tbuckley/cabot-search huggingface dataset:
Early PSA decline as a predictor of progression in patients with metastatic castration-naïve prostate cancer (mCNPC) treated with abiraterone acetate and prednisone (AA/P).
Authors: Pedro C. Barata, Iris Yeong- Fung Sheng, Jaleh Fallah, Ruby Gupta, Hong Li, Kimberly D. Allman, Allison Martin, Moshe Chaim Ornstein, Timothy D. Gilligan, Brian I. Rini, Jorge A. Garcia
Journal: Journal of Clinical Oncology (2020)

e17542 Background: Treatment intensification with androgen deprivation therapy (ADT) plus AA/P is a standard of care in patients with metastatic castration naïve prostate cancer (mCNPC). Despite initial responses, nearly all men will eventually progress to castration resistant disease (CRPC). Early changes in PSA while on ADT plus AA/P has significant clinical and therapeutic implications for mCNPC patients, yet limited data is available. We aimed to assess PSA patterns while on therapy with ADT plus AA/P and time to CRPC. Methods: mCNPC patients treated with ADT plus AA/P between June 2017 and February 2019 at the Cleveland Clinic, were included. The primary objective was to describe patterns of PSA change evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. Other endpoints of interest included PSA progression by PCWG3 and CRPC-free survival at 12 and 18 months. Results: A total of 130 patients, 82% Caucasian, median age 69 years, with 50% with de-novo mCNPC, 47% high-volume (60.8% Gleason score ≥8, 16.2% visceral disease, and 53.8%had ≥3 bony lesions) were included. Half of the patients achieved undetectable PSA ( &lt; 0.03) while on therapy. The median time to PSA &lt; 0.03 was 13.1 months (95%CI, 7.6-NE). The greatest PSA reduction occurred at the first 3 months (80%, p &lt; 0.0001), changes after 3 months were small, (4% from 3 to 6 months, p &lt; 0.0001; 3% from 6 to 9 months, p &lt; 0.0001) and not significant from 9 to 12 months. The 12 and 18-months mCRPC-free survival after initiation of ADT plus AA/P was 88.1% and 81.3%, respectively. A PSA &gt; 0.2 at 3 months was associated with a shorter time to mCRPC (p = 0.002). Similarly, a PSA reduction &lt; 98% at 3 months was associated with worse outcomes (12 mo CRPC survival 68.0% vs. 94.9%, respectively; p &lt; 0.001). Conclusions: In this data set, timing and depth of serologic response predicted the early development of CRPC in patients receiving ADT plus AA/P. Further validation is ongoing using data from large randomized clinical trials.
生长迅速的尖锐湿疣一例
Authors: 汪春蕾
Journal: BMJ (2007)

患者男,43岁,因右侧腋窝、双侧腹股沟、肛周出现菜花状物1个月余,于2005年9月3日就诊.患者经常在外出差,3个月前曾有非婚性生活史.1个多月前,患者左侧腹股沟处出现数个粟粒大丘疹,瘙痒,自己使用曲安奈德益康唑膏、新霉素氟轻松乳膏外擦,随之在肛周、右侧腹股沟以及右侧腋窝出现类似的菜花状物,数目不断增多、增大,皮损局部有腥臭味,触之易出血,遂来我科就诊.体格检查:体形肥胖,系统检查未见异常。
Assessment of left ventricular systolic function by echocardiography
Authors: Zhilong Wang, Wenying Jin
Journal: BMJ (2018)

Assessment of left ventricular systolic function is the basis of clinical decision making for heart diseases, and is the most common application of echocardiography. Understanding and mastering the methods of left ventricular systolic function assessment is the basic requirement for learning echocardiographic techniques. This article describes the assessment of global systolic function and local systolic function of left ventricle with echocardiography.


