tbuckley/cabot-search huggingface dataset:
The National Cancer Data Base report on the utilization of an adjuvant immunotherapy in stage III melanoma in relation to age.
Authors: Arden Fredeking, Suraj S. Venna, Sekwon Jang
Journal: Journal of Clinical Oncology (2012)

e19000 Background: The 5-year survival of Stage III melanoma ranges from 30-70%. High dose interferon alfa-2b (IFN) is an adjuvant immunotherapy approved in 1995 for stage III melanoma, however, its use has been limited by its significant toxicity and modest benefit. We hypothesized the utilization of adjuvant immunotherapy is less in older age group compared to younger patients. Methods: Using the National Cancer Data Base (NCDB) aggregate data, demographic, socioeconomic, insurance information, and treatment data were analyzed. Proportions were compared using Pearson Chi squared tests. Results: From 2000-2008, 27,365 cases of stage III melanoma were reported to NCDB. Most patients were male (63%) and Caucasian (94.2%). Twenty-nine percent were over the age of 70. Educational and socioeconomic factors across all age groups were not significantly different. The primary insurer for patients younger than 60 was a managed care plan (54.3%) as compared to Medicare with supplemental insurance for patients older than 60 (47.4%). In terms of systemic therapy, 23% received immunotherapy alone, 6% received chemotherapy alone, 2% received both, and 66% received no therapy. When compared to patients under age 39, older age groups were significantly less likely to receive adjuvant immunotherapy as shown in the table below. Conclusions: There is an inverse relationship between age and the use of adjuvant immunotherapy. Further study is planned to adjust for comorbidity, socioeconomic status using patient-level data. [Table: see text]
THE HIGH RISK OF TRANSFERS FROM EXTERNAL HOSPITALS TO TERTIARY CARDIAC INTENSIVE CARE UNITS: DATA FROM THE CRITICAL CARE CARDIOLOGY TRIALS NETWORK (CCCTN) REGISTRY
Authors: Nicholas Phreaner, Lori B. Daniels, Jason Katz, Sean Van Diepen, Jianping Guo, David Berg, Erin Ann Bohula, David A. Morrow
Journal: Journal of the American College of Cardiology (2020)
TRANSSEPTAL VSD CLOSURE IN A PATIENT WITH MECHANICAL AORTIC AND TRICUSPID VALVES
Authors: Kevin Leung, Hardik M. Bhansali, Nicholas Ghiloni, Luis Alonso Hernandez Mejia, Nader Hanna, Eduardo Perez, Diana Miranda Ruiz, Jose Sleiman, Roberto J. Cubeddu, Elsy Navas
Journal: Journal of the American College of Cardiology (2020)
Adjuvant sunitinib in high-risk patients with uveal melanoma: A pilot study.
Authors: Matias Emanuel Valsecchi, Nancy Shockley, Deborah Summers, Carol L Shields, Jerry A Shields, Michael J. Mastrangelo, Takami Sato
Journal: Journal of Clinical Oncology (2012)

8560 Background: Uveal melanoma is the most common primary intraocular cancer in adults. Despite the successful treatments for primary tumors, up to 50% of the patients later die of distant metastases. Currently no effective adjuvant treatment is available for these patients. Our group previously reported that sunitinib stabilized systemic metastases in 65% of uveal melanoma patients who failed prior treatments. In this pilot study, we tested sunitinib in an adjuvant setting in high-risk patients with primary uveal melanoma. Methods: Patients with estimated metastatic death rate ≥ 50% based on the following criteria were eligible: (1) monosomy 3 and 8q amplification; (2) large tumor (≥ 15 mm in diameter and ≥7 mm in thickness); (3) monosomy 3 and other risk factors (large tumor, epithelioid dominant cell type, local recurrence, or extra-scleral extension). Sunitinib was given at 25 mg PO daily for at least 6 months. Primary endpoint was disease-free survival (DFS) and overall survival (OS), estimated with Kaplan-Meier analysis (SPSS 17.0). Secondary endpoint was safety. Results: A total of 23 Caucasian patients (median, 54 years; range: 25 – 77) were enrolled. All patients received sunitinib for at least 6 months (range: 6 – 12). Eighteen patients had confirmed monosomy 3, from whom 13 (72%) also showed 8q amplification. The median