tbuckley/cabot-search huggingface dataset:
Sentinel Contributions of US Department of Veterans Affairs Surgeons in Shaping the Face of Health Care
Authors: Kenneth A. Lipshy, Kamal Itani, Danny Chu, Anil Bahadursingh, Seth Spector, Kathleen Raman, Alan Dardik, Edith Tzeng, Garth H. Ballantyne, Preeti R. John, Brian Cmolik, James Maloney, Robert Kozol, Walter E. Longo
Journal: JAMA Surgery (2021)

The vast accomplishments of the US Department of Veterans Affairs (VA) during the past century have contributed to the advancement of medicine and benefited patients worldwide. This article highlights some of those accomplishments and the advantages in the VA system that promulgated those successes. Through its affiliation with medical schools, its formation of a structured research and development program, its Cooperative Studies Program, and its National Surgical Quality Improvement Program, the VA has led the world in the progress of health care. The exigencies of war led not only to the organization of VA health care but also to groundbreaking, landmark developments in colon surgery; surgical treatments for vascular disease, including vascular grafts, carotid surgery, and arteriovenous dialysis fistulas; cardiac surgery, including implantable cardiac pacemaker and coronary artery bypass surgery; and the surgical management of many conditions, such as hernias. The birth of successful liver transplantation was also seen within the VA, and countless other achievements have benefited patients around the globe. These successes have created an environment where residents and medical students are able to obtain superb education and postgraduate training and where faculty are able to develop their clinical and academic careers.
SAT0109 Expression of bcl-2 in juvenile chronic arthritis
Authors: E Tuszkiewicz-Misztal, A Bojarska-Junak, P Krawczyk, J Roliñski, V Opoka-Winiarska
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The aim of this study was to investigate the relationship between levels of molecules regulating of apoptosis in T lymphocytes and the clinical manifestation of juvenile chronic arthritis (JCA). <h3>Objectives</h3> Apoptosis is involved in the regulation of an immune response to foreign and autoantigens. We determined the expression of Bcl-2 mitochondrial oncoprotein, which inhibit apoptosis, in different subtypes of lymphocytes obtained from peripheral blood from healthy children (n = 14, age:12,4 ± 5,4) and JCA patients with pauciarticular onset (n = 17, age: 12,2 ± 3,8) and polyarticular onset (n = 30, age: 11,8 ± 3,2). <h3>Methods</h3> All samples were analysed using monoclonal antibodies and flow cytometry technique. <h3>Results</h3> Peripheral blood T lymphocytes from patients with pauciarticular onset JCA expressed a significantly lower amount of the Bcl-2 protein than T lymphocytes from patients with polyarticular onset JCA (p &lt; 0,01) and healthy children (p &lt; 0,05). This differences concerned both CD4<sup>+</sup> and CD8<sup>+</sup> T cells but CD4<sup>+</sup> lymphocytes expressed significantly (p &lt; 0,05) lower level of Bcl-2 protein in comparison with CD8<sup>+</sup> cells in patients with polyarticular onset JCA. There were no correlations between the expression of Bcl-2 and the age of children in all subgroup of patients. There was significant positive correlation (R = 0,562, p &lt; 0,05) between the percentage of T lymphocytes with receptor for IL-2 (CD25) and expression of Bcl-2 protein in T cells in children with pauciarticular onset JCA. <h3>Conclusion</h3> Our data supported the notion that disturbances in T cell apoptosis may play a role in the immunopathological processes leading to clinical manifestation of JCA, These data suggest also that both polyarticular onset and pauciarticular onset JCA have different pathogenesis and probably distinct aetiologies.
Factors influencing adjuvant treatment decision making among Chinese patients with hepatocellular carcinoma (HCC): Results of a patient survey.
Authors: Hui-Chuan Sun, Xiao-Dong Zhu, Li Xu, Ying-Hao Shen, Cheng Huang, Jian Zhou, Jia Fan
Journal: Journal of Clinical Oncology (2021)

