tbuckley/cabot-search huggingface dataset:
An evaluation of administrative data linkage for measurement of real-world outcomes of large clinical panel sequencing for advanced solid tumors.
Authors: Ramy Saleh, Philippe L. Bedard, Paul Nguyen, Eoghan Ruadh Malone, Celeste Yu, Eitan Amir, Craig Earle, Bishal Gyawali, Aaron Richard Hansen, Nicole Mittmann, Yingwei Peng, Trevor John Pugh, Albiruni Ryan Abdul Razak, Peter Sabatini, Anna Spreafico, Tracy Stockley, Jonathon Torchia, Christine Williams, Lillian L. Siu, Timothy Hanna
Journal: Journal of Clinical Oncology (2020)

283 Background: There is limited real-world evidence of impact of large clinical panel sequencing on treatment-matching for patients with advanced solid tumors. The province of Ontario has a single payer, publicly funded health care system. We linked genomic testing results from a prospective province-wide trial, OCTANE (Ontario-Wide Cancer TArgeted Nucleic Acid Evaluation), to administrative data to determine the feasibility of this approach for evaluating survival and the impact of sequencing on treatment matching. Methods: We linked all Ontario patients from Princess Margaret (PM) with panel testing results (tumor-only 555-gene panel) to province-wide administrative data on treatments and outcomes. Patients were recruited from August 2016 to August 2018. Only clinically actionable variants based upon OncoKB annotation (Level 1 and 2) were assessed for genotype-informed treatment matching. Results: All 888 eligible patients were successfully linked to administrative data. Mean age was 58 (±13) years, 635 (71.5%) were female. Most common disease sites were ovary (26.4%), uterus (14.0%), colorectal (11.8%) and breast (9.5%). Administrative data vital status was more complete than trial collected data with 262 of 476 deaths only recorded in administrative data. Median survival was 1.70 years (95% confidence interval 1.50-1.91). 247 (27.8%) had actionable mutations, most commonly PIK3CA (54.7%), BRCA1 (15.8%), BRCA2 (15.0%) and BRAF (8.9%). 37 (15.0%) and 42 (17.0%) patients with actionable mutations received targeted therapy within 6 and 12 months of test report date, respectively. Conclusions: This is the first known feasibility study of linked administrative data to measure outcomes of large clinical panel sequencing for patients with advanced solid tumors. Vital status was more complete with administrative data compared to trial-collected data, and treatment data was successfully linked. About one in twenty-one enrolled patients received genome-informed treatments within 12 months, or about one in six of all patients with actionable mutations. This may be due to short interval follow up, trial and drug access, successful standard of care treatments, early patient deterioration or limited alterations covered by the panel, among other causes.
Research progress of dietary fiber in chronic kidney disease
Authors: Chao Wang
Journal: BMJ (2017)

Dietary fiber is an essential nutrient for human health, known as the seventh nutrient after carbohydrate, fat, protein, vitamins, water and minerals. Recent studies have shown that dietaty fiber intake can delay progress of chronic kidney disease. This review focuses on the definition and classification of dietary fiber and its preventive and therapeutic effect in chronic kidney disease.


Key words: 
Dietary fiber; Kidney diseases, chronic; Therapeutic uses
Bioinspired kirigami metasurfaces as assistive shoe grips
Authors: Sahab Babaee, Simo Pajovic, Ahmad Rafsanjani, Yichao Shi, Katia Bertoldi, Giovanni Traverso
Journal: Nature Biomedical Engineering (2020)

