tbuckley/cabot-search huggingface dataset:
Efficacy of maintenance therapy with zoledronic acid in patients with localized Ewing sarcoma: Report from the international Ewing 2008 trial.
Authors: Uta Dirksen, Raphael Koch, Vivek Bhadri, Bénédicte Brichard, Trude Butterfass-Bahloul, Sona Cyprova, Hans Gelderblom, Peter Hauser, Lianne Havemann, Lars Hjorth, Heribert Juergens, Jukka Kanerva, Thomas Kuehne, Ruth Lydia Ladenstein, Anna Raciborska, Jelena Rascon, Arne Streitbuerger, Beate Timmermann, Andreas Ranft, Andreas Faldum
Journal: Journal of Clinical Oncology (2020)

11523 Background: Ewing 2008R1 (EudraCT2008-003658-13, Sponsor UKM) was conducted in 12 countries. It evaluated the effect of zolendronic acid (ZOL) maintenance therapy on event-free (EFS, primary endpoint) and overall survival (OS) from randomization in standard risk Ewing Sarcoma (EwS). Methods: Phase III, open label, prospective, multi-center, randomized controlled clinical trial. Eligible patients (pts) had localized EwS with either good histological response to induction chemotherapy and/or small tumors ( &lt; 200ml). Pts received 6 cycles VIDE induction and 8 VAI (male) or 8 VAC consolidation (female) and were randomized to receive either 9 cycles of maintenance ZOL or no further treatment (control;ctrl). ZOL cycles started parallel to the 6 th consolidation cycle. Randomization was stratified by tumor site (pelvis/no pelvis). Two-sided adaptive inverse-normal 4-stage design, changed after the 1 st interim analysis via Müller-Schäfer method. Initial sample size 448 pts, type I error rate 5%, power 80%. Results: 284 pts were randomized between 2009 and 2018 (142 ZOL / 142 ctrl). With a median follow-up of 3.9 years, the primary endpoint EFS was not significantly different between the ZOL and ctrl group in the adaptive design (HR 0.74, 95% CI 0.43-1.28, intention to treat). 3-year (3y) EFS rates were 84.0% (95% CI 77.7-90.8%) for ZOL vs 81.7% (95% CI 75.2-88.8%) for ctrl. Results were similar in the per protocol collective. Cause-specific HR for local recurrence in ZOL was csHR 0.30 (95% CI 0.08 -1.09; p = 0.07), for metastatic progress/new metastases csHR 1.0 (CI 0.5-2.2), for combined relapse/progress csHR 0.3 (95% CI 0.1-1.7), for second malignancies csHR 4.0 (95% CI 0.45-36.1) compared to ctrl. The 3y OS was 92.8% (95% CI 88.4-97.5%) for ZOL and 94.6% (95% CI 90.9-98.6%) for ctrl. For ZOL the 5y OS was 87.3% (95% CI 80.7-94.5%) and 89% (95% CI 83.7-95.9%) for ctrl. Noticeable more renal, neurological and gut toxicities were observed for ZOL (p &lt; 0.05), with severe renal toxicities occurring more often in the ZOL arm (p = 0.003). Conclusions: In patients with standard risk localized Ewing Sarcoma there is no benefit from maintenance treatment with zoledronic acid, but significant side effects were observed. Clinical trial information: NCT00987636 .
The impact of neoadjuvant and/or adjuvant treatment modalities in resectable gastric cancer (rGC).
Authors: Camille Ng, Sungjin Kim, Michelle Guan, Andrew Eugene Hendifar, Haesoo Kim, Jar-Yee Liu, Sejal Mehta, Veronica Placencio-Hickok, Alexandra Gangi, Samuel J Klempner, Miguel Burch, Joseph Chao, May Thet Cho, Mitchell Kamrava, Katelyn Mae Atkins, Jun Gong
Journal: Journal of Clinical Oncology (2020)

