tbuckley/cabot-search huggingface dataset:
AB0111 Prognostic significance of limited and difusse form of skin changes in systemic sclerosis
Authors: N Damjanov, G Dobrosavljevic, S Pavlov, G Radunovic, I Djurdjic, N Todorvic, M Milenkovic, P Ostojic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To assess the difference in frequency of pulmonary and renal involvement, as well as lungs insufficiency and renal failure between patients (pts) with limited cutaneous Systemic Sclerosis (lcSSc) and difusse cutaneous Systemic Sclerosis (dcSSc). <h3>Methods</h3> Group of 138 pts with Systemic Sclerosis (SSc), 127 females and 11 males, age 28–75 years (median 53), were followed for 3–26 (median 13) years period. Extent of skin involvement was recorded, and pts were examined for radiographic signs of pulmonary fibrosis, carbon monoxide transfer (TCO) factor (done in 28 pts), and renal involvement and failure (urine sediment, creatinin clearance, arterial tension). Difference of visceral involvement, pulmonary insufficiency and renal failure between pts with lcSSc and dcSSc was correlated. <h3>Results</h3> Among 138 pts, 105(76%) had lcSSc, and 33(24%) dcSSc. Pulmonary lession were found in 40/105 pts with lcSSc, and in 25/33 pts with dcSSc (p = 0,004-χ<sup>2 </sup>test). Renal lession was detected in 11/105 pts with lcSSc, and in 8/33 pts with dcSSc (p = 0,04-χ<sup>2 </sup>test). Signs of lung insufficiency developed in 30/105 pts with lcSSc, and in 18/33 pts with dcSSc (p = 0,04-χ<sup>2 </sup>test). Lower creatinin clearance and high arterial blood preasure were detected in all patients with recorded renal lession during the follow up period (in 11/105 pts with lcSSc, and in 8/33 pts with dcSSc). Renal failure was significantly more frequent in dcSSc pts (p = 0,04-χ<sup>2 </sup>test). In 7(21%) pts with dcSSc no criteria for pulmonary and renal involvement were present during the follow up period. On the other hand, in 14(13%) pts with lcSSc pulmonary insufficiency or renal. <h3>Conclusion</h3> Difusse cutaneous lessions were prognostic sign of lungs and kidneys involvement, as well as pulmonary insufficiency and renal failure in most of the patients, but about 20% of the dcSSc patients were without severe visceral lessions during the 13 years of follow up period. On the other hand, 13% of patients with limited cutaneous lessions had bad prognosis and developed pulmonary insufficiency or renal failure in first 5 years of disease duration.
De Novo Presentation of Sarcoidosis on Restaging FDG PET/CT in Rectal Carcinoma With Self-resolution
Authors: Sampath Santhosh, Godwin Jeeva, Raja Thirumalairaj
Journal: Clinical Nuclear Medicine (2020)

Sarcoidosis is a systemic disorder of unknown etiology characterized by development of noncaseating granulomas in more than 1 organ system. Development of sarcoidosis during or immediately after chemotherapy and immunotherapy is not uncommon. We present a 61-year-old woman in whom restaging F-FDG PET/CT detected asymptomatic sarcoidosis after neoadjuvant chemoradiotherapy for carcinoma rectum, which resolved spontaneously by the end of adjuvant chemotherapy with no specific treatment. Recognition of anatomic-metabolic pattern of sarcoidosis could prevent erroneous upstaging of the primary malignancy during restaging PET/CT following chemotherapy, and such lesions may show self-resolution.
Breaking the wave of peri‐implantitis
Authors: Jia‐Hui Fu, Hom‐Lay Wang
Journal: Periodontology 2000 (2020)

Abstract Peri‐implant diseases are prevalent with a weighted mean prevalence rate of 43% across Europe and 22% across South and North America. Although the main etiologic agent is bacterial biofilm, a myriad of factors influence the initiation and progression of the disease. Unfortunately, the treatment of peri‐implant diseases is at best favorable in the short term with a high rate of persistent inflammation and recurrence. Therefore, it is sensible to consider and control all potential factors that may predispose an implant to peri‐implant tissue inflammation in an attempt to avoid the disease. This paper reviews recent evidence on factors that may predispose implants to peri‐implantitis and measures that can be taken to prevent it.
Covering covid-19: stories from <i>The BMJ</i> ’s news desk
Authors: Anna Harvey
Journal: BMJ (2020)

