tbuckley/cabot-search huggingface dataset:
Abstract 145: High Mobility Group Box 1 (HMGB1) is a Major Mediator of the Post-cardiac Arrest Syndrome
Authors: Emilie Boissady, Cynthia El Hedjaj, Matthias Kohlhauer, Fanny Lidouren, Bijan Ghaleh, Renaud Tissier
Journal: Circulation (2020)

Introduction: Profound immune disorders are triggered by cell death and subsequent release of danger signals after cardiac arrest (CA). Hypothesis: High mobility group box-1 (HMGB1) is one of the main endogenous mediators released by ischemic cell death. Our goal was to determine whether its inhibition could provide neuroprotection and improve the outcome after experimental CA. Methods: After 10 min of ventricular fibrillation and resuscitation, rabbits either received an administration of saline (CT group, n=10) or glycyrrhizin (GL group, n=10), a direct inhibitor of HMGB1 (4 mg/kg, i.v.). Animals were followed during 3 days after CA to evaluate the neurological dysfunction. Additional animals were submitted to the same protocol with brain withdrawal 2 or 6 h after CA for immune cell count by cytometry. Results: After CA, HMGB1 blood levels was significantly reduced in CT vs GL group (30±7 vs 17±2 ng/ml at t=30 min after CA). The systemic inflammatory response was subsequently attenuated in GL vs CT, as shown by reduced interleukin-6 concentration (231±34 vs 993±331 pg/ml at 180 min, respectively). In the CT group, a rapid accumulation of neutrophils (CD11b+) and T cells (CD3+, CD4+ and CD8+) was also evidenced in the brain after cardiac arrest. GL specifically reduced the influx of T cells (e.g., 2.7±0.3 vs 7.3±2.6% of CD3+ cells in the brain at 6 h after CA in GL vs CT, respectively) without modifying neutrophils counts. This effect was neither related to differences in blood cells counts nor a modification of blood-brain-barrier permeability between groups, which then suggests a specific inhibition of cerebral chemo-attraction of T cells by glycyrrhizin. Those modifications were ultimately associated with a reduction in neuronal cell death (fluorojade C staining), as well as improved neurological recovery in GL vs CT groups (mean neurological dysfunction scores at day 3 = 58±13 vs 100±0 %, respectively). Conclusion: HMGB1 is a major mediator of the cerebral early infiltration by T cells following CA. Its inhibition by glycyrrhizin could be a relevant therapeutic target to prevent the propagation of neurological damages.
Abstract 16458: Trends in Treatment and Outcomes of Cardiogenic Shock in the Adult Congenital Heart Disease Population: A Nationwide Analysis From 2007-2017
Authors: Harsh Mehta, Krishna Kurpad, Mohit Pahuja, Nishith Sutaria, Luis AFONSO
Journal: Circulation (2020)

Introduction: Heart failure (HF) is common in the adult congenital heart disease (ACHD) population. We sought to assess outcomes of cardiogenic shock (CS) and assess the trends of utilization of mechanical circulatory support (MCS) in these patients. Methods: Using the nationwide inpatient sample (NIS) database for the years 2007-2017, adult patients with a primary discharge diagnosis of HF, and a co-diagnosis of CS were identified. They were divided into 2 groups - patients with ACHD and those without ACHD. Statistical significance was assigned at p&lt;.05. Results: Out of the 114420 patients with HF who developed CS, 2572 (2.3%) patients had ACHD, and demonstrated an increasing yearly trend (Figure 1). Patients with ACHD were younger (55 vs 64.7 years, p&lt;.01), and had lower rates of comorbidities like hypertension (24.8 vs 38.3 %, p&lt;.01), diabetes mellitus (15.9 vs 27.5 %, p&lt;.01) and chronic ischemic heart disease (27.1 vs 42.1 %, p&lt;.01). Utilization of temporary MCS (25.9 vs 14.8 %, p&lt;.01), Left ventricular assist device (LVAD) (28.4 vs 7.6 %, p&lt;.01), and orthotopic heart transplantation (OHT) (8.0 vs 2.9 %, p&lt;.01) was higher in the ACHD group. Yearly trends are shown in Figure 2. Patients with ACHD had lower in-hospital mortality (16.6 vs 23.7 %, p&lt;.01) and lower adjusted odds of death [0.79 (CI 0.62,0.99), p&lt;.04], but had longer length of stay (22.6 vs 14.6 days, p&lt;.01) and total charges during hospitalization ($444007 vs $212972, p&lt;.01). Conclusion: Although low, the rates of CS in ACHD patients is increasing, however, these patients had a lower mortality, likely driven by lower age, fewer comorbidities, and increased utilization of MCS and heart transplantation.
The Transcription Factor Foxp3 Shapes Regulatory T Cell Identity by Tuning the Activity of trans-Acting Intermediaries
Authors: Joris van der Veeken, Ariella Glasner, Yi Zhong, Wei Hu, Zhong-Min Wang, Regina Bou-Puerto, Louis-Marie Charbonnier, Talal A. Chatila, Christina S. Leslie, Alexander Y. Rudensky
Journal: Immunity (2020)

