tbuckley/cabot-search huggingface dataset:
Is Physiological Equivalent Temperature (PET) a superior screening tool for heat stress risk than Wet-Bulb Globe Temperature (WBGT) index? Eight years of data from the Gothenburg half marathon
Authors: Sofia Thorsson, David Rayner, Gunnar Palm, Fredrik Lindberg, Eric Carlström, Mats Börjesson, Finn Nilson, Amir Khorram-Manesh, Björn Holmer
Journal: British Journal of Sports Medicine (2020)

Background The Wet-Bulb Globe Temperature (WBGT) index is a common tool to screen for heat stress for sporting events. However, the index has a number of limitations. Rational indices, such as the physiological equivalent temperature (PET) and Universal Thermal Climate Index (UTCI), are potential alternatives. Aim To identify the thermal index that best predicts ambulance-required assistances and collapses during a city half marathon. Methods Eight years (2010–2017) of meteorological and ambulance transport data, including medical records, from Gothenburg’s half-marathon were used to analyse associations between WBGT, PET and UTCI and the rates of ambulance-required assistances and collapses. All associations were evaluated by Monte-Carlo simulations and leave-one-out-cross-validation. Results The PET index showed the strongest correlation with both the rate of ambulance-required assistances (R 2 =0.72, p=0.008) and collapses (R 2 =0.71, p=0.008), followed by the UTCI (R 2 =0.64, p=0.017; R 2 =0.64, p=0.017) whereas the WBGT index showed substantially poorer correlations (R 2 =0.56, p=0.031; R 2 =0.56, p=0.033). PET stages of stress, match the rates of collapses better that the WBGT flag colour warning. Compared with the PET, the WBGT underestimates heat stress, especially at high radiant heat load. The rate of collapses increases with increasing heat stress; large increase from the day before the race seems to have an impact of the rate of collapses. Conclusion We contend that the PET is a better predictor of collapses during a half marathon than the WBGT. We call for further investigation of PET as a screening tool alongside WBGT.
A multi-stakeholder platform to prospectively link longitudinal real-world clinico-genomic, imaging, and outcomes data for patients with metastatic lung cancer.
Authors: Michael W Lu, Guneet Walia, Katja Schulze, Michelle Yuri Doral, Sophia L. Maund, Sarah Gaffey, Moran N Cabili, Ariel B. Bourla, Robert J. Green, Eric C. Santos, Roy S. Herbst, Anne C. Chiang, Lee S. Schwartzberg
Journal: Journal of Clinical Oncology (2020)

TPS2087 Background: Making personalized diagnostics and treatments a reality for every cancer patient necessitates comprehensively capturing the patient journey. Real-world data has shown promise for the future of clinical research and advancing precision medicine. However, certain limitations exist such as data quality management as well as bias and confounding factors associated with retrospective analyses. We present a multi-stakeholder platform to prospectively collect and link real-world clinico-genomic, imaging, and outcomes data to longitudinal blood genomic profiling for lung cancer. Methods: This study is enrolling approximately 1000 patients with metastatic non-small cell lung cancer or extensive-stage small cell lung cancer who will initiate standard-of-care systemic anti-neoplastic treatment, regardless of line of therapy, at 20 community oncology and academic practices within the Flatiron Health network. Relevant clinical data points from both structured and unstructured fields will be collected through the electronic health records via technology-enabled abstraction, eliminating the need for case report forms. Digital pathology and clinical images at standard-of-care visits will be collected. Blood samples for circulating tumor DNA (ctDNA) profiling using FoundationOne Liquid will be collected at three timepoints: enrollment, first tumor assessment, and end of treatment. Tumor tissue samples may be submitted at baseline for genomic profiling using FoundationOne CDx. Overall survival follow-up will occur until death, withdrawal of consent, loss to follow-up, or end of study. The objectives are to evaluate 1) the feasibility of building a scalable, prospective platform and 2) the associations between ctDNA and real-world clinical outcomes, including overall survival. Enrollment is ongoing. Clinical trial information: NCT04180176.
老年短暂性脑缺血发作患者颈部大动脉的彩色多普勒超声检测及意义
Authors: 马磊, 封飞, 潘旭东, 石义亭, 李德洋
Journal: BMJ (2004)