Falls and subsequent complications are major contributors to morbidity and mortality, especially in older adults. Here, by taking inspiration from claws and scales found in nature, we show that buckling kirigami structures applied to footwear outsoles generate higher friction forces in the forefoot and transversally to the direction of movement. We identified optimal kirigami designs capable of modulating friction for a range of surfaces, including ice, by evaluating the performance of the dynamic kirigami outsoles through numerical simulations and in vitro friction testing, as well as via human-gait force-plate measurements. We anticipate that lightweight kirigami metasurfaces applied to footwear outsoles could help mitigate the risk of slips and falls in a range of environments. Buckling kirigami structures applied to footwear outsoles generate higher friction forces transversally to the direction of movement.
Effect of cognitive-behavioral intervention on mental state and quality of life in elderly patients with coronary heart disease
Authors: 杨伯泉, 朱慧民, 王灵红, 凌爱香, 林祖近
Journal: BMJ (2011)

Ninety elderly patients with coronary heart disease were randomly divided into 2 groups:in study group (n = 45) the cognitive-behavioral intervention as well as conventional medical treatment were performed and in control group ( n = 45 ) only conventional treatment was given. Short Form-36 ( SF-36),symptom checklist 90(SCL-90), Hamilton anxiety scale( HAMA), Hamilton depression scale( HAMD)were evaluated before and after intervention, the serum total cholesterol (TC), triglyceride (TG)and body mass index (BMI)were measured, the smoking and drinking behaviors were recorded. After 6-month of intervention the smoking [(0. 6 ± 0. 2)cigarettes/d] and drinking [(10. 1 ± 2. 3)g/d] behaviors, the scores of SF-36 (85 ± 16), SCL-90 (104 ±4), HAMA (10 ±4) and HAMD (12 ±3), the systolic blood pressure [( 123 ± 11 ) mm Hg ( 1 mm Hg = 0. 133 kPa)], diastolic blood pressure [(77 ± 5 ) mm Hg], the fasting blood glucose [(4. 2 ± 2. 6 ) mmol/L] and BMI ( 22.5 ± 0. 5 ) in study group were significantly improved compared to control group ( P ＜ 0. 01 ). The results indicate that cognitive-behavioral intervention can improve the mental state and quality of life in elderly patients with coronary heart disease.

Key words: 
Coronary disease ;  Cognitive therapy ;
Effect of chemokine signaling signatures on resolving discrepancy between TMB and checkpoint expression.
Authors: Christopher Szeto, Saihitha Veerapaneni, Rahul Parulkar, Sandeep K. Reddy, Shahrooz Rabizadeh, Stephen Charles Benz
Journal: Journal of Clinical Oncology (2020)

3131 Background: Tumor mutation burden (TMB) and PD1/L1 expression are independent biomarkers for immune checkpoint blockade therapy, as seen in the Checkmate227 trial. Here we explore whether chemokine activity, an intermediate step between neoantigen presentation and immune-infiltration, can resolve this lack of association between existing biomarkers. We further use this novel biomarker to corroborate recent findings from Crowther et al. for a role of MHC class 1-related gene ( MR1) downregulation in immune evasion. Methods: 1,395 clinical samples from the NantHealth database with matched tumor:normal whole exomes and deep whole-transcriptomic sequencing (&gt; 200M reads) were available for analysis. The most common indications in the cohort were Breast (18%), Colon (9.8%), Lung (7.8%), Soft-tissue/Sarcomas (7.7%), and Pancreatic (6.1%). TMB was calculated by counting non-synonymous exonic mutations as per Rizvi, 2015. Immune-infiltration and chemokine signaling were inferred from RNAseq expression of published immune-cell-specific genesets (Bindea, 2013) and chemokine ligands (Nagarsheth, 2017) respectively. Significant associations between TMB, chemokine activity, immune-infiltration, and checkpoint expression were analyzed by ranksums test and corrected for multiple-hypothesis testing using Benjamini-Hochberg adjustment. Results: As expected, TMB and PD1/L1 mRNA expression were not correlated in this cohort (r = 0.08 and r = 0.07 respectively). 36.3% of patients classified as highly immune-infiltrated by unsupervised clustering of immune-cell scores, and this subgroup significantly overexpressed all 11 targetable checkpoint genes analyzed including PD1, PDL1, CTLA4, IDO1, and VISTA (adj. p 9.7e-68 to 4e-168). There was no association between immune-infiltrated samples and TMB (t = 0.9, p = 0.35). Twice as many patients classified as chemokine-active (70.0%) and there was significant agreement between immune-infiltrated and chemokine-active patients (OR = 34.8, p = 6.5e-81). Interestingly, there was a weak but significant association between high chemokine-activity and increased TMB (t = 3.3, p = 0.001). Within patients that were chemokine-active but lacked immune-infiltration, MR1 expression was significantly depleted (t = -10.7, p = 1e-26). Conclusions: Chemokine signatures can help resolve discordance between TMB and checkpoint expression. Analysis of discordance between chemokine-active but immune-depleted tumors may aid in identifying targets for converting from cold to hot tumor microenvironments.
Clinical analysis of 76 cases with endocardial fibroelastosis
Authors: Yan-yan Han, Jin-xin Zhang, Jing-hui Sun, Shu-bo Zhai
Journal: BMJ (2011)

