tbuckley/cabot-search huggingface dataset:
Ventilatory efficiency and exercise capacity during exercise in patients with idiopathic pulmonary fibrosis
Authors: Dandan Huang, Jinming Liu, Wenlan Yang, Xingguo Sun, Shujuan Chen, Changwei Wu
Journal: BMJ (2014)

Objective
To explore the characteristics of ventilatory efficiency and exercise capacity during cardiopulmonary exercise testing in patients with idiopathic pulmonary fibrosis (IPF).


Methods
Pulmonary function test, arterial blood gas analysis and cardiopulmonary exercise testing were performed in 28 IPF patients (IPF group) from April 2012 to April 2013 and 28 healthy volunteers (control group). And the relevant parameters were measured and compared.


Results
No significant differences existed in age [(57.8±9.8) vs. (59.2±5.5) years], gender or body mass index (BMI) [(23.8±2.7) vs. (25.0±2.8)kg/m2,P>0.05]. The parameters of pulmonary function test, such as forced vital capacity % predicted (74.8±14.6 vs.101.8±10.8), forced expiratory volume in 1 second % predicted (73.8±14.6 vs.97.0±10.1), maximum voluntary ventilation % predicted (77.5±14.9 vs. 95.4±24.5), total lung capacity % predicted (75.6±12.4 vs. 99.8±5.4), residual volume % predicted (80.7±15.4 vs.95.8±11.3), diffusing capacity of lung for carbon monoxide % predicted (66.2±13.7 vs. 103.2±17.3) in the IPF group, were significantly lower than those of the control group (P<0.01). The parameters of arterial blood gas analysis, such as PaO2 [(72.7±7.3) vs. (92.6±3.8)mmHg] and SaO2 (94.3±2.1 vs. 98.3±0.7), were lower than those of the control group (P<0.01). Thus P(A-a)O2 in the IPF group was higher than that in the control group (33.3±5.7 vs. 17.8±1.9, P<0.01). These results strongly suggested that IPF group had restrictive ventilatory dysfunction and impaired gas exchange .The IPF patients had higher VE/VCO2-slope (37.4±5.3 vs. 25.7±2.5, P<0.01) and lowest VE/VCO2 (39.2±6.7 vs. 30.6±2.7, P<0.01) than the controls; VE/VCO2 and VD/VT during every period were significantly higher in the IPF group than those in the control group(P<0.01); during peak exercise, peakLoad%pred (70.4±29.9 vs. 104.8±29.7, P<0.01) and peakVO2%pred (68.7±29.8 vs. 98.7±36.4, P=0.001) were significantly lower in the IPF group than those in the control group. In the IPF group, VE/VCO2@AT, VE/VCO2-slope and lowest VE/VCO2 had a negative correlation with DLCO%pred (r=-0.589, P<0.01; r=-0.481, P<0.05; r=-0.527, P<0.05). In the IPF group, VE/VCO2@AT, VE/VCO2-slope and lowest VE/VCO2 had a negative correlation with peakVO2%pred (r=-0.548, P<0.05; r=-0.539, P<0.05; r=-0.564, P<0.05). So the exercise tolerance and ventilation efficiency of the IPF group decreased significantly.


Conclusion
Cardiopulmonary exercise testing reveals that the ventilation efficiency of IPF patients decreases significantly so as to seriously affect their exercise tolerance .


Key words: 
Pulmonary fibrosis; Exercise test; Respiratory function tests; Blood gas analysis
The frequency of HPD gene mutation profile in solid tumors with PD-L1 expression positive.
Authors: Sanyuan Tang, Shunli Zhao, Zhiqi Liu, Huiping Zhao, Caixia Gao, Minqi Tian, Xing Zhang, Chuang Qi, Chao Song
Journal: Journal of Clinical Oncology (2020)