e16564 Background: In rGC ( &gt; cT2), we investigated the impact of various neoadjuvant and/or adjuvant treatment modalities on pathologic complete response (pCR), surgical margins, and overall survival (OS). Methods: The National Cancer Database (NCDB) was interrogated to identify rGC patients (pts) between 2004-2015. Gastric adenocarcinoma cases that were cT2-T4b, any N, M0 and underwent definitive surgery were included. We analyzed the association of 9 treatment groups: neoadjuvant chemoradiation only (nCRT), neoadjuvant chemo only (nCT), adjuvant chemo only (aCT), adjuvant chemoradiation only (aCRT), neoadjuvant chemo and adjuvant radiation (nCTaRT), received any chemo at all (any CT), received any chemoradiation at all (any CRT), received any radiation at all (any RT), and no perioperative therapy (NT) across 3 endpoints: pCR, margin status, and OS using logistic regression and Cox proportional hazards models with adjustment for baseline characteristics. Results: From 183,204 GC cases screened, a total 3061 pts were available with a median follow-up of 41.6 mos and median OS of 29.0 mos. On multivariable analyses, nCRT was associated with the greatest odds of having a pCR (odds ratio or OR 59.6, 95% confidence interval (CI) 10.6-334.1, p &lt; 0.001) with NT as the reference. Having received any RT (OR 0.42, 0.10-1.86), nCRT (OR 0.68, 0.33-1.37), or nCT (OR 0.83, 0.60-1.15) was associated with the lowest odds for having positive surgical margins although none reached p &lt; 0.05. For OS, having received any CT (hazard ratio or HR 0.41, 0.35-0.48) was associated with the lowest risk of death followed by nCRT (HR 0.48, 0.35-0.66), aCT (HR 0.52, 0.43-0.62), aCRT (HR 0.55, 0.48-0.63), any CRT (HR 0.61, 0.41-0.91), nCT (HR 0.62, 0.54-0.71), and nCTaRT (HR 0.67, 0.52-0.87, all p &lt; 0.05). Median OS was greatest in pts treated with any CT (53.9 mos) followed by nCRT (39.1 mos) and aCT (36.1 mos) with 2-year OS rates being 65.6% (95% CI 61.3-69.5%), 63.6% (52.3-73.0%), and 59.7% (54.2-64.7%), respectively. Conclusions: Although nCRT had a high pCR rate, receipt of any CT (neoadjuvant and/or adjuvant) afforded the greatest OS in this modality-by-modality comparison in a large cohort of rGC pts.
Targeted Depletion of Bacteria from Mixed Populations by Programmable Adhesion with Antagonistic Competitor Cells
Authors: See-Yeun Ting, Esteban Martínez-García, Shuo Huang, Savannah K. Bertolli, Katherine A. Kelly, Kevin J. Cutler, Elizabeth D. Su, Hui Zhi, Qing Tang, Matthew C. Radey, Manuela Raffatellu, S. Brook Peterson, Víctor de Lorenzo, Joseph D. Mougous
Journal: Cell Host & Microbe (2020)
Staging the cancer ecosystem: Survival data from a registry study of patients with active cancer.
Authors: James R. Cunningham, Jon Rittenbach, Cheryl Dodd, Mitch Clemens
Journal: Journal of Clinical Oncology (2020)