Regulatory T (Treg) cell identity is defined by the lineage-specifying transcription factor (TF) Foxp3. Here we examined mechanisms of Foxp3 function by leveraging naturally occurring genetic variation in wild-derived inbred mice, which enables the identification of DNA sequence motifs driving epigenetic features. Chromatin accessibility, TF binding, and gene expression patterns in resting and activated subsets of Treg cells, conventional CD4 T cells, and cells expressing a Foxp3 reporter null allele revealed that the majority of Foxp3-dependent changes occurred at sites not bound by Foxp3. Chromatin accessibility of these indirect Foxp3 targets depended on the presence of DNA binding motifs for other TFs, including TCF1. Foxp3 expression correlated with decreased TCF1 and reduced accessibility of TCF1-bound chromatin regions. Deleting one copy of the Tcf7 gene recapitulated Foxp3-dependent negative regulation of chromatin accessibility. Thus, Foxp3 defines Treg cell identity in a largely indirect manner by fine-tuning the activity of other major chromatin remodeling TFs such as TCF1.
Abstract 213: Disruption of Mitochondrial Cristae Integrity in Lethal Myocardial Ischemia-Reperfusion Injury: Association or Cause-and-Effect?
Authors: Andrew R Kulek, Vishnu V.R. Undyala, Sarita Raghunayakula, Thomas H Sanderson, Karin Przyklenk
Journal: Circulation (2020)

Background: Considerable attention has focused on the concept that disruption of mitochondrial structure/function is a determinant of cell death in cardiomyocytes subjected to ischemia-reperfusion (IR). However, the details of this relationship, and the precise mitochondrial event(s) that precipitate lethal IR injury, remain unresolved. Aim: Emerging evidence has revealed that cardiomyocytes subjected to IR display: i) degradation of optic atrophy protein-1 (OPA1), the inner mitochondrial membrane protein responsible for maintaining cristae junction integrity, followed by ii) inappropriate release of OPA1 into the cytosol. Accordingly, our goal was to establish whether degradation of OPA1 plays a causal, mechanistic role in determining cardiomyocyte fate. Methods and Results: In Protocol 1 , HL-1 cardiomyocytes underwent 2.5 hrs of simulated ischemia. This was preceded by either a classic intervention known to attenuate IR injury (ischemic preconditioning: IPC) or a matched control period. Cell viability was quantified at 24 hrs post-R, and release of OPA1 into the cytosol was measured at 30 min post-R. In Controls, IR resulted in ~50% cell death and a &gt;15-fold increase in OPA1 in the cytosol - effects that were both attenuated by IPC (Figure: top). In Protocol 2 : to discern whether these data reflect an association between OPA1 degradation and cell death or cause-and-effect , HL-1 cells were transfected with either siRNA targeting OPA1 (resulting in near-total knockdown of OPA1 expression: data not shown) or scrambled siRNA. Cardiomyocytes then underwent IPC/no intervention and IR as in Protocol 1. If OPA1 disruption contributes to IR injury, we reasoned that OPA1 knockdown would exacerbate cell death in Controls and attenuate IPC-mediated protection. However, OPA1 knockdown had no effect on cell death in either cohort (Figure: bottom). Conclusion: Disruption of OPA1 and loss of cristae junction integrity does not play a causal role in lethal IR injury.
Prescription Opioid Use and Risk for Major Depressive Disorder and Anxiety and Stress-Related Disorders
Authors: Daniel B. Rosoff, George Davey Smith, Falk W. Lohoff
Journal: JAMA Psychiatry (2020)