The clinical data of 76 children with EFE admitted from June, 1998 to December, 2009 was retrospectively analyzed. Tachypnea、 cough and cyanosis were common and all presented with heart failure. Electrocardiogram revealed sinus tachycardia 、left ventricular hyperthrophy and ST-T alterations. On chest radiograph 54 cases (54/76) had a cardiothoracic ratio ＞ 0. 65 and 33 with pneumonia.Echocardiopraphy revealed lowered left ventricular systolic function in all cases and decreased left ventricular diastolic function in 21 (21/76). 63 cases (63/76) presented with thickened and enhanced left ventricular endocardium and 11 (11/76) with thickened interventricular septals. All were treated with digitalis. 58children were improved and discharged, 10 gave up therapy and 8 died during hospitalization. 41 out of 58 improved cases were followed for 1 - 4 years, with 2. 6 years on average. Among them 28 were clinically cured, 7 deteriorated and 6 died of heart failure. Echocardiography is of diagnostic value for ERE. Systolic and diastolic function of the heart can be used to predict the outcome. Pulmonary infection is a major risk factor associated with deterioration. Long-term treatment is imperative to improve the prognosis.

Key words: 
Endocardial fibroelastosis;  Retrospective studies
假结核耶尔森杆菌败血症性肺炎一例
Authors: 于东祥
Journal: BMJ (2005)

患者女,26岁,因发热伴喘息2 d,于2002年9月27日入院.病史:7 d前于某医院行剖腹产手术,术前4次行阴道检查.术后第5天岀现发冷、发热,体温38℃～39℃;伴有喘息;恶露多、有臭味;无腹泻及腹痛.查体:体温40℃,血压85/60 mm Hg(11.3/8 kPa),呼吸54次/min,心率140次/min,急性病容,精神萎靡,鼻翼扇动,口唇紫绀,双肺可闻及湿性啰音;
Beyond Sedlis: A novel, histology-based nomogram for predicting recurrence risk and need for adjuvant radiation in cervical cancer—A NRG/GOG ancillary analysis.
Authors: Kimberly Levinson, Anna Beavis, Christopher Purdy, Anne Rositch, Akila Viswanathan, Aaron Howard Wolfson, Michael Greg Kelly, Krishnansu Tewari, Leah McNally, Saketh R Guntupalli, Omar Ragab, Yi-Chun Lee, David S. Miller, Warner King Huh, Kelly Jeanes Wilkinson, Nicola M. Spirtos, Linda Van Le, Yovanni Casablanca, Laura L. Holman, Amanda Nickles Fader
Journal: Journal of Clinical Oncology (2020)

