tbuckley/cabot-search huggingface dataset:
Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial
Authors: Elisabeth Bandak, Robin Christensen, Anders Overgaard, Lars Erik Kristensen, Karen Ellegaard, Jørgen Guldberg-Møller, Cecilie Bartholdy, David J Hunter, Roy Altman, Henning Bliddal, Marius Henriksen
Journal: Annals of the Rheumatic Diseases (2021)

Objective To compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA). Methods In this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)–100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients’ global assessment of disease impact. Results 206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI −0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups. Conclusion In individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks. Trial registration number NCT03843931 .
Outcomes of Screening for Prostate Cancer Among Men Who Use Statins
Authors: Arla Vettenranta, Teemu J. Murtola, Jani Raitanen, Paavo Raittinen, Kirsi Talala, Kimmo Taari, Ulf-Håkan Stenman, Teuvo L. J. Tammela, Anssi Auvinen
Journal: JAMA Oncology (2021)

Prostate-specific antigen (PSA) screening for prostate cancer has resulted in a slight reduction in prostate cancer mortality but also a concomitant overdiagnosis of low-risk tumors. Prostate-specific antigen levels are affected by use of cholesterol-lowering statin drugs, but the association of statin use with PSA screening performance is unknown.To investigate whether statin use was associated with outcomes of a randomized PSA-based prostate cancer screening intervention.This post hoc subgroup analysis of a cohort from a population-based randomized clinical trial used data from the population-based Finnish Randomized Study of Prostate Cancer Screening, which randomized men to PSA screening or routine care from March 1, 1996, to December 31, 1999, with follow-up continuing until December 31, 2015. The population included all men aged 55 to 67 years at baseline and residing in the Tampere or Helsinki districts of Finland. Information on statin purchases from 1996 to 2009 was obtained from a national prescription registry. Eligible men were identified from the population registry of Finland. Prevalent prostate cancer cases at baseline were excluded. Data were analyzed from January 1, 2019 to March 31, 2021.Three invitations for PSA screening at 4-year intervals from 1996 to 2007 vs routine care.Risk for prostate cancer overall, high-risk disease, and prostate cancer mortality in the screening group vs the control group as an intention-to-treat analysis. The analysis was stratified by statin use.The study comprised 78 606 men (median age, 59 years [range, 55-67 years]) with statin purchase data available. Although PSA screening was associated with increased prostate cancer incidence among statin nonusers (screening vs control, 11.2 vs 8.6 per 1000 person-years); rate ratio [RR], 1.31; 95% CI, 1.24-1.38), no similar increase in incidence was observed among statin users (6.9 vs 5.9 per 1000 person-years; RR, 1.02; 95% CI, 0.95-1.10; P < .001 for interaction). Incidence of low-risk (Gleason score 6) and localized tumors was lower among statin users, whereas detection of tumors with a Gleason score of 8 to 10 was similar. Screening was associated with a lower incidence of metastatic tumors regardless of statin use.In this post hoc subgroup analysis of a cohort from a population-based randomized clinical trial, PSA screening among statin users was associated with a decreased incidence of advanced prostate cancer that was similar among statin nonusers, but with less increase in detection of low-grade localized tumors in statin users than in nonusers. These findings suggest that statin use does not materially compromise benefits of PSA-based screening.
Abstract 13723: Gender, Racial, and Socioeconomic Disparities in Patients With Heart Failure and Psychiatric Disorders
Authors: Salma Ramadan, Yasser Sammour, kevin kennedy, Brett Sperry
Journal: Circulation (2021)

