tbuckley/cabot-search huggingface dataset:
Video vs. in-person genetic counseling for men considering germline prostate cancer testing: A patient-choice study.
Authors: Veda N. Giri, Nicholas Bowler, Sarah Hegarty, Laura Gross, Colette Hyatt, William Kevin Kelly, Leonard G. Gomella
Journal: Journal of Clinical Oncology (2020)

1577 Background: Germline testing (GT) for prostate cancer (PCA) is rapidly increasing with higher demand for genetic counseling (GC). Alternate GC strategies need to be studied to address pretest informed consent. Here we conducted a patient-choice study of pretest video-based genetic education (VBGE) or in-person GC (IPGC) and assessed men’s preference and patient-reported outcomes from the first cohort of the Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER) study. Methods: Eligibility for EMPOWER includes any male with PCA or at-risk for PCA based on family history or African American race. Men may choose pretest IPGC or VBGE. All receive results by a genetic professional. Demographics and PCA features were collected at baseline. The following outcomes and scales were assessed: baseline anxiety (GAD-7 scale), change in cancer genetics knowledge from baseline (Giri 2019), decisional conflict for GT (O’Connor 1993), and satisfaction (DeMarco 2004). Understanding of personal GT results was assessed after disclosure (Giri 2019). Descriptive statistics summarized results with counts and percentages for categorical variables and mean and standard deviation for continuous variables. Data were compared with Fisher’s exact, Chi-squared, or Wilcoxon two-sample tests, as appropriate. Mean change in cancer genetics knowledge was compared with t-tests. Significance level was set a priori at 0.05. All analyses were performed with SAS 9.4 (Cary, NC). Results: At the time of this analysis, 94 men were enrolled. Characteristics of the cohort were: White (88.3%), bachelor’s degree (67%), PCA diagnosis (93%), mean age of consent 59 years (IPGC) and 61 years (VBGE), Gleason &gt; = 8 (32%), and &gt; = T3 (31%). The majority preferred VBGE (77%) vs. IPGC (23%). Men who opted for IPGC had lower educational levels ( &lt; = high school/GED) (18% IPGC vs 7% VBGE) and reported higher baseline anxiety (45% IPGC vs. 24% VBGE). Cancer genetics knowledge improved significantly with IPGC vs. VBGE (+2.5 vs +0.8; p &lt; 0.01). No differences were observed in decisional conflict, satisfaction, or understanding of personal GT results between IPGC vs. VBGE. Both groups had high rates of GT uptake (IPGC 91%, VBGE 93%). Pathogenic mutations were identified in 15% in IPGC group and 10.4% in VBGE group. Conclusions: A substantial proportion of men opted for VBGE, and results suggest that VBGE is comparable to IPGC for men considering PCA GT. IPGC may be more suitable for men with lower knowledge of cancer genetics and greater levels or anxiety. Further study is warranted.
Impact of Left Atrial Appendage Exclusion on Short-Term Outcomes in Isolated Coronary Artery Bypass Graft Surgery
Authors: Eitezaz Mahmood, Robina Matyal, Feroze Mahmood, Xinling Xu, Aidan Sharkey, Omar Chaudhary, Sadia Karani, Kamal Khabbaz
Journal: Circulation (2020)