6019 Background: In GOG 49, factors associated with a 3-year, 30% recurrence risk in squamous cell carcinoma of the cervix (SCC) after surgery alone were defined. These "intermediate" risk factors [tumor size (TS), depth of tumor invasion (DOI), and lymphvascular space invasion (LVSI)] were then studied in GOG 92, which demonstrated the utility of treating patients (pts) with ≥2 intermediate risk factors with adjuvant radiation (RT), Sedlis Criteria. However, pts with &lt; 30% recurrence risk were not eligible and few pts with adenocarcinoma (AC) were included. Our study purpose was 1) to evaluate recurrence risk factors for AC vs SCC, and 2) to define contemporary nomograms for adjuvant treatment in pts with both histologies. Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included Stage I pts who received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were created separately for AC and SCC to evaluate independent risk factors for recurrence. Model accuracy was tested with ROC curves. Prognostic nomograms were generated for 2-year recurrence risk for AC and SCC. Results: We identified 715 with SCC and 105 pts with AC; 142 with SCC (19.9%) and 18 with AC 17.1%) recurred. For SCC, factors associated independently with recurrence were: LVSI [HR 1.58 (CI 1.12-2.22)], DOI [middle 1/3, HR 4.31 (CI 1.81-10.26); deep 1/3, HR 7.05 (CI 2.99-16.64)] and TS [≥4cm HR 2.67 (CI 1.67-4.29)]. In contrast, for AC, only TS ≥4cm was independently associated with recurrence [HR 4.69 (CI 1.25-17.63)]. At 3 years, ROC curves for these models predicted recurrence with 76% and 75% accuracy for SCC and AC, respectively. Utilizing a nomogram generated from these models, for SCC, DOI had the greatest impact on recurrence, with mid 1/3 conferring an 18% risk and deep 1/3 a 32% risk, while LVSI and TS increased risk by 4-10%, respectively. In contrast, for AC, TS alone had the greatest impact on recurrence risk with TS 2-4cm conferring a 20% risk over 3 years and TS ≥4cm, a 28% risk. Conclusions: Our nomogram differs from the Sedlis Criteria in demonstrating that single, as well as a combination of risk factors predict substantial 3-year recurrence rates in Stage I cervical cancer. Furthermore, these factors differ by AC and SCC subtypes, suggesting that distinct, histology-specific nomograms may have greater utility in identifying pts who will most benefit from adjuvant therapy.
Clinical efficacy of immunotherapy for the treatment of solid tumors in patients with chronic kidney disease.
Authors: Teja Ganta, Tomi Jun, Qian Qin, Vaibhav G. Patel, Bo Wang, George Mellgard, Mahalya Gogerly-Moragoda, Amanda Leiter, Emily J. Gallagher, William K. Oh, Matt D. Galsky, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

e15109 Background: Regulatory T cells play a key role in protecting kidney cells from ischemic injury. Immune checkpoint inhibitors (ICIs) may increase the risk of acute kidney injury via inhibition of regulatory T cells [1, 2]. Prospective clinical trials have largely excluded patients with chronic kidney disease (CKD); thus, we have limited knowledge of the safety and efficacy of ICI in these patients. Herein, we hypothesize that patients with CKD receiving ICIs have worse clinical outcomes. Methods: This single-institution retrospective cohort study included adult patients with solid tumors who were treated with ICIs at The Mount Sinai Hospital between 2011 and 2017. Clinical endpoints [response to treatment, progression of disease (POD) on treatment, mortality] were compared between patients with and without CKD using multivariate logistic regression. Odds ratios were controlled for demographics, primary tumor type, presence of cardiovascular comorbidities, smoking status, incidence of renal adverse events, and a composite of stage of illness with indication for treatment [localized—neoadjuvant, localized—adjuvant, regionally advanced, metastatic disease]. Data were analyzed using R version 3.5.1 with the following packages: readr, dplyr, broom, lubridate, tableone. Results: 420 patients met inclusion criteria: 399 patients without CKD and 21 patients with CKD. Cohorts are well matched for demographics, smoking status, stage/indication for treatment. The CKD cohort has a higher proportion of patients with urothelial cancer compared to patients without CKD (33% vs 11%) as well as a higher proportion of patients with HTN (81% vs 53%), HF (14% vs 3%), and DM (48% vs 21%). There was no statistical difference in odds of response to treatment [OR 0.76, 95% CI 0.26-2.23], POD [OR 0.42, 95% CI 0.15-1.17], or mortality [OR 2.05, 95% CI 0.71-5.96] between the CKD and non-CKD cohort. Conclusions: The data suggest the presence of CKD is not associated with worse clinical outcomes in cancer patients treated with ICIs. As a small retrospective study, the conclusions are hypothesis-generating but support continued use of immunotherapy in CKD in clinical practice and the inclusion of patients with CKD in immunotherapy clinical trials to further clarify safety and efficacy. [Table: see text]
Comparative effectiveness of immune-checkpoint inhibitors as first-line treatment for advanced nonsquamous non-small cell lung cancer patients: A network meta-analysis and a systematic review.
Authors: Roberto Jorge Bitton, Natalia Jacob, Juan Manuel Carrera, Ezequiel Cayetano Perez
Journal: Journal of Clinical Oncology (2020)