The covid-19 pandemic has been the biggest public health crisis of a generation.The avalanche of media around the disease-19 has been dubbed an "infodemic."Anyone can turn on their smartphone and access more information on the covid-19 outbreak than they could consume in a lifetime.Although other groups of essential workers hit headlines, it might be easy to forget the group of key workers who put them there-the journalists and editors who produce the media we consume.
The Changing Characteristics of Technologies Covered by Medicare’s New Technology Add-on Payment Program
Authors: Christopher R. Manz, Justin E. Bekelman, Jalpa A. Doshi
Journal: JAMA Network Open (2020)

This economic evaluation explores how Medicare’s new technology add-on payment program (NTAP), which provides reimbursement for newly available drugs and devices, has changed during its lifetime since its initiation in 2013.
TRAIL and Cancer Immunotherapy: Take a Walk on the Short Side
Authors: Diego de Miguel, Julian Pardo
Journal: Clinical Cancer Research (2020)

Recent work shows that TRAILshort, a membrane-bound short form of TRAIL, is expressed by human cancer cells and protects them from TRAIL-induced cell death. A mAb that selectively targets TRAILshort enhances cancer susceptibility to TRAIL and increases the efficacy of autologous CD8+ T cells in ex vivo primary tumors.See related article by Aboulnasr et al., p. 5759.
Durvalumab activity in previously treated patients who stopped durvalumab without disease progression
Authors: Siddharth Sheth, Chen Gao, Nancy Mueller, Natasha Angra, Ashok Gupta, Caroline Germa, Pablo Martinez, Jean-Charles Soria
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Limited data exist on potential clinical benefit with anti-programmed cell death ligand-1 (PD-L1) retreatment in patients who stop initial therapy for reasons other than disease progression or toxicity and develop disease progression while off treatment. Patients and methods NCT01693562 was a phase I/II study evaluating durvalumab monotherapy in advanced solid tumors. Patients benefiting from treatment were taken off durvalumab at 1 year per protocol and prospectively followed. At disease progression, they were eligible for durvalumab retreatment. Outcomes evaluated during retreatment included best overall response (BOR2), duration of response (DoR2), disease control rate (DCR2), and progression-free survival (PFS2). Results Of 980 patients enrolled and treated with durvalumab 10 mg/kg every 2 weeks (Q2W) in the dose-expansion cohorts, 168 completed 1 year of initial durvalumab treatment with confirmed BOR1 of complete response in 20 (11.9%), partial response (PR) in 84 (50%), stable disease (SD) in 52 (31%), and disease progression in 12 (7.1%). All 168 patients stopped treatment and were eligible for retreatment at progression; 70 patients (41.7%) representing 14 primary tumor types were retreated and response evaluable. Confirmed BOR2 was PR in 8 patients (11.4%), SD in 42 (60.0%), disease progression in 16 (22.9%), and unevaluable in 4 (5.7%). Median DoR2 was 16.5 months. DCR2 ≥24 weeks (DCR2 24) was 47.1%. PFS2 rate at 12 months was 34.2%, and median PFS2 was 5.9 months. Median overall survival (OS2) was 23.8 months. Response rates, DCR2 24, and median DoR2 were generally greater in patients with high PD-L1 expression than those with low/negative expression. No new safety signals were observed during retreatment. Conclusion Retreatment restored antitumor activity, resulting in high rates of durable disease control with an acceptable safety profile. This evidence supports retreatment of patients who stop anti-PD-L1 therapy for reasons other than progression or toxicity, and supports further investigation.
Incidence, Distribution, and Lethality of Firearm Injuries in California From 2005 to 2015
Authors: Sarabeth A. Spitzer, Veronica A. Pear, Christopher D. McCort, Garen J. Wintemute
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Little is known about nonfatal firearm injuries in the United States, and national estimates based on emergency department samples may not be accurate. <h3>Objective</h3> To describe the incidence and distribution of nonfatal firearm injuries and estimate case fatality ratios (CFRs) for firearm injuries by external cause of injury code within California overall and by race/ethnicity, including an assessment of trends over time and geographic variation within the state. <h3>Design, Setting, and Participants</h3> This serial cross-sectional study used complete statewide data for firearm-related mortality, emergency department visits, and hospitalizations among California residents from January 1, 2005, through December 31, 2015, to analyze incidence, distribution, and CFRs of firearm injury. Data were analyzed from 2018 to 2019. <h3>Exposures</h3> All individuals in California with a firearm injury based on<i>International Classification of Diseases, Ninth Revision</i>or<i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision</i>codes were included. <h3>Main Outcomes and Measures</h3> Counts and rates of nonfatal firearm injuries overall and stratified by external cause, sex, and race/ethnicity; total and clinical CFRs. Clinical CFR was calculated based on individuals treated in emergency departments or hospitals. <h3>Results</h3> Over the study period, there were 81 085 firearm-related emergency department visits and hospitalizations among individuals with a mean (SD) age of 27.5 (11.9) years, 72 567 (89.6%) of whom were men. Nonfatal firearm injuries in California decreased by 38.1% between 2005 and 2015, driven by a 46.4% decrease in assaultive injuries. Self-inflicted injuries and unintentional injuries remained relatively stable. The overall CFR for firearm injuries increased from 27.6% in 2005 to 32.2% in 2015 for a relative increase of 20.7%, while the clinical CFR remained stable between 7.0% and 9.0%. <h3>Conclusions and Relevance</h3> These findings suggest that although the number of firearm injuries has decreased in California, the lethality of these injuries has not. Similar studies from other states could provide more information about these trends nationwide.
COVID-19– versus non–COVID-19–related Acute Respiratory Distress Syndrome: Differences and Similarities
Authors: Clément Brault, Yoann Zerbib, Loay Kontar, Ugo Fouquet, Mathieu Carpentier, Matthieu Metzelard, Thierry Soupison, Bertrand De Cagny, Julien Maizel, Michel Slama
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Central ethics committee might have to face hostile locals
Authors: M I L Watling, J K Dewhurst
Journal: BMJ (1995)