对99例老年短暂性脑缺血发作(TIA)患者颈部大动脉进行彩色多普勒超声检查,发现有硬化斑块者70例(发生率71%),且动脉粥样硬化多发生在血管分叉处,不同分型的老年TIA患者其颈部大动脉的病变各有特点。
Is there a high risk of renal dysfunction and the need for its prevention in patients with gynecological cancers after surgery?
Authors: Sergey V. Tumanyan, Tatiana I. Moiseenko, Ekaterina V. Verenikina, Elena M. Frantsiyants, Anna P. Menshenina, Oksana V. Oros, Elizaveta Yu. Sugak
Journal: Journal of Clinical Oncology (2020)

e18037 Background: Renal dysfunction in cancer patients is an urgent problem of clinical practice in oncology which can often challenge the efficacy of anticancer treatment and the disease prognosis. The purpose of the study was to reveal risk factors for renal dysfunction in oncogynecological patients. Methods: A prospective randomized study of the renal function included 174 patients aged 54-82 years with reproductive tumors. The control group included 34 patients with benign uterine tumors. Glomerular filtration rate (GFR) was estimated using the CKD-EPI equation. Results: GFR in the main group was 71.6±2.3 mL/min/1.73m 2 . Renal dysfunction was found in 42.5%. The majority of patients (115 patients, 66.1%) had concomitant diseases classified as modifiable risk factors for the development and progression of chronic kidney disease (KDIGO, 2017), including hypertonic disease in 46.6% (χ 2 = 4.4, p &lt; 0.05), diabetes in 39.1% (χ 2 = 7.9, p &lt; 0.05), cardiovascular diseases in 27.6% (χ 2 = 3.9, p &lt; 0.05), and morbid obesity in 68.9%. This confirmed the decisive importance of hypercholesterolemia, hyperglycemia and hypertension as risk factors for reduced GFR. 52.9% of patients had a combination of these factors, which together with the initial renal dysfunction suggested a high probability of acute renal failure in the perioperative period. Conclusions: The assessment of kidney function in patients with gynecological cancers is required to determine the intensity of treatment in the perioperative period, the general disease prognosis and risks of possible complications.
Serum uric acid level in patients with Parkinson′s disease
Authors: Shuhua Cheng
Journal: BMJ (2019)

回顾性分析112例帕金森病（PD）患者临床资料，与同期101例健康体检者比较，显示PD患者的血清尿酸（UA）水平为（290.2±82.6）μmol/L，低于对照组的（333.9±88.5）μmol/L（P 0.05）。提示PD患者的UA水平较低。
OSU-03012 induces apoptosis of gastric cancer cells through endoplasmic reticulum stress triggered inhibition of Akt and STAT3 signaling pathways.
Authors: Wei Peng, Xia Xu, Xiaoxiang Chen, Jifeng Feng, Bo Shen, Jianwei Lu
Journal: Journal of Clinical Oncology (2020)

e15630 Background: As the chemotherapeutic resistance and postoperative relapse rates of gastric cancer rise year by year, searching for novel chemoprevention compounds has become fairly imminent. 2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide (OSU-03012), a derivative of anti-inflammatory drug celecoxib, has recently been shown to have anti-tumor effects. But its roles and underling mechanisms in gastric cancer is rather unknown. Methods: In this study, we show for the first time that OSU-03012 inhibits the growth and potently induces the apoptosis of gastric cancer cells in vitro in a time- and dose-dependent manner. Results: We demonstrate that OSU-03012 induces cell death through endoplasmic reticulum stress (ERS) mediated up-regulation of PTEN, sequentially followed by the suppression of Akt-STAT3 axis, the activation of the mitochondrial membrane protein Bim, mitochondrial damage and finally the release of the caspase family proteases. Conclusions: Our data provide evidences to support OSU-03012 as a potential therapeutic agent for gastric cancer, which may facilitate further preclinical development of anti-tumor drugs.
Relationship between nocturnal hypoglycemia and cognitive function in aged type 2 diabetic patients
Authors: Yuanyuan Chen, Hua Zhang
Journal: BMJ (2016)

Two hundred and eleven aged patients with type 2 diabetes were enrolled in the study. Blood glucose levels were monitored with continuing glucose monitoring system(CGMS) for 3 days and the cognitive function was evaluated with Mini-Mental State Examination(MMSE) scale. The correlation between hypoglycemia(or nocturnal hypoglycemia) and MMSE scores was evaluated. CGMS recorded hypoglycemia in 47% patients(100/211), 82% of whom(82/100) had nocturnal hypoglycemia. Patients with hypoglycemia had lower MMSE scores than those without hypoglycemia(25.1±5.1 vs. 26.8±3.0, P 24(P 24(P<0.05). Stepwise regression analysis showed that the total time and maximal time of hypoglycemia(or nocturnal hypoglycemia), age, and education level were the main factors influencing MMSE scores in aged type 2 diabetic patients(all P<0.05).