e15175 Background: Program death-ligand (PD-L1) expression and tumor mutational burden (TMB) are the promising predictive biomarkers in immunotherapy for solid tumors. Immunotherapy could be harmful in patients harboring hyper-progressive disease (HPD) gene mutations. Nevertheless, the distributions of HPD gene mutation profile in patients with PD-L1 positive solid tumors especially in East Asian populations have not been well characterized yet. Methods: In this study, tumor tissues from 354 patients using 539 genes panel based on next generation sequencing were performed. Single nucleotide variants (SNVs) of DNMT3A gene and copy number variants (CNVs) of M DM2, MDM4, C CND1, F GF3, F GF4 and F GF19 genes were evaluated as HPD mutations. The protein expression of PD-L1 was divided into three groups as g1 (TC &lt; 1%), g2 (1% ≤ TC &lt; 50%) and g3 (TC ≥ 50%) via the percentage of positive tumor cells (TC value) identified by immunohistochemistry (IHC) method. The ratios of patients with or without HPD mutations in different PD-L1 expression groups were calculated by χ 2 test using program SPSS v22.0. Results: In 354 patients with solid tumors, 33 of 354 (9.3%) were found harboring HPD mutations. The ratios of patients with HPD mutations in three PD-L1 expression groups were 8.6% in g1, 10.4 % in g2 and 8.7% in g3, respectively. Meanwhile, the ratios of patients without HPD related mutations in three PD-L1 expression groups were 91.4%, 89.6 % and 91.3%, respectively. There were no significant differences of HPD frequency between different PD-L1 expression groups via χ 2 test (χ 2 = 0.323, p = 0.851). Conclusions: The frequency of HPD gene mutations was not significantly heterogeneous between different PD-L1 expression groups and indicated that immunotherapy for patients with PD-L1 expression positive needed to test HPD related gene mutations. Our study provided meaningful information to the precise administration of immunotherapy in cancer clinical practice. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
Growth differentiation factor 15 (GDF-15) as a key regulator of cachexia induced by platinum-based chemotherapy.
Authors: Danna Breen, Kevin Beaumont, Donald Bennett, Julia Brosnan, Roberto A Calle, Jeffrey Chabot, Susie Collins, Ryan Esquejo, Stephanie Joaquim, Alison Joyce, Hanna Kim, Laura Lin, Betty A Pettersen, Shuxi Qiao, Michelle I Rossulek, Karen Walters, Gregory Weber, Zhidan Wu, Bei Betty Zhang, Morris J Birnbaum
Journal: Journal of Clinical Oncology (2020)

e24162 Background: Platinum-based drug use in cancer treatment is restricted by dose-limiting side effects, including nausea/emesis, anorexia and weight loss that reduce patient quality of life and limit treatment adherence. Cisplatin increases GDF-15, a cytokine that induces aversion, anorexia and weight loss in preclinical models. GDF-15 signals through the hindbrain receptor glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) and cisplatin-induced weight loss was attenuated in a GFRAL knockout mouse. Methods: In the current study, using mouse and/or nonhuman primate models, we examined whether GDF-15 inhibition via a potent and selective monoclonal antibody (mAB1) prevents platinum-induced emesis, anorexia, weight loss, with increased survival. Results: Circulating GDF-15 levels in NSCLC and colorectal cancer were higher (~1.5 fold) in patients on platinum therapy compared to non-platinum-based therapy. Higher levels of circulating GDF-15 were also associated with greater weight loss in colorectal cancer patients prior to receiving FOLFOX as part of cancer treatment. In wildtype mice, cisplatin, oxaliplatin and carboplatin each increased circulating GDF-15 (≥ 5-fold) and induced anorexia, skeletal muscle wasting, and weight loss. These effects were prevented in GDF-15 knockout mice, however only a partial blockade of carboplatin was observed. The GDF-15 neutralizing efficacy of mAB1 was confirmed by reversing AAV-GDF-15-induced weight loss in wildtype mice. In nonhuman primates, cisplatin treatment for 5 days (96% of the daily recommended clinical dose) also increased circulating GDF-15 ( &gt; 5-fold), and induced anorexia and emesis. Treatment with mAB1 resulted in no detectable circulating levels of free GDF-15 and attenuated both cisplatin-induced anorexia and emesis. In a mouse cachectic tumor model (subcutaneous; NSCLC patient derived xenograft), cisplatin inhibited tumor growth; however, GDF-15 levels remained elevated and additional weight loss occurred compared to control. When mAB1 was given in combination with cisplatin, weight loss was reversed and tumor growth inhibition was maintained, resulting in greater survival compared to cisplatin alone. Conclusions: Taken together, these data support that GDF-15 inhibition with mAB1 holds the potential as an effective therapeutic approach to alleviate GDF-15 mediated emesis, anorexia and weight loss, with the aim to enable optimal cancer treatment as well as to improve patient quality of life and potentially survival.
Prospective investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement.
Authors: Rebecca Levin-Epstein, Joshua Rusheen, Preetham Kumar, Rubine Gevorgyan, Zoe McWatters, Won Kim, Tania Betty Kaprealian, Brian West, Jonathan Tobis
Journal: Journal of Clinical Oncology (2020)