346 Background: This study aimed to understand patient decision-making factors for post-operative adjuvant treatment after resection of hepatocellular carcinoma (HCC) in China. Methods: Patients who had received surgical resection of HCC in the last 2 years at 27 hospitals in China were surveyed using a questionnaire (https://pro.wenjuan.com/t/jUZFU). Feedback was collected by telephone or online. The survey covered three domains: adjuvant treatment decision making, selection of treatment regimen and the influence of recurrence risk on willingness to receive adjuvant treatment. For each domain, participants were asked to identify decision makers and to score decision-making factors from 1 (no influence) to 7 (high influence). All factors with an average score of 6 or 7 points were considered impactful, and those with scores ≤5 were not considered impactful. Descriptive statistics were used to summarize the findings. This study was approved by the ethics committee of Zhongshan hospital and patients provided informed consent. Results: In total, 2,220 valid responses were collected (2,183 patients from Zhongshan Hospital, 37 from 26 other hospitals); 75% of respondents were male, 60% were aged 50-70 years, and 50% had a monthly family income ≤5,000 Chinese Yuan (~$740 USD). Among respondents, 62% had received adjuvant treatment: 56% received systemic therapy (chemotherapy, tyrosine kinase inhibitors, immune therapy and traditional Chinese medicine), 27% transarterial chemoembolization (TACE) plus systemic therapy and 17% TACE alone. The majority of respondents (75%) identified physicians as the decision makers for use of adjuvant therapy and selection of treatment regimen. Of the 38% of respondents who did not receive adjuvant treatment, 90% gave ‘physician recommendation’ as the reason. When patients were the decision makers, factors influencing decisions to use adjuvant treatment and selection of treatment regimen, ranked from most to least influential, were efficacy (for prevention of tumor recurrence), reimbursement status, treatment side effects and cost. Patient willingness to receive adjuvant treatment was influenced by predicted risk of recurrence; among respondents with an estimated 2-year recurrence risk &gt; 10% and &gt; 30%, 40% and 56%, respectively, believed they should receive adjuvant therapy. Conclusions: A majority of patients surveyed received adjuvant therapy, the most common of which were systemic therapy and TACE. Patients who underwent resection had a strong desire to reduce postoperative recurrence by using adjuvant therapy. Physician opinion was identified as the most important factor in treatment decision making, followed by economic factors. When patients were the decision maker, the most influential factors were treatment effectiveness followed by reimbursement status.
AB0460 INTERLEUKIN-6 INHIBITION WITH TOCILIZUMAB FOR THE TREATMENT OF GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA IN PATIENTS WITH SERIOUS COMORBIDITIES
Authors: T. Beketova, E. Otteva, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2020)

Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related inflammatory conditions affecting people aged over 50 years. Objectives: We present our experience of using tocilizumab (TCZ) therapy for management of GCA/PMR aggravated by severe concurrent pathologies that potentially increase the risk of side effects of glucocorticoids (GCs). Methods: 22 patients were recruited into the prospective study: six patients with GCA, 13- PMR, and three- with both GCA and PMR, 95.5% were females, mean age 72.8±6.5 years. Mean disease duration was 3.5 (0.5-19) months. All patients had active GCA/PMR with mean CRP 30.3±32.7 mg/l. Seven patients had visual ischemic complications, and another one- aortitis. All patients had serious comorbidities, 59% of patients had three and more severe concurrent diseases. All patients were administered TCZ i/v 2.3-8.8 mg/kg Q4W. 50% patients were also treated with prednisone at mean 20 (10-70) mg/day. The follow-up period was 24 (6-60) months. Results: All patients demonstrated good clinical response to TCZ i/v 2.3-8.8 mg/kg Q4W given for average 4,5 (2-11) months, achieving remission in 100% of cases. Some patients showed a very rapid improvement after initiation of treatment, including TCZ monotherapy. Prednisone dose was discontinued in 6/11, or was reduced to 2.5 (2.5-10) mg in 4/11. There was one relapse after TCZ discontinuation, although this patient managed to regain the remission after resumption of TCZ i/v 4 mg/kg. There was one (4.6%) serious complication (septic olecranon bursitis 1 month after TCZ discontinuation), one patient died of myocardial infarction 12 months later after TCZ discontinuation. Three remaining complications included one case of peripheral artery disease (claudication), one- psoriasis, and one- sural lipodermatosclerosis. Conclusion: Interleukin-6 inhibitors should be considered as potentially effective and relatively safe treatment for GCA/PMR patients with serious comorbidities, intolerance or contraindications to standard therapy. More data is necessary to identify the optimal dosing regimen and duration of TCZ therapy, as well as cost-effectiveness aspects. Disclosure of Interests: None declared
Affordable Care Act Litigation
Authors: Lawrence O. Gostin, Kelli K. Garcia
Journal: JAMA (2012)