Key words: 
Diabetes mellitus, type 2, aged; Nocturnal hypoglycemia; Cognitive disorders; Retrospective study
TP53 mutation analysis in gastric cancer and clinical outcomes of patients with metastatic disease treated with anti-angiogenic or standard chemotherapy regimens.
Authors: Nicholas William Fischer, Francesco Graziano, Irene Bagaloni, Maria Di Bartolomeo, Sara Lonardi, Bruno Vincenzi, Lorenzo Fornaro, Elena Ongaro, Giuseppe Aprile, Renato Bisonni, Michele Prisciandaro, Jean Gariépy, Fotios Loupakis, Donatella Sarti, Michela Del Prete, Vincenzo Catalano, Mauro Magnani, Annamaria Ruzzo
Journal: Journal of Clinical Oncology (2020)

e16571 Background: Current data support the angiogenic potential of cancer cells with mutant p53 and VEGF-A up-regulation in solid tumors. These findings have renewed interest in the p53 role as a predictive/prognostic factor in cancer therapy. We investigated TP53 mutations in gastric adenocarcinoma (GA) samples of metastatic patients (pts) who underwent anti-angiogenic Paclitaxel-Ramucirumab (PR) therapy. The analysis was also performed in a control group of pts who received first-line chemotherapy (CT) with platinum derivates and fluoropyrimidines. Methods: TP53 mutations were identified by next-generation sequencing in 110 GA primary tumors of two retrospective metastatic series including 48 pts who were treated with second-line PR and 62 pts who received first-line CT with Cisplatin or Oxaliplatin plus 5-Fluorouracil or Capecitabine. Detected TP53 mutations were classified for TP53 mutant-specific residual transcriptional activity scores ( TP53 RTAS ) (Fischer NW et al JCI Insight 2018). TP53 RTAS results were used for stratifying pts in survival analyses. Primary end-point was overall survival (OS). Results: In the PR group, TP53 mutations were detected in 29 out of 48 tumor samples (60.4%) with 10 having TP53 RTAS 0%-to-&lt;1%. In the CT group, TP53 mutations were found in 40 out of 62 tumor samples (64.5%) with 11 having TP53 RTAS 0%-to-&lt;1%. In the PR group, the 10 cases with a TP53 mutation causing no residual or minimal activity ( TP53 RTAS 0%-to-&lt;1%) showed better OS in comparison with pts in the remaining groups (wild-type and TP53 RTAS &gt; 1%). This effect was retained in the multivariate model analysis (Hazard Ratio = 0.29, 95% confidence interval 0.17-0.85, p = 0.02). An opposite effect was seen in the CT group with the worst OS in carriers of TP53 RTAS 0%-to-&lt;1% mutations (Hazard Ratio = 2.64, 95% confidence interval 1.17-5.95, p = 0.02). Notably, in the whole group of 110 pts, TP53 mutations (any type) occurred more frequently in the intestinal-type GA group (p = 0.02). Conclusions: Additional studies are warranted to explore the favorable role of TP53 mutations in cancer pts undergoing anti-angiogenic therapies. TP53 mutations frequently occur in GA and these findings would lead to novel tailored therapy strategies in this lethal disease.
Peripheral blood immune correlates associated with TGF-β inhibition (galunisertib) and stereotactic body radiotherapy (SBRT) in patients with advanced hepatocellular carcinoma (HCC).
Authors: Max Miller Wattenberg, Kim Anna Reiss, Michael Giannone, Nevena Damjanov, Elizabeth Prechtel Dunphy, Lisa DiCicco, Luis Garcia-Marcano, Thomas Benjamin Karasic, Emma Furth, Andrzej Wojcieszynski, Robert H. Vonderheide, Edgar Ben-Josef, Gregory Lawrence Beatty
Journal: Journal of Clinical Oncology (2020)

