tbuckley/cabot-search huggingface dataset:
AB1288-HPR BURTON PATIENT REPORTED OUTCOME MEASURES (B-PROM): STEPS TOWARDS VALIDATION
Authors: R. Laxminarayan, A. Dean, H. Nutland, L. Bembridge, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2020)

Background: Patient reported outcome measure (PROMS) and experience measures (PREMS) are becoming of vital importance in the assemment of treating the rheumatic diseases. There have been a variety measuring different elements of a patients disease journey. To date few have been developed specifically in rheumatology outpatients, to that end the Burton rheumatology unit in the Midlands UK developed a 12 question PROM looking at the three domains of emotional, physical and functional health, this has been mindful of previois PROMS and PREMS developed 1,2,3 . Objectives: To validate a new PROM questionnaire in an unselected group of rheumatology outpatients with osteoarthritiss (OA) Methods: Consecutive patients with OA attending outpatients in Burton were asked to fill in the questionnaire at the beginning and after completing education and exercise programme designed by the physiotherapists to treat OA. The results collated were analysed using STATA ™. Cronbach’s alpha was calculated to look internal validity within domain and overall to assess validity of the questionannire. This was done within domain and with the overall questionnaire. Results: 130 patients were included, mean age was 65 and diagnosis was osteoarthritis. 71.5% patients were female. Cronbachs alpha results for the communication, relationship and reliability within the first domain were 0.80, 0.82 and 0.82 respectively. Domain 1: alpha for all three questions was 0.93. Domain 2: alpha for questions on knowledge was 0.60, reliability 0.81, fatigue 0.79 and pain 0.85. Domain two overall agreed with the other two domains was 0.95 . Domain 3: the alpha for movement was 0.81, strength was 0.73, independence was 0.81, mobility was 0.91 and social was 0.92. Domain three had an alpha overall of 0.93 Conclusion: The B-PROM shows good validity and could be used in patients with OA, further work using it on other patient groups will be performed. References: [1]Nutland H et al. A New Patient Reported Tool in The Assessment of Physiotherapy for Patients with Knee Osteoarthritis. doi.org/10.1136/annrheumdis-2016-eular.5926 [2]Nisar M et al. Development of A Patient Reported Self-Assessment Tool for Rheumatology Patients. doi.org/10.1136/annrheumdis-2016-eular.4670 [3]Bosworth A, Cox M, O’Brien A, Jones P, Sargeant I, Elliott A, Bukhari M. Development and validation of a Patient Reported Experience Measure (PREM) for patients with rheumatoid arthritis (RA) and other rheumatic conditions.Curr Rheumatol Rev. 2015 May 21. Clinical Rheumatology. February 2016, Volume 35, Issue 2, pp 513-516 Disclosure of Interests: Ramasharan Laxminarayan Speakers bureau: Novartis, Pfizer and Lilly, Allison Dean: None declared, Helen Nutland: None declared, Lisa Bembridge: None declared, Marwan Bukhari Speakers bureau: Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen and Novartis.
Patent Foramen Ovale Closure Is Effective in Divers
Authors: Jakub Honěk, Martin Šrámek, Tomáš Honěk, Aleš Tomek, Luděk Šefc, Jaroslav Januška, Jiří Fiedler, Martin Horváth, Štěpán Novotný, Josef Veselka
Journal: Journal of the American College of Cardiology (2020)
Safety and Activity of a Dose-Dense Short-Term Chemoimmunotherapy in HIV-Positive Patients with Burkitt Lymphoma (HIV-BL pts): Final Results of the Carmen Phase II Trial
Authors: Andrés J M Ferreri, Michele Spina, Chiara Cattaneo, Luisa Verga, Bernardino Allione, Daris Ferrari, Luigi Rigacci, Luca Fumagalli, Giovanni Donadoni, Arben Lleshi, Marianna Sassone, Giuseppe Rossi, Alessandro Re
Journal: Blood (2017)
A novel locus for exertional dyspnoea in childhood asthma
Authors: Sanghun Lee, Jessica Ann Lasky-Su, Christoph Lange, Wonji Kim, Preeti Lakshman Kumar, Merry-Lynn N. McDonald, Carlos A. Vaz Fragoso, Cecelia Laurie, Benjamin A. Raby, Juan C. Celedón, Michael H. Cho, Sungho Won, Scott T. Weiss, Julian Hecker
Journal: European Respiratory Journal (2020)