EDITOR,--We welcome the interest being shown in the organisation and operation of local research ethics committees.1 The difficulties experienced in using these committees is a constant irritant to those of us who have to make frequent applications to them.

Some of the problems have apparently fairly simple solutions. The use of a common application form should not be difficult, and such a form is presented in Standard Operating Procedures for Local Research Ethics Committees,2 which was given quasiofficial status by being used in workshops by the …
Multifaceted Effects of Antigen Valency on B Cell Response Composition and Differentiation In Vivo
Authors: Yu Kato, Robert K. Abbott, Brian L. Freeman, Sonya Haupt, Bettina Groschel, Murillo Silva, Sergey Menis, Darrell J. Irvine, William R. Schief, Shane Crotty
Journal: Immunity (2020)
Are We Ready for Hyperthermic Intraperitoneal Chemotherapy in the Upfront Treatment of Ovarian Cancer?
Authors: Raanan Alter, Kiran Turaga, Ernst Lengyel
Journal: JAMA Network Open (2020)

Ziying Lei, MD; Yue Wang, MD; Jiahong Wang, MD; Ke Wang, MD; Jun Tian, MD; Ying Zhao, MD; Lipai Chen, MD; Jin Wang, MD; Jiali Luo, PhD; Manman Jia, MD; Hongsheng Tang, MD; Qingjun He, MD; Quanxing Liao, MD; Xiansheng Yang, MD; Tianpei Guan, MD; Li Wang, MD; Shuzhong Cui, MD, PhD; Chinese Peritoneal Oncology Study Group (Gynecologic Oncology Study Group)
Unplanned hospital admissions as an early surrogate indicator of patient (pt) attrition in phase I trials
Authors: D. S. Tan, A. T. Brunetto, J. Ang, D. Olmos, J. Barriuso, S. Frentzas, H. Arkenau, T. A. Yap, J. S. de Bono, S. B. Kaye
Journal: Journal of Clinical Oncology (2009)