e14510 Background: Brain metastases can lead to significant morbidity and mortality in patients with advanced cancer. Preventing metastatic disease to the brain could thus substantially improve outcomes. The mechanism of brain metastasis is incompletely understood. Circulating tumor cells drain to the right heart and through the pulmonary circulation, where they may manifest as lung metastases, and can circulate further to the left heart and then to the brain. However, in patients who develop brain metastases without prior lung involvement, metastatic cells may take an alternate route. We hypothesized that cancer cells may pass directly from the right to left heart via a patent foramen ovale (PFO), akin to paradoxical embolism. The prevalence of PFO is approximately 20-30% in the general population; if further elevated in this population, PFO may play a role in brain metastasis development, and ultimately, prophylactic PFO closure may provide benefit. We conducted a pilot study to investigate whether PFO is associated with brain metastases in patients without prior lung involvement. Methods: We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding lung metastases. Participants underwent a transcranial Doppler study to assess for PFO. Agitated saline was injected intravenously at rest and with Valsalva maneuver. High intensity signals were counted in the middle cerebral arteries for 1 minute after each injection. Spencer grade ≥3 indicated a positive study, consistent with the presence of PFO. Results: We accrued 9 participants who met inclusion criteria. Primary cancers were breast (6 participants), upper gastrointestinal (2 participants), and thyroid (1 participant). A positive study was identified in 2/9 (22.2%) participants. One individual was a female with breast cancer who had no preceding extracranial metastases, and the other individual was a male with duodenal adenocarcinoma whose only prior metastatic disease was distant lymphadenopathy, not active at brain metastasis diagnosis. No participants have developed lung metastases as of their most recent imaging. Conclusions: In this prospective pilot study, we found no increased prevalence of PFO in patients who develop brain metastases without preceding lung involvement compared to estimates for the general population. Though a larger study is needed, the development of brain metastases in these patients may reflect tumors’ biological factors directing metastasis organotropism, rather than a structural pathway.
Influential factors of brachial-ankle artery pulse wave velocity in healthy subjects
Authors: Jie Sun, Zhen-jie Wang, Sheng-sheng Wang, Xiao-rong Gai
Journal: BMJ (2011)

Objective To investigate the influential factors of brachial-ankle artery pulse wave velocity (baPWV) in healthy individuals.Methods Total 716 healthy subjects including 503 males and 213 females,who underwent health check up in 2010,were enrolled in the study Bilateral baPWV was examined in all subjects and multiple factor linear regression was applied to evaluate the correlations of baPWV with sex,age,body mass index,arterial blood pressure,ankle-brachial index and biochemical variables.Results The mean baPWV of 716 healthy subjecs was ( 1224 ± 162) cm/s,and there was significant difference between men and women [ ( 1257 ± 159) cm/s vs.( 1144 ± 143) cm/s].There was a significant linear correlation of baPWV with sex,age,mean arterial blood pressure and plasma homocysteine concentration ; and the linear regression equation was:mean PWV =6.635 × age + 7.285 × mean arterial blood pressure + 2.682 × homocysteine concentration - 64.334 × sex + 347.500 ( sex:man =0,woman =1 ).Conclusion Age,sex,mean arterial blood pressure and plasma homocysteine concentration are independent influential factors of baPWV.

Key words: 
Arteries;  Pulse wave velocity;  Regression analysis
Blockchain-authenticated sharing of cancer patient genomic and clinical outcomes data.
Authors: Shohei Burns, Eric Andrew Collisson
Journal: Journal of Clinical Oncology (2020)