Background: The objective of this study was to evaluate the impact of left atrial appendage (LAA) exclusion on short-term outcomes in patients with atrial fibrillation undergoing isolated coronary artery bypass graft surgery. Methods: We queried the 2010 to 2014 National Readmissions Database for patients who underwent coronary artery bypass graft repair with and without LAA ligation by using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes ( International Classification of Diseases, Ninth Revision, Clinical Modification : 36.1xx). Only patients with a history of atrial fibrillation were included in our analysis. The primary outcome of our study was 30-day readmissions following discharge. Secondary outcomes were in-hospital mortality and stroke. To assess the postoperative outcomes, we used multivariate logistic regression models to adjust for clinical and demographic covariates. Results: In total, we analyzed 253 287 patients undergoing coronary artery bypass graft surgery, 7.0% of whom received LAA closure. LAA exclusion was associated with a greater risk of postoperative respiratory failure (8.2% versus 6.2%, P &lt;0.0001) and acute kidney injury (21.8% versus 18.5%, P &lt;0.0001), but it did not significantly change the rate of blood transfusions or occurrence of cardiac tamponade. LAA exclusion was associated with a nonsignificant reduction in stroke (7.9% versus 8.6%, P =0.12), no difference in in-hospital mortality (2.2% versus 2.2% P =0.99), and a greater risk of 30-day readmission (16.0% versus 9.6%, P &lt;0.0001). After covariate adjustment, LAA ligation remained a significant predictor of 30-day readmission (odds ratio, 1.640 [95% CI, 1.603–1.677], P &lt;0.0001). Conclusions: LAA exclusion during isolated coronary artery bypass graft surgery in patients with atrial fibrillation is associated with a higher rate of 30-day readmission. Postoperative measures to mitigate the loss of the hormonal and hemodynamic effects of the LAA may increase the therapeutic benefit of this procedure.
Genomic analysis of castration sensitive and resistant prostate cancer patients by multiple-gene targeted sequencing.
Authors: Liancheng Fan, Xiaochen Fei, Baijun Dong, Wei Xue, Tingting Zhao, Xuan Zou
Journal: Journal of Clinical Oncology (2020)

e17525 Background: Previous studies showed the significant diversity of the genomic landscapes between castration sensitive prostate cancer (CSPC) and castration resistant prostate cancer (CRPC). AR, TP53/RB1, and BRCA2/ATM have been reported to contribute to the development of CRPC. In addition, CDK12 has recently reported to lead to the worse response to AR-targeted therapies. We are aimed to clarify the landscape of somatic gene alterations in CSPC and CRPC by multiple-gene targeted sequencing and discover the differential genes between the two treatment stages in order to guide clinical treatment. Methods: We recruited 413 prostate cancer patients including 230 CSPC and 183 CRPC. Cell-free DNA was extracted from plasma samples. Targeted sequencing of 50 genes was performed, which involved in DNA damage repair (DDR) pathway, AR pathway, TP53/RB1, etc. Chi square test or Fisher test were used to analyze the differences between two cohorts. Results: A total of 33.04% (76/230) CSPC patients carried somatic gene alterations, including 16.96% (39/230) in DDR pathway, 19.57% (45/230) in AR pathway and 7.39% (17/230) in TP53/RB1. The most frequent altered gene in CSPC was FOXA1 (9.13%,21/230), followed by NCOR2 (6.52%,15/230) and TP53 (5.65%,13/230). For CRPC patients, 66.67% (122/183) carried somatic gene alterations, including 44.81% (82/230) in DDR pathway, 49.73% (91/230) in AR pathway and 25.68% (47/183) in TP53/RB1. The most frequent mutated gene in CRPC was AR (33.33%,61/183), followed by FOXA1 (23.50%,43/183) and CDK12 (17.49%,32/183). Mutation frequencies of certain genes in CRPC patients were significantly higher than CSPC patients, including CDK12 (p &lt; 0.001), BRCA2 (p = 0.006), ATM (p = 0.003), ATR (p = 0.007), AR (p &lt; 0.001), FOXA1 (p = 0.001), SPOP (p = 0.002), ZBTB16 (p = 0.02), TP53 (p = 0.001), RB1 (p = 0.04) and PTEN (p = 0.001). Conclusions: It was the first study which explored the genomic alterations in Chinese CSPC and CRPC patients by liquid biopsy. These findings confirmed the genomic diversity between CSPC patients and CRPC patients, which could guide the individualized and precise management of prostate cancer in general practice. Furthermore, our findings indicated that somatic alterations in AR, CDK12, BRCA2, ATM and TP53/RB1 might contribute to the development of CRPC.
Obstetrical and perinatal complications in survivors of childhood, adolescent, and young adult cancer: A population-based study.
Authors: Alina Zgardau, Paul C. Nathan, Sumit Gupta, Joel G. Ray, Nancy N. Baxter, Chenthila Nagamuthu, Cindy Lau, Alison Park
Journal: Journal of Clinical Oncology (2020)

