tbuckley/cabot-search huggingface dataset:
Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial
Authors: Alexander H Nave, Torsten Rackoll, Ulrike Grittner, Holger Bläsing, Anna Gorsler, Darius G Nabavi, Heinrich J Audebert, Fabian Klostermann, Ursula Müller-Werdan, Elisabeth Steinhagen-Thiessen, Andreas Meisel, Matthias Endres, Stefan Hesse, Martin Ebinger, Agnes Flöel
Journal: BMJ (2019)

To determine the safety and efficacy of aerobic exercise on activities of daily living in the subacute phase after stroke.Multicentre, randomised controlled, endpoint blinded trial.Seven inpatient rehabilitation sites in Germany (2013-17).200 adults with subacute stroke (days 5-45 after stroke) with a median National Institutes of Health stroke scale (NIHSS, range 0-42 points, higher values indicating more severe strokes) score of 8 (interquartile range 5-12) were randomly assigned (1:1) to aerobic physical fitness training (n=105) or relaxation sessions (n=95, control group) in addition to standard care.Participants received either aerobic, bodyweight supported, treadmill based physical fitness training or relaxation sessions, each for 25 minutes, five times weekly for four weeks, in addition to standard rehabilitation therapy. Investigators and endpoint assessors were masked to treatment assignment.The primary outcomes were change in maximal walking speed (m/s) in the 10 m walking test and change in Barthel index scores (range 0-100 points, higher scores indicating less disability) three months after stroke compared with baseline. Safety outcomes were recurrent cardiovascular events, including stroke, hospital readmissions, and death within three months after stroke. Efficacy was tested with analysis of covariance for each primary outcome in the full analysis set. Multiple imputation was used to account for missing values.Compared with relaxation, aerobic physical fitness training did not result in a significantly higher mean change in maximal walking speed (adjusted treatment effect 0.1 m/s (95% confidence interval 0.0 to 0.2 m/s), P=0.23) or mean change in Barthel index score (0 (-5 to 5), P=0.99) at three months after stroke. A higher rate of serious adverse events was observed in the aerobic group compared with relaxation group (incidence rate ratio 1.81, 95% confidence interval 0.97 to 3.36).Among moderately to severely affected adults with subacute stroke, aerobic bodyweight supported, treadmill based physical fitness training was not superior to relaxation sessions for maximal walking speed and Barthel index score but did suggest higher rates of adverse events. These results do not appear to support the use of aerobic bodyweight supported fitness training in people with subacute stroke to improve activities of daily living or maximal walking speed and should be considered in future guidelines.ClinicalTrials.gov NCT01953549.
RUNX1 associated Familial Platelet Disorder with Myeloid Malignancy (FPD-MM) in Children: A Novel New Phenotype with Juvenile and Chronic Myelomonocytic Leukemia (JMML/CMML) Characteristics
Authors: Katherine Regling, Shruti Bagla, Ahmar Urooj Zaidi, Erin Wakeling, Michael C. Chicka, Leigh Flores, Manisha Gadgeel, Steven Buck, Meera B. Chitlur, Charles A. Schiffer, Yaddanapudi Ravindranath
Journal: Blood (2018)
The multi-factorial nature of clinical multidrug resistance in cancer
Authors: Yehuda G. Assaraf, Anamaria Brozovic, Ana Cristina Gonçalves, Dana Jurkovicova, Aija Linē, Miguel Machuqueiro, Simona Saponara, Ana Bela Sarmento-Ribeiro, Cristina P.R. Xavier, M. Helena Vasconcelos
Journal: Drug Resistance Updates (2019)
Glycemic Outcomes in Adults With T1D Are Impacted More by Continuous Glucose Monitoring Than by Insulin Delivery Method: 3 Years of Follow-Up From the COMISAIR Study
Authors: Jan Šoupal, Lenka Petruželková, George Grunberger, Aneta Hásková, Milan Flekač, Martin Matoulek, Ondřej Mikeš, Tomáš Pelcl, Jan Škrha, Eva Horová, Jan Škrha, Christopher G. Parkin, Štěpán Svačina, Martin Prázný
Journal: Diabetes Care (2019)

