tbuckley/cabot-search huggingface dataset:
Postmortem Kidney Pathology Findings in Patients with COVID-19
Authors: Dominick Santoriello, Pascale Khairallah, Andrew S. Bomback, Katherine Xu, Satoru Kudose, Ibrahim Batal, Jonathan Barasch, Jai Radhakrishnan, Vivette D’Agati, Glen Markowitz
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement More than one third of hospitalized patients with coronavirus disease 2019 (COVID-19) develop AKI. The pathogenesis of AKI in this setting is poorly understood, and pathologic descriptions are limited. The authors examined kidney histopathology of 42 patients who died of COVID-19. The most significant findings included mild acute tubular injury as well as the absence of classic viral nephropathy, diffuse thrombotic microangiopathy, or acute GN. In situ hybridization could not identify definitive positivity for SARS-CoV-2. The finding of only mild acute tubular injury in the setting of severe creatinine elevation suggests a pathogenesis involving tubular injury and hemodynamic factors (such as aggressive fluid management) and potential for recovery of renal function upon resolution of infection. Background AKI is common among hospitalized patients with coronavirus disease 2019 (COVID-19) and is an independent risk factor for mortality. Although there are numerous potential mechanisms underlying COVID-19–associated AKI, our current knowledge of kidney pathologic findings in COVID-19 is limited. Methods We examined the postmortem kidneys from 42 patients who died of COVID-19. We reviewed light microscopy findings in all autopsies and performed immunofluorescence, electron microscopy, and in situ hybridization studies for SARS-CoV-2 on a subset of samples. Results The cohort had a median age of 71.5 years (range, 38–97 years); 69% were men, 57% were Hispanic, and 73% had a history of hypertension. Among patients with available data, AKI developed in 31 of 33 patients (94%), including 6 with AKI stage 1, 9 with stage 2, and 16 with stage 3. The predominant finding correlating with AKI was acute tubular injury. However, the degree of acute tubular injury was often less severe than predicted for the degree of AKI, suggesting a role for hemodynamic factors, such as aggressive fluid management. Background changes of hypertensive arterionephrosclerosis and diabetic glomerulosclerosis were frequent but typically mild. We identified focal kidney fibrin thrombi in 6 of 42 (14%) autopsies. A single Black patient had collapsing FSGS. Immunofluorescence and electron microscopy were largely unrevealing, and in situ hybridization for SARS-CoV-2 showed no definitive positivity. Conclusions Among a cohort of 42 patients dying with COVID-19, autopsy histologic evaluation revealed acute tubular injury, which was typically mild relative to the degree of creatinine elevation. These findings suggest potential for reversibility upon resolution of SARS-CoV-2 infection.
SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70
Authors: He-wei Jiang, Hai-nan Zhang, Qing-feng Meng, Jia Xie, Yang Li, Hong Chen, Yun-xiao Zheng, Xue-ning Wang, Huan Qi, Jing Zhang, Pei-Hui Wang, Ze-Guang Han, Sheng-ce Tao
Journal: Cellular and Molecular Immunology (2020)

COVID-19 is caused by SARS-CoV-2. 1 As of July 16th, 2020, there were 13,579,581 diagnosed cases and 584,782 deaths attributed to COVID-19 reported globally (https://coronavirus.jhu.edu/map.html). 2 Unfortunately, there is still no effective drug or vaccine for treating this disease.To accelerate drug development, there is an urgent need to identify critical molecular targets and the role they play in infection.Herein, we reported that Orf9b localizes on the membrane of mitochondria and suppresses type I interferon (IFN-I) responses through association with TOM70, and TOM70 overexpression could largely rescue this inhibition.Our results suggest the potential of targeting Orf9b-TOM70 interaction as a novel therapeutic strategy of COVID-19.Induction of IFN-I is a central event of the immune defense against viral infection. 3Upon exposure to RNA viruses, an intracellular antiviral response is initiated by activation of RIG-I like receptors.In particular, when RIG-I/MDA5 detects viral RNA, they trigger a signaling complex on the mitochondrial outer membrane, including the adapter proteins MAVS/TRAF3/TRAF6/TOM70, which
Evolution of soluble hla-g levels before and after heart transplantation: prognostic value
Authors: Eduardo Barge Caballero, Marisa Crespo Leiro, Laura Fernandez Arias, Nieves Domenech García, Alfonso Castro Beiras, Natalia Suárez Fuentetaja, María Jesús Paniagua Martín, Zulaika Grille Cancela, Raquel Marzoa Rivas
Journal: European Journal of Heart Failure (2014)
One Anastomosis/Mini Gastric Bypass (OAGB-MGB) as revisional bariatric surgery after failed primary adjustable gastric band (LAGB) and sleeve gastrectomy (SG): A systematic review of 1075 patients
Authors: Chetan D. Parmar, Jonathan Gan, Christine Stier, Zhiyong Dong, Sonja Chiappetta, Luciana El-Kadre, Moataz M. Bashah, Cunchuan Wang, Nasser Sakran
Journal: International Journal of Surgery (2020)
Abstract 10320: Left Atrial Strain is Associated With Atrial Fibrosis and MicroRNA-21 Expression in Cardiovascular Surgery Patients
Authors: Suguru Hirose, Toshiaki Nakajima, Akiko Haruyama, Hiroyuki Kaneda, Syotarou Obi, Takahisa Nasuno, Shu Inami, Ikuko Shibasaki, Takuo Arikawa, Satoshi Sakuma, Shigeru Toyoda, Masao Nishimura, Hirotsugu Fukuda, Shichirou Abe, Teruo Inoue
Journal: Circulation (2019)