Key words: 
Left ventricle; Systolic function; Echocardiography
Circulating tumor DNA as a promising biomarker of relapse risk for stage II-III colorectal cancer.
Authors: Gong Chen, Feng Wang, Jun-Jie Peng, San-Jun Cai, Ke-Feng Ding, Qian Xiao, Fu-Long Wang, Xiao-Jun Wu, Zhi-Zhong Pan, Pei-Rong Ding, Ling-Heng Kong, De-Sen Wan, Xiaojun Fan, Rui Liu, Hua Bao, Junli Zhang, Jiaohui Pang, Xue Wu, Yang Shao, Rui-hua Xu
Journal: Journal of Clinical Oncology (2020)

4079 Background: About 30-50% colorectal cancer patients undergoing a curative resection will experience disease recurrence ultimately. Early detection of recurrence is of great significance for improving the prognosis of colorectal cancer patients. Circulating tumor DNA (ctDNA) has been suggested to be a promising biomarker for postoperative surveillance and prognosis prediction in various cancers including colorectal cancer. However, its performance in predicting early recurrence of colorectal cancer as well as appropriate testing procedures still needs large-scale prospective studies to evaluate. Methods: A total of 246 patients with stage II-III colorectal cancer and underwent curative resection from three clinical centers of China were enrolled in this multicenter prospective cohort study. Tissue samples as well as serial plasma samples before surgery, 7 days and 6 months after surgery and 3 months interval afterwards until recurrence were collected, and subjected to deep targeted-panel sequencing containing 425 cancer-related genes. ctDNA baseline genomic alterations and dynamic changes were analyzed. Its performance in predicting early recurrence was evaluated and compared with other clinical routine investigations, including serum biomarkers CEA and CA199, and CT examination. Results: The ctDNA positive rates at baseline (before surgery) and 7 days after surgery were 72.9% and 18.1% respectively. Among 199 patients with complete survival data, 18 patients were recurrent during follow up period with a median disease-free survival of 280.5 days (114-461 days). At baseline, high clinical stage (p = 0.035), and PTEN mutation (p = 0.009) were significantly associated with increased recurrent risk; while APC mutation (p = 0.04) predicted a decreased recurrent risk. Detection of ctDNA 7 days after surgery [HR: 5.9 (1.94-17.97); p = 0.0004] or any time point before clinical recurrence [HR: 6.14 (2.3-16.38); p &lt; 0.0001] was associated with a significantly higher recurrent risk, and the HR increased accordingly with ctDNA mutation level. In multivariate analyses, ctDNA status was independently associated with relapse after adjusting for known clinicopathological risk factors. CEA status was not significantly (p &gt; 0.4) associated with disease-free survival. A risk scoring model comprising of clinical variables and ctDNA detection after surgery was constructed and can predict 18-month recurrence with an AUC of 0.77. Conclusions: ctDNA is a promising marker of risk stratification, and early relapse detection in resected stage II/III CRC patients. Clinical trial information: NCT03312374 .
Author Correction: Respiratory virus shedding in exhaled breath and efficacy of face masks
Authors: Nancy H. L. Leung, Daniel K. W. Chu, Eunice Y. C. Shiu, Kwok-Hung Chan, James J. McDevitt, Benien J. P. Hau, Hui-Ling Yen, Yuguo Li, Dennis K. M. Ip, J. S. Malik Peiris, Wing-Hong Seto, Gabriel M. Leung, Donald K. Milton, Benjamin J. Cowling
Journal: Nature Medicine (2020)
Prooxidant effect of α-tocopherol in pancreatic tumors.
Authors: Ekaterina I. Surikova, Elena M. Frantsiyants, Irina A. Goroshinskaya, Vladimir S. Trifanov, Viacheslav A. Aleynov, Ludmila A. Nemashkalova, Irina V. Neskubina, Maksim N. Chernyak, Sergey V. Sanamyants, Petr N. Gabrichidze, Oleg I. Kit, Galina V. Zhukova, Yuriy A. Fomenko, Dmitry S. Petrov
Journal: Journal of Clinical Oncology (2020)