OBJECTIVE This study assessed the clinical impact of four treatment strategies in adults with type 1 diabetes (T1D): real-time continuous glucose monitoring (rtCGM) with multiple daily insulin injections (rtCGM+MDI), rtCGM with continuous subcutaneous insulin infusion (rtCGM+CSII), self-monitoring of blood glucose with MDI (SMBG+MDI), and SMBG with CSII (SMBG+CSII). RESEARCH DESIGN AND METHODS This 3-year, nonrandomized, prospective, real-world, clinical trial followed 94 participants with T1D (rtCGM+MDI, n = 22; rtCGM+CSII, n = 26; SMBG+MDI, n = 21; SMBG+CSII, n = 25). The main end points were changes in A1C, time in range (70–180 mg/dL [3.9–10 mmol/L]), time below range (&amp;lt;70 mg/dL [&amp;lt;3.9 mmol/L]), glycemic variability, and incidence of hypoglycemia. RESULTS At 3 years, the rtCGM groups (rtCGM+MDI and rtCGM+CSII) had significantly lower A1C (7.0% [53 mmol/mol], P = 0.0002, and 6.9% [52 mmol/mol], P &amp;lt; 0.0001, respectively), compared with the SMBG+CSII and SMBG+MDI groups (7.7% [61 mmol/mol], P = 0.3574, and 8.0% [64 mmol/mol], P = 1.000, respectively), with no significant difference between the rtCGM groups. Significant improvements in percentage of time in range were observed in the rtCGM subgroups (rtCGM+MDI, 48.7–69.0%, P &amp;lt; 0.0001; and rtCGM+CSII, 50.9–72.3%, P &amp;lt; 0.0001) and in the SMBG+CSII group (50.6–57.8%, P = 0.0114). Significant reductions in time below range were found only in the rtCGM subgroups (rtCGM+MDI, 9.4–5.5%, P = 0.0387; and rtCGM+CSII, 9.0–5.3%, P = 0.0235). Seven severe hypoglycemia episodes occurred: SMBG groups, n = 5; sensor-augmented insulin regimen groups, n = 2. CONCLUSIONS rtCGM was superior to SMBG in reducing A1C, hypoglycemia, and other end points in individuals with T1D regardless of their insulin delivery method. rtCGM+MDI can be considered an equivalent but lower-cost alternative to sensor-augmented insulin pump therapy and superior to treatment with SMBG+MDI or SMBG+CSII therapy.
Phase I/II study of cetuximab, capecitabine and oxaliplatin (CAPOX) combined with standard radiotherapy (RTX) as neoadjuvant treatment of advanced rectal cancer (RC)
Authors: D. Arnold, M. Hipp, T. Reese, W. Hohenberger, T. Liersch, F. Lordick, H. Sülberg, R. Sauer, C. Rödel
Journal: Journal of Clinical Oncology (2006)