e13505 Background: Predicting cancer evolutionary trajectories remains an unmet goal for current cancer staging systems. Understanding the influence of selection pressures operating in the host-cancer environment and capable of effecting neoplastic evolution may be a means of informing such predictions. Methods: An IRB-approved cancer ecology registry study was begun, recruiting subjects whose cancer required active treatment. A set of 22 clinical and laboratory parameters obtained at time of entry onto the registry were compiled into eight separate profiles ( tumor microenvironment, inflammation, energy balance, psychosocial stress, GI microbiome, endocrine, skeletal remodeling, mutagenic) to help define a subjects’ ecological landscape. Parameters were chosen based on previous evidence of selection influence and scored using a trichotimzation of data (0, 1, 2). Resulting quantitative profiles from each subject were then aggregated using a geometric figure, an octomer, (an ‘ecogram’), length of vertices representing individual profile scores and whose net area, bounded by the ecogram, it is hypothesized will reflect strength of net selection pressure occurring at the level of the whole-patient. Survival data from the enrolled registry subjects was then correlated with ecogram area. Results: Complete ecological assessments were obtained in 15 subjects participating in the registry. Resulting ecograms demonstrated considerable variation among participants both in derived ecogram area of over 12-fold (range 0-12.7 arbitrary units, mean 4.7±2.9) as well as in morphologic appearance suggesting sensitivity and specificity for strength and character of active selection pressures. Overall survival for registry participants ranged from 14-198 months (median 47 mos.). For 12 subjects with advanced stage disease, survival from time of initial cancer diagnosis demonstrated a moderate degree of inverse correlation with ecogram area (r = -.38, R 2 = 0.144). Conclusions: A method for making a quantitative ecological assessment of patients with active cancer demonstrated both sensitivity and specificity for differences among participants in a cancer ecology registry study. Overall survival among subjects with advanced disease demonstrated inverse correlation with ecogram area supporting further study to predict cancer evolutionary tendency.
再生障碍性贫血转化为急性白血病一例
Authors: 刘海军, 位岩平, 孙英莉
Journal: BMJ (2008)

患者女,27岁.因月经增多伴皮肤出血点4个月余于1999年3月入院.既往健康.体格检查:贫血貌,全身皮肤散在粟粒状出血点,浅表淋巴结未触及肿大,胸骨无压痛,心肺查体无异常,肝脾脏无肿大.实验室检查:白细胞3.0×109/L,血红蛋白61g/L,血小板36×109/L,网织红细胞(Ret)0.016。
Longitudinal evaluation of alanine aminotransferase after treatment for childhood cancer. A report from the St. Jude Lifetime Cohort Study.
Authors: Daniel M. Green, Mingjuan Wang, Matthew J. Krasin, Deokumar Srivastava, Mary V. Relling, Carrie R. Howell, Kirsten K. Ness, Sue C. Kaste, William Greene, Dennis W. Jay, Andrew M. Davidoff, Ching-Hon Pui, Sima Jeha, Michael William Bishop, Wayne Lee Furman, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2020)

e22525 Background: Many childhood cancer survivors have been exposed to hepatotoxic agents. We assessed longitudinal hepatic injury, using alanine aminotransferase (ALT) elevation, and associated factors in a large cohort of long-term survivors. Methods: We evaluated SJLIFE participants ( &gt; 10 years post-diagnosis, age ≥18 years) who had two or more determinations of ALT (T1 baseline, T2 last evaluation). Elevated ALT was defined as ALT &gt; Upper Limit of Normal (ULN, 30 IU/mL for males and 19 IU/mL for females). Elastic net was used to perform model selection for elevated ALT at T2. Modified Poisson regression was used to identify risk factors for elevated ALT at T2. Results: Serial ALT assessments were available for 1941 survivors (49.6% female, 82.2% non-Hispanic white [NHW]). Their median age at diagnosis and T1 were 7.6 years (interquartile range [IQR] = 3.4-13.5) and 31.7 years (IQR = 26.1-38.1), respectively. Elapsed time from diagnosis to T1, and T1 to T2, were 23.3 years (IQR = 17.8-29.6) and 5.2 years (IQR = 4.4-5.7). ALT was normal at T1 and T2 in 45.7%, and persistently (25.9%) or newly (11.7%) abnormal in 37.6%. Compared to those with normal ALT at T1, those with elevated ALT at T2 were more likely to have NHW race/ethnicity, treatment with busulfan, increasing volume of the liver exposed to 10 Gray (Gy) or more (V10), body mass index (BMI) &gt; 25 kg/m 2 , hepatitis C, metabolic syndrome, or treatment with atorvastatin, rosuvastatin or simvastatin at T2. History of hematopoietic stem cell transplantation (HSCT), but not busulfan, were additional risk factors included in the models for V15 and V20 (Table). Conclusions: Demographic, treatment, lifestyle, and non-oncologic interventions increase the risk for ALT elevation in survivors. These results may guide future treatment designs and lifestyle interventions. [Table: see text]
Clinical features of central post-stroke pain
Authors: Xiaoling Zhang, Liping Zhai, Qiaobing Guan, Shuxia Qian, Sichao Chen, Zhongdong Chen, Minchu Zhu, Congying Xu, Bo Yu, Yanping Wang
Journal: BMJ (2016)

Objective
To analyze the clinical features of central post-stroke pain (CPSP). 