In Florida v. HHS, a lawsuit brought on behalf of 26 states challenging the constitutionality of the Patient Protection and Affordable Care Act (ACA), the Supreme Court will determine the future direction of health care reform in the United States. During the unprecedented 5-1/2 hours of oral arguments, the Court will hear 4 issues: the individual purchase mandate, severability, the Medicaid expansion and the Anti-Injunction Act. The states challenging the ACA maintain that the purchase mandate uniquely penalizes individuals for failing to purchase insurance. Uninsured individuals, however, rarely do nothing. Instead, they self-insure, rely on family, and cost-shift to hospitals, the insured, and tax payers. Because most uninsured people will eventually require uncompensated care, they impose costs on everyone through higher taxes and insurance premiums. Further, although the ACA’s mandate is unusual, it is not unprecedented. Mandatory worker contributions to Medicare, for example, are a compelled purchase of health insurance. The necessary and proper clause, which permits Congress to pass laws rationally related to the exercise of federal powers, may be the best argument in favor of the mandate because the mandate is necessary for the other insurance market reforms to work. If the Court were to strike down the mandate, it would then have to determine whether the mandate is severable from the rest of the ACA. Although the ACA did not explicitly state that if part of the act were deemed unconstitutional the rest would survive, most ACA reforms are severable because they are unrelated to the mandate, such as funding for public health and community health centers. The more difficult question is whether the mandate is so intertwined with the ACA’s still unimplemented market reforms that the Court must strike them down. The Court will also review the constitutionality of expanding Medicaid to all individuals with household incomes below 138% of the federal poverty level. The states argue that Medicaid expansion is unduly coercive because they could lose all Medicaid funding and not just the funding related to the expansion. The Court, however, is unlikely to uphold the coercion theory because state participation in Medicaid has always been optional and some states have openly discussed exercising their option to discontinue the program. Finally, the Court will hear technical arguments concerning the Anti-Injunction Act (AIA), which prohibits lawsuits “for the purpose of restraining the assessment or collection of any tax.” The Court is unlikely to invoke the AIA because neither the administration nor the states contend that it applies. The ACA will achieve near universal coverage, something that seemed unimaginable just a short time ago. Health reform envisages a social contract in which everyone shares the cost, recognizing that virtually everyone will become ill one day. The ACA and its individual mandate are not unjustified limits on freedom, but rather are vital to a decent society.
Abstract 15790: Effects of an Investigational RNAi Therapeutic Targeting PCSK9 on Immunological and Hematological Parameters: A Safety Analysis From ORION-1
Authors: Arash Haghikia, Kausik K Ray, Lawrence A Leiter, R. S Wright, David Kallend, Peter Wijngaard, John Kastelein, Ulf Landmesser
Journal: Circulation (2018)

Introduction: Antisense based RNA therapies have been associated with off-target immunological and hematological side-effects, in particular thrombocytopenia. The safety of alternative RNA based th...
Abstract 11790: Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis From Coronary Computed Tomographic Angiography Registry
Authors: Gyung-Min Park, Young-Rak Cho, Yong-Giun Kim, Ki-Bum Won, Soe Hee Ann, Shin-Jae Kim, Sang-Gon Lee
Journal: Circulation (2017)