3574 Background: CAPOX given concurrently to neoadjuvant RTX in RC is well tolerated and yielded high rates of pathologic complete responses in phase II trials. Cetuximab, a monoclonal antibody targeted against the EGF receptor, is active in metastatic colorectal cancer. Furthermore, synergy of cetuximab with RTX was shown in improved survival vs. RTX alone in head and neck cancer. This trial was to evaluate maximal tolerated dose (MTD), feasibility and efficacy of CAPOX + RTX with cetuximab in RC. Method: Patients (pts) had to have unpretreated T3–4 and/or N+ disease, with distant metastases allowed. During a conventionally fractionated RTX (1.8 Gy for 28 days [d]), cetuximab was given in standard dosage (400mg/m 2 on d-7, then 6 weekly doses of 250 mg/m 2 , to d35). CAPOX was given on the basis of a previously examined schedule with oxaliplatin (50 mg/m 2 d 1,8,22 and 29) in combination with capecitabine (d1–14 and d22–35) at 3 dose levels: 1000, 1300 and 1650mg/m 2 bid. In phase I, a standard 3+3 design was used, allowing for dose escalation in 0/3 or 1/6 pt with dose-limiting toxicity (DLT). Results: 13 pts were enrolled: Median age 58 [35–75] yrs., m/f 7/6 pts. T3 85%, T4 15%; N+ 92%, M1 46%; G2 92%, G3 8%. As on dose level 1 one DLT (diarrhea grade 3) occurred, it was extended to 7 pts. No further DLT was observed as it was on levels 2 and 3 with 3 pts each. Full RTX course was administered in all pts, while CAPOX-cetuximab was stopped in the DLT case and cetuximab in 1 pt with hypersensitivity reaction. Toxicities are displayed in the table . Conclusion: CAPOX can safely be combined with cetuximab without requiring chemotherapy dose reduction. The multicenter phase II part of the trial with 31 pts. included so far is ongoing and updated results (including resectability) will be presented. [Table: see text] [Table: see text]
Triple Therapy with MerTK and PD1 Inhibition Plus Radiotherapy Promotes Abscopal Antitumor Immune Responses
Authors: Mauricio S. Caetano, Ahmed I. Younes, Hampartsoum B. Barsoumian, Michael Quigley, Hari Menon, Chan Gao, Thomas Spires, Timothy P. Reilly, Alexandra P. Cadena, Taylor R. Cushman, Jonathan E. Schoenhals, Ailin Li, Quynh-Nhu Nguyen, Maria Angelica Cortez, James W. Welsh
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Radiotherapy (RT) traditionally has been used for local tumor control in the treatment of cancer. The recent discovery that radiotherapy can have anticancer effects on the immune system has led to recognition of its ability to sensitize the tumor microenvironment to immunotherapy. However, radiation can also prompt adverse immunosuppressive effects that block aspects of systemic response at other tumor sites. Our hypothesis was that inhibition of the MER proto-oncogene tyrosine kinase (MerTK) in combination with anti-programmed cell death-1 (α-PD1) checkpoint blockade will enhance immune-mediated responses to radiotherapy. Experimental Design: We tested the efficacy of this triple therapy (Radiation + α-PD1 + α-MerTK mAbs) in 129Sv/Ev mice with bilateral lung adenocarcinoma xenografts. Primary tumors were treated with stereotactic radiotherapy (36 Gy in 3 12-Gy fractions), and tumors were monitored for response. Results: The triple therapy significantly delayed abscopal tumor growth, improved survival rates, and reduced numbers of lung metastases. We further found that the triple therapy increased the activated CD8+ and NK cells populations measured by granzyme B expression with upregulation of CD8+CD103+ tissue-resident memory cells (TRM) within the abscopal tumor microenvironment relative to radiation only. Conclusions: The addition of α-PD1 + α-MerTK mAbs to radiotherapy could alter the cell death to be more immunogenic and generate adaptive immune response via increasing the retention of TRM cells in the tumor islets of the abscopal tumors which was proven to play a major role in survival of non-small cell lung cancer patients.
Trends in Chronic Opioid Use Around Inpatient Surgery Within the Veterans Health Administration
Authors: Karthik Raghunathan, Neil Ray, William Bryan, Marc Pepin, Robert Overman, Atilio Barbeito, Vijay Krishnamoorthy
Journal: JAMA Surgery (2019)

This study assesses outcomes of veterans who have undergone inpatient surgery since the Veterans Health Administration’s opioid safety initiative was initiated.
Mohs micrographic surgery vs. standard surgical excision?: reply from authors
Authors: C.B. Lee, A.L. Mooyaart, R.R. Bos
Journal: British Journal of Dermatology (2019)

Linked Articles:Slater. Br J Dermatol 2020; 182:517. van Lee et al. Br J Dermatol 2019; 181:338–343.
Response to: ‘New 2019 SLE EULAR/ACR classification criteria are valuable for distinguishing patients with SLE from patients with pSS’ by Assan<i>et al</i>
Authors: Martin Aringer, Karen Costenbader, Thomas Dörner, Sindhu R Johnson
Journal: Annals of the Rheumatic Diseases (2019)

In addressing the differential classification of systemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (pSS), Dr Florence Assan and colleagues1 focus on an important and frequently challenging issue.