Introduction: Atrial fibrosis plays an essential role in atrial remodeling and developing atrial fibrillation (Af). Left atrial strain (LAS) measured by two-dimensional speckle tracking (2DS) metho...
SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition
Authors: Issei Tomita, Shinji Kume, Sho Sugahara, Norihisa Osawa, Kosuke Yamahara, Mako Yasuda-Yamahara, Naoko Takeda, Masami Chin-Kanasaki, Tatsuroh Kaneko, Eric Mayoux, Michael Mark, Motoko Yanagita, Hisakazu Ogita, Shin-ichi Araki, Hiroshi Maegawa
Journal: Cell Metabolism (2020)
Preliminary Results of Gau-PED Study: Prevalence of Gaucher Disease in Paediatric Patients Selected By an Appropriate Diagnostic Algorithm
Authors: William Morello, Mirella Filocamo, Marina Stroppiano, Maja Di Rocco, Nicola Tovaglieri, Giovanna Russo, Francesca Furlan, Roberta Burnelli, Andrea Pession
Journal: Blood (2017)
Abstract 1918 P122 Protein, a Positive Regulator for Phospholipase C-σ1, Is Upregulated and Involved in Enhanced Calcium Signaling in Human Coronary Spasm
Authors: Reiichi Murakami, Tomohiro Osanai, Hirofumi Tomita, Ken Okumura
Journal: Circulation (2008)

We previously showed that the activity of phospholipase C (PLC)-σ1, a key enzyme for Ca 2+ signaling in the coronary artery smooth muscle, was enhanced threefold in patients with coronary spastic angina (CSA) compared with control subjects. Structural mutation of PLC-σ1 (864G-A) variant with the amino acid replacement of arginine 257 by histidine is one mechanism for the enhanced PLC-σ1 activity, but this was observed in only 10% of CSA patients. PLC-σ1 was shown to be positively regulated by p122 protein. We examined the possible role of p122 protein in the mechanism for enhanced PLC-σ1 activity. In 11 patients with CSA and 9 control subjects without CSA, skin fibroblasts were obtained at the coronary angiography and were cultured. Protein and gene expressions of p122 were determined by Western blot analysis and real-time quantitative RT-PCR, respectively. The protein expression of p122 was enhanced in CSA threefold compared with control subjects (237±17 vs 85±13 units, p&lt;0.0001). The gene expression of p122 was also enhanced in CSA by 36.1±8.7% compared with control (p&lt;0.01). We further examined whether the upregulated p122 protein is associated with the enhancement of intracellular Ca 2+ signaling. Human embryonic kidney cells (HEK293) were cultured and transfected by muscarine M1 receptor. In the cells expressing normal PLC-σ1, acethylcholine (ACh) at 10 −6 and 10 −5 mol/L caused a dose-dependent, rapid transient increase in [Ca 2+ ] i followed by a lower but sustained phase of the increase. We further transfected the HEK293 cells by p122, which resulted in the increased expression of p122 protein two-to threefold. [Ca 2+ ] i at baseline was 23±1 nmol/L in the cells without p122 transfection and 39±2 nmol/L in those with p122 (P&lt;0.01). The peak increase in [Ca 2+ ] i from the baseline after ACh was significantly greater in the cells transfected with p122 than in those without transfection (68±6 versus 33±4 nmol/L at 10 −6 mol/L Ach, and 128±11 versus 67±8 nmol/L at 10 −5 mol/L ACh, both P&lt;0.01). The sustained phase of [Ca 2+ ] i increase was prolonged in the cells with p122 transfection compared with those without transfection. In conclusion, the enhanced p122 protein expression is involved in the pathogenesis of CSA by enhancing intracellular Ca 2+ signaling.
68Ga–Prostate-Specific Membrane Antigen PET–Positive Paget Bone Disease With Metastatic Prostatic Carcinoma
Authors: Ceren Ozge Engur, Halil Turgut Turoglu, Salih Ozguven, Yiloren Tanidir, Tanju Yusuf Erdil
Journal: Clinical Nuclear Medicine (2020)