follow-up was 24 months (range 12 – 54 months). Only one patient died of unknown cause (OS: 30.4 months). A total of seven patients (30%) developed systemic metastases, all of which were liver metastases. The DFS and OS rates at 2 years were 70% (95% CI: 47 – 86%) and 100%, respectively. The OS rate at 2 years was better than historical control with monosomy 3 patients (51%, 95% CI: 31 – 71%) (Invest Ophthalmol Vis Sci 2003; 44:1008). In those patients who relapsed, the median time to progression after finishing sunitinib was 2 months (range: 0 – 8). The most common adverse events were: diarrhea (47%), fatigue (39%), dermatitis (30%), stomatitis (13%), leucopenia (8%), and nausea (4%). Most were grade 1 or 2 (88%) and only one was considered grade 4 (diarrhea). Conclusions: In high-risk uveal melanoma patients with estimated metastatic death rate of ≥ 50%, adjuvant sunitinib showed promising results and deserves further investigation.
Establishment and Validation of a Risk Prediction Model for Early Diabetic Kidney Disease Based on a Systematic Review and Meta-Analysis of 20 Cohorts
Authors: Wenhui Jiang, Jingyu Wang, Xiaofang Shen, Wenli Lu, Yuan Wang, Wen Li, Zhongai Gao, Jie Xu, Xiaochen Li, Ran Liu, Miaoyan Zheng, Bai Chang, Jing Li, Juhong Yang, Baocheng Chang
Journal: Diabetes Care (2020)

Identifying patients at high risk of diabetic kidney disease (DKD) helps improve clinical outcome.To establish a model for predicting DKD.The derivation cohort was from a meta-analysis. The validation cohort was from a Chinese cohort.Cohort studies that reported risk factors of DKD with their corresponding risk ratios (RRs) in patients with type 2 diabetes were selected. All patients had estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) <30 mg/g at baseline.Risk factors and their corresponding RRs were extracted. Only risk factors with statistical significance were included in our DKD risk prediction model.Twenty cohorts including 41,271 patients with type 2 diabetes were included in our meta-analysis. Age, BMI, smoking, diabetic retinopathy, hemoglobin A1c, systolic blood pressure, HDL cholesterol, triglycerides, UACR, and eGFR were statistically significant. All these risk factors were included in the model except eGFR because of the significant heterogeneity among studies. All risk factors were scored according to their weightings, and the highest score was 37.0. The model was validated in an external cohort with a median follow-up of 2.9 years. A cutoff value of 16 was selected with a sensitivity of 0.847 and a specificity of 0.677.There was huge heterogeneity among studies involving eGFR. More evidence is needed to power it as a risk factor of DKD.The DKD risk prediction model consisting of nine risk factors established in this study is a simple tool for detecting patients at high risk of DKD.
The Effects of a Video Intervention on Posthospitalization Pulmonary Rehabilitation Uptake. A Randomized Controlled Trial
Authors: Ruth E. Barker, Sarah E. Jones, Winston Banya, Sharon Fleming, Samantha S. C. Kon, Stuart F. Clarke, Claire M. Nolan, Suhani Patel, Jessica A. Walsh, Matthew Maddocks, Morag Farquhar, Derek Bell, Jadwiga A. Wedzicha, William D.-C. Man
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions. However, posthospitalization PR uptake is low. To date, no trials of interventions to increase uptake have been conducted.Objectives: To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake.Methods: The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, FEV1 % predicted, frailty, transport availability, and previous PR experience.Measurements and Main Results: The primary outcome was PR uptake within 28 days of hospital discharge. A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV1% predicted, 36 [interquartile range, 27–48]). PR uptake was 41% and 34% in the usual care and intervention groups, respectively (P = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints. A total of 6 of the 15 participants interviewed could not recall receiving the video.Conclusions: A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion.