Growing evidence suggests that prescription opioid use affects depression and anxiety disorders; however, observational studies are subject to confounding, making causal inference and determining the direction of these associations difficult.To investigate the potential bidirectional associations between the genetic liability for prescription opioid and other nonopioid pain medications and both major depressive disorder (MDD) and anxiety and stress-related disorders (ASRD) using genetically based methods.We performed 2-sample mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) to assess potential associations of self-reported prescription opioid and nonopioid analgesics, including nonsteroidal anti-inflammatories (NSAIDs) and acetaminophen-like derivatives use with MDD and ASRD. The GWAS data were derived from participants of predominantly European ancestry included in observational cohorts. Data were analyzed February 20, 2020, to May 4, 2020.Major depressive disorder, ASRD, and self-reported pain medications (opioids, NSAIDs, anilides, and salicylic acid).The GWAS data were derived from participants of predominantly European ancestry included in the population-based UK Biobank and Lundbeck Foundation Initiative for Integrative Psychiatric Research studies: approximately 54% of the initial UK Biobank sample and 55.6% of the Lundbeck Foundation Initiative for Integrative Psychiatric Research sample selected for the ASRD GWAS were women. In a combined sample size of 737 473 study participants, single-variable MR showed that genetic liability for increased prescription opioid use was associated with increased risk of both MDD (odds ratio [OR] per unit increase in log odds opioid use, 1.14; 95% CI, 1.06-1.22; P < .001) and ASRD (OR, 1.24; 95% CI, 1.07-1.44; P = .004). Using multivariable MR, these opioid use estimates remained after accounting for other nonopioid pain medications (MDD OR, 1.14; 95% CI, 1.04-1.25; P = .005; ASRD OR, 1.30; 95% CI, 1.08-1.46; P = .006), and in separate models, accounting for comorbid pain conditions. Bidirectional analyses showed that genetic liability for MDD but not ASRD was associated with increased prescription opioid use risk (OR, 1.18; 95% CI, 1.08-1.30; P < .001). These estimates were generally consistent across single-variable and multivariable inverse variance-weighted (MV-IVW) and MR-Egger sensitivity analyses. Pleiotropy-robust methods did not indicate bias in any MV-IVW estimates.The findings of this mendelian randomization analysis suggest evidence for potential causal associations between the genetic liability for increased prescription opioid use and the risk for MDD and ASRD. While replication studies are necessary, these findings may inform prevention and intervention strategies directed toward the opioid epidemic and depression.
Flying After Concussion and Symptom Recovery in College Athletes and Military Cadets
Authors: Tara L. Sharma, Julia Morrow Kerrigan, David L. McArthur, Kevin Bickart, Steven P. Broglio, Thomas W. McAllister, Michael McCrea, Christopher C. Giza
Journal: JAMA Network Open (2020)

Concussions are a common occurrence in young athletes. Hypobaric hypoxemia, such as that experienced during airplane travel, can potentially cause alterations to cerebral blood flow and increased neuroinflammatory response. It remains unknown whether flying early after a concussion may influence the clinical course of injury.To determine whether there is an association between concussion recovery and airplane travel in collegiate athletes and military cadets.This cohort study was conducted by the National Collegiate Athletic Association and US Department of Defense Concussion Assessment, Research, and Education Consortium from August 3, 2014, to September 13, 2018. Participant groups were categorized by those who flew within 72 hours of injury and those who did not fly. All participants included in the final analyses had complete data of interest and only 1 injury during the study. Data analysis was performed from September 2018 to March 2020.Recovery outcome measures were defined as time (in days) from injury to return to activity, school, and baseline symptoms. Symptom and headache severity scores were derived from the Sports Concussion Assessment Tool-Third Edition. Scores for both groups were taken at baseline and a median of 2 days after injury.A total of 92 participants who flew (mean [SD] age, 19.1 [1.2] years; 55 male [59.8%]) and 1383 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 809 male [58.5%]) were included in the analysis of symptom recovery outcomes (analysis 1). Similarly, 100 participants who flew (mean [SD] age, 19.2 [1.2] years; 63 male [63.0%]) and 1577 participants who did not fly (mean [SD] age, 18.9 [1.3] years; 916 male [58.1%]) were included in the analysis of symptom severity outcomes (analysis 2). No significant group differences were found regarding recovery outcome measures. Likewise, there were no group differences in symptom (estimated mean difference, 0.029; 95% CI, -0.083 to 0.144; P = .67) or headache (estimated mean difference, -0.007; 95% CI, -0.094 to 0.081; P = .91) severity scores.Airplane travel early after concussion was not associated with recovery or severity of concussion symptoms. These findings may help guide future recommendations on flight travel after concussion in athletes.
Abstract 13331: Impact of Longer Hemodialysis Vintage With Higher Serum Phosphorus Level on Clinical Outcomes in Patients With Chronic Limb-threatening Ischemia
Authors: Naoko Higashino, Osamu Iida, ASAI MITSUTOSHI, Masaharu Masuda, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Takashi Kanda, Takuya TSUJIMURA, Yasuhiro Matsuda, Yosuke Hata, Hiroyuki Uematsu, Taku Toyoshima, Hiroaki Nohara, Masaya Kusuda, Takashige Sakio, Satoshi Nakawatase, Toshiaki Mano
Journal: Circulation (2020)