e16698 Background: The coexistence of neuroendocrine tumors and pancreatic adenocarcinoma is rare, and treatment of such mixed tumors is challenging due to the differences in their natural course and response to systemic therapy. There is growing evidence that vitamins affect the biology of pancreatic tumors. The purpose of the study was to measure concentrations of retinol (RET), α-tocopherol (α-TCP) and diene conjugates (DC) in the blood of patients with pancreatic cancer in order to reveal its pathogenetic characteristics. Methods: Blood levels of RET and α-TCP (ELISA methods, Cloud-Clone Corp, USA), their ratio and DC concentrations (biochemical method) were measured before treatment if 42 patients with pancreatic cancer: adenocarcinoma (AC), T1-3N0-1M0, n = 9; AC with a neuroendocrine component (AC+NE) (up to 30%), n = 21; neuroendocrine tumors (NET), T1-3N0-1M0, n = 12. 22 healthy men of similar age were controls. All patients gave their voluntary informed consent for the study. Results: RET levels in all patient were statistically significantly lower than in controls: in AC by 3.8 times, in AC+NE by 1.9 times, in NET by 3.7 times (p = 0.0000). Concentrations of α-TCP in AC were 1.6 times (p = 0.0011) lower than in controls, in AC+NE were similar, and in NET α-TCP was 1.5 times higher than in controls (p = 0.0000). The ratio of α-TCP/RET in all patients significantly exceeded control values: in AC by 2.2 times, in AC+NE by 1.6 times, in NET by 5.7 times (p = 0.0000). Levels of DC in all patients were higher than in controls: in AC by 2.5, in AC+NE by 2.1, in NET by 2.7 times (p = 0.0001). Conclusions: Changes in serum levels of RET and α-TCP differ in patients with AC, NET and mixed tumors, which causes changes in the balance of vitamins and can contribute to a prooxidant effect, as evidenced by an increase in DC levels.
The influence of different postures on the efficacy of mechanical ventilation in critically ill patients with 2009 H1N1 influenza
Authors: Zhi-gang Zhang, Bin Shi, Bin Li
Journal: BMJ (2010)

28 patients with acute respiratory distress syndrome caused by 2009 H1N1 influenza were mechanically ventilated for 1 hour in the supine, lateral, semi-supine, lateral prone, and prone position respectively. Changes of heart rate, respiratory parameters and arterial partial pressure of oxygen ( PaO2 )were measured. There were no significant differences ( P ＞ 0. 05 ) of heart rate and mean arterial pressure among these postures. Lateral prone ( P ＜ 0. 05 ) and prone posture ( P ＜ 0. 01 ) , however, can both significantly improve tidal volume, mean airway pressure, PaO2, static lung compliance and oxygenation index. We concluded that mechanical ventilation delivered in the prone position can remarkably improve oxygenation in patients with H1N1 influenza-associated acute lung injury.

Key words: 
Influenza A virus,H1N1 subtype;  Posture;  Respiration,artificial
Electrocardiographic Changes in Acute Subendocardial Infarction
Authors: RODERICK W. COOK, JESSE E. EDWARDS, RAYMOND D. PRUITT
Journal: Circulation (1958)

Among 24 cases of small subendocardial infarctions included in this report are 10 cases of anteroseptal distribution in which the electrocardiogram was characterized by the presence of deeply inverted T waves in some or all of the precordial leads. Two other types of change encountered among the remaining 14 cases are described. Electrocardiographic changes in this group of 24 cases are compared with changes encountered in 5 cases of large and near circumferential acute subendocardial infarction described in part I of this study.
Economic evaluation of neoadjuvant chemotherapy for operable breast cancer.
Authors: Nicholas Zdenkowski, Shefi Mary D'Silva, Kenny Lawson, Penny Reeves, Frances M. Boyle
Journal: Journal of Clinical Oncology (2020)