THE EFFECT OF BODY MASS INDEX ON HOSPITALIZATION IN HEART FAILURE WITH PRESERVED EJECTION FRACTION AND DIABETES MELLITUS
Authors: Zeba Hashmath, Abhishek Bose, Parag Anilkumar Chevli, Fnu Avinashsingheswarsingh, Akil Sherif, Shubhi Pandey, Tanvi Shah, Joseph Kirkpatrick
Journal: Journal of the American College of Cardiology (2020)
Speed of accrual into published phase III oncology trials: A comparison across geographic locations.
Authors: Nancy R. Ruther, Alcee Jumonville, Michelle A. Mathiason, Ann E. Emmel, Sandra K Wee, Ronald S. Go
Journal: Journal of Clinical Oncology (2012)

6074 Background: There is a perception that patient accrual may be slower in the US than it is in Europe (Wang-Gillam A et al, J Clin Oncol 2010;28:3803-3807). However, a systematic study has not been performed. We seek to determine the speed at which patients are accrued into published phase III oncology trials across geographic locations and to identify factors that may influence this process. Methods: We searched MEDLINE and identified all original phase III oncology therapeutic trials published in 2006-2010 (N = 567). Trials with no reported activation and completion dates were excluded (n = 20). Accrual speed per trial was expressed as patients per month and was calculated by dividing the number of patients enrolled by number of months a trial was open. Results: The 547 trials included in our study enrolled 281,340 patients. Most trials were for adults only (95.6%), late stage cancers (77.5%), and involved multinational participation (44.1%). Funding sources were cooperative groups (45.5%), industry (33.8%) and academic centers (20.5%). The top 5 cancers studied were hematologic (19.2%), gastrointestinal (16.5%), lung (16.3%), breast (15.4%), and gynecologic (8.4%). Trial results were negative (57.4%), positive (38.2%), or equivalent (4.4%). The mean (+SD) accrual speeds varied according to trial location (multinational [25.0+25.4], US [13.3+16.5], other countries [11.4+15.7], Europe [8.7+11.8]; [P= .001]), funding source (industry [28.3+24.7], cooperative groups [13.3+19.0], academic [6.8+6.5]; [P= .001]), and cancer type (breast [24.0+29.4], gastrointestinal [20.2+24.2], lung [19.3+22.7], gynecologic [15.3+19.2], hematologic [11.2+10.7]; [P= .001]). After adjusting for funding source, accrual speeds were significantly different across trial locations only in 2 cancers: gastrointestinal (multinational [25.2+3.7], US [24.1+8.2], Europe [11.5+3.7], other [7.5+8.5]; P= .046) and gynecologic (multinational [28.9+5.4], other [10.5+7.8], US [6.6+5.3], Europe [4.2+5.9]; P= .004) studies. Conclusions: Among published phase III oncology trials, multinational studies accrued patients faster in gastrointestinal and gynecologic cancers and at a similar speed in other cancers.
MicroRNAs induced in melanoma treated with combination targeted therapy of temsirolimus and bevacizumab.