Background: Although hemodialysis vintage and serum phosphorus level adversely impact on outcomes in the field of general population on hemodialysis, it has not systematically studied whether these have similar prognostic impacts on clinical outcomes in population with chronic limb-threatening ischemia (CLTI). Methods: The current study retrospectively analyzed 374 hemodialysis patients with CLTI presenting ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 39.6%, Rutherford 5: 75.9%, 6: 24.1%, WIFI stage 4: 50.0%) primarily treated with endovascular therapy (EVT) between April 2007 and December 2016. Primary outcome measure was 1-year amputation-free survival (AFS), while secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. Result: One-year rate of AFS and wound healing rate were 70.5±2.5%, and 57.1±3.0%, respectively. Multivariate analysis demonstrated that body mass index (hazard ratio [HR], 0.918; 95% confidence interval [CI], 0.859-0.981; p=0.012), non-ambulatory status (HR, 1.887; 95% CI, 1.222-2.913; p=0.004), lower serum albumin level (HR, 0.591; 95% CI, 0.414-0.844; p=0.004), WIfI stage 4 (HR, 1.782; 95% CI, 1.156-2.748; p=0.009) and longer vintages for hemodialysis with higher serum phosphorus levels (HR, 1.670; 95% CI, 1.099-2.537; p=0.016) were significantly associated with 1-year AFS (Figure), while WIfI stage 4 (HR, 0.713; 95% CI, 0.519-0.979; p=0.037) was associated and longer vintages for hemodialysis with higher serum phosphorus levels was close to significant association (HR, 0.684; 95% CI, 0.467-1.000; p=0.050) with 1-year wound healing. Conclusion: Longer hemodialysis vintage with higher serum phosphorus level would adversely affect clinical outcomes after EVT for hemodialysis patients with CLTI presenting ischemic tissue loss.
사례보고 : 급성 A형간염에 의해 발생한 혈구포식증후군 1예
Authors: 서지영 ( Ji Young Seo ), 서동대 ( Dong Dae Seo ), 전태주 ( Tae Joo Jeon ), 오태훈 ( Tae Hoon Oh ), 신원창 ( Won Chang Shin ), 최원충 ( Won Choong Choi ), 유수진 ( Soo Jin Yoo ), 한태희 ( Tae Hee Han )
Journal: Clinical and Molecular Hepatology (2010)

혈구포식증후군은 매우 드물지만 발생할 경우 매우 심각한 임상 경과를 보인다. 조직병리학적으로는 활성화된 대식세포나 조직구가 골수나 세망내피계에서 혈구를 포식하는 모습을 관찰할 수 있으며 임상적으로는 고열, 간비종대, 혈구감소, 간기능이상 및 고페리틴혈증을 보인다. A형간염바이러스는 이차성 혈구포식증후군을 일으키는 매우 드문 원인이다. 저자들은 급성 A형간염 후 혈구포식증후군이 합병된 22세 여자 환자를 보고한다. 환자는 급성 A형간염의 전형적인 경과를 보이며 검사실 검사 및 임상적으로 호전되다가 혈구포식증후군이 발생하면서 간부전 및 파종혈관내응고가 진행되었고 결국 복강 내 출혈로 사망하였다.
Abstract 14903: Single Center STEMI Experience in New York During COVID-19 Pandemic
Authors: Giorgio A Medranda, Kunal Brahmbhatt, Kevin P Marzo, Richard K Schwartz, Stephen J Green
Journal: Circulation (2020)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged the highly contagious and lethal virus, devastating healthcare systems throughout the world. The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to rapidly evolve, as does our understanding of its implications on the cardiovascular system. The purpose of our study was to describe a single center STEMI experience at the epicenter of the COVID-19 pandemic. Methods: This was a retrospective, observational study, which included consecutive suspected STEMI patients from March 1 2020 through May 31 2020 compared to with the same time period in 2019, at a tertiary referral center in New York. Cohort 1 (2019 pre-pandemic period) included all patients with suspected STEMI from March 1 2019 to May 31 2019. Cohort 2 (2020 pandemic period) included all patients with suspected STEMI from March 1 2020 to May 31 2020. Statistical analysis was performed using t-test and chi-squared test. Results: Cohort 2 saw a similar number (n=46) of acute myocardial infarction (AMI) team activations when compared to cohort 1 (n=42) (Figure 1). As expected during the pandemic, infection control measures and additional investigation were required to clarify the diagnosis in cohort 2 resulting in significantly longer door to balloon times (96.3 minutes vs. 72.7 minutes, p=0.0307). Despite this, we observed similar inpatient length of stay (4.3 days vs. 4.9 days, p=0.1807) and mortality (11.1% vs. 12.1%, p=0.5141). Conclusions: Our single center study, at the epicenter of the pandemic, demonstrated similar AMI team activations compared to 2019, but longer door-to-balloon time. Despite this, inpatient length of stay and mortality remained unchanged. As we continue to manage these patients amidst this dynamic pandemic, our approach should continue to focus on the safety of healthcare workers with an understanding that primary PCI remains the standard of care for patients with STEMI.
Activity of Alzheimer’s γ-secretase is linked to changes of interferon-induced transmembrane proteins (IFITM) in innate immunity
Authors: Annie Y. Yao, Riqiang Yan
Journal: Molecular Neurodegeneration (2020)