e21731 Background: Over the last decade six different immune-checkpoint inhibitors (ICI) have obtained approval in 42 tumor types, several of them are indeed competing for the same indication and there is a lack of direct comparative data to guide the medical oncologist. Network meta-analysis (NMA) is a technique developed as an extension of pairwise meta-analysis to allow comparisons of multiple treatments, using both direct and indirect evidence. This NMA evaluates the effectiveness of several ICIs, either in combination or as single agents, as frontline therapy for patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: We conducted a systematic review of randomized controlled trials (RCT) through Pubmed, Embase, Cochrane Central register of Controlled trial databases, Clinicaltrial.gov database and ASCO abstracts (up to June 2019), to identify phase III RCTs on advanced non-squamous NSCLC in the first-line setting. Both the search and study screening were performed for two independent reviewers. NMA of survival outcomes in different subsets of PD-L1 expression groups was performed and ICIs indirect comparisons were performed. Results: 6 RCTs with 5860 patients were included for the NMA. ICIs were evaluated in combination with several chemotherapy regimens and in the case of Nivolumab in combination with ipilimumab. Atezolizumab was evaluated in one of the RCTs in combination with chemotherapy and bevacizumab. Both Pembrolizumab and Nivolumab were evaluated as monotherapy, either in a separate treatment arms within a trial or in a separate trial. Overall ICI in combination improved survival across PD-L1 expression level subgroups compared with chemotherapy (platinum doublets +/- bevacizumab). Indirect comparisons of ICIs in combination therapy for first-line treatment in advanced non-squamous NSCLC showed little evidence of differences between pembrolizumab or atezolizumab in combination with chemotherapy and nivolumab/ipilimumab. Evaluated as monotherapy pembrolizumab seems to have more evidence of effectiveness than nivolumab. Conclusions: ICIs in combination therapy improve survival in previously untreated advanced NSCLC across PD-L1 expression levels compared with standard first line chemotherapy regimens. There is little evidence of survival difference between pembrolizumab and atezolizumab in combination, and nivolumab requires a combination with ipilimumab to reach similar levels of effectiveness.
Utility of circulating cell-free DNA (cfDNA) analysis in patients with carcinoma of unknown primary (CUP) in identifying alterations with strong evidence for response or resistance to targeted therapy.
Authors: Caroline Weipert, Shumei Kato, Jennifer Saam, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2020)