10529 Background: Women who survive cancer diagnosed in childhood, adolescence or young adulthood may develop long-term health issues. Data are lacking on adverse reproductive outcomes such as infertility and obstetrical and perinatal complications. Methods: Using linked Ontario provincial cancer and obstetrical registries, we assembled a cohort of female cancer survivors diagnosed before age 21 years from 1985-2012. We matched survivors by age and geographic region to females without a prior cancer diagnosis. Outcomes included i) any recognized and past 20 weeks’ gestation pregnancy; ii) perinatal complications; and iii) obstetrical complications (including a broad composite of severe maternal morbidity [SMM]). Multivariable Cox proportional hazard and modified Poisson models compared survivors to a non-cancer group and assessed demographic, diagnostic and treatment risk factors in survivors. Results: 3,486 survivors were matched to 17,428 women without prior cancer. Median age at cancer diagnosis was 12 years (IQR 5-16) and median follow-up was 26 years (IQR 21-32). 599 (17.2%) survivors had at least one recognized pregnancy compared to 3,885 (22.3%) women without prior cancer (Hazard Ratio [HR] 0.79, 95% Confidence Interval [CI] 0.7-0.9, p &lt; .0001). Among those who had a recognized pregnancy, 581 (97.0%) survivors carried a pregnancy &gt; 20 weeks’ gestation vs. 3791 (97.6%) in the non-cancer group (Relative Risk [RR] 1.0, CI 0.98-1.04). Factors significantly associated with a decreased likelihood of achieving at least one recognized pregnancy among survivors included brain tumour, cranial radiation, exposure to an alkylating agent or hematopoietic stem cell transplantation (HSCT). Among women who had a livebirth or stillbirth, survivors had a RR of 2.3 (CI 1.5-3.6) for SMM and 3.2 (CI 1.6-6.6) for cardiac morbidity. Factors associated with SMM among survivors included brain tumour and pre-existing kidney disease. Among livebirth pregnancies, cancer survivors were at higher risk of preterm birth (RR 1.6, CI 1.2-2.0), especially those who received an alkylating agent or HSCT. Conclusions: Survivors of childhood, adolescence or young adulthood cancer are less likely to achieve a recognized pregnancy compared to women without prior cancer. Those who carry a pregnancy &gt;20 weeks’ gestation are at higher risk for SMM and preterm birth. Fertility planning and counseling can be informed by cancer diagnosis and treatment, and high-risk obstetrical care is recommended for survivors at elevated risk of an adverse pregnancy outcome.
Prevention and treatment for hypertension in community:long way to go
Authors: 张晓林
Journal: BMJ (2009)

高血压是最常见的心血管疾病,是全球重大公共卫生问题.我国1991年对94万15岁以上人群抽样调查,高血压标化患病率为11.26%,与1979-1980年数据相比,10年间患病率增加25%[1-3].2002年高血压标化患病率则为17.7%,10年间增加31%,平均每10个成人有2人是高血压病患者[4].由于高血压控制不良,导致脑卒中和心脏病发病率和死亡率居高不下。
Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization
Authors: Jing Zhang, Jonathan Muri, Gillian Fitzgerald, Tatiane Gorski, Roberto Gianni-Barrera, Evi Masschelein, Gommaar D’Hulst, Paola Gilardoni, Guillermo Turiel, Zheng Fan, TongTong Wang, Mélanie Planque, Peter Carmeliet, Luc Pellerin, Christian Wolfrum, Sarah-Maria Fendt, Andrea Banfi, Christian Stockmann, Inés Soro-Arnáiz, Manfred Kopf, Katrien De Bock
Journal: Cell Metabolism (2020)

Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype. Mechanistically, loss of pfkfb3 reduced lactate secretion by ECs and lowered lactate levels in the ischemic muscle. Addition of lactate to pfkfb3-deficient ECs restored M2-like polarization in an MCT1-dependent fashion. Lactate shuttling by ECs enabled macrophages to promote proliferation and fusion of muscle progenitors. Moreover, VEGF production by lactate-polarized macrophages was increased, resulting in a positive feedback loop that further stimulated angiogenesis. Finally, increasing lactate levels during ischemia rescued macrophage polarization and improved muscle reperfusion and regeneration, whereas macrophage-specific mct1 deletion prevented M2-like polarization. In summary, ECs exploit glycolysis for angiocrine lactate shuttling to steer muscle regeneration from ischemia.
Fine-needle aspiration biopsy for thyroid nodules: a clinical and pathological study of 782 patients
Authors: Xiao-pin Cai, Yao Wang, Zhao-jun Fang, Jin-ping Zhang, Yi-fan He, Guang-wei Li
Journal: BMJ (2010)