Authors: Aubrey G Wagenseller, Amber L Shada, Kevin D'Auria, Cheryl F. Murphy, Dandan Sun, Kerrington R. Molhoek, Jason A Papin, Anindya Dutta, Craig L. Slingluff
Journal: Journal of Clinical Oncology (2012)

8597 Background: Targeted therapies directed at commonly overexpressed pathways in melanoma have clinical activity in numerous trials. Little is known about how these therapies influence microRNA expression, particularly with combination regimens. A better understanding of how microRNAs are altered with treatment may contribute to understanding mechanisms of therapeutic effects as well as mechanisms of tumor escape from therapy. Methods: Using microRNA arrays, we analyzed microRNA expression levels in melanoma samples from a Cancer Therapy Evaluation Program-sponsored phase II trial of combination temsirolimus and bevacizumab in stage III or IV melanoma, which elicited clinical benefit in a subset of patients. Seventeen patients were treated with temsirolimus for one week, then combination of both temsirolimus and bevacizumab. Metastatic melanoma biopsies were evaluated days 1, 2, and 23. Tumor samples were evaluated from 12 patients. Results: microRNA expression remained unchanged with temsirolimus alone; however, expression of 15 microRNAs was significantly upregulated (1.4 to 2.5-fold) with combination treatment, compared to pre-treatment levels. Interestingly, twelve of these fifteen microRNAs have been reported to possess tumor suppressor capabilities in various cancer types, including melanoma. We identified 15 putative oncogenes and B7-H3, IGF-1, and IGF-1R as potential targets of the 12 tumor suppressor microRNAs, based on published experimental evidence. For 18 of 25 pairings of microRNA and target-mRNA, changes in gene expression from pretreatment to post-combination treatment samples were inversely correlated with changes in microRNA expression, suggesting a functional effect of the microRNA changes induced by combination therapy. Clustering analysis based on selected microRNAs revealed signatures characteristic of clinical response to combination treatment and of tumor BRAF mutational status. Conclusions: We have identified microRNAs that may be involved in the mechanism of action of combination temsirolimus and bevacizumab in metastatic melanoma, possibly through inhibition of oncogenic pathways.
REVIEW OF RE-OPERATIVE SURGICAL MITRAL VALVE REPLACEMENT VERSUS TRANSCATHETER MITRAL VALVE-IN-VALVE REPLACEMENT
Authors: Aditya Sengupta, Farhang Yazdchi, Akash Premkumar, Edward Percy, Sameer Hirji, Prem S. Shekar, Tsuyoshi Kaneko, Gilbert Tang
Journal: Journal of the American College of Cardiology (2020)
The Interplay between Slow-Cycling, Chemoresistant Cancer Cells and Fibroblasts Creates a Proinflammatory Niche for Tumor Progression
Authors: Jaebeom Cho, Hyo-Jong Lee, Su Jung Hwang, Hye-Young Min, Han Na Kang, A-Young Park, Seung Yeob Hyun, Jeong Yeon Sim, Ho Jin Lee, Hyun-Ji Jang, Young-Ah Suh, Sungyoul Hong, Young Kee Shin, Hye Ryun Kim, Ho-Young Lee
Journal: Cancer Research (2020)

Quiescent cancer cells are believed to cause cancer progression after chemotherapy through unknown mechanisms. We show here that human non-small cell lung cancer (NSCLC) cell line-derived, quiescent-like, slow-cycling cancer cells (SCC) and residual patient-derived xenograft (PDX) tumors after chemotherapy experience activating transcription factor 6 (ATF6)-mediated upregulation of various cytokines, which acts in a paracrine manner to recruit fibroblasts. Cancer-associated fibroblasts (CAF) underwent transcriptional upregulation of COX2 and type I collagen (Col-I), which subsequently triggered a slow-to-active cycling switch in SCC through prostaglandin E2 (PGE2)- and integrin/Src-mediated signaling pathways, leading to cancer progression. Both antagonism of ATF6 and cotargeting of Src/COX2 effectively suppressed cytokine production and slow-to-active cell cycling transition in SCC, withholding cancer progression. Expression of COX2 and Col-I and activation of Src were observed in patients with NSCLC who progressed while receiving chemotherapy. Public data analysis revealed significant association between COL1A1 and SRC expression and NSCLC relapse. Overall, these findings indicate that a proinflammatory niche created by the interplay between SCC and CAF triggers tumor progression. SIGNIFICANCE: Cotargeting COX2 and Src may be an effective strategy to prevent cancer progression after chemotherapy.
Psychological impact of exercise in women with breast cancer receiving adjuvant therapy: What is the optimal dose needed?