105 Background: CUP is a rare, heterogeneous group of cancers with an overall poor prognosis; the standard treatment remains chemotherapy. The OncoKB database is a curated list of somatic molecular alterations. Alterations with the highest classification must be an FDA-recognized biomarker associated with response to an FDA-approved drug (Level 1), be recommended by major guidelines or expert panels as predictive of response to an FDA-approved drug (Level 2) or be predictive of resistance to an FDA-approved drug (R1). We explored the landscape of alterations classified as Level 1, 2 or R1 based on the OncoKB scale in a large cohort of CUP patients tested via a well-validated cfDNA assay. Methods: We queried consecutive samples from advanced cancer patients with a listed diagnosis of CUP who underwent testing via a commercially available liquid biopsy assay (Guardant360) between November 2016 and November 2019. The cfDNA assay included targeted next-generation sequencing of 73- to 74-genes specifically curated to include genes with potential targeted therapy options. Alterations were classified based on their ranking in the OncoKB database as of January 2020. Results: In total we identified 2,022 samples with a diagnosis of CUP, and 90.0% of these samples had &gt;1 cfDNA alteration detected. The median age of patients was 68 years and 51% were female. Overall, 20.7% of patients had a Level 1 alteration, 9.5% had a Level 2 alteration, and 23.9% had an R1 alteration (select alterations outlined in Table). Conclusions: cfDNA analysis of patients with advanced CUP identified a significant number of patients with alterations associated with strong evidence for either response or resistance to treatment based on the OncoKB classification schema. While many of these alterations are associated with approvals in specific cancer types, the identification of these alterations suggests many CUP patients may have targeted therapy options. We will present case examples illustrating patient outcomes from CUP patients who received targeting therapy based on cfDNA results. [Table: see text]
The use of PET/CT to detect early recurrence after resection of high-risk stage III melanoma, prior to the start of adjuvant therapy and during follow-up.
Authors: Bernies Van Der Hiel, Emma H.A. Stahlie, Marcel P Stokkel, Michel W.J.M. Wouters, Yvonne Schrage, Winan J. van Houdt, Alexander Christopher Jonathan Van Akkooi
Journal: Journal of Clinical Oncology (2020)

e22039 Background: To date, international consensus concerning the use of PET/CT as a surveillance tool in the follow-up of high-risk melanoma patients after complete resection of disease is lacking. Moreover, with the rise of adjuvant therapy it seems appropriate to investigate the role of this imaging modality to exclude newly developed metastases after resection and prior to starting treatment. The aim of this study was to investigate the use of PET/CT as surveillance tool in the follow-up and prior to adjuvant therapy in asymptomatic patients with complete resection of stage IIIB and IIIC melanoma. Methods: Prospectively two cohorts were set up with stage III melanoma patients with complete resection of disease. In the first cohort (stage IIIB/C AJCC 7 th ) surveillance PET/CT was performed 6-monthly for two years if patients stayed asymptomatic with normal serum S100B, with a final scan at three years. In the second cohort (stage IIIB/C/D AJCC 8 th ) patients underwent one screening PET/CT after resection and prior to starting adjuvant treatment. Results: Eighty patients entered follow-up in cohort 1. Of these, the majority did not undergo surveillance scans, because they required treatment for newly detected clinical metastases. Thirty-five patients remained asymptomatic and were included in surveillance cohort one (105 scans) with a median follow-up of 33 months. Twelve patients (34%) developed a recurrence, seven (20%) of which were detected on the first scan at six months. Seven recurrences involved stage IIIC patients, five stage IIIB patients. Sensitivity and specificity were 92% and 100% respectively. Forty-two patients were included in cohort 2. Recurrence was suspected on nine scans, four (10%) of which were true positive. One patient proceeded to undergo a node dissection and then started adjuvant therapy. The other three patients had progressed to stage IV and therefore started radiotherapy and/or systemic immunotherapy. Five (12%) scans were false positive, the suspected lesions were not related to the preceded surgery. The number of scans needed to find one asymptomatic recurrence were 8.8 and 10.5 in cohort one and two, respectively. Conclusions: This study shows that PET/CT is a useful surveillance tool for detecting recurrence in asymptomatic high-risk resected stage III melanoma patients, especially within the first six months after surgery and therefore should be considered when monitoring these patients during follow-up as well as prior to starting adjuvant therapy.