Distinguishing between SLE and pSS has been a theme from the very beginning of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria project. For example, the similarities to pSS led to antibodies against Ro/SS-A or La/SS-B being neither of positive nor of negative …
Association of Serum Ustekinumab Levels With Clinical Response in Psoriasis
Authors: Teresa Tsakok, Nina Wilson, Nick Dand, Floris C. Loeff, Karien Bloem, David Baudry, Michael Duckworth, Shan Pan, Angela Pushpa-Rajah, Joseph F. Standing, Annick de Vries, Ali Alsharqi, Gabrielle Becher, Ruth Murphy, Shyamal Wahie, Andrew Wright, Christopher E. M. Griffiths, Nick J. Reynolds, Jonathan Barker, Richard B. Warren, A. David Burden, Theo Rispens, Deborah Stocken, Catherine Smith
Journal: JAMA Dermatology (2019)

High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab.To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis.A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria.Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay.Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less.A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5).This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.
Abstract 10565: Association of Elevated Circulating Fibroblast Growth Factor 21 Levels With Prevalent and Incident Metabolic Syndrome: The Multi-Ethnic Study of Atherosclerosis
Authors: Kwok Leung Ong, Robyn L McClelland, Matthew A Allison, John Kokkinos, Ben J Wu, Philip J Barter, Kerry-Anne Rye
Journal: Circulation (2018)

Introduction: Fibroblast growth factor 21 (FGF21) plays an important role in glucose and lipid metabolism. In participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated the relationship of plasma FGF21 levels with both prevalent and incident metabolic syndrome (MetS).Methods
Endotoxin, food allergen sensitization, and food allergy: A complementary epidemiologic and experimental study
Authors: Angela Tsuang, Alexander Grishin, Galina Grishina, Anh N. Do, Joanne Sordillo, Ginger L. Chew, Supinda Bunyavanich
Journal: Allergy (2019)