Most children diagnosed with asthma have respiratory symptoms such as cough, dyspnoea and wheezing, which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated genetic susceptibility to asthma itself, but few have focused on important respiratory symptoms that characterise childhood asthma. Using whole-genome sequencing (WGS) data for 894 asthmatic trios from a Costa Rican cohort, we performed family-based association tests (FBATs) to assess the association between genetic variants and multiple asthma-relevant respiratory phenotypes: cough, phlegm, wheezing, exertional dyspnoea and exertional chest tightness. We tested whether genome-wide significant associations were replicated in two additional studies: 1) 286 asthmatic trios from the Childhood Asthma Management Program (CAMP), and 2) 2691 African American current or former smokers from the COPDGene study. In the 894 Costa Rican trios, we identified a genome-wide significant association (p=2.16×10 −9 ) between exertional dyspnoea and the single nucleotide polymorphism (SNP) rs10165869, located on chromosome 2q37.3, that was replicated in the CAMP cohort (p=0.023) with the same direction of association (combined p=3.28×10 −10 ). This association was not found in the African American participants from COPDGene. We also found suggestive evidence for an association between SNP rs10165869 and the atypical chemokine receptor 3 ( ACKR3 ). Our finding encourages the secondary association analysis of a wider range of phenotypes that characterise respiratory symptoms in other airway diseases/studies.
Respiratory follow-up of patients with COVID-19 pneumonia
Authors: Peter M George, Shaney L Barratt, Robin Condliffe, Sujal R Desai, Anand Devaraj, Ian Forrest, Michael A Gibbons, Nicholas Hart, R Gisli Jenkins, Danny F McAuley, Brijesh V Patel, Erica Thwaite, Lisa G Spencer
Journal: Thorax (2020)

The COVID-19 pandemic has led to an unprecedented surge in hospitalised patients with viral pneumonia. The most severely affected patients are older men, individuals of black and Asian minority ethnicity and those with comorbidities. COVID-19 is also associated with an increased risk of hypercoagulability and venous thromboembolism. The overwhelming majority of patients admitted to hospital have respiratory failure and while most are managed on general wards, a sizeable proportion require intensive care support. The long-term complications of COVID-19 pneumonia are starting to emerge but data from previous coronavirus outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) suggest that some patients will experience long-term respiratory complications of the infection. With the pattern of thoracic imaging abnormalities and growing clinical experience, it is envisaged that interstitial lung disease and pulmonary vascular disease are likely to be the most important respiratory complications. There is a need for a unified pathway for the respiratory follow-up of patients with COVID-19 balancing the delivery of high-quality clinical care with stretched National Health Service (NHS) resources. In this guidance document, we provide a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia. We define two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge. To mitigate NHS pressures, virtual solutions have been embedded within the pathway as has safety netting of patients whose clinical trajectory deviates from the pathway. For all patients, we suggest a holistic package of care to address breathlessness, anxiety, oxygen requirement, palliative care and rehabilitation.
Phase II study of pemetrexed (P) and gemcitabine (G) in patients with advanced head and neck cancer (SCCHN)
Authors: R. Mehra, E. Sherman, K. Ruth, S. Litwin, J. Sylvester, H. Tuttle, B. Burtness, R. B. Cohen, C. Langer
Journal: Journal of Clinical Oncology (2009)