Introduction: There are limited data regarding the relationship between diabetes control and the risk of subclinical coronary atherosclerosis assessed by coronary computed tomographic angiography (...
OP0081 The effectiveness of aerobic exercise and education in fibromyalgia syndrome
Authors: O Kuru, N Yildiz, A Bilgici
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Fibromyalgia is a common syndrome found predominantly in women. It is characterised by chronic, diffuse, musculoskeletal pain and a sleep disorder, without evidence of arthritis or myositis. <h3>Objectives</h3> The purpose of this study was to compare the effectiveness of aerobic exercise and education with the control group in fibromyalgia syndrome and to evaluate the patients treated with this method after the treatment program. <h3>Methods</h3> Sixty women, aged 18–55 years, diagnosed as fibromyalgia according to 1990 ACR criteria were randomly divided into two groups. Group I was given aerobic exercise and stretching exercise for 8 weeks following an education program. Group II was the control group. Both groups took sertralin 50 mg/day. The patients were evaluated before and after the treatment. We used VAS, number of tender points, total myalgic score for pain, Beck depression inventory (BDI) for depression, Patient and doctor global assessment scale, Fibromyalgia attitudes index (FAI) for global assessment, Fibromyalgia impact questionnaire (FIQ), Health assessment questionnaire (HAQ) for functional evaluation, Astrand test for aerobic capacity. <h3>Results</h3> The results of VAS, number of tender points, total myalgic score, BDI, FAI, FIQ, HAQ and patient and doctor global assessment scale showed significant improvement in both groups (p &lt; 0.001, p &lt; 0.01). In the first group, the results of VO2max showed significant improvement (p &lt; 0.001). The results of some groups of FIQ, SELF function subscale, FAI and BDI were not statistically different among the two groups (p &gt; 0.05). We found significant improvement in other parameters in exercise group than the control group. <h3>Conclusion</h3> Fibromyalgia is a multifactorial syndrome, and the best treatment will encompass multiple strategies, that include education, stress management treatment and aerobic exercise.
Isolevuglandin-Modified Cardiac Proteins Drive CD4+ T-Cell Activation in the Heart and Promote Cardiac Dysfunction
Authors: Njabulo Ngwenyama, Annet Kirabo, Mark Aronovitz, Francisco Velázquez, Francisco Carrillo-Salinas, Ane M. Salvador, Tania Nevers, Venkataraman Amarnath, Albert Tai, Robert M. Blanton, David G. Harrison, Pilar Alcaide
Journal: Circulation (2021)

Despite the well-established association between T-cell-mediated inflammation and nonischemic heart failure, the specific mechanisms triggering T-cell activation during the progression of heart failure and the antigens involved are poorly understood. We hypothesized that myocardial oxidative stress induces the formation of isolevuglandin (IsoLG)-modified proteins that function as cardiac neoantigens to elicit CD4+ T-cell receptor (TCR) activation and promote heart failure.
Evaluation of Nutritional Support and In-Hospital Mortality in Patients With Malnutrition
Authors: Nina Kaegi-Braun, Marlena Mueller, Philipp Schuetz, Beat Mueller, Alexander Kutz
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Malnutrition affects a considerable proportion of patients in the hospital and is associated with adverse clinical outcomes. Recent trials found a survival benefit among patients receiving nutritional support. <h3>Objective</h3> To investigate whether there is an association of nutritional support with in-hospital mortality in routine clinical practice. <h3>Design, Setting, and Participants</h3> This cohort study was conducted from April 2013 to December 2018 among a population of patients from Swiss administrative claims data. From 114 264 hospitalizations of medical patients with malnutrition, 34 967 patients (30.6%) receiving nutritional support were 1:1 propensity score matched to patients with malnutrition in the hospital who were not receiving nutritional support. Patients in intensive care units were excluded. Data were analyzed from February 2020 to November 2020. <h3>Exposures</h3> Receiving nutritional support, including dietary advice, oral nutritional supplementation, or enteral and parenteral nutrition. <h3>Main Outcomes and Measures</h3> The primary outcome was all-cause in-hospital mortality. Secondary outcomes were 30-day all-cause hospital readmission and discharge to a postacute care facility. Poisson and logistic regressions were used to estimate incidence rate ratios (IRRs) and odds ratios (ORs) of outcomes. <h3>Results</h3> After matching, the study identified 69 934 hospitalizations of patients coded as having malnutrition in the cohort (mean [SD] age, 73.8 [14.5] years; 36 776 [52.6%] women). Patients receiving nutritional support, compared with those not receiving nutritional support, had a lower in-hospital mortality rate (2525 of 34 967 patients died [7.2%] vs 3072 of 34 967 patients died [8.8%]; IRR, 0.79 [95% CI, 0.75-0.84];<i>P</i> &lt; .001) and a reduced 30-day readmission rate (IRR, 0.95 [95% CI, 0.91-0.98];<i>P</i> = .002). In addition, patients receiving nutritional support were less frequently discharged to a postacute care facility (13 691 patients [42.2%] vs 14 324 patients [44.9%]; OR, 0.89 [95% CI, 0.86-0.91];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> These findings suggest that nutritional support was associated with reduced mortality among patients in the medical ward with malnutrition. The results support data found by randomized clinical trials and may help to inform patients, clinicians, and authorities regarding the usefulness of nutritional support in clinical practice.
Insight into next-generation CAR therapeutics: designing CAR T cells to improve clinical outcomes
Authors: Emiliano Roselli, Rawan Faramand, Marco L. Davila
Journal: Journal of Clinical Investigation (2021)