Abstract Paget bone disease is a chronic benign bone disease characterized by excessive and abnormal bone remodeling. The scintigraphic and bone SPECT/CT hybrid imaging appearances of the affected bone(s) depend on the stage of the disease. We report the case of a patient newly diagnosed with prostate cancer who was found to have multiple osseous metastases, with coexisting Paget disease in the left hemipelvis diagnosed because of typical scintigraphic and SPECT/CT appearance. 68 Ga–prostate-specific membrane antigen PET/CT was also performed for initial staging. Pagetoid bones showed increased prostate-specific membrane antigen uptake like skeletal metastases.
Safety and immunogenicity of an alum-adjuvanted whole-virion H7N9 influenza vaccine: a randomized, blinded, clinical trial
Authors: Shilei Wang, Zhiqiang Xie, Lili Huang, Xu Zhou, Jian Luo, Yuelian Yang, Changgui Li, Peng Duan, Wenting Xu, Dandan Chen, Bing Wu, Yongli Yang, Xueying Liu, Yanxia Wang, Zhenghong Yuan, Di Qu, Ze Chen, Shengli Xia
Journal: Clinical Microbiology and Infection (2020)
Application of an anti-aerosol box for esophagogastroduodenoscopy during the COVID-19 pandemic: double up the protection
Authors: Wong Zhiqin, Khairul Najmi Muhammad Nawawi, Raja Affendi Raja Ali
Journal: Endoscopy (2020)

See also: Suggestions for infection prevention and control in digestive endoscopy during current 2019-nCoV pneumonia outbreak in Wuhan, Hubei province, ChinaEndoscopy 2020; 52(04): 312-314DOI: 10.1055/a-1128-4313
Severe persistent visual field constriction associated with vigabatrin
Authors: E. A Wilson, M. J Brodie, I C K Wong, G E Mawer, J W A S Sander, N. Blackwell, J. Hayllar, G. Kelly, G F A Harding, J. T Backstrom, R. L Hinkle, M. R Flicker
Journal: BMJ (1997)

Editor—T Eke and colleagues report three cases of severe, symptomatic constriction of the visual fields associated with vigabatrin treatment.1 We have had experience of a similar case. A 34 year old man who had had refractory partial onset seizures since the age of 8 was taking vigabatrin 3000 mg daily (since 1989), carbamazepine 1200 mg daily, and sodium valproate 5000 mg daily (both since 1982) when he suddenly developed visual deterioration with blurring and loss of peripheral vision in July 1995.

Surface electroencephalography suggested a left hemispheric focus, but magnetic resonance imaging of the brain showed no abnormality. On examination he had impaired visual acuity, with corrective lenses to 6/9 in both eyes. Pupillary responses were normal and confrontation visual fields full. There was pronounced bilateral optic atrophy and a maculopathy, both more evident in the right eye. His electro-oculogram was flat, and he had subnormal cone and rod electroretinograms. Visual evoked responses were normal. Vigabatrin was stopped, but his damaged retinal pigment epithelium and photoreceptors did not improve.

Vigabatrin was licensed in Britain and the Republic of Ireland in 1989; these were its first markets.2 The mechanism by which the drug might produce retinal damage is unknown, and the symptoms did not improve in this patient when the drug was withdrawn. In addition, all of the patients reported on were taking other antiepileptic drugs at presentation. Our own patient had been treated previously with phenytoin, primidone, and lamotrigine. Chronic refractory epilepsy may also have a role in causing these unusual lesions. For example, disseminated intravascular coagulation associated with prolonged seizure activity may have been responsible,3 rather than a toxic effect of lamotrigine.