e12637 Background: Neoadjuvant chemotherapy is widely and increasingly used for patients with operable breast cancer that is large or highly proliferative. Advantages include downstaging of the breast and. axilla, post-neoadjuvant salvage treatments for poor responders, surgical and reconstruction planning, prognostication and to give time for genetic testing. After neoadjuvant therapy, treatment options may change. We aimed to determine the financial impact to the health system, of neoadjuvant chemotherapy compared with surgery first. Methods: A literature search identified data on the probability of receiving certain investigations and treatments, and associated outcome probabilities for neoadjuvant and surgery-first patients. Published health utility results were used. These data were incorporated into a decision analytic economic model. A cost-utility analysis was undertaken, with sensitivity analyses to evaluate the impact of uncertainties in the data. Pricing was based on publicly available costings of investigations and treatment in Australian Dollars (AUD). A value of information analysis was undertaken to determine the value of further research to reduce uncertainty in results. Results: Expected costs for neoadjuvant vs surgery first differed by $77. Neoadjuvant therapy showed higher effectiveness that surgery first (QALY 0.708 vs 0.698 respectively. The average cost per QALY of neoadjuvant therapy was $7,232 AUD (ca. $4825 USD), below the threshold of $50,000 per QALY. In a sensitivity analysis, neoadjuvant therapy dominated when axillary dissection rate was lower than 60% and postmastectomy reconstruction rate was more than 27%. These factors had the greatest impact on results, which were otherwise robust. Probabilistic sensitivity analysis found that neoadjuvant therapy was cost-effective 71% of the time at a willingness-to-pay threshold of $50,000 per QALY. Value of information analysis found that primary research into treatment probabilities and outcome utilities is needed to validate these results. Conclusions: Neoadjuvant systemic therapy is a potentially cost-effective treatment. However, primary contemporary data in directly comparable patient populations is needed, including the impact of post-neoadjuvant systemic therapy.
Lifestyle and comorbid conditions as risk factors for community-acquired pneumonia in outpatient adults (NEUMO-ES-RISK project)
Authors: Rivero-Calle Irene, Cebey-López Miriam, Pardo-Seco Jacobo, Yuste José, Redondo Esther, Vargas Diego A, Mascarós Enrique, Díaz-Maroto Jose Luis, Linares-Rufo Manuel, Jimeno Isabel, Gil Angel, Molina Jesus, Ocaña Daniel, Martinón-Torres Federico, 崔晓霞
Journal: BMJ (2019)

背景
社区获得性肺炎（CAP）风险在初级保健中的信息是有限的。我们评估了不同生活方式和共病条件作为初级保健成人CAP的危险因素。


方法
一项回顾性观察对照研究。使用国家初级保健数据监测系统检索了2009至2013年在西班牙初级保健部门诊断的成人CAP病例。匹配年龄和匹配性别的对照组采用发病率密度抽样（比例2∶1）。以百分比和比值比来表示关联分析。为了避免偏倚效应，建立二项回归模型。


结果
51 139例患者和102 372例对照组做比较。平均年龄为61.4（19.9）岁。危险因素与CAP的显著相关性如下：艾滋病[比值比（95%可信区间）5.21（4.35~6.27）]、慢性阻塞性肺病（COPD）[2.97（2.84~3.12）]、哮喘[2.16（2.07~2.26）]、吸烟[1.96（1.91~2.02）]和口腔卫生问题[1.45（1.41~1.49）]。患者组中有危险因素存在的平均患病率为82.2%，对照组为69.2%。CAP患病率的增加与危险因素和年龄的累积有关：1个危险因素时，在18~60岁老人中的风险相关性是1.42，在>60岁人中是1.57；2个危险因素时，是1.88和2.35；≥3个危险因素时，是3.11和4.34。


结论
成人CAP初级保健中的危险因素普遍较高。主要与危险因素相关的是艾滋病、COPD、哮喘、吸烟、口腔卫生问题。我们的风险叠加结果可以帮助临床医生确定肺炎风险较高的患者。
Immunotherapy efficacy of strong positive PD-L1 expression non-small cell lung cancer (NSCLC) patients: A systematic review and meta-analysis.
Authors: Hongmin Lu, Longgang Cui, Yuezong Bai, Yuzi Zhang, Zhengyi Zhao
Journal: Journal of Clinical Oncology (2020)