2516 Background: We have previously reported a high Royal Marsden Hospital (RMH) prognostic score (RPS) of 2- 3 predicts 90-day mortality and reduced overall survival (Arkenau et al BJC &amp; EJC 2008). In this study, we explored the significance of unplanned hospital admissions (UHA) as a potential surrogate indicator of poor clinical outcome. Methods: All pts admitted to RMH Phase I Unit, UK, during 2-month intervals over 3 consecutive years were included in this analysis (2005–2007). We collated pt baseline characteristics, demographic and laboratory profiles, reasons for hospital admissions and relevant clinical trial data. Results: A total of 172 pts accounting for 310 admissions were seen on the Phase I unit during the stipulated time periods (amounting to 6 months in total). Median age: 61 years (range: 19–84); male to female admissions ratio 1.3:1. Pts were on trials of single-agent targeted therapies (69%), cytotoxic combinations (26%), vaccine/viruses (3%) and hormonal modulation (2%). Reasons for planned admissions (n=246) included treatment commencement, PK/PD sampling, paired pre/post treatment biopsies and insertion of central lines. 20.6% (64/310) of overall admissions were unplanned: 50 (78%) were due to disease-associated symptoms/complications and 14 (22%) treatment-related toxicities (TRT). 71% of pts with TRT were on cytotoxic combination trials. Median duration of UHA was 2 days (range:1–20) and there was no relation between length of stay and predicted outcome. 78% of pts in the UHA cohort had a high RPS of 2–3 (i.e. poor outcome) vs 43% in patients whose admission was planned (p=0.001). Of pts who required UHA, only 27% resumed their trial drug after recovery. The main statistically significant risk factors for UHA include &gt;2 metastatic sites, (RR 2.6 [1.64 - 4.38], p=0.001), poor performance status (RR 2.47 [1.48 - 3.72] p=0.003), low albumin (RR 2.17 [1.36 - 3.52] p=0.001) and cytotoxic combination trials (RR 1.7 [1.09 - 2.86] p=0.025). Conclusions: Unplanned admissions constitute 20.6% of Phase I inpatients, with the majority being disease rather than treatment-related. Regardless of length of stay, UHA portend poor outcomes for patients who are on treatment, with a risk profile underscoring the importance of pt and trial selection. No significant financial relationships to disclose.
Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma*
Authors: E.E.A.P. Mulder, J.T. Dwarkasing, D. Tempel, A. Spek, L. Bosman, D. Verver, A.L. Mooyaart, A.A.M. Veldt, C. Verhoef, T.E.C. Nijsten, D.J. Grunhagen, L.M. Hollestein
Journal: British Journal of Dermatology (2020)