6052 Background: Unresectable/metastatic squamous cell cancer of the head and neck (SCCHN) has a poor prognosis despite standard therapy with cisplatin. Given the substantial toxicities of cisplatin and its widespread use in combination with RT in LA- SCCHN, we investigated an alternative regimen of gemcitabine (G) and pemetrexed (P). A phase II study of pemetrexed in SCCHN had a response rate (RR) of 26.5%. A phase I study of the P and G combination showed the doses and schedule below to be feasible. Methods: Eligibility stipulated measurable, incurable, unresectable recurrent/metastatic SCCHN; Karnofsky PS of &gt; 60%, and adequate bone marrow, renal and hepatic function. One prior therapy for recurrent disease was allowed. Patients were treated with P 500 mg/m 2 and G 1,500 mg/m 2 every 2 weeks. Each cycle was 28 days. Primary endpoint was RR. Secondary endpoints included overall survival and toxicity. Patients were re-imaged every 2 cycles. In a 2-step design, 16 patients were to be accrued during stage 1, and 16 were projected for stage 2. If 1 or fewer responses were observed during the first stage, then the trial was to be stopped and the regimen deemed insufficiently active. Results: 17 patients were enrolled in stage 1. Median age was 64 years (range, 49–82); 10 males; 13 smokers (including 4 current smokers). 15 patients previously received definitive therapy with surgery and/or chemo-RT, and 9 had prior systemic therapy for recurrent/metastatic disease. Median number of cycles administered was 2 (range, &lt;1 to 10). Reasons for treatment discontinuation included progressive disease in 15 patients and decreased PS in 1. Grade 3 toxicities included neutropenia (1), anemia (3), thrombocytopenia (1), dysphagia (11), fatigue (4), hypertension (4), and hyperglycemia (4). 1 pt had grade 4 anemia. Best response: 1 confirmed PR, 1 unconfirmed PR, 3 SD, 10 PD, 2 not evaluable. 7 patients received subsequent treatment. Estimated median overall survival is 5.5 months. Conclusions: The combination of P and G for advanced HNSCC was well tolerated, but its clinical efficacy was marginal in an unselected population. Due to early stopping rules, the study was closed to accrual after stage 1 for lack of efficacy. Further study of this regimen should be considered in patients enriched for TS and RRM1 status. [Table: see text]
Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial
Authors: Kati Mokkala, Niklas Paulin, Noora Houttu, Ella Koivuniemi, Outi Pellonperä, Sofia Khan, Sami Pietilä, Kristiina Tertti, Laura L Elo, Kirsi Laitinen
Journal: Gut (2020)

Objective Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics. Design The gut microbiota of 270 overweight/obese women participating in a mother–infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test. Results Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions. Conclusions The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.
Sex Differences in Coronary Computed Tomography Angiography–Derived Fractional Flow Reserve
Authors: Timothy A. Fairbairn, Rebecca Dobson, Lyne Hurwitz-Koweek, Hitoshi Matsuo, Bjarne L. Norgaard, Niels Peter Rønnow Sand, Koen Nieman, Jeroen J. Bax, Gianluca Pontone, Gilbert Raff, Kavitha M. Chinnaiyan, Mark Rabbat, Tetsuya Amano, Tomohiro Kawasaki, Takashi Akasaka, Hironori Kitabata, Sukumaran Binukrishnan, Campbell Rogers, Daniel Berman, Manesh R. Patel, Pamela S. Douglas, Jonathon Leipsic
Journal: JACC. Cardiovascular imaging (2020)

This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)–derived fractional flow reserve (FFRCT) according to sex. Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFRCT improves sex-based patient management decisions compared to CCTA alone is unknown. Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFRCT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFRCT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates. A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFRCT. Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFRCT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFRCT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFRCT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFRCT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm3/g vs. 24.76 ± 7.22 mm3/g; p < 0.0001) that is associated with higher FFRCT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFRCT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284). FFRCT differs between the sexes, as women have a higher FFRCT for the same degree of stenosis. In FFRCT-positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFRCT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679)
Randomized Study of CPX-351 for Medically Less-Fit Adults with Newly Diagnosed Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasm
Authors: Roland B. Walter, Megan Othus, Kaysey F. Orlowski, Emily N. McDaniel, Bart L. Scott, Pamela S. Becker, Mary-Elizabeth M. Percival, Paul C. Hendrie, Bruno C Medeiros, Michael T. Chiarella, Arthur C. Louie, Elihu H. Estey
Journal: Blood (2017)
Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective Cohort
Authors: Peng Xia, Yubing Wen, Yaqi Duan, Hua Su, Wei Cao, Meng Xiao, Jie Ma, Yangzhong Zhou, Gang Chen, Wei Jiang, Huanwen Wu, Yan Hu, Sanpeng Xu, Hanghang Cai, Zhengyin Liu, Xiang Zhou, Bin Du, Jinglan Wang, Taisheng Li, Xiaowei Yan, Limeng Chen, Zhiyong Liang, Shuyang Zhang, Chun Zhang, Yan Qin, Guoping Wang, Xuemei Li
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Coronavirus disease 2019 (COVID-19) is a new contagious disease. Previous studies reported AKI with varying results regarding the incidence, severity, and outcomes. This study provides detailed clinical data of 81 patients critically ill with COVID-19 and a prolonged disease course, and provides renal pathologic findings from ten deceased patients with AKI in a single intensive care unit in Wuhan, China. The incidence of AKI was 50.6%, with 41.5% of cases of AKIs were Kidney Disease Improving Global Outcomes (KDIGO) stage 3. The primary pathological findings were those of acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. Older age and serum IL-6 levels were risk factors of AKI. KDIGO stage 3 AKI independently predicted death. Background The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail. Methods This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI. Results A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5–26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P =0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P =0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. Conclusions AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.
β-Catenin regulates tumor-derived PD-L1
Authors: Chuanhui Han, Yang-Xin Fu
Journal: The Journal of Experimental Medicine (2020)