Authors: Marion Carayol, Paquito Bernard, Julie Boiche, Francois Riou, Betty Mercier, Florence Cousson-Gelie, Ahmed Jerome Romain, Gregory Ninot
Journal: Journal of Clinical Oncology (2012)

9074 Background: Several meta-analyses have examined the role of exercise interventions in improving psychological outcomes in cancer survivors but most did not focus on adjuvant therapy period and did not investigate the optimal dose of exercise needed. Methods: The present meta-analysis examines the impact of exercise interventions delivered at this particular period on fatigue, anxiety, depression and quality-of-life (QoL) as well as dose-response relationships between volume of prescribed exercise and these psychological outcomes. Randomized controlled trials that proposed an exercise intervention to breast cancer patients undergoing chemotherapy and/or radiotherapy were systematically identified and coded. Standardized mean differences (SMDs) of psychological outcomes were weighted by the inverse of their variances to obtain a pooled estimate using random effects model. Linear and quadratic regressions were carried out to explore dose-response relationships. Results: In total, 17 studies involving 1380 participants and 20 exercise interventions were included. Intervention subjects significantly reduced their fatigue and depression levels showing pooled effect sizes (EF) and their associated 95% confidence interval (95%CI) of -0.28 [95%CI: -0.54; -0.03] and -0.28 [95%CI: -0.46; -0.09] respectively. Levels of anxiety also appeared to be reduced but pooled estimate did not reach significance (p=0.06). Significantly increased QoL was observed: EF=0.34 [95%CI: 0.07; 0.62] favouring intervention. Consistent and significant inverse associations of weekly and total volume of prescribed exercise were observed with fatigue (F test: p=0.04, R²=0.19 and p=0.009, R²=0.26 respectively) and QoL (F test: p=0.01, R²=0.14 and p=0.02, R²=0.29 respectively), implying that SMDs magnitude decreased as exercise dose increased. Conclusions: Exercise intervention enhanced fatigue, depression and QoL in breast cancer patients undergoing adjuvant therapy. Prescription of relatively low doses of exercise (&lt;12 MET.h per week) consisting in approximately 90-120 min of weekly moderate physical exercise seems more efficacious in improving fatigue and QoL than higher doses.
Immune signature and molecular profiling of radiation-induced sarcoma (RIS).
Authors: Eoghan Ruadh Malone, Nathaniel Anderson, Jeremy Howard Lewin, Brian O'Sullivan, Brendan Dickson, Adam Shlien, Albiruni Ryan Abdul Razak
Journal: Journal of Clinical Oncology (2019)

11040 Background: RIS is a rare subset of soft tissue sarcoma (STS) with poor prognosis and limited treatment options. We hypothesize that subsets of STS that carry genomic complexity, such as RIS, will have a neoepitope and immune signature that predicts response to immunotherapy as these mutations act as strong antigenic targets for eliciting immune response. Methods: Cases of RIS were identified from an institutional database. Formalin fixed paraffin embedded (FFPE) samples were stained for PD-1, PD-L1, CD3, CD4, CD8. Immune scoring was performed. Tumor-infiltrating lymphocytes (TILs) were assessed using a 4-tiered scale: 0 (no lymphocytes); 1 (1-10/HPF); 2 (11-50/HPF), 3 (51-100/HPF); 4 ( &gt; 100/HPF). TIL staining with PD-1 and PD-L1 was also scored whereby the overall percentage of positive cells on the entire slide was quantified. Tumor DNA was extracted from FFPE samples and underwent whole exome sequencing (WES). Results: FFPE samples from 20 cases of RIS were selected for analysis. PD-1 and PD-L1 expression (threshold set at ≥ 1% positive cells) was seen in 35% and 45% of the cases respectively. CD3 + , CD4 + , CD8 + T cell infiltration (threshold set ≥ 11 cells /HPF) was seen in 45%, 15% and 20% of cases respectively. 12 exomes of unpaired RIS samples were successfully sequenced. The most common histologies were angiosarcoma (n = 3), undifferentiated spindle cell sarcoma (n = 3), de-differentiated liposarcoma (n = 2) and radiation induced spindle cell sarcoma (n = 2). Provisional analysis did not reveal any pattern to the relative mutational burden between the RIS’s. There does however seem to be relatively higher rate of mutation than that seen in other cancer subtypes. Half the samples had at least one pathogenic or likely pathogenic variant. Different HRAS mutations were seen in two samples (sarcoma NOS and angiosarcoma) and FGFR4 mutation was present in two samples, both spindle cell sarcomas. Conclusions: To our knowledge this is the first study to investigate the immune profile in RIS. Up to 45% of these tumors were positive for PD1/PDL1 expression, as well as presence of tumour infiltrating lymphocytes. Results from WES demonstrate that RIS may benefit from immunotherapy due to a relatively higher mutational burden.