Methods
A total of 1 130 patients including 289 cases of hemorrhagic stroke and 841 cases of ischemic stroke, who visited the neurology department one month after stroke during July 2013 to June 2014, were enrolled in the study. The patients were divided into 3 groups: CPSP group (n=80), non-CPSP pain group (n=467) and no-pain group (n=583). The general conditions and clinical features of patients were documented; depression and anxiety was evaluated with Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS); the severity of pain was assessed with Visual Analogue Scale (VAS), pain drawing, sensory tests and brief pain inventory (BPI). 


Results
There were no statistically significant differences in age, course of disease, types of stroke, size of lesions, lesion distribution in cerebral regions and coexistent diseases among three groups. Compared with non-CPSP pain group and no-pain group, CPSP group had higher proportion of lesions in right side [66.2%(53/80) vs. 40.5%(189/467), 66.2%(53/80) vs. 38.9%(227/583), χ2=13.86, 25.97, both P=0.001]. Sensory tests in CPSP group were all abnormal. No significant differences were found in scores of VAS(60.4±6.8 vs. 58.7±5.8), BPI(5.4±1.8 vs. 5.2±1.6), SAS(56.7±4.3 vs. 52.8±3.9) and SDS (54.9±4.1 vs. 55.1±4.4) between CPSP group and non-CPSP pain group(t=0.851, 0.350, 0.674, 0.335, P=0.397, 0.727, 0.503, 0.742). But compared with no-pain group, patients in CPSP group had higher scores of SAS and SDS (t=68.38, 33.65, both P=0.000). Ratio of mRS≤2 in CPSP group [36.6%(29/80)] was lower than that of no pain group [61.6%(359/583), χ2 =12.503, P=0.000]. Patients in CPSP group received more combined analgesic therapy than non-CPSP pain group [32.5%(26/80) vs. 14.6%(68/467), χ2 =8.651, P=0.001]. 


Conclusion
CPSP may affect the prognosis of patients with stroke, clinical evaluation and effective intervention are necessary.


Key words: 
Stroke; Neuralgia; Central; Pathological conditions, signs and symptoms; Questionaires
一氧化碳中毒治疗中出现ST段压低一例
Authors: 何春来, 王平静, 崔荣恩
Journal: BMJ (2005)

患者男,70岁,因意识不清1 h就诊.1 h前患者被发现躺于室内地上,意识丧失,室内有炉火,家人立即将其抬到室外,1 h后送到我院急诊.既往有糖尿病及支气管扩张,否认冠心病史.查体:血压120/80 mm Hg(1 mm Hg=0.133 kPa),呼吸14次/min,嗜睡,双瞳孔等大等圆,直径约2.5 mm,对光反射迟钝,双肺可闻粗大干啰音.心率150次/min,律不齐,第一心音强弱不等,未闻及杂音.腹部无阳性体征。
Correlation between JAK1/2 expression and immune-related genes and JAK2 gene variants: A pan-cancer analysis.
Authors: Lichao Xu, Ding Zhang, Guoqiang Wang, Chao Chen, Ying Wang, Haozhe Huang, Zhenghua Zhang
Journal: Journal of Clinical Oncology (2020)