4575 Background: TGF-β is a pleiotropic cytokine with immunosuppressive activity. In mouse models, blockade of TGF-β signaling enhances the activity of radiation and invokes T cell dependent anti-tumor immunity. We previously reported preliminary safety and efficacy results from a pilot study combining galunisertib (LY2157299), an oral TGF-β inhibitor, with SBRT for the treatment of patients with advanced HCC. Here, we investigate immunological mechanisms and potential biomarkers associated with therapeutic activity. Methods: Patients with advanced HCC who had progressed on or refused sorafenib were treated with galunisertib (150 mg PO BID) on days 1-14 of each 28-day cycle. SBRT (18 Gy) was delivered in a single dose between days 15-28 of cycle 1. Blood was collected at baseline, following two weeks of galunisertib and following SBRT for high-dimensional analysis using a 37-marker CyTOF panel. Patients were dichotomized based on best response as either progressor (PD) or non-progressor (PR+SD). The frequency of immune subsets was compared between groups. Results: Fifteen patients were enrolled and treated. One patient was not evaluable. The most common adverse event was grade 1 or 2 fatigue in 53% of patients. The only possibly-related grade 3 event was achalasia in one patient which coincided with disease progression. Two patients achieved a PR and six patients had SD (DCR 57%) with a median progression-free survival of 3.7 months and a median overall survival of 9.0 months. For most patients, regardless of outcome, galunisertib treatment was associated with a decrease in activated Ki67+ Treg cells. However, pre-treatment immune composition within the blood of progressors and non-progressors was distinct. At baseline, progressors had an increased frequency of naive-like CD8+ T cells, whereas non-progressors had an increased frequency of non-classical monocytes. After combination therapy, only non-progressors showed a significant increase in CD8+PD1+TIGIT+ T cells. Conclusions: Galunisertib combined with SBRT was well-tolerated with modest efficacy. Immune profiling of the blood revealed distinct pre- and post-treatment signatures that differentiated patients with progression versus non-progression. These findings show that the combination of anti-TGF-β therapy with radiation can mediate disease control and identify potential correlates of efficacy. Clinical trial information: NCT02906397 .
Updated analysis of a phase I/II study of venetoclax in combination with daratumumab and dexamethasone, +/- bortezomib, in patients with relapsed/refractory multiple myeloma.
Authors: Jonathan L. Kaufman, Rachid C. Baz, Simon J. Harrison, Hang Quach, Shir-Jing Ho, Annette J. Vangsted, Philippe Moreau, Simon DJ Gibbs, Ahmed H. Salem, Sheryl Coppola, Jeremy A. Ross, Abdullah A. Masud, Sally Westrup, Jenny Vue, Paulo Cesar Maciag, Orlando Bueno, Nizar J. Bahlis
Journal: Journal of Clinical Oncology (2020)

8511 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor that induces apoptosis in multiple myeloma (MM) cells in vitro. It has shown synergistic activity with bortezomib (V) and dexamethasone (d). Combination of the CD38 monoclonal antibody daratumumab (D) with Ven is hypothesized to further increase anti-myeloma activity based on dual mechanisms of pro-apoptotic effects on tumor cells and enhanced immune stimulation. Methods: This ongoing Phase 1/2, nonrandomized, multicenter study (NCT03314181) is evaluating safety, efficacy and pharmacokinetics (PK) of VenDd +/- V in patients (pts) with relapsed/refractory MM. In Part 1, pts with t(11;14) who received ≥1 prior line of therapy (PI and an immunomodulatory drug) were treated with VenDd [Ven QD + D 16 mg/kg IV + d 40 mg weekly]. In Part 2, pts irrespective of t(11;14) status, non-refractory to PIs and who received 1–3 prior lines of therapy were treated with VenDVd [Ven QD + D 16 mg/kg IV + V (1.3 mg/m 2 ) + d (20 mg)]. A randomized, open-label expansion (Part 3) will further evaluate and compare safety and efficacy of VenDd (400 or 800 mg Ven dose levels) with control DVd in pts with t(11;14). Results: As of Dec 05, 2019, 48 pts were enrolled. Part 1 included 24 pts with t(11;14), median age 63 (range 51–76). Part 2 included 24 pts, median age 65 (range 41–80) of which 6 (25%) had t(11;14). Frequent adverse events (AEs; VenDd/VenDVd) were fatigue (71%/25%), diarrhea (58%/46%), nausea (46%/50%), insomnia (33%/50%), upper respiratory tract infection (33%/21%), cough (42%/9%), and dyspnea (25%/25%). Frequent Grade ≥ 3 AEs in pts on VenDd were neutropenia (17%), hypertension (12%), fatigue and hyperglycemia (8% each), and in pts on VenDVd were insomnia (21%), diarrhea and thrombocytopenia (8% each). Nine pts had infection-related Grade ≥ 3 AEs (5 VenDd, 4 VenDVd). Eighteen pts had a serious AE (11 VenDd, 7 VenDVd) with pyrexia (n = 3) being most common. One pt on VenDVd died of progressive disease. PK analyses showed that addition of D and V did not impact Ven exposure. Median follow-up time (VenDd/VenDVd) was 10 and 9 months. Overall response rate in VenDd/VenDVd was 96%/92% and 96%/79% had ≥ very good partial response rate. Median progression free survival and duration of response were not reached. Conclusions: Pts treated with VenDd +/- V continue to demonstrate a tolerable safety profile with encouraging efficacy, notably among pts with t(11;14) treated with VenDd. Safety, efficacy, PK, and cytogenetics analyses will be updated for presentation. Clinical trial information: NCT03314181 .
Adherence to remote versus clinic-based collection of patient-reported outcomes in patients with advanced lung cancer.
Authors: Peter Edward Gabriel, Tara L. Kaufmann, Abigail N. Blauch, Donna A. Pucci, Linda A. Jacobs, Justin E. Bekelman, Lawrence N. Shulman, Samuel U Takvorian
Journal: Journal of Clinical Oncology (2020)