Although it is reasonable to recommend ophthalmological review in patients with visual symptoms taking vigabatrin, we are still a long way from establishing a …
Use of Factory-Calibrated Real-time Continuous Glucose Monitoring Improves Time in Target and HbA1c in a Multiethnic Cohort of Adolescents and Young Adults With Type 1 Diabetes: The MILLENNIALS Study
Authors: Hood Thabit, Joshi Navis Prabhu, Womba Mubita, Catherine Fullwood, Shazli Azmi, Andrea Urwin, Ian Doughty, Lalantha Leelarathna
Journal: Diabetes Care (2020)

OBJECTIVE International type 1 diabetes registries have shown that HbA1c levels are highest in young people with type 1 diabetes; however, improving their glycemic control remains a challenge. We propose that use of the factory-calibrated Dexcom G6 CGM system would improve glycemic control in this cohort. RESEARCH DESIGN AND METHODS We conducted a randomized crossover trial in young people with type 1 diabetes (16–24 years old) comparing the Dexcom G6 CGM system and self-monitoring of blood glucose (SMBG). Participants were assigned to the interventions in random order during two 8-week study periods. During SMBG, blinded continuous glucose monitoring (CGM) was worn by each participant for 10 days at the start, week 4, and week 7 of the control period. HbA1c measurements were drawn after enrollment and before and after each treatment period. The primary outcome was time in range 70–180 mg/dL. RESULTS Time in range was significantly higher during CGM compared with control (35.7 ± 13.5% vs. 24.6 ± 9.3%; mean difference 11.1% [95% CI 7.0–15.2]; P &amp;lt; 0.001). CGM use reduced mean sensor glucose (219.7 ± 37.6 mg/dL vs. 251.9 ± 36.3 mg/dL; mean difference −32.2 mg/dL [95% CI −44.5 to −20.0]; P &amp;lt; 0.001) and time above range (61.7 ± 15.1% vs. 73.6 ± 10.4%; mean difference 11.9% [95% CI −16.4 to −7.4]; P &amp;lt; 0.001). HbA1c level was reduced by 0.76% (95% CI −1.1 to −0.4) (−8.5 mmol/mol [95% CI −12.4 to −4.6]; P &amp;lt; 0.001). Times spent below range (&amp;lt;70 mg/dL and &amp;lt;54 mg/dL) were low and comparable during both study periods. Sensor wear was 84% during the CGM period. CONCLUSIONS CGM use in young people with type 1 diabetes improves time in target and HbA1c levels compared with SMBG.
Increased mortality in patients waiting for biliary stent replacement during the COVID-19 pandemic
Authors: Iyad Khamaysi, Sacha Michlin
Journal: Endoscopy (2020)

See also: ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemicEndoscopy 2020; 52(06): 483-490DOI: 10.1055/a-1155-6229
Trust was wrong to exclude parents from meeting about care of disabled child, says judge
Authors: Clare Dyer
Journal: BMJ (2020)

The NHS trust that runs Great Ormond Street Hospital in London failed to take sufficient account of a severely disabled child’s quality of life in concluding that she should have only palliative care if her condition deteriorated, a High Court judge has ruled.1

Ms Justice Russell said that it was “essential” to involve parents where the quality of life of a disabled child was a central issue at a clinical ethics committee meeting. A decision by Great Ormond Street Hospital for Children NHS Foundation Trust not to involve the parents in a meeting, but to explain the outcome to them later that day, “had the effect of both raising their anxiety and contributing to their feelings of alienation and exclusion,” said the judge.

She added, “The absence of any prior consultation or participation cannot be good practice and should generally be unacceptable. Even at hastily assembled meetings there should be notice taken of the …
Abstract 16687: Aging-Related Klotho Deficiency in Human Aortic Valve Interstitial Cells Exaggerates the Inflammatory Response Through Down-Regulation of Autophagy Activity
Authors: Qingzhou Yao, Xinsheng Deng, Lihua Ao, Joseph Cleveland, David Furllerton, Xianzhong Meng
Journal: Circulation (2018)