Objective To evaluate clinical application of thyroid fine-needle aspiration biopsy (FNAB) and its diagnostic value.Methods FNAB was performed for 782 cases during 2005-2009 at China-Japan Friendship Hospital,Beijing and their clinical pathological data were retrospectively analyzed.Cytopathological diagnoses by FNAB were classified as unsatisfactory,benign,atypical cellular lesions,follicular neoplasm,suspicious malignancy and definite malignancy.Results of thyroid cytological and histological examinations of 76 patients with subsequent thyroidectomies were compared to those with FNAB to evaluate its diagnostic accuracy.Results Of 782 FNAB specimens,74.4 % (582/782) were classified as benign,2.6 % (20/782) as malignant,5.6 % (44/782) as follicular neoplasm,3.2 % (25/782) as atypical cellular lesion,2.9% (23/782) as suspicious malignancy and 11.3 % (88/782) as unsatisfactory.Among 76 patients with thyroidectomies,65.8 % of them (50/76) were histologically diagnosed as benign lesion,28.9 % (22/76) as definite malignancy and only 5.3 % (4/76) as benign follicular adenoma.Agreement between FNAB cytological diagnoses and histologically confirmed diagnoses for benign lesion and malignancy was 16/16 and 16/17,respectively.Conclusion FNAB is a reliable diagnostic method for evaluation of thyroid nodules.

Key words: 
Thyroid nodule; Biopsy,fine-needle; Pathology,clinical
Assessment of Climate-Health Curricula at International Health Professions Schools
Authors: Brittany Shea, Kim Knowlton, Jeffrey Shaman
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Researchers have published surveys on health professionals' perceptions of the possible association between climate change and health (climate-health) and assessed climate-health or planetary health curricula in medical schools. However, curricula on climate-health are still lacking and gaps in knowledge persist. <h3>Objective</h3> To understand the state of climate-health curricula among health professions institutions internationally. <h3>Design, Setting, and Participants</h3> A survey of 160 institutional members of the Global Consortium on Climate and Health Education, which includes international health professions schools and programs, was conducted from August 3, 2017, to March 1, 2018. The survey, hosted by Columbia University Mailman School of Public Health, used an online survey tool for data collection. <h3>Main Outcomes and Measures</h3> The survey assessed climate-health curricular offerings across health professions institutions internationally, including existing climate-health educational offerings, method of teaching climate-health education, whether institutions are considering adding climate-health education, whether institutions received a positive response to adding climate-health curricula and/or encountered challenges in adding curricula, and opportunities to advance climate-health education. <h3>Results</h3> Overall response rate to the survey was 53%, with 84 of 160 institutional responses collected; 59 of the responses (70%) were from schools/programs of public health, health sciences, or health professions; 15 (18%) were from medicine; 9 (11%) were from nursing; and 1 (1%) was from another type of health profession institution. Among respondents, 53 (63%) institutions offer climate-health education, most commonly as part of a required core course (41 [76%]). Sixty-one of 82 respondents (74%) reported that climate-health offerings are under discussion to add, 42 of 59 respondents (71%) encountered some challenges trying to institute the curriculum, and most respondents have received a positive response to adding content, mainly from students (39 of 58 [67%]), faculty (35 of 58 [60%]), and administration (23 of 58 [40%]). <h3>Conclusions and Relevance</h3> Current climate-health educational offerings appear to vary considerably among health professions institutions. Students, faculty, and administration are important groups to engage when instituting curricula, and awareness, support, and resources may be able to assist in this effort.
Smoking Pattern in Men and Women: A Possible Contributor to Sex Differences in Smoke-related Lung Diseases
Authors: Mario Polverino, Antonio Capuozzo, Gaetano Cicchitto, Francesco Ferrigno, Immacolata Mauro, Carlo Santoriello, Emanuela Sirignano, Andrea Aliverti, Bartolome Celli, Francesca Polverino
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