Abstract The activity of γ-secretase is critical to the pathogenesis of Alzheimer’s disease (AD). How its activity is regulated is intriguing and highly important for any AD therapy that focuses on reduction of toxic amyloid peptides and amyloid deposition in patients. Recently, interferon-induced transmembrane protein 3 (IFITM3) has been identified as a novel regulator of γ-secretase through a specific interaction. This commentary highlights this exciting study and provides an updated link of γ-secretase activity to innate immunity through IFITM3.
SAT0069 Sapho syndrome
Authors: K Fazekas, ZS Károlyi, J Gombos, I Harhai, N Erös, L Tamási
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The acronym SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) was first introduced by Chamot <i>et al</i>. in 1987.<sup>1</sup> The syndrome is characterised by variable bone involvement, with or without concurrent pustular dermatoses. The affected bones include the chest wall (clavicle, sternum, sternoclavicular joints), sacroiliac joints and long bones. Bone changes include hyperostosis, aseptic osteomyelitis and arthritis. Skin diseases include palmoplantar pustulosis, acne conglobata or acne fulminans and hidradenitis suppurativa. <h3>Objectives</h3> To determine the frequency of clinical and bone scintigraphic changes in patients with SAPHO syndrome. <h3>Methods</h3> Authors analyse the clinical and radiological findings and outcome of the disease in 6 cases of SAPHO syndrome (3 males, 3 females) between 1997 and 2000 retrospectively. <h3>Results</h3> Authors treated 6 cases with SAPHO syndrome between 1997 and 2000 of whom 3 patients suffered from acne fulminans and 3 patients from palmoplantar pustulosis. Acne fulminans was found exclusively in young males (mean age: 20 years) including one patient who suffered from inflammatory bowel disease (ulcerative colitis). Sacroileitis was found in all acne patients, and 2 cases had chest wall arthroosteitis and peripheral arthritis also. The joint involvement was preceded by the acneiform eruption. Treatment with isotretinoin was suspected playing a role in the development of joint involvement in 2 cases. All patients with palmoplantar pustulosis were middle-aged women (mean age: 45 years). All of these 3 patients suffered from anterior chest wall involvement and one had peripheral joint symptoms. The diagnosis of SAPHO syndrome based on clinical symptoms, laboratory findings (elevated erythrocyte sedimentation rate, leukocyte count, and C-reactive protein), and the results of the bone scintigraphy. Bone scintigraphy is an important examination which can reveal the early pathologic signs when the X-ray examinations are still negative. <h3>Conclusion</h3> Bone scintigraphy is a sensitive examination in the early diagnosis of the SAPHO syndrome. Cases with acne fulminans have more favourable prognosis, whereas cases with palmoplantar pustulosis have a chronic course. <h3>References</h3> Chamot AM, Benhamou CL, Kahn MF, <i>et al</i>. Synovitis-acne-pustulosis-hyperostosis- osteitis. Results of a national survey 85 cases. Rev Rhum Mal Osteoartic. 1987;54(3):187–96 Gutzner R, Herbst RA, Kapp A, Weiss I. SAPHO syndrome. Case description of 3 patients with acne conglobata and osteoarticular symptoms. Hautarzt 1997;48(3):186–90 Károlyi ZS, Fazekas K. SAPHO syndrome. Bõrgyógy Vener Szle (Hungary) 1998;74(1):23–6