The Clinicopathological and Gene Expression Profile (CP-GEP) model was developed to accurately identify patients with T1-T3 primary cutaneous melanoma at low risk for nodal metastasis.To validate the CP-GEP model in an independent Dutch cohort of patients with melanoma.Patients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP-GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP-GEP model were calculated, resulting in CP-GEP high risk or low risk for nodal metastasis.In total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP-GEP model had a negative predictive value (NPV) of 90·5% [95% confidence interval (CI) 77·9-96.2], with an NPV of 100% (95% CI 72·2-100) in T1, 89·3% (95% CI 72·8-96·3) in T2 and 75·0% (95% CI 30·1-95·4) in T3 melanomas. The CP-GEP indicated high risk in all T4 melanomas.The CP-GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP-GEP model has shown the potential to reduce SLNB procedures in patients with melanoma.
SAT0248 Pharmacoepidemiological profile of patients treated for osteoarthritis
Authors: F Marchetta, E Degli Esposti, S Buda
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Public health decision makers and healthcare payers have become increasingly interested in collecting epidemiological and economic information to improve the allocation of limited health care resources. <h3>Objectives</h3> The purpose of this preliminary study was to describe a pharmacoepidemiological profile of patients treated for osteoarthritis (OA) by 21 general practitioners in the Local Health Unit (LHU) of Ravenna. <h3>Methods</h3> Retrospective chronological reading of all prescriptions written for OA. All patients receiving a prescription for a NSAID or rofecoxib were included. The computerised data file, housed in the LHU of Ravenna since January 1996, contains all demographic characteristics of each patient (including diagnosis by ICD9 code) as well as the ATC code, number of packs, number of tablets per package, and cost for each drug dispensed. Rofecoxib in comparison to conventional NSAIDs and the frequency of use of GI protective agents (proton pump inhibitors, sucralfate, H2-antagonists, misoprostol, and antiacids) were considered in a period of follow-up lasted from 3 months (rofecoxib) to 18 months (NSAIDs). <h3>Results</h3> A total of 2,935 patients received a treatment on a basis of health assisted population of 26,125 subjects: 2,878 had a NSAID and 57 rofecoxib. Among patients treated with NSAIDs 62% were female and 38% male with a mean age of 63 ± 16 and 59 ± 16 years respectively. The mean age of the patients in therapy with rofecoxib was 69 ± 13 years for female (p = 0.004 vs. NSAIDs) and 62 ± 15 years for male. Sixty-eight percent of patients treated with rofecoxib were female. The distribution by age showed that 68% of all treated patients was over 55 years old. The mean prevalence of treatment for OA was 11%. Patients belonging to the CP group who received also a GPA were treated with a significantly higher number of different NSAIDs versus those treated without a GPA (2.30 ± 1.09 vs. 2.04 ± 1.01, p &lt; 0.001 in patients previously treated and 1.92 ± 0.87 vs. 1.78 ± 0.69, p = 0.018 in patients without previous treatment). <h3>Conclusion</h3> These results confirm previous findings that a large part of elderly population (&gt; = 55 years) suffers from OA and is treated with NSAIDs. The remarkable usage of GI protective agents in these patients leads to a consequent increasing of medical costs. Our preliminary data show that rofecoxib significantly improved resources utilisation reducing the frequency of use of GI protective agents (by 56% to 77%). This study provided a high number of drug utilisation data and suggested that a complete prescriptive reading in general practice might be the basis for a larger future work on pharmacoepidemiology and managed care in OA.
Human-Derived Model Systems in Gynecological Cancer Research
Authors: Kadi Lõhmussaar, Matteo Boretto, Hans Clevers
Journal: Trends in cancer (2020)

Tumors of the FRT represent a major gynecological burden, with high-grade serous ovarian cancer incurring the highest mortality rate.Recent advances in sequencing technology and data mining have started to uncover the complex heterogeneity of gynecological cancers, reshaping our modeling approach.Clinical management and overall 5-year survival rate have not substantially improved, due to decades of unsatisfactory models.Tumor-derived organoids have emerged as an optimal compromise between in vitro and in vivo models, maintaining the flexibility of the former while capturing the complexity of the latter. The human female reproductive tract (FRT) is a complex system that combines series of organs, including ovaries, fallopian tubes, uterus, cervix, vagina, and vulva; each of which possesses unique cellular characteristics and functions. This versatility, in turn, allows for the development of a wide range of epithelial gynecological cancers with distinct features. Thus, reliable model systems are required to better understand the diverse mechanisms involved in the regional pathogenesis of the reproductive tract and improve treatment strategies. Here, we review the current human-derived model systems available to study the multitude of gynecological cancers, including ovarian, endometrial, cervical, vaginal, and vulvar cancer, and the recent advances in the push towards personalized therapy. The human female reproductive tract (FRT) is a complex system that combines series of organs, including ovaries, fallopian tubes, uterus, cervix, vagina, and vulva; each of which possesses unique cellular characteristics and functions. This versatility, in turn, allows for the development of a wide range of epithelial gynecological cancers with distinct features. Thus, reliable model systems are required to better understand the diverse mechanisms involved in the regional pathogenesis of the reproductive tract and improve treatment strategies. Here, we review the current human-derived model systems available to study the multitude of gynecological cancers, including ovarian, endometrial, cervical, vaginal, and vulvar cancer, and the recent advances in the push towards personalized therapy.