Background: Psychiatric diseases are common in patients with heart failure (HF) resulting in higher morbidity and mortality. Disparities in healthcare are well-described in cardiovascular medicine. Minorities often suffer from more frequent mental illnesses. Whether disparities related to gender, racial and socioeconomic status affect outcomes in patients with HF and mental illnesses remains unknown. Methods: We queried ICD-10 codes in the national inpatient sample (2016-2018) for patients with HF and psychiatric disorders including psychotic (F20-29), mood (F30-39), and/or anxiety (F40-43) disorders. Multivariable analysis, adjusting for age and 29 HCUP comorbidities, assessed outcomes of in-hospital mortality, length of stay, and hospital charges based upon gender, race, and household income. Results: Among 685,912 admissions for patients with HF and psychiatric disorders, 63.5% had mood disorders, 55.2% anxiety disorders, and 6.8% psychotic disorders. Mean age was 68.7±14.2 years, 59.8% were females, 75.8% Caucasians, 14.2% African Americans, and 6.6% Hispanics. In multivariable analysis, females, African Americans, Hispanics, and lower median household income were associated with lower in-hospital mortality (Table, p&lt;0.001 for all). There were minimal absolute differences in length of stay and hospital cost (Table). Conclusion: In patients with both HF and psychiatric illness, disparities related to gender, race, and income exist and may modify outcomes. Further data are necessary to determine the impact of these disparities on care delivery among this patient population.
Renewing the Call for Reforms to Medical Device Safety—The Case of Penumbra
Authors: Kushal T. Kadakia, Adam L. Beckman, Joseph S. Ross, Harlan M. Krumholz
Journal: JAMA Internal Medicine (2021)

Strengthening premarket and postmarket surveillance of medical devices has long been an area of focus for health policy makers. The recent class I recall (the most serious of the US Food and Drug Administration [FDA] recalls) of reperfusion catheters manufactured by Penumbra, a US-based medical device company, illustrates issues of device safety and oversight that mandate attention.To review the regulatory history and clinical evidence of the Penumbra JET 7 Reperfusion Catheter with Xtra Flex Technology (JET 7) and use the device recall as a case study of the challenges associated with clinical evaluation, transparency, and oversight of medical devices in the US.Regulatory history and clinical evidence for the Penumbra medical devices were analyzed through a qualitative review of decision letters in the Access FDA database for medical devices and medical device reports in the Manufacturer and User Facility Device Experience database and a review of market data (eg, earnings calls, company communications) and clinical literature.The JET 7 device was subjected to a class I recall following more than 200 adverse event reports, 14 of which involved patient deaths. Regulatory analysis indicated that each of the Penumbra reperfusion catheters was cleared under the 510(k) pathway (which allows devices to be authorized with limited to no clinical evidence), with limited submission of either new clinical or animal data. Clinical evidence for Penumbra devices was generated from nonrandomized, single-arm trials with small sample sizes. The regulatory issues raised by JET 7 are reflective of broader challenges for medical device regulation. Opportunities for reform include strengthening premarket evidence requirements, requiring safety reporting with unique device identifiers, and mandating active methods of postmarket surveillance.The case study of JET 7 highlights the long-standing gaps in medical device oversight and renews the impetus to build on the Institute of Medicine recommendations and reform FDA medical device regulation to protect public health.
Abstract 13920: Temporal Changes in Metabolism and Gene Expression in Murine Heart Following Exercise
Authors: Kyle L Fulghum, Helen E Collins, Bradford G Hill
Journal: Circulation (2021)