e14109 Background: Routine collection of patient-reported outcomes (PROs) is an evidence-based practice to improve communication, symptom management, and health outcomes in cancer care. However, optimal implementation strategies are poorly understood. Previous studies have mostly assessed PROs collected during clinic visits, which may be less actionable and more subject to recall bias than those collected in real time. Behavioral economics-informed digital approaches have shown increasing promise as sustainable and scalable strategies for remote patient monitoring. We compared remote text-messaging versus usual clinic-based PRO collection approaches. Methods: Between September 2018 and May 2019, we conducted a prospective pilot feasibility study of remote PRO monitoring via text-messaging among 20 patients with advanced non-small cell lung cancer (NSCLC). Pilot participants consented to enroll in a HIPAA-compliant, bidirectional text-messaging platform, which allowed for direct reporting of PRO measures at home. Data were integrated into the electronic health record in real time, and clinicians were notified of severe or escalating symptoms. We compared patient-level adherence over 12 weeks among: 1) pilot participants and 2) patients with advanced NSCLC reporting via usual clinic-based collection methods. We identified predictors of adherence using multivariable logistic regression, and surveyed pilot participants on feasibility outcomes. Results: During the study period, 20 patients with advanced NSCLC participated in the remote text-messaging pilot study (mean age, 63y; 60% male; 85% white), and 328 patients with advanced NSCLC participated in usual clinic-based PRO collection (mean age, 66y; 48% male; 69% white). Baseline characteristics were similar between groups. Mean adherence was 88.4% for remote text-messaging vs 71.2% for clinic-based collection (p &lt; 0.001). Pilot participation predicted &gt; 80% adherence after adjusting for age, sex, race, and marital status (OR 3.5, p = 0.029). Pilot participants reported high levels of usability (97%) and satisfaction (96%) with text-messaging, and 90% noted that text messages reminded them to report symptoms to their clinical team. Conclusions: Among patients with advanced NSCLC, remote PRO monitoring via text-messaging was feasible and enabled significantly higher adherence to reporting than usual clinic-based collection. These results are based on a small pilot study, and further research on text messaging as a PRO implementation strategy is warranted. Clinical trial information: NCT03616522.
Imaging features of the initial chest high resolution CT scan in juvenile patient with coronavirus disease 2019
Authors: Yunjiang Li, Yunfeng Ye, Weiling Xuan, Yangjun Chen, Baoliang Wu, Zuhua Chen
Journal: BMJ (2020)

The coronavirus disease 2019 (COVID-19) was confirmed by nucleic acid test in 15 juvenile patients aged 4-17 years in Hangzhou Xixi Hospital from January 24 to February 10, 2020. The clinical data and the initial chest high resolution CT (HRCT) findings were retrospectively analyzed.Among 15 cases, 8 patients with a mean age of (6.5±2.3) years (4-11 year) had normal HRCT manifestations (mild disease), while 7 patients with a mean age of (11.9±3.0) years (7-17 years) showed abnormal manifestations (moderate disease). In the 7 moderate cases the CT findings included local thickening of bronchial wall in 2 cases, single lesion in 1 case, bilateral pulmonary lesions in 4 cases. There were total 11 lesions, 6 of which were ground glass and slightly high-density nodules, 5 of which were speckled ground glass and 2 with a little consolidation. There were 10 subpleural lesions, including 7 in the lower lobe of the two lungs, and 1 non-subpleural lesion; the thickened local bronchioles were observed in 3 cases. None of them had hilum and mediastinal lymph node enlargement or pleural effusion.

Key words: 
Coronavirus infection; Coronavirus disease 2019; Minors; Tomography, X-ray computed; Diagnosis