tbuckley/cabot-search huggingface dataset:
Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients
Authors: Frances Humby, Myles Lewis, Nandhini Ramamoorthi, Jason A Hackney, Michael R Barnes, Michele Bombardieri, A. Francesca Setiadi, Stephen Kelly, Fabiola Bene, Maria DiCicco, Sudeh Riahi, Vidalba Rocher, Nora Ng, Ilias Lazarou, Rebecca Hands, Désirée van der Heijde, Robert B M Landewé, Annette van der Helm-van Mil, Alberto Cauli, Iain McInnes, Christopher Dominic Buckley, Ernest H Choy, Peter C Taylor, Michael J Townsend, Costantino Pitzalis
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally. Methods 144 consecutive treatment-naïve early RA patients (&lt;12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression. Results Cellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) d iffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression. Conclusions We demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.
Abstract P323: Youth Characteristics Related to Participation in Accelerometer-Measured Physical Activity
Authors: Erin M Delker, Patricia East, David Wing, Raquel Burrows, Susanne Reyes, Patricio Peirano, Cecilia Algarin, Sheila Gahagan
Journal: Circulation (2019)

Introduction: Accelerometer-measured physical activity is considered the ‘gold standard’ of physical activity (PA) measurement. However, previous studies have found that adults in accelerometer studies are more likely to be male, healthier and employed. Little is known about the correlates of participation among youth. We assessed characteristics associated with participation in accelerometer-measured PA among a cohort of healthy Chilean adolescents. Methods: Participants were 670 youth from an ongoing observational study who have been studied since infancy. The adolescent follow-up included measurement of PA with a hip-accelerometer worn for ≥10 hrs/day for ≥5 days or ≥3000 min over a 4-day period. We used multinomial logistic regression to evaluate socioeconomic, lifestyle, and cardiometabolic factors associated with providing sufficient accelerometry data (“Completers”), insufficient data (“Incompleters”), and not participating (“Non-participants”) in adolescence. Results: The study sample was 47% female and 17 years of age. About 33% (n=223) were Completers, 10% (n=68) were Incompleters, and 57% (n=379) were Non-participants. Completers reported lower neighborhood crime, 50% less cigarette and alcohol use, had healthier diets, healthier cholesterol, and mothers with higher IQs compared to the other two groups (all p&lt;0.05). Incompleters did not significantly differ from Non-participants. Conclusions: Participants providing complete accelerometer data were not representative of the full sample; they had healthier behaviors and perceived less neighborhood crime. There may be additional unmeasured variables, such as attitudes towards the wearable device, that contributed to participation. Selective participation in studies using accelerometry inhibits generalizability and threatens internal validity when analyzing PA as a predictor of cardiometabolic outcomes. More effort is needed in the design of studies to reduce incomplete and refused participation in accelerometry.
Abstract 24055: Naturally Occurring Hypertension is Related to Cardiac Diastolic Dysfunction in Rhesus Monkeys
Authors: Yinan Liang, Zunyuan Yang, Zunwei Yao, Li Gong, Zhigang Liang, Yubo Shen, Yuanhai Chen, Wen Zeng, Barbara C Hansen
Journal: Circulation (2017)