Abstract Background Household endotoxin levels have been variably associated with risk for asthma and atopy. Methods We studied participants from the 2005‐2006 National Health and Nutrition Examination Survey (NHANES, n = 6963), a large cohort representative of the US population (aged 1‐84 years). We built logistic regression models to test for associations between house dust endotoxin and sensitization to specific foods (milk, egg, and peanut). To experimentally explore the detected epidemiologic associations, peripheral blood mononuclear cells (PBMCs) were collected from 21 children (aged 1‐19 years) mono‐food allergic (ie, sensitized and clinically reactive) to milk, egg, or peanut and nonallergic controls for stimulation with endotoxin and secreted cytokine measurement. For each food allergy, linear mixed‐effects models were built to test the association between endotoxin stimulation and cytokine level. Results Among NHANES subjects, the geometric mean household endotoxin level was 15.5 EU/mg (GSE 0.5). Prevalence of food allergen sensitization (sIgE ≥ 0.35 kU A /L) varied by food: milk 5.7%, egg 4.0%, and peanut 7.9%. In models adjusted for potential confounders (age, race, country of birth, total people per household, US region, and history of wheezing in the past year), household endotoxin level was associated with sensitization to milk (OR 1.7, 95% CI 1.2‐2.1) and egg (OR 1.4, 95% CI 1.01‐1.9), but not peanut (OR 0.98, 95% CI 0.8‐1.2). Interferon‐γ levels of endotoxin‐stimulated PBMCs from children allergic to milk or egg, but not peanut, were significantly lower compared to controls in linear mixed‐effects models adjusted for repeated measures, experimental variables, age, and inter‐individual variability ( P ‐values .007, .018, and .058, respectively). Conclusion Higher household endotoxin is associated with increased odds of milk and egg sensitization. Altered cytokine responsiveness to endotoxin is also observed in PBMCs from individuals with milk and egg allergy.
Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Authors: Thomas H. Marwick, Kerstin Amann, Sripal Bangalore, João L. Cavalcante, David M. Charytan, Jonathan C. Craig, John S. Gill, Mark A. Hlatky, Alan G. Jardine, Ulf Landmesser, L. Kristin Newby, Charles A. Herzog, Michael Cheung, David C. Wheeler, Wolfgang C. Winkelmayer, Mark J. Sarnak, Debasish Banerjee, Carlo Briguori, Tara I. Chang, Chien-Liang Chen, Christopher R. deFilippi, Xiaoqiang Ding, Charles J. Ferro, Jagbir Gill, Mario Gössl, Nicole M. Isbel, Hideki Ishii, Meg J. Jardine, Philip A. Kalra, Günther Laufer, Krista L. Lentine, Kevin W. Lobdell, Charmaine E. Lok, Gérard M. London, Jolanta Małyszko, Patrick B. Mark, Mohamed Marwan, Yuxin Nie, Patrick S. Parfrey, Roberto Pecoits-Filho, Helen Pilmore, Wajeh Y. Qunibi, Paolo Raggi, Marcello Rattazzi, Patrick Rossignol, Josiah Ruturi, Charumathi Sabanayagam, Catherine M. Shanahan, Gautam R. Shroff, Rukshana Shroff, Angela C. Webster, Daniel E. Weiner, Simon Winther, Alexander C. Wiseman, Anthony Yip, Alexander Zarbock
Journal: Kidney International (2019)

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research.
Abstract 12143: Time-Course of Effects of Rosuvastatin Therapy on Carotid Adventitial Angiogenesis and Plaque Neovascularization as Assessed by Magnetic Resonance Imaging
Authors: Xue-Qiao Zhao, Ruixue Du, Jianming Cai, Bao Cui, Hong-Mei Wu, Ping Ye
Journal: Circulation (2018)

Introduction: Atherosclerotic plaque neovascularization mainly originates from the adventitia. It serves as a pathway for plaque inflammatory infiltration and a major cause of intra-plaque hemorrha...
Abstract 14933: Long (&gt;12 Months) and Short (&lt;6 Months) versus Standard Duration of Dual Antiplatelet Therapy After Coronary Stenting: A Systematic Review and Meta-Analysis
Authors: Shikha Sharma, Alexandros Briasoulis, Sagar Mallikethi-Reddy, Mohan Palla, Rajeev Sudhakar, Fayez Siddiqui, Luis Afonso
Journal: Circulation (2015)

Background: Dual antiplatelet therapy (DAPT) is recommended for 6-12 month after drug-eluting stent (DES) implantation to prevent ischemic events and late stent thrombosis. The optimal duration of DAPT has not been established. Methods: We performed a meta-analysis of the comparative effects of short- and long- vs standard DAPT duration on adverse cardiovascular and major bleeding. We conducted an EMBASE and MEDLINE search for studies in which patients were randomized to treatment with a different duration of DAPT. Results: We identified 5 prospective randomized studies comparing short- vs standard DAPT and 3 comparing long vs. standard DAPT duration with a total of 28,343 patients. Short term DAPT has similar incidence of stent thrombosis, MI and death compared to standard DAPT whereas major bleeding was significantly lower in short DAPT therapy. Long term DAPT was associated with lower rates of stent thrombosis and MI but significantly increased major bleeding and all-cause mortality compared to standard therapy Conclusion: We found that short DAPT is safer and as effective as standard DAPT in patients with second generation DES. Extended DAPT is associated with less ischemic events at the expense of high bleeding and mortality rates.