e19358 Background: Efficiently sharing health data produced during standard care could dramatically accelerate progress in cancer treatments but various barriers make this difficult. Not sharing these data to ensure patient privacy is at the cost of little to no learning from real-world data produced during cancer care. Furthermore, recent research has demonstrated a willingness of cancer patients to share their treatment experiences to fuel research, despite potential risks to privacy. The objective of this study was to design, pilot, and release a decentralized, scalable, efficient, economical, and secure strategy for dissemination of de-identified clinical and genomic data with a focus on late stage cancer. Methods: We created and piloted a blockchain-authenticated system to enable securely sharing de-identified patient data derived from standard of care imaging, genomic testing, and electronic health records (EHR), called the Cancer Gene Trust (CGT). We prospectively consented and collected data for a pilot cohort (n = 18), which we uploaded to CGT. EHR data were extracted from both a hospital cancer registry and a common data model format to identify optimal data extraction and dissemination practices. Specifically, we scored and compared the level of completeness between two EHR data extraction formats against the gold-standard source documentation for patients with available data (n = 17). Results: While the total completeness scores were greater for the registry reports than the common data model, this difference was not statistically significant. We did find that some specific data fields, such as histology site, were better captured using the registry reports, which can be used to improve the continually adapting common data model. In terms of the overall pilot study, we found that CGT enables rapid integration of real-world cancer patient data in a more clinically useful timeframe. We also developed an open-source web application to allow users to seamlessly search, browse, explore, and download CGT data. Conclusions: Our pilot demonstrates the willingness of cancer patients to participate in data sharing and how blockchain-enabled structures can maintain relationships between individual data elements while preserving patient privacy, empowering findings by third party researchers and clinicians. We demonstrate the feasibility of CGT as a framework to share health data trapped in silos to further cancer research. Further studies to optimize data representation, stream, and integrity are required.
Sarcomatoid urothelial carcinoma: Oncologic outcomes from a tertiary center and SEER-Medicare data.
Authors: Rishi Robert Sekar, Leonidas Nikolaos Diamantopoulos, Ali Raza Khaki, Funda Vakar-Lopez, Maria S. Tretiakova, Sarah P. Psutka, Sarah K Holt, John L. Gore, George R. Schade, Daniel W. Lin, Andrew Caleb Hsieh, John Kyung Lee, Todd Yezefski, Michael Thomas Schweizer, Heather H. Cheng, Evan Y. Yu, Lawrence D. True, Robert B. Montgomery, Petros Grivas, Jonathan L. Wright
Journal: Journal of Clinical Oncology (2020)

e17033 Background: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive bladder cancer variant with little evidence regarding prognostic characteristics and response to neoadjuvant chemotherapy (NAC). In this study, we delineate oncologic outcomes in patients with SUC after radical cystectomy (RC), presenting data from our institutional database and SEER-Medicare. Methods: We retrospectively queried our institutional database to identify consecutive patients with cT2-4 SUC and conventional (non-variant) UC (CUC) who underwent RC (2003-2018). SEER-Medicare database was also searched for patients with cT2-4 SUC (2004-2015). Clinicopathologic/treatment data were captured. Overall survival (OS – diagnosis to death) was estimated with the Kaplan-Meier method. T-test, χ 2 test and log-rank test were used for group comparison analysis. Factors significant in univariate analysis for OS were included in the multivariate (MVA) Cox proportional hazards model. Results: Institutional RC database yielded 38 patients with SUC and 287 with CUC, while 190 patients with SUC were identified from SEER-Medicare [83 (44%) had RC]. Platinum-based NAC was given to 17/38 (45%), 162/287 (56%) and 26/83 (31%) patients, respectively. Institutional patients with SUC had significantly higher rates of pT3/4 disease at RC (66% vs. 35%, p &lt; .001) and lower rates of complete pathologic response (ypT0N0) following NAC (6% vs 35%, p = .02). Median OS in patients who had RC was significantly inferior in our institutional SUC vs. CUC group (20 vs. 121 months, p &lt; .001) and 21 months in the SEER-SUC cohort. No significant difference in OS was identified between NAC+RC vs. RC alone, both in the institutional (17 vs. 20 months, p = 0.66) and SEER-SUC cohort (24 vs. 20 months, p = 0.56). In MVA for the entire institutional cohort (SUC+CUC combined), SUC was independently associated with worse OS, when adjusted for advanced age, pT/N stage, performance status, NAC, lymphovascular invasion, surgical margins (HR, 95% CI: 2.3, 1.4 - 3.8, p = .001). Five patients had an abdomino-pelvic cystic recurrence, with median time to recurrence &lt; 5 months. Conclusions: Patients with SUC treated with RC had high rates of extravesical extension, poor response to platinum-based NAC and worse OS compared to patients with CUC. Data from SEER showed a comparable OS to our SUC cohort. NAC was not associated with improved OS in any SUC cohort (institutional or SEER). A unique pattern of rapid abdomino-pelvic cystic recurrence, mimicking post-RC abdominal fluid collections, was also identified.
Inappropriate colorectal and breast cancer screening in patients with advanced cancer.
Authors: Jonathan Pirruccello, Jonathan Calderon, Rakesh Surapaneni
Journal: Journal of Clinical Oncology (2020)