Introduction: The lack of effective treatment for Diastolic Dysfunction (DD) is partially due to the differences between widely used preclinical rodent models and humans in the physiology and function of the heart. In previous studies, we have demonstrated that rhesus monkeys with naturally occurring adult onset Type 2 Diabetes (T2DM) frequently have DD that is similar in characteristics to DD in diabetic patients. To further characterize DD in rhesus monkeys, we studied the relationship between hypertension and DD, and evaluated the response of rhesus monkeys with DD to Entresto (sacubitril/valsartan). Methods: Blood pressure, fasting plasma glucose and cardiac function were measured in 322 adult rhesus monkeys ( Macaca mulatta , 7-22 yrs) under light anesthesia with ketamine. Monkeys with LV hypertrophy, e'&lt;8 cm/s and E/e'&gt;10 were defined as DD. Ten monkeys with DD were enrolled in the validation study and divided into the Entresto group (n=5) and the vehicle group (n=5). Cardiac function and blood pressure were measured before and at the end of 13 weeks of treatment. Results: Among the 322 adult rhesus monkeys studied, 53 monkeys (16.46%) had SBP&gt;140 mm Hg or DBP&gt;90 mm Hg. Among the 174 monkeys with fasting glucose &gt;80 mg/dL, 67 monkeys had isolated DD, and 8 had DD+ SD (systolic dysfunction). The incidence of isolated DD was 31% in monkeys with SBP&lt;140 mm Hg and 74% in monkeys with SBP&gt;140 mm Hg. Following Entresto administration (1.66 to 13.33 mg/kg) for 13 weeks, DD and BP evaluation showed an increase of e’ (5.27±0.51 to 6.43±1.27 cm/s), a decrease of E/e’ (12.74±2.23 to 10.53±2.09) and a decrease of SBP (128±5 to 113±16 mm Hg). These parameters remained stable and unchanged in the vehicle group. Conclusions: The incidence of naturally occurring hypertension in adult rhesus monkeys was similar to that in adult humans. Entresto reduced blood pressure, but led to no significant improvement of DD in monkeys. The extent of change in rhesus monkeys was similar to that observed in clinical trials. In rhesus monkeys, as in patients, hypertension is significantly related to cardiac diastolic dysfunction. These monkeys, therefore, provide important new opportunities to understand the pathogenesis of DD, as well as to predict the human response to new therapeutic agents.
The advantages of adding rib fixations during VATS for retained hemothorax in serious blunt chest trauma – A prospective cohort study
Authors: Hsing-Lin Lin, Yih-Wen Tarng, Tung-Ho Wu, Fong-Dee Huang, Wen-Yen Huang, Yi-Pin Chou
Journal: International Journal of Surgery (2019)

Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fracture. Early video-assisted thoracoscopic surgery (VATS) to evacuate retained hemothorax is one commonly used treatment. In this study, a new strategy was implemented to combine VATS with fractured rib fixation simultaneously.This prospective observational study was performed from January 2013 to April 2018. All patients were aged 18 years or older and had blunt chest trauma with displaced fractures in more than three ribs. No patients had acute respiratory failure within 24 h after trauma. Patients with retained hemothorax who received VATS constituted the study cohort. Subsequently, patients who received rib fixation during VATS procedures were compared with those who did not. Clinical outcomes such as dose of analgesics, and length of hospital stay were recorded.During the study period, 128 patients were enrolled. Available demographic characteristics of the 2 groups were compared, and no statistical differences were observed. The rates of shorter temporary ventilator dependence after operations were lower in the rib fixation group (0% vs. 24.7%, P = 0.017). Persistent air leakage more than 5 days after operations were also lower in the rib fixation group (0% vs. 10.4%, P = 0.001). The length of stay in overall hospital stay were longer for patients who received VATS without rib fixation (9.29 ± 2.51 days vs. 12.39 ± 4.65, P = 0.001). Furthermore, the rib fixation group were administered much lower doses of opiates during their hospital stays (52.45 ± 15.67 mg vs. 77.24 ± 50.42 mg, P = 0.001).Adding rib fixation during VATS in the management of retained hemothorax can contribute to shorten whole treatment courses. Rib fixation can also reduce pain, thus reducing dependence on analgesics.
Evaluation of Journal Registration Policies and Prospective Registration of Randomized Clinical Trials of Nonregulated Health Care Interventions
Authors: Marleine Azar, Kira E. Riehm, Nazanin Saadat, Tatiana Sanchez, Matthew Chiovitti, Lin Qi, Danielle B. Rice, Brooke Levis, Claire Fedoruk, Alexander W. Levis, Lorie A. Kloda, Jonathan Kimmelman, Andrea Benedetti, Brett D. Thombs
Journal: JAMA Internal Medicine (2019)