Chimeric antigen receptor (CAR) T cell therapy has shown considerable promise for hematologic malignancies, leading to the US Food and Drug Administration approval of two CAR T cell–based therapies for the treatment of B cell acute lymphoblastic leukemia and large B cell lymphoma. Despite success in hematologic malignancies, the treatment landscape of CAR T cell therapy for solid tumors has been limited. There are unique challenges in the development of novel CAR T cell therapies to improve both safety and efficacy. Improved understanding of the immunosuppressive tumor microenvironment and resistance mechanisms has led to encouraging approaches to mitigating these obstacles. This Review will characterize challenges with current CAR T designs for hematologic malignancies and solid tumors and emphasize preclinical and clinical strategies to overcome them with novel CAR T cell therapies.
Evolutionary conservation and divergence of the human brain transcriptome
Authors: William G. Pembroke, Christopher L. Hartl, Daniel H. Geschwind
Journal: Genome biology (2021)

Abstract Background Mouse models have allowed for the direct interrogation of genetic effects on molecular, physiological, and behavioral brain phenotypes. However, it is unknown to what extent neurological or psychiatric traits may be human- or primate-specific and therefore which components can be faithfully recapitulated in mouse models. Results We compare conservation of co-expression in 116 independent data sets derived from human, mouse, and non-human primate representing more than 15,000 total samples. We observe greater changes occurring on the human lineage than mouse, and substantial regional variation that highlights cerebral cortex as the most diverged region. Glia, notably microglia, astrocytes, and oligodendrocytes are the most divergent cell type, three times more on average than neurons. We show that cis-regulatory sequence divergence explains a significant fraction of co-expression divergence. Moreover, protein coding sequence constraint parallels co-expression conservation, such that genes with loss of function intolerance are enriched in neuronal, rather than glial modules. We identify dozens of human neuropsychiatric and neurodegenerative disease risk genes, such as COMT, PSEN-1, LRRK2, SHANK3, and SNCA, with highly divergent co-expression between mouse and human and show that 3D human brain organoids recapitulate in vivo co-expression modules representing several human cell types. Conclusions We identify robust co-expression modules reflecting whole-brain and regional patterns of gene expression. Compared with those that represent basic metabolic processes, cell-type-specific modules, most prominently glial modules, are the most divergent between species. These data and analyses serve as a foundational resource to guide human disease modeling and its interpretation.
Anthony Barrington (“Barry”) Kay: part of the team that unequivocally established the Th2 T lymphocyte hypothesis for bronchial asthma
Authors: Rebecca Wallersteiner
Journal: BMJ (2021)

Photo credit: Rebecca Sutherland

Anthony Barrington (“Barry”) Kay, whose work transformed the lives of many patients with asthma, has died at the age of 81 from an acute illness, after being treated for metastatic bladder cancer for several years.

Kay was born in Northampton to Tony Chambers, an area manager for Darling Washing Machines, who claimed to be a widower, and Eva Gertrude Pearcey, a dressmaker. In 1944, when only 4, Kay was left at the King’s (The Cathedral) School Boarding House in Peterborough, his mother having discovered her husband was a bigamist. Beautiful and resourceful, she reinvented herself in London. She became a successful fashion designer and married a Jewish businessman, Harry Kay, pretending that she and her son were Jewish.

In his blackly funny, dramatised memoir, Whatever Happened to Barry Chambers? , Kay explored his unusual beginnings and his double life in school and at home, as he swung between being Barry Chambers, a confirmed Anglican, at school, and Barry Kay, a Jewish boy, at home during the school holidays in London. A “loveable rogue,” his stepfather was imprisoned for selling stolen radios.

At 17, Kay successfully applied for medical school in Edinburgh, where he made many friends and qualified in 1963. He trained in respiratory medicine at Edinburgh City Hospital, achieved his doctorate with Robin Coombs at Cambridge, and obtained a postdoctoral fellowship at Harvard. In the 1970s, he moved to London to become professor …