hoc test odds would be 0.076 [0.25 3 0.303] and corresponding to a post hoc test probability of 7.6% [0.076/(1 1 0.076)]) (8).We designed the classifier to assess organ quality for donor pool expansion strategies, to identify organs for possible rehabilitation on ex vivo lung perfusion, and to identify potential targets for directed therapies in clinical trials.The validation of the pathways identified in this transcript panel highlights the importance of the innate immune system in the development of PGD and identifies its constituent genes as potential therapeutic targets.This work builds on previous work identifying associated pathways and developing clinical predictors important in PGD to assess risk prior to procurement to facilitate decision making for potential therapeutics and advanced surgical therapies (3, 4, 7).Although these results are promising, there are limitations to consider.The cohort sample size was small, therefore reducing overall power.Nonetheless, this study represents a temporal validation in tissue of prior findings in blood and BAL using a conventional machine learning approach.Tissue biopsy is an invasive procedure with associated risks.We validated our classifier in tissue to ensure that all lung compartments were sampled (endothelial, epithelial, and lymphoid), and we acknowledge that further refinement will be necessary to scale to clinical practice.Additionally, translating gene expression prediction to the bedside will require development of point-of-care technologies using abbreviated gene sets, such as those using microfluidics (9).As this study cohort did not overlap with our prior cohorts, we were unable to assess interactions between blood, BAL, and tissue compartments.Although this work is supported by several other studies that show association (3, 4, 10), additional validation will be necessary to confirm discriminant and diagnostic validity and generalizability.In summary, we have demonstrated that transcript analysis of donor lung tissue, using an innate immunity pathway classifier, can be used in conjunction with clinical variables to predict PGD with excellent discrimination and precision.With the ability to identify organ risk, this panel has the potential to alter future PGD clinical trial designs and lead to the development of precision medical approaches.As PGD drives morbidity and mortality associated with lung transplant, further research in this area has the potential to improve outcomes following transplantation.
RICTOR amplification as a novel therapeutic target for lung cancer brain metastases.
Authors: Haiying Cheng, Ni Fan, Ethan Sokol, Feng Wang, Yiyu Zou, Monica Feng, Garrett M. Frampton, Tushar Bhagat, Amit Verma, Balazs Halmos, Roman Perez-Soler
Journal: Journal of Clinical Oncology (2020)

3597 Background: Approximately 20% to 50% of patients with advanced lung cancer develop brain metastases, which are associated with debilitating neurologic impairment and a dismal prognosis. There have been very limited studies investigating the genomics of brain metastases in lung cancer. Methods: We comprehensively investigated the frequency of PI3K/AKT/RICTOR/mTOR pathway aberrations in primary and metastatic sites using an extensive database of 11845 cases of lung adenocarcinoma by NGS (FoundationOne). The potential roles of RICTOR amplification in the development of brain metastases were studied both in vitro and in vivo in orthotopic mouse models. Results: Compared to the primary tumor, PI3K/AKT/mTOR gene alterations were more frequent in metastatic sites, with particular enrichment noted in brain metastases. RICTOR amplification alone accounted for the observed higher frequency both in brain metastases (brain vs. primary: 9.73% vs 3.50%, P = 2.6E-14; brain vs. other mets: 9.73% vs. 7.3%, P = 0.03) and other metastatic sites (other mets vs. primary: 7.3% vs.3.5%, P = 10E-15), whereas the frequency of PTEN, AKT1, PK3CA or mTOR genetic alterations was not different in the primary tumor, brain and other metastatic sites. In vitro, inducible RICTOR knockdown in H23 lung cancer cells (parental line with RICTOR amplification) was associated with reduced cell migration and invasion, whereas upregulation of RICTOR in HCC827 lung cancer cells (parental line with normal RICTOR copy numbers) was associated with an increase of both processes. These results were confirmed with pharmacological inhibition using mTOR1/2 inhibitors with known CNS penetration. In vivo, both inducible ablation of RICTOR and the mTOR1/2 inhibitor TAK228 (Sapanisertinib) significantly inhibited lung cancer H23-R4-Luc tumor growth in the brain, including a number of near complete responses. Mechanistic studies suggest that RICTOR may regulate the brain metastasis process through AKT and CXCL12 chemokine-CXCR4 axis. Conclusions: RICTOR amplification is the first identified actionable target that is markedly enriched in brain metastases. Our study provides a strong rationale for the development of RICTOR-targeted therapeutic strategies for the treatment and/or prevention of these major causes of lung cancer morbidity and mortality.