e15057 Background: Loss of function mutations for Janus kinases 1/2 (JAK1/2) have shown to be the underling mechanism of primary resistance to immune checkpoint inhibitors (ICIs). However, the correlation between JAK1/2 expression and immune-related genes have not been studied. Methods: Survival, mRNA expression and whole-exome sequencing data from 32 pan-cancer atlas studies were obtained from The Cancer Genome Atlas (TCGA). Correlations between JAK1/2 expression and immune-related genes were depicted in heatmaps. We also analyzed the association between JAK2 gene variants and JAK2 expression. Results: In total, 10071 samples with mRNA expression data were included for analysis. Expression of 46 immune-related genes were positively correlated with JAK2 expression in 25 tumors instead of JAK1 expression. Patients with higher expression of JAK2 had better prognosis than patients with lower expression of JAK2 in 13 tumors. Among 10071 patients, 363 (3.60%) patients harbored JAK2 variants, including 8 with frame shift mutations, 44 with nonsense mutations, 142 with missense mutations, 11 with splices, 8 with fusions, 90 with copy-number reduction and 116 with copy-number amplification. There was no difference in JAK2 expression between patients with JAK2 variants and those without JAK2 variants. However, JAK2 fusion (2.20%, 8/363) and amplification (31.96%, 116/363) were associated with higher JAK2 expression. Conclusions: Our pan-cancer analysis found that JAK2 expression was correlated with immune-related genes and the prognosis of cancer patients. JAK2 fusion and amplification increased the expression of JAK2. Altogether, patients with high JAK2 expression may benefit from ICIs.
Blocking immunosuppressive neutrophils deters pY696-EZH2–driven brain metastases
Authors: Lin Zhang, Jun Yao, Yongkun Wei, Zhifen Zhou, Ping Li, Jingkun Qu, Akosua Badu-Nkansah, Xiangliang Yuan, Yu-Wen Huang, Kazutaka Fukumura, Xizeng Mao, Wei-Chao Chang, Jodi Saunus, Sunil Lakhani, Jason T. Huse, Mien-Chie Hung, Dihua Yu
Journal: Science Translational Medicine (2020)

G-CSF antibodies and immune checkpoint blockade with Src inhibitors block neutrophil infiltration to impede pY696-EZH2–driven brain metastasis.
Feasibility and acceptability of yoga to improve psychosocial and physical function among patients with lung cancer: A pilot study.
Authors: Mary E Medysky, Donald Richard Sullivan, Anna Tyzik, Charles R. Thomas, Kerri M. Winters-Stone
Journal: Journal of Clinical Oncology (2020)

e24068 Background: Patients with lung cancer suffer from depression symptoms, reduced quality of life (QOL), and declines in physical function during and after cancer treatment. Since yoga is a low energy demand form of exercise, we hypothesized that yoga is a feasible, safe, and efficacious strategy to mitigate these problems in lung cancer patients. Purpose: 1) Determine the feasibility, acceptability, and safety of a yoga program in patients (pts) with lung cancer during or soon after cancer treatment; 2) Determine the preliminary efficacy of yoga to improve depressive symptoms, quality of life, and physical function among pts with lung cancer. Methods: This study was a single group 12-week (wk) pilot trial of low-moderate intensity yoga among pts with stages I-IV lung cancer (n = 20) during (n = 14) or after (n = 6) cancer treatment. Assessments conducted at baseline, 6- and 12-wks included the Patient Health Questionnaire-8, Functional Assessment of Chronic Illness Therapy-Lung (FACT-L), 6-minute walk distance (6MWD), hand grip strength, chair stand time, and flexibility (back scratch and sit-reach) tests. Results: At baseline, 20 pts, including those with metastatic disease (n = 8), enrolled and 7 pts (35%) withdrew by 6-wks due to poor/worsening health. No further withdrawals occurred at 12-wks. Among pts (n = 13) who completed the study, adherence to the intervention was 75% and 78% at 6 and 12-wks, respectively. No moderate or serious adverse events were reported. Over 12 wks, depressive symptoms (average = -1.8 ±1.23, 43.9% change) decreased, improvements in QOL improved (average = +4 ±2.9, 6.5% change),6MWD (average = +22.6m ±15.9, 6.5% change), hand grip strength (average = +1.6kg ±1.2, 5.7% change), chair stand time (average = -3sec ±2.1, 5.8% change), and upper (average = -10.8cm ±7.5, 49.4% change) and lower (average = -11.9cm ±8.4, 74.6% change) body flexibility occurred. Conclusions: In this sample of lung cancer pts, a 12-week yoga program was modestly feasible, was shown to be safe and potentially beneficial for psychosocial and physical function. Though retention was lower than expected due to early pt withdrawal for poor health, adherence to supervised practice among those pts who were able to complete the intervention exceeded the target goal. Among pts with stage I-IV lung cancer yoga may be a useful strategy to improve psychosocial outcomes and physical functioning, though alternate delivery approaches for pts with advanced disease deserves further exploration. Clinical trial information: NCT03649737 .
The role of HIF-1α in regulating NLRP3 inflammasome activation in bladder cancer.
Authors: Yuan-Ru Chen, Hsin-Chih Yeh, Fang-Yen Chiu, Hsin-En Wu, Huei-Chen Fang, Chia-Yang Li
Journal: Journal of Clinical Oncology (2020)