In this issue of JEM, Du et al. (https://doi.org/10.1084/jem.20191115) report that enhancement of the β-catenin signaling by Wnt or EGF treatment increases the expression of PD-L1 in an AKT and β-catenin–dependent manner, and blocking the AKT pathway synergizes with anti–PD-1 in a glioblastoma model.
Effect of adherence to monthly zoledronic acid treatment on risk and frequency of skeletal complications and follow-up duration in breast cancer patients
Authors: H. T. Hatoum, S. Lin, M. R. Smith, A. Lipton
Journal: Journal of Clinical Oncology (2009)

9593 Background: Bone is the most common site of metastasis in breast cancer patients (pts). Clinical trials and outcome studies have demonstrated benefit of zoledronic acid (ZA) in reducing risk of skeletal complications (SC). This study explored relationships between persistency on ZA and the intended treatment (TX) outcomes. Methods: Female breast cancer pts with first bone metastasis (BM) diagnosed between Jan 03 to Oct 06 were identified from PharMetrics database. Persistency was defined as duration from initiating ZA TX to date of first TX gap of &gt;45 days. Pts were divided into short (≤90 days, 230 pts), medium (91–180, 171 pts) and long (&gt;180, 313 pts) persistency groups. TX selection bias was handled by calculating propensity scores using year of first BM diagnosis, having other metastases or &gt;1 BM claim, use of opioids and oral bisphoshonate before BM. Propensity scores, age and Charlson's Comorbidity Index (CCI) were included in multiple regressions to investigate impact of ZA persistency on follow-up duration, risk and rate of SC. Results: 2394 pts were enrolled, with 714 (29.72%) ZA treated. Three persistency groups had similar age. Short group had higher CCI than long group (mean 8.53 vs 8.34, p&lt;0.05). Frequency of ZA TX decreased over time in all groups. For short, medium and long persistency groups, means of follow-up durations were 9.8 (median, 7.0), 13.0 (9.0), 19.3 (18.1) months, and means of time to first SC after BM were 249 (median: 167), 323 (217), 418 (365) days. Means of SC rates were 0.27, 0.21, and 0.12 per month for patients who experienced at least 1 SC among the three groups. Medium and long persistency groups had 41% and 139% longer follow-up than short group (p&lt;0.05). Long group had lower risk of SC than short group (HR=0.576, p&lt;0.05). In patients who developed at least 1 SC, long group experienced 39% less SCs (p&lt;0.005) than short group. Conclusions: TX with zoledronic acid in breast cancer pts with BM positively impacts the risk, frequency of SC and follow-up duration. Also, longer persistency on ZA TX is associated with significantly longer follow-up and lower risk of SC. [Table: see text]
Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations
Authors: Michelle C. Turner, Zorana J. Andersen, Andrea Baccarelli, W. Ryan Diver, Susan M. Gapstur, C. Arden Pope, Diddier Prada, Jonathan Samet, George Thurston, Aaron Cohen
Journal: CA A Cancer Journal for Clinicians (2020)

Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health-based air-quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution-derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described.