Many interventions that are important to the health care of patients are not subject to regulation by the US Food and Drug Administration (FDA) or comparable regulatory bodies in other nations.To determine whether specialty journals that publish trials of primarily nonregulated health care interventions require prospective registration and whether the prospective registration policies are associated with the publication of prospectively registered trials, trials with adequately registered outcomes, and trials with primary outcomes consistent with the registered primary outcomes.PubMed was searched daily, from March 18, 2016, to September 17, 2016, for nonregulated intervention randomized clinical trials. The search included all journals in the Clarivate Analytics Science Citation Index Expanded categories of behavioral sciences, nursing, nutrition and dietetics, psychology, rehabilitation, and surgery. Trials of interventions not subject to FDA regulation were included. One investigator extracted journal registration policy and trial registration status. Two investigators independently extracted trial registration and publication characteristics.For journals, the main outcome was the trial registration policy. For trials, the main outcomes were prospective registration, adequacy of outcome registration, and concordance of registered with published primary outcomes.In total, 953 nonregulated intervention trials published in 254 journals were identified. Prospective registration was required for publication by 29 (11.4%) of 254 journals, and an additional 12 journals (4.7%) had conditional date-based requirements. Only 189 (19.8%) of the 953 trials were registered prospectively, including 33 of 98 published in journals with prospective registration policies as compared with 156 of 855 in journals without policies (33.7% vs 18.2%; P = .004). Among the 17 journals that required prospective registration and had at least 2 included trials, none had a prospective registration of more than 50%. In journals with policies, only 3 of 98 trials included primary outcomes consistent with prospectively, adequately registered outcomes, as compared with 34 of 852 trials in journals without policies (3.1% vs 4.0%; P = .62).Few journals in behavioral sciences or psychology, nursing, nutrition and dietetics, rehabilitation, and surgery require prospective trial registration, and those with existing registration policies rarely enforce them; this finding suggests that strategies for encouraging prospective registration of clinical trials not subject to FDA regulation should be developed and tested.
Abstract O.08: Rashless Kawasaki Disease (KD): Colorado’s Experience
Authors: Marsha S Anderson, Samuel R Dominguez, Heather R Heizer, Pei-Ni Jone, Jesse Davidson, Mary P Glode
Journal: Circulation (2015)

Objective: Published studies describe Incomplete KD, but rashless KD has not been well characterized. We describe a 10 year experience with rashless KD patients, diagnosed based on the presence of a compatible illness and coronary artery lesions (CALs). Methods: We prospectively collected cases of rashless KD with CALs diagnosed at Children’s Hospital Colorado from 7/1/2004-6/30/2014. Patient charts were reviewed for demographic, clinical, laboratory, and diagnostic information. Results: 11 patients were identified (median age 3.7 yrs), representing 10.3% (11/107) of all KD patients with CALs diagnosed during the same time period. Diagnosis was made on median day of illness (DOI) 8 (range 4-17 days), and patients had a median of 4 (range 2-7) healthcare contacts prior to diagnosis. All patients (100%) had the presence or history of conjunctival injection and 8/11 (72.7%) had oral changes. Five patients had only 2 major clinical features in addition to fever; 1 patient had one. All patients had very elevated inflammatory markers. Infectious Disease consultants suspected KD and recommended treatment prior to echocardiogram (ECHO) results in 8/11 (72.7%), recommended treatment if ECHO abnormal in 2/11 (18.1%), and in 1/11 (9.2%) KD was thought to be unlikely, but the diagnosis was made by ECHO. Conclusions: 10.3% of KD patients with CALs at our institution presented without a rash. As rash is often considered a defining characteristic of KD, some children with rashless KD are likely not being identified and treated. Providers should consider the diagnosis of KD in patients with unexplained fever, conjunctivitis, and elevated inflammatory markers.
Genetic counseling processes and outcomes among prostate cancer patients (ProGen).
Authors: Donna Rachel Vatnick, Sandjida Aktar, Jill E. Stopfer, Lindsay Kipnis, Samantha K. Culver, Diane R. Koeller, Alexander E. Husband, Kyle Allen, Kerry L. Kilbridge, Bradley Alexander McGregor, Christopher Sweeney, Virginia Speare, Brigette Tippin Davis, Jill S. Dolinsky, Judy Ellen Garber, Huma Q. Rana, Mary-Ellen Taplin, Mark Pomerantz
Journal: Journal of Clinical Oncology (2019)

