steroid-indicated conditions, including asthma, chronic obstructive pulmonary disease, and various autoimmune diseases. We calculated the proportion receiving systemic steroids within 7 days of the ARTI diagnosis and determined its significant predictors. We identified 9,763,710 patients with an eligible ARTI encounter (mean age 39.6, female 56.0%) and found 11.8% were prescribed systemic steroids (46.1% parenteral, 47.3% oral, 6.6% both). All ARTI diagnoses but influenza predicted receiving systemic steroids. There was high geographical variability: the adjusted odds ratio (aOR) of receiving parenteral steroids was 14.48 (95% confidence interval [CI] 14.23–14.72, p < 0.001) comparing southern versus northeastern US. The corresponding aOR was 1.68 (95% CI 1.66–1.69, p < 0.001) for oral steroids. Other positive predictors for prescribing included emergency department (ED) or urgent care settings (versus regular office), otolaryngologist/ED doctors (versus primary care), fewer comorbidities, and older patient age. There was an increasing trend from 2007 to 2016 (aOR 1.93 [95% CI 1.91–1.95] comparing 2016 to 2007, p < 0.001). Our findings are based on patients between 18 and 64 years old with commercial medical insurance and may not be generalizable to older or uninsured populations. Conclusions In this study, we found that systemic steroid use in ARTI is common with a great geographical variability. These findings call for an effective education program about this practice, which does not have a clear clinical net benefit.
Leprosy: Clinical aspects and diagnostic techniques
Authors: Mayra B.C. Maymone, Melissa Laughter, Samantha Venkatesh, Mara M. Dacso, P. Narasimha Rao, Barbara M. Stryjewska, Jeremy Hugh, Robert P. Dellavalle, Cory A. Dunnick
Journal: Journal of the American Academy of Dermatology (2020)
MAP4K4 negatively regulates CD8 T cell–mediated antitumor and antiviral immunity
Authors: Emel Esen, Ismail Sergin, Rajiv Jesudason, Patricia Himmels, Joshua D. Webster, Hua Zhang, Min Xu, Robert Piskol, Erin McNamara, Stephen Gould, Aude-Hélène Capietto, Lélia Delamarre, Kevin Walsh, Weilan Ye
Journal: Science Immunology (2020)

MAP4K4 inhibition augments CD8 T cell antitumor and antiviral responses.
Sleep Duration Patterns in Early to Middle Adulthood and Subsequent Risk of Type 2 Diabetes in Women
Authors: Megu Y. Baden, Frank B. Hu, Celine Vetter, Eva Schernhammer, Susan Redline, Tianyi Huang
Journal: Diabetes Care (2020)

To identify sleep duration trajectories from early to middle adulthood and their associations with incident type 2 diabetes.Using a group-based modeling approach, we identified sleep duration trajectories based on sleep duration in ages 20-25, 26-35, 36-45, and 46+ years, which were retrospectively assessed in 2009 among 60,068 women from the Nurses' Health Study II (median age 54.9 years) who were free of diabetes, cardiovascular disease, and cancer. We investigated the prospective associations between sleep duration trajectories and diabetes risk (2009-2017) using multivariable Cox proportional hazards models.We documented 1,797 incident diabetes cases over a median follow-up of 7.8 years (442,437 person-years). Six sleep duration trajectories were identified: persistent 5-, 6-, 7-, or 8-h sleep duration and increased or decreased sleep duration. After multivariable adjustment for diabetes risk factors, compared with the persistent 7-h sleep duration group, the hazard ratio was 1.43 (95% CI 1.10, 1.84) for the 5-h group, 1.17 (1.04, 1.33) for the 6-h group, 0.96 (0.84, 1.10) for the 8-h group, 1.33 (1.09, 1.61) for the increased sleep duration group, and 1.32 (1.10, 1.59) for the decreased sleep duration group. Additional adjustment for time-updated comorbidities and BMI attenuated these associations, although a significantly higher risk remained in the decreased sleep duration group (1.24 [1.03, 1.50]).Persistent short sleep duration or changes in sleep duration from early to middle adulthood were associated with higher risk of type 2 diabetes in later life. These associations were weaker after obesity and metabolic comorbidities were accounted for.
Interpretation of vulnerability and cumulative disadvantage among unaccompanied adolescent migrants in Greece: A qualitative study
Authors: Divya Mishra, Paul B. Spiegel, Vasileia Lucero Digidiki, Peter J. Winch
Journal: PLoS Medicine (2020)