Introduction: Previous studies report that many systemic adaptations occur early in an exercise training program, but how exercise leads to cardiac adaptations remain unclear. In this study, we characterized time-dependent changes in cardiac metabolism and gene expression following an acute session of aerobic exercise. Methods: We used untargeted metabolomics to identify the temporal nature of metabolic changes in male and female mouse hearts after an acute bout of forced treadmill running. We freeze-clamped hearts immediately, 1 h, or 24 h following exercise to compare alongside sedentary controls. Additionally, we measured the expression of key metabolic enzymes known to influence cardiac growth via qRT-PCR and immunoblotting. Results: Untargeted metabolomics analyses of male and female mouse hearts ( n =9/gp) revealed exercise-induced changes in branched chain amino acids as well as pentose phosphate, nucleotide, and Krebs cycle intermediates. In both male and female hearts, exercise acutely increased the abundances of corticosterone and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which could indicate a transient role in exercise-induced signaling. AICAR is known to activate AMPK, but immunoblots showed minimal changes in cardiac AMPK phosphorylation immediately after exercise. However, when measured 24 h following an acute bout of exercise, we saw a modest increase in phosphorylation (p=0.07, n =3-4/gp) which suggests time-dependent activation after exercise. Phosphorylation of AKT and PFKFB2 were acutely reduced in the heart following exercise (p&amp;lt;0.05, n =3-4/gp), but normalized 1 h post exercise. At these same timepoints, we observed few changes in expression of genes related to the physiological growth program; however, we did observe an increase in Ppargc1a expression 1 h following exercise (p&amp;lt;0.0001, n =3/gp). Conclusions: These findings show that aerobic exercise acutely changes cardiac metabolism, metabolic signaling pathways, and mitochondrial biogenetic capacity following one bout of aerobic exercise. Temporal changes in cardiac metabolism and gene expression could compound with chronic exercise training and facilitate an exercise-adapted phenotype.
RADT-18. NEOADJUVANT (PRE RADIOTHERAPY) TEMOZOLOMIDE FOLLOWED BY RADIATION THERAPY WITH CONCURRENT AND ADJUVANT TEMOZOLOMIDE IN GLIOBLASTOMA MULTIFORME
Authors: Chinmaykumar Prajapati, Maitrik Mehta, U Suryanarayan Kunikullaya
Journal: Neuro-Oncology (2021)

Abstract BACKGROUD AND PURPOSE To evaluate the effect of neoadjuvant [pre-radiotherapy(RT)] temozolomide (TMZ) in glioblastoma multiforme (GBM) patients in terms of overall survival(OS) and progression free survival (PFS). MATERIAL AND METHODS Patients with diagnosed GBM are treated with neoadjuvant( pre RT) TMZ followed by concurrent RT-TMZ and adjuvant TMZ. The Kaplan-Meier method is used to estimate OS the differences between groups. RESULTS Twenty five patients are match with inclusion criteria. Age group, Recurvsive partitioning analysis (RPA) class and extent of surgery are found to effect on overall survival but statistically not significant. At end of study, 40 percent patients are alive with 9 months PFS and 11 months OS. CONCLUSION The neo-adjuvant TMZ with concomitant and adjuvant TMZ is feasible and safe which is associated with an encouraging favorable long-term survival with acceptable toxicity.
Back to the Future: The Role of Metabolic Studies in Therapeutic Advances
Authors: Dawn S. Milliner, John C. Lieske
Journal: Journal of the American Society of Nephrology (2021)

Isotope infusion studies, such as those used by Garrelfs and colleagues[1][1] in this issue, have been used for decades to elucidate metabolic pathways. In human subjects, their application has been uniquely beneficial in rare metabolic diseases that lacked animal models,[2][2] or to elucidate
膝および股関節の変形性関節症における疼痛の治療のための非ステロイド性抗炎症薬の有効性:ネットワークメタ分析【Powered by NICT】
Authors: da Costa Bruno R, Reichenbach Stephan, Keller Noah, Nartey Linda, Wandel Simon, Jueni Peter, Trelle Sven
Journal: The Lancet (2017)
Real Life Experience of Brentuximab Vedotin Plus CHP As First-Line Treatment in CD30 + Peripheral T-Cell Lymphomas
Authors: Domingo Domenech Eva, Juan-Manuel Sancho, Eva González-Barca, Nicholas Kelleher, Marta Rodriguez-Luaces, Jordina Rovira Sole, Silvia Verdesoto, Maite Encuentra, Damir Blazevic, Ana C Oliveira, Lourdes Escoda, Josep-Maria Ribera, Anna Sureda
Journal: Blood (2021)
Abstract 10940: Leptin Treatment Protects the Endothelium from Inflammation, Increased Permeability and Endothelial-to-Mesenchymal Transition
Authors: Marie R Schubert, Paulina Stuerzebecher, Susan Kralisch, Annett Hoffmann, Matthias Bluher, Mathias Fasshauer, Ulrich Laufs, Anke Tönjes, Jes-Niels Boeckel
Journal: Circulation (2021)