e17028 Background: Bladder cancer is one of the most common malignancies of urinary system with the forth incidence rate and the eighth leading mortality rate in male genitourinary tumors. Hypoxia environment activates the hypoxia‐signalling pathway, principally via hypoxia‐inducible transcription factors (HIF) to activate numerous target genes which mediate embryonic vascularization, metabolism, tumor angiogenesis and the other processes to supply tissues with blood and oxygen. Inflammasomes are multiprotein signal responsible for the maturation of proinflammatory cytokines IL-1β and IL-18 as well as trigger the inflammatory cell pyroptosis. Recent study showed that HIF-1α promotes NLRP3 inflammasome activation in bleomycin-induced acute lung injury. However, the role of HIF1α in regulating the progression of bladder cancer has not been examined so far. The present study aimed to investigate the effect of HIF-1α on NLRP3 inflammasome activation in urothelial carcinoma. Methods: In this research, urothelial carcinoma cell lines were treated with NLRP3 inflammasome inducers, LPS/ATP, to induce NLRP3 inflammasome activation. Results: Our preliminary results showed that both T24 and 5637 bladder cancer cells can be induced NLRP3 inflammasome activation and IL-1β secretion. In addition, hypoxia also induces the secretion of IL-1β in T24 cells. We further investigated the effect of NLRP3 inflammasome activation in modulating EMT-related protein levels, migration and invasion in bladder cancer T24 cells. Our results demonstrated that NLRP3 inflammasome activation promotes tumor growth and metastasis in bladder cancer cells. Furthermore, knockdown of HIF1α reduces both inflammatory response and migratory activity in bladder cancer. Conclusions: Collectively, these results suggest that targeting NLRP3 inflammasome might offer potential to treat hypoxic malignant tumor in bladder carcinoma.
A Sociotechnical Framework for Safety-Related Electronic Health Record Research Reporting: The SAFER Reporting Framework
Authors: Hardeep Singh, Dean F. Sittig
Journal: Annals of Internal Medicine (2020)

Electronic health record (EHR)–based interventions to improve patient safety are complex and sensitive to who, what, where, why, when, and how they are delivered. Success or failure depends not only on the characteristics and behaviors of individuals who are targeted by an intervention, but also on the technical characteristics of the intervention and the culture and environment of the health system that implements it. Current reporting guidelines do not capture the complexity of sociotechnical factors (technical and nontechnical factors, such as workflow and organizational issues) that confound or influence these interventions. This article proposes a methodological reporting framework for EHR interventions targeting patient safety and builds on an 8-dimension sociotechnical model previously developed by the authors for design, development, implementation, use, and evaluation of health information technology. The Safety-related EHR Research (SAFER) Reporting Framework enables reporting of patient safety–focused EHR-based interventions while accounting for the multifaceted, dynamic sociotechnical context affecting intervention implementation, effectiveness, and generalizability. As an example, an EHR-based intervention to improve communication and timely follow-up of subcritical abnormal test results to operationalize the framework is presented. For each dimension, reporting should include what sociotechnical changes were made to implement an EHR-related intervention to improve patient safety, why the intervention did or did not lead to safety improvements, and how this intervention can be applied or exported to other health care organizations. A foundational list of research and reporting recommendations to address implementation, effectiveness, and generalizability of EHR-based interventions needed to effectively reduce preventable patient harm is provided. The SAFER Reporting Framework is not meant to replace previous research reporting guidelines, but rather provides a sociotechnical adjunct that complements their use.