Background In settings of mass displacement, unaccompanied minors (UAMs) are recognized as a vulnerable group and consequently prioritized by relief efforts. This study examines how the interpretation of vulnerability by the national shelter system for male UAMs in Greece shapes their trajectories into adulthood. Methods and findings Between August 2018 and April 2019, key informant interviews were carried out with child protection staff from Greek non-governmental organizations that refer UAMs to specialized children's shelters in Athens to understand how child protection workers interpret vulnerability. In-depth interviews and life history calendars were collected from 44 male migrant youths from Afghanistan, Pakistan, Bangladesh, and Iran who arrived in Greece as UAMs but had since transitioned into adulthood. Analysis of in-depth interviews and life history calendars examined how cumulative disadvantage and engagement with the shelter system altered youths' trajectories into adulthood. Younger adolescents were perceived as more vulnerable and prioritized for shelters over those who were "almost 18" years old. However, a subset of youths who requested shelter at the age of 17 years had experienced prolonged journeys where they spent months or years living on their own in socially isolated environments that excluded them from experiences conducive to adolescent development. The shelter system for UAMs in Greece enabled youths to develop new skills and networks that facilitated integration into society, and transferred them into adult housing when they turned 18 years old so that they could continue developing new skills. Those who were not in shelters by age 18 years could not access adult housing and lost this opportunity. Limitations included possible underrepresentation of homeless youth as well as the inability to capture all nationalities of UAMs in Greece, though the 2 most common nationalities, Afghan and Pakistani, were included. Conclusions Due to the way vulnerability was interpreted by the shelter system for UAMs, youths who had the greatest need to learn new skills to facilitate their integration often had the least opportunity to do so. To avoid creating long-lasting disparities between UAMs who are placed in shelters and those who are not, pathways should be developed to allow young adult males to enter accommodation facilities and build skills and networks that facilitate integration. Furthermore, cumulative disadvantages should be taken into account while assessing UAMs' vulnerability. Following UAMs' trajectories into early adulthood was critical for capturing this long-term consequence of the shelter system's interpretation of vulnerability.
MLKL-dependent signaling regulates autophagic flux in a murine model of non-alcohol-associated fatty liver and steatohepatitis
Authors: Xiaoqin Wu, Kyle L. Poulsen, Carlos Sanz-Garcia, Emily Huang, Megan R. McMullen, Sanjoy Roychowdhury, Srinivasan Dasarathy, Laura E. Nagy
Journal: Journal of Hepatology (2020)
Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms
Authors: Xi Jin, Jiang-Shan Lian, Jian-Hua Hu, Jianguo Gao, Lin Zheng, Yi-Min Zhang, Shao-Rui Hao, Hong-Yu Jia, Huan Cai, Xiao-Li Zhang, Guo-Dong Yu, Kai-Jin Xu, Xiao-Yan Wang, Jue-Qing Gu, Shan-Yan Zhang, Chan-Yuan Ye, Ci-Liang Jin, Ying-Feng Lu, Xia Yu, Xiao-Peng Yu, Jian-Rong Huang, Kang-Li Xu, Qin Ni, Cheng-Bo Yu, Biao Zhu, Yong-Tao Li, Jun Liu, Hong Zhao, Xuan Zhang, Liang Yu, Yong-Zheng Guo, Jun-Wei Su, Jing-Jing Tao, Guan-Jing Lang, Xiao-Xin Wu, Wen-Rui Wu, Ting-Ting Qv, Dai-Rong Xiang, Ping Yi, Ding Shi, Yanfei Chen, Yue Ren, Yun-Qing Qiu, Lan-Juan Li, Jifang Sheng, Yida Yang
Journal: Gut (2020)

Objective The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. Design COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. Results Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever &gt;38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m 6 A methylation and changed binding capacity with ACE2. Conclusion We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.
CNS-localized myeloid cells capture living invading T cells during neuroinflammation
Authors: Beatrice Wasser, Dirk Luchtman, Julian Löffel, Kerstin Robohm, Katharina Birkner, Albrecht Stroh, Christina Francisca Vogelaar, Frauke Zipp, Stefan Bittner
Journal: The Journal of Experimental Medicine (2020)

To study the role of myeloid cells in the central nervous system (CNS) in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), we used intravital microscopy, assessing local cellular interactions in vivo in EAE animals and ex vivo in organotypic hippocampal slice cultures. We discovered that myeloid cells actively engulf invading living Th17 lymphocytes, a process mediated by expression of activation-dependent lectin and its T cell–binding partner, N-acetyl-D-glucosamine (GlcNAc). Stable engulfment resulted in the death of the engulfed cells, and, remarkably, enhancement of GlcNAc exposure on T cells in the CNS ameliorated clinical EAE symptoms. These findings demonstrate the ability of myeloid cells to directly react to pathogenic T cell infiltration by engulfing living T cells. Amelioration of EAE via GlcNAc treatment suggests a novel first-defense pathway of myeloid cells as an initial response to CNS invasion and demonstrates that T cell engulfment by myeloid cells can be therapeutically exploited in vivo.