e21701 Background: Immune-checkpoint inhibitors (ICIs) based therapy has been approved as the new 1L standard of care in advanced PD-L1 strong positive (&gt;=50%) non-small cell lung cancer (NSCLC). However, little is known about the differences of efficacy between monotherapy and combined therapy of checkpoint inhibitors. We did a systematic review and meta-analysis to assess the heterogeneity of efficacy between monotherapy and combined therapy in 1L PD-L1 strong positive NSCLC patients. Methods: We systematically searched PubMed, Cochrane library, Embase and and major conference proceedings from January 2000 to November 2019 for randomized controlled trials that had available hazard ratios (HRs) for death according to PD-L1 expression (&gt;=50%). The primary outcome was the difference in overall survival (OS). We calculated the pooled overall survival HR and 95% CI in monotherapy and combined therapy in 1L PD-L1 strong positive NSCLC patients using a random-effects model. Results: A total of 2211 publications were retrieved through initial literature search, 10 randomized controlled trials were included for this meta-analysis. No statistical differences were found between ICIs monotherapy and combined therapy (HR 1.09, 95% CI 0.88- 1.35). Subgroup analysis showed that immune monotherapy has similar effects to immune combined chemotherapy (HR 1.24, 95% CI 0.90-1.71) and immune combined immunotherapy (HR 1.01, 95% CI 0.81-1.27). Conclusions: For PD-L1 strong positive (&gt;=50%) NSCLC patients, ICIs monotherapy had similar efficacy when compared with ICIs combination therapy.
Disease monitoring and TKI resistance mutations of EGFR mutation-positive NSCLC patients via circulating tumor DNA.
Authors: Corinna Woestmann, Christine Ju, Bernd Hinzmann, Stephanie J. Yaung, Michael Thomas, Claus Peter Heussel, Mark Kriegsmann, Michael Meister, Marc Schneider, Felix Herth, Thomas Muley, Birgit Wehnl, John F. Palma, Yuqiu Jiang
Journal: Journal of Clinical Oncology (2020)

e21627 Background: 15–40% of NSCLC adenocarcinoma patients harbor EGFR sensitizing mutations. Tyrosine kinase inhibitors (TKI) provide significant clinical benefit in this population, yet all patients will develop resistance. Liquid biopsy has been demonstrated to reliably identify tumor associated somatic EGFR mutations. Quantitative assessment of mutated EGFR driven tumors could potentially be used to monitor disease progression, to assess therapeutic response, and to identify resistance mechanisms. Methods: 106 longitudinal plasma samples from 16 NSCLC patients who were treated with osimertinib as either first line or second line therapy were collected. A series of plasma samples collected during treatment and at the time of disease progression were analyzed with the AVENIO ctDNA Surveillance kit*. Mutations at each time point were identified and reported by the AVENIO software v2.0*. The mutation profile of each patient at different timepoints along with the treatment journey was examined in combination with clinical outcome data. Results: EGFR sensitizing mutations were detected in all plasma samples by sequencing except in 3 cases. Patients responsive to anti-EGFR therapy showed a rapid decrease of EGFR driver mutations to non-detectable levels. Meanwhile, patients who had stable disease or rapid disease progression had stable or slightly decreasing ctDNA levels after receiving the treatment. One patient had a MET amplification, FBXL7 SNV, and EGFR T790M detected at the time of disease progression which were not detected at baseline. One patient had both EGFR L858R and T790M mutations. This patient progressed very quickly on erlotinib. Detection of the T790M mutation decreased upon osimertinib administration, however, the L858R mutation level stayed the same. TP53 mutations were elevated in 3 patients at the time of progression, and could potentially be related to anti-EGFR resistance. Conclusions: This study clearly demonstrated that liquid biopsy could identify resistance mutations beyond EGFR prior to clinical progression. Plasma samples collected prior to or at disease progression could facilitate identification of novel resistant mutations to TKI therapy. Further studies to demonstrate the clinical utility of serial blood EGFR testing in NSCLC management are necessary. *For Research Use Only. Not for use in diagnostic procedures.
Correlation of heart rate recovery after exercise test with exercise capacity in patients with stable chronic obstructive pulmonary disease
Authors: Hai-jian Liu, Jin-ming Liu, Wen-lan Yang, Xing-guo Sun, Shu-juan Chen, Yan Zhang
Journal: BMJ (2013)

Objective
To explore the correlation between heart rate recovery after exercise test and disease severity in patients with chronic obstructive pulmonary disease (COPD) and assess its impact on the exercise capacity of COPD patients.


Methods
Arterial blood gas analysis, pulmonary lung function test and cardiopulmonary exercise testing were performed in 60 patients with stable COPD and 50 healthy volunteers. Based on the heart rate recovery after exercise test, COPD patients were divided into normal heart rate recovery group(n=41)and abnormal heart rate recovery group(n=19).


Results
The COPD patients had lower exercise capacity (peak oxygen uptake as percentage of predicted value, peak V·O2%pred) (66±15 vs. 89±11, P<0.01), peak heart rate [(134±21) vs. (149±13) beats/min, P<0.01], heart rate recovery[(18±9) vs. (27±10) beats/min, P<0.01] and higher resting heart rate [(83±13