e19197 Background: Despite the low five-year expected survival of patients with advanced cancer, it has been suggested that up to 1.7% of patients aged 65 and older with advanced cancer may continue to undergo screening for colorectal cancer and up to 8.9% of female patients 65 and older with an advanced cancer may receive a screening mammography. 1 The intent of our study was to determine the rate of colorectal and breast cancer screening in men ages 50-75 and women ages 40-75 after these patients were diagnosed with an advanced cancer. Methods: The medical records of 208 patients (median age 63.5, range 42-75) with a diagnosis of stage IV colorectal, prostate, breast, liver, gastroesophageal, skin, uterine, bladder, kidney and stage III-IV pancreatic and lung cancer were reviewed for documentation of a screening mammography, colonoscopy or FIT-DNA testing after the patient was diagnosed with an advanced cancer. Results: Overall, 4.8% of patients were screened for colorectal cancer and 10% of the females received at least one mammogram. The screening mammography rate in patients less than 64 years of age was 13.3% and the colorectal screening rate in this age group was 4.4%. In patients 65 and older, the screening mammography rate was 7% and the colorectal screening rate was 5.2%. Conclusions: Colorectal and breast cancer screening rates in patients with advanced cancer were higher within our fully integrated healthcare system in comparison to previously reported findings in patients 65 and older. In addition, the rate of screening with mammography may be more prevalent amongst patients 64 or younger with advanced cancer in comparison to patients 65 and older with a similar diagnosis. The next phase of this quality improvement project involves disabling health maintenance prompts within the electronic medical record of patients with advanced cancer. References: 1. Sima, C. S., Panageas, K. S., &amp; Schrag, D. (2010). Cancer screening among patients with advanced cancer. Jama, 304(14), 1584-1591. doi:10.1001/jama.2010.1449 [doi].
SWOT analysis and strategy for construction of community children′s rehabilitation base: a case study
Authors: Jing Zhang, Shuhao Wang, Wei Shi, Daidai Lai
Journal: BMJ (2017)

With Minglou Community Children′s Rehabilitation Base as a case, which was jointly founded by tertiary specialized hospital and community health service center, the paper introduced how to use SWOT model to systematically analyze the strengths and weaknesses of the internal environment, opportunities and threats of external condition. Based on the analysis, the solutions, suggestions and policy of children′s rehabilitation were proposed, providing reference for decision making to promote the community children′s rehabilitation.


Key words: 
Rehabilitation; Community health services
Developing a breast cancer tissue biobank in low and middle income countries (LMICs): A research program-based approach for improving molecular profiling.
Authors: Avinash Sharma, Oluwole O. Odujoko, Olusegun Isaac Alatise, Marcia Edelweiss, Peter Ntiamoah, Gbenga Samson Ogunleye, T. Peter Kingham, Neil M. Iyengar
Journal: Journal of Clinical Oncology (2020)

e12585 Background: Breast cancer incidence and mortality is increasing in LMICs especially in sub-Saharan Africa, attributed to changes in lifestyle and possible biological differences. To study putative relationships among lifestyle factors, tumor biology, and the microenvironment, we aimed to develop a breast cancer tissue biobank linked with clinicopathologic and patient reported data in this resource constrained setting. Methods: We prospectively enrolled patients undergoing mastectomy at Obafemi Awolowo University Teaching hospital in Ile-Ife, Nigeria. Pre-operatively, a locally validated survey tool assessed lifestyle factors (diet and exercise); BMI and body composition (by bioimpedence) were measured. Fresh breast tissue was frozen or preserved in 10% neutral buffered formalin, or RNA later for future metabolomic work. Immunohistochemistry (IHC) for ER/PR and HER2 status was performed and read in Nigeria by a locally-trained pathologist, and Memorial Sloan Kettering. The primary outcome was feasibility assessed by successful collection of tissue, clinicopathologic data, and survey completion. Secondary outcomes were completion rate of tumor receptor IHC compared to historic rates and concordance of local vs MSK IHC. Results: From April 2018 to June 2019, 50 patients were enrolled (49 treatment and 1 risk reduction mastectomy). Clinicopathologic, body composition, and survey data, along with breast tissue were collected from all 50 patients. Patient characteristics in table below. Receptor IHC was complete in all patients (100%) compared to a historic rate of 29% (83/286) between 2010-17. Concordance of IHC between sites was 86%, 81% and 84% for subtypes (ER/PR/HER2). Conclusions: Establishing a tissue biobank with clinicopathologic and lifestyle data using locally-adapted protocols is feasible in Nigeria. Patient enrolment is ongoing and updated data will be presented. This initiative also increased local capacity for breast tumor phenotyping, which has critical implications for improving patient care. [Table: see text]