Calcific aortic valve disease (CAVD) is prevalent in the elderly. The inflammatory response of aortic valve interstitial cells (AVICs) contributes to the mechanism of CAVD progression. Our previous work demonstrated that the innate immunity mediated by Toll-like receptors (TLRs) in human AVICs up-regulates the production of inflammatory mediators and pro-osteogenic activity and that human AVICs express anti-aging protein Klotho, and Klotho deficiency is responsible for the enhanced osteogenic activity in diseased AVICs. Autophagy plays an important role in modulating cellular inflammatory response. Currently, the effect of Klotho on AVIC autophagy function and inflammatory response is unknown. We hypothesis that Klotho suppresses AVIC inflammatory response through maintaining cellular autophagy activity. Methods: Levels of autophagy proteins (LC3-I, and LC3-II), Klotho and ICAM-1 were determined in AVICs of normal valves from young (25.3±2.7 years) and older (61.5±4.3 years) donors by immunoblotting. Autophagy modulators (rapamycin, 2.0 μM; Autophinib, 100 nM and Bafilomysin A1, 10 nM) and recombinant Klotho (5.0 μg/ml) were applied to AVICs to assess their impact on inflammatory responses. Results: AVICs from older donors have lower levels of Klotho and autophagy activity, but produce higher levels of ICAM-1. TLR4 stimulation in AVICs from young donors reduces cellular levels of Klotho and autophagy activity, and increases ICAM-1 production. Further, recombinant Klotho enhances autophagy activity in AVICs from older donors through induction of PTEN and inhibition the Akt-mToR-p70S6K pathway, and it suppresses the inflammatory response in unstimulated AVICs from older donors and stimulated cells from young donors. Down-regulation of autophagy enhances, while up-regulation of autophagy reduces, the inflammatory response in AVICs. Conclusions: Autophagy plays an important role in suppression of human AVIC inflammatory response. Klotho deficiency in AVICs associated with aging exaggerates the inflammatory response through down-regulation of autophagy activity. Recombinant Klotho may have the therapeutic potential for suppression of valvular inflammation associated with CAVD progression.
Gain of Function Mutant p53 Drives Clonal Hematopoiesis and the Pathogenesis of Myelodysplastic Syndromes
Authors: Sisi Chen, Hao Yu, Rui Gao, Sarah C. Nabinger, Michihiro Kobayashi, Chonghua Yao, Linsey Mayo, Reuben Kapur, Mervin C. Yoder, Hal E. Broxmeyer, Zhonghua Gao, Yan Liu
Journal: Blood (2017)
Synergy Between Cytokines and Risk Factors in the Cytokine Storm of COVID‐19: Does Ongoing Use of Cytokine Inhibitors Have a Protective Effect?
Authors: Pierre Miossec
Journal: Arthritis & Rheumatology (2020)

The severity of severe acute respiratory syndrome coronavirus 2 results from an abnormal immune response with massive local and systemic inflammation, referred to as a cytokine storm (1,2).A key question is why patients with obesity or diabetes are at such high risk for severe disease while patients treated with cytokine inhibitors are evidently not (3).Key inflammatory cytokines often interact through synergy (4).During the cytokine storm, similar amplification may result from interactions between acute viral inflammation, chronic inflammation from high-risk diseases, and additional events such as bacterial infections.Its understanding may provide better control, and even prevention, of the cytokine storm.
Gut Microbiota and Cardiovascular Disease
Authors: Marco Witkowski, Taylor L. Weeks, Stanley L. Hazen
Journal: Circulation Research (2020)

Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota-dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota-dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)-a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.
A Woman in Her 70s With Mitral Stenosis, Mitral Regurgitation, and Abnormal Morphology of the Mitral Valve
Authors: Anderson H. Kuo, Rahul A. Sakhuja, Sandeep S. Hedgire
Journal: JAMA Cardiology (2020)

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Is the Outcome of Patients with High Risk T-Cell Acute Lymphoblastic Leukemia Improving in the Era of Pediatric—Inspired Protocols? a Comparison of 2 Consecutive Pethema Trials
Authors: Pere Barba, Mireia Morgades, Pau Montesinos, Cristina Gil, Maria Laura Fox, Juana Ciudad, maria Jose Moreno, José González-Campos, Eulalia Genesca, Daniel Martínez-Carballeira, Rodrigo Martino, Susana Vives, Ramon Guàrdia, Santiago Mercadal, Maria Teresa Artola, Antonia Cladera, Mar Tormo, Jordi Esteve, Juan Bergua, Ferran Vall-Llovera, Jordi Ribera, Pilar Martínez-Sánchez, María-Luz Amigo, Arancha Bermudez, María Calbacho, Jesús-María Hernández-Rivas, Evarist Feliu, Josep-Maria Ribera
Journal: Blood (2017)