TPS343 Background: Prostate cancer (PC) is among the leading causes of cancer mortality in males. Recent studies found 8-12% of advanced PC cases may be hereditary. Germline mutations have been reported in BRCA1/2, other DNA repair genes including ATM, CHEK2, PALB2 and DNA mismatch repair genes. Genetic testing can inform treatment decisions including drug targeting, such as PARP inhibitors for men with BRCA mutations, and checkpoint inhibitors for those with pathogenic mutations in mismatch repair genes 2 . Discovering a pathogenic mutation associated with increased cancer risk also prompts dissemination of this information to family, where subsequent testing can lead to risk stratification and impactful opportunities for cancer screening and prevention. It is critical that men with high risk and potentially lethal prostate cancer routinely be offered genetic testing as a component of their cancer care. Genetic counseling services are limited, and more efficient services are needed. Methods: We are investigating video education prior to genetic testing compared with in-person pretest counseling with a licensed genetic counselor (GC). ProGen is an ongoing randomized trial evaluating two distinct models of cancer genetics service delivery in 450 PC cases over a two-year period. The study is conducted in collaboration with Ambry Genetics utilizing a 67-gene cancer panel. The primary aim is analysis of the proportion and type of germline mutations identified. Secondary aims include testing uptake by arm, evaluation of distress, knowledge, satisfaction with testing services, family communication, and impact on cancer care. Results are communicated by telephone with a GC. Inclusion criteria are: potentially lethal PC (metastatic, localized with Gleason score ≥8, rising/persistent PSA after local therapy), early diagnosis (≤ 55 years), prior malignancy, and/or family history potentially indicating a hereditary cancer risk. Enrollment is 74% completed at a single institution. (NCT03328091). 1 Pritchard CC, et al. Inherited DNA‐repair gene mutations in men with metastatic prostate cancer. NEJM. 2016;375:443 2 Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. NEJM . 2015;373(18):1697-1708 Clinical trial information: NCT03328091.
Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality
Authors: Victor W. Zhong, Linda Van Horn, Marilyn C. Cornelis, John T. Wilkins, Hongyan Ning, Mercedes R. Carnethon, Philip Greenland, Robert J. Mentz, Katherine L. Tucker, Lihui Zhao, Arnita F. Norwood, Donald M. Lloyd-Jones, Norrina B. Allen
Journal: JAMA (2019)

<h3>Importance</h3> Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial. <h3>Objective</h3> To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality. <h3>Design, Setting, and Participants</h3> Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol. <h3>Exposures</h3> Dietary cholesterol (mg/day) or egg consumption (number/day). <h3>Main Outcomes and Measures</h3> Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors. <h3>Results</h3> This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all<i>P</i>values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, −0.47% [95% CI, −1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, −0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption. <h3>Conclusions and Relevance</h3> Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.
Prognostic markers at adolescence in patients requiring liver transplantation for biliary atresia in adulthood
Authors: Vandana Jain, Charlotte Burford, Emma C Alexander, Harry Sutton, Anil Dhawan, Deepak Joshi, Mark Davenport, Nigel Heaton, Nedim Hadzic, Marianne Samyn
Journal: Journal of Hepatology (2019)
Safety and feasibility of nephrectomy after receipt of immune checkpoint inhibitors for renal cell carcinoma.
Authors: Nirmish Singla, Roy Elias, Rashed Ghandour, Yuval N Freifeld, Alex Isaac Bowman, Solomon L. Woldu, Jeffrey Gahan, Aditya Bagrodia, James Brugarolas, Hans J. Hammers, Vitaly Margulis
Journal: Journal of Clinical Oncology (2019)

619 Background: With the approval of immune checkpoint inhibitors (ICI) for metastatic renal cell carcinoma (RCC), the role, timing, and safety of surgically excising the primary tumor remain unclear. We sought to evaluate the safety and feasibility of nephrectomy following receipt of ICI for RCC. Methods: We reviewed our experience of RCC patients who underwent nephrectomy from 2016-2018 following exposure to nivolumab or combination ipilimumab/nivolumab. Demographics, IMDC risk score, and pathology were collected. Surgical outcomes including operative time (OT), estimated blood loss (EBL), hospital length of stay (LOS), readmission rates, and 30- and 90-day complication rates were analyzed using descriptive statistics. Results: 11 nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 98 days. 6 patients received 1-4 cycles of ipilimumab/nivolumab, while 5 received 2-12 infusions of nivolumab preoperatively. One patient with non-metastatic, synchronous bilateral renal masses underwent staged left radical nephrectomy and right partial nephrectomy. 5 surgeries were performed laparoscopically, and 4 patients underwent thrombectomy. IMDC score for metastatic patients was intermediate (7/9) or poor (2/9). One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 mL, and 4 days, respectively. One patient died of progressive disease &gt; 3 months after surgery; one patient required thoracentesis and another required paracentesis of a sterile fluid collection in the hepatic resection bed. No complications were noted in the remaining 7 patients, none of whom required readmission. Conclusions: Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. As multimodal management in the era of ICI continues to evolve, use of neoadjuvant ICI for selected patients may warrant attention.