Introduction: Patients with lipodystrophy (LD) are characterized by a loss of adipose tissue and are associated with a higher risk for cardiovascular diseases (CVD). As a consequence of adipose tissue reduction in LD patients, the systemic concentration of the adipokine leptin decreases, representing the pathological cause of this disease. Hypothesis: We hypothesized that the reduction of leptin may impair endothelial cells, leading to the development of CVD. Therefore, we analyzed the effects of leptin treatment on vascular inflammation, endothelial-to-mesenchymal transition (EndMT), endothelial permeability and atherosclerotic plaque characteristics. Methods &amp; Results: Treatment of endothelial cells with leptin (200 ng/ml, 6 h) potently reduced IL1β-induced inflammation, as measured by expression of ICAM1 (-25.1%) and E-Selectin (-22.7%), (both p&lt;0.05). Leptin further reduced the induction of EndMT, as determined by expression of calponin (-41.3%) and SM22 (-23.8%), (both p&lt;0.05), as well as the EndMT-induced endothelial permeability (-20.7%, p&lt;0.05). These data were confirmed in a combined lipodystrophic and atherosclerosis prone mouse model (LDLR -/- ;aP2-nSREBP). Treatment with leptin (3.0 mg/kg) for 8 w reduced the number of EndMT-positive endothelial cells (-69%, p&lt;0.05) as well as the total number of mesenchymal cells in the atherosclerotic lesions (-34.8%), (both p&lt;0.05). Further analysis of the atherosclerotic lesions revealed a reduction of atherosclerotic plaque protrusion into the vessel lumen (-31%) and reduced macrophage infiltration (-21.9%) (p&lt;0.05), which is a hallmark of instable atherosclerotic plaques that are prone to rupture, whereas the total plaque area was not affected. The expression of the leptin receptor (LepR) was reduced in endothelial cell inflammation, EndMT (-69%, p&lt;0.05) and in atherosclerotic lesions, suggesting reduced leptin effects under these conditions. Conclusions: Leptin treatment exerts beneficial effects protecting endothelial function and identity in lipodystrophy. Downregulation of the leptin receptor in diseased endothelial cells is likely to reduce the identified positive vascular effects of leptin signaling in lipodystrophy.
Abstract 10431: Impact of Cardiac Rehabilitation on Reducing Cardiovascular Events and Subsequent Medical Expenses for One Year in Patients with Transcatheter Aortic Valve Implantation
Authors: Yuya Yokota, Shinji Koba, Fumiyoshi Tsunoda, Makoto Shoji, Toshiro Shinke
Journal: Circulation (2021)

Introduction: It remains unclear whether cardiac rehabilitation (CR) can reduce medical expenses (ME)in patients with Transcatheter Aortic Valve Implantation (TAVI). Hypothesis: Outpatients CR reduced the cardiovascular events (CEs) and the total ME for one year in patients after TAVI. Methods: This retrospective analysis enrolled consecutive 148 patients who admitted TAVI treatment at the Showa University Hospital, between December 2015 and September 2019. Exclusion criteria was in-hospital death, difficulty walking at discharge and patients who could not be followed up after the hospital discharge. The subsequent ME for outpatient clinic and/or rehospitalization due to CEs in avarage 1.5 years after the discharge were compared between the CR group and non-CR group. CEs were defined as death, ACS, angina, stroke, and heart failure. Results: The CR group was significantly reduced the CEs compared with the non-CR group (logrank = 4.538 p = 0.033). (figure1)The CR group was significantly increased the outpatient ME (p &lt; 0.001). However, rehospitalization and total ME were significantly lower in the CR group (p = 0.003, p = 0.002). (figure2) Conclusions: Outpatients CR reduced the CEs and the total ME for one year in patients after TAVI.
Abstract 10581: Sexual Dimorphism in Acute Myocardial Infarction-Induced Acute Kidney Injury
Authors: Nada J Habeichi, Rana Ghali, Ali MROUEH, ABDULLAH KAPLAN, Cynthia Tannous, Abdo Jurjus, Ghadir Amin, George Booz, Ahmed El-Yazbi, Fouad A Zouein
Journal: Circulation (2021)