Local infiltration of lymphocytes in large bowel tissue cancer and chronic colitis.
Authors: Elena A Nikipelova, Oleg I Kit
Journal: Journal of Clinical Oncology (2012)

e21101 Background: comparative analysis of concentrations of lymphocyte subpopulations in tissue of various intestinal zones in cancer of large bowel and chronic atrophic colitis. Methods: subpopulation composition of T- (CD3, CD4, CD8) and B- (CD19) lymphocytes, natural killers NK (CD16CD56), and T-lymphocytes with antigen-recognizing receptors TCRαβ and TCRγδ were examined in bowel adenocarcinoma tissue, peritumoural zone (1-3 cm away from tumour) and in resection line (10 cm away from tumour edge) and in chronic colitis tissue. Flow cytofluorimetry was used for immunophenotyping of the lymphocytes Results: 52 cases of adenocarcinoma and 24 cases of chronic colitis were examined. CD3 level in tumour tissue (64.2±3.6%) didn’t differ from this in colitis samples (65.6±3.5%); CD3 level was significantly lower in peritumoural zone and resection line (54.9±4.0% and 51.9±3.6%, correspondingly, p&lt;0.05) than in colitis samples. The quantaty of lymphocytes with TCRαβ receptor in all tissue samples with cancer was significantly higher in comparison with one in chronic colitis samples. The level of lymphocytes with TCRαβ receptor in all tissue samples with cancer was 49.8±7.25, in peritumoural zone – 39.3±5.9%, in resection line 46.5±6.0%, compared to chronic colitis – 20.7±5.7%, p&lt;0.05. Concentration of lymphocytes with TCRγδ receptor in cancer samples was 3-5 times less (tumour – 14.2±4.8%, peritumoural zone – 9.5±1.5%, resection line – 11.3+2.1%) than in samples colitis ones (42.9±9.9%) p&lt;0.05. It was found that tumour tissue, in contrast to peritumoural tissue, accumulated T-lymphocytes (64.2±3.6% and 51.9±3.6%, correspondingly) due to CD4 cells (35.5±2.3% and 24.3±2.1%, correspondingly, p&lt;0.05). Lower level of B-cells was found in tumour (18.0±2.8% and 30.1±3.7%, correspondingly, p&lt;0.05). Conclusions: abnormalities of local cellular immunity at diseases of large bowel are probably related not only to imbalance of lymphocyte subpopulations, but also to change of local correlation of levels of αβ-T-lymphocytes capable of recirculation, and tissue γδ-T-lymphocytes. This may cause inadequacy of immune protection at cancer of large bowel.
CARDIAC MAGNETIC RESONANCE IMAGING TIMING AND IDENTIFICATION OF THE ETIOLOGY OF MYOCARDIAL INFARCTION WITH NON-OBSTRUCTIVE CORONARY ARTERIES: A SYSTEMATIC REVIEW AND META ANALYSIS
Authors: Mahmoud El Iskandarani, Bara El Kurdi, Bhogal Sukhdeep, Marwan Refaat, Timir K. Paul
Journal: Journal of the American College of Cardiology (2020)