Introduction: Acute kidney injury (AKI) is a common complication of acute myocardial infarction (AMI) in both males and females, increasing mortality rate substantially. Premenopausal females appear to be more protected, suggesting a potential protective role of estrogen. Hypothesis: We hypothesized that premenopausal female mice are more protected against AMI-induced AKI and that is potentially due to female sex hormones. Materials and Methods: AMI was induced by ligating the left anterior coronary artery in male and premenopausal female mice. Kidney histological, molecular, and functional parameters were assessed after 7 days. Surgical menopause was induced in AMI-female mice to evaluate estrogen-mediation of the observed renal protection. Results: 7days post-AMI enhanced fibrosis and glomerular retraction were observed in AMI-males, only. Both sexes exhibited a comparable marked increase in glomerular reactive oxygen species (ROS) and DNA fragmentation that was associated with a marked decrease in total NAD kidney levels. Increased release of IL-1β, a pro-inflammatory cytokine, and caspase-3, a proapoptotic marker, and α-smooth muscle actin, a profibrotic biomarker, was seen in AMI-male mice, only. NAD + biosynthetic enzymes, including nicotinamide phosphoribosyl transferase and nicotinamide riboside kinase-1, increased only in AMI-females, whereas male counterparts showed a substantial decrease in mitochondrial bioenergetic enzymes such as Sirtuins 1 and 3, along with an increase in Poly [ADP-ribose] polymerase 1, an NAD + consuming enzyme. Exacerbated kidney damage in AMI-females post-ovariectomy was seen with aggravated morphological alterations, increased ROS generation, and enhanced pro-inflammatory cytokine release, and altered NAD + biosynthetic and mitochondrial bioenergetic enzymes. These changes translated into exacerbated kidney function as evidenced by a decrease in creatinine clearance in AMI-male and female mice, while urine output declined in AMI-male mice only. A further decrease in creatinine clearance and urine output was observed in AMI-female mice following ovariectomy. Conclusion: Our findings suggest that AMI induced AKI in both sexes with pre-menopausal female mice being more protected.
PATH-44. RAMAN SPECTROSCOPY AS A DIAGNOSTIC TOOL IN NEUROPATHOLOGY
Authors: Gilbert Georg Klamminger, Laurent Mombaerts, Karoline Klein, Finn Jelke, Giulia Mirizzi, Redouane Slimani, Jean-Jacques Gerardy, Andreas Husch, Frank Hertel, Michel Mittelbronn, Felix Kleine Borgmann
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Although microscopic assessment is still the diagnostic gold standard in pathology, non-light microscopic methods such as new imaging methods and molecular pathology have considerably contributed to more precise diagnostics. As an upcoming method, Raman spectroscopy (RS) offers a "molecular fingerprint" which could be used to differentiate tissue heterogeneity or diagnostic entities. RS has so far been successfully applied on fresh and frozen tissue, however more aggressively, chemically treated tissue such as formalin-fixed, paraffin-embedded (FFPE) samples are challenging for RS. METHODS To address this issue, we examined FFPE samples of a broad range of intracranial tumors (e.g. glioblastoma and primary CNS lymphoma) and also different areas of morphologically highly heterogeneous glioblastoma tumor tissue. The latter in order to classify not only the tumor entity but also histologically defined GBM areas according to their spectral properties. We applied linear and nonlinear machine learning algorithms (Logistic Regression, Random Forest, Support Vector Machine) on our spectroscopic data and compared statistical performance of resulting classifiers. RESULTS We found that Random Forest classification distinguished between glioblastoma and primary CNS lymphoma with a balanced accuracy of 94%, only using Raman measurements on FFPE tissue. Furthermore, our established support vector machine-based classifier identified distinct histological areas in glioblastoma such as tumor core and necroses with an overall accuracy of 70.5% and showed a clear separation between the areas of necrosis and peritumoral zone. CONCLUSIONS This relatively cheap and easy-to-apply tool may serve useful to complement histopathological and molecular diagnostics. It provides an unbiased approach to tumor diagnostics with very little requirements (e.g. histopathological feature completeness of the tumor entity) to the sample. As a conclusion, we propose RS as a potential future additional method in the (neuro)-pathological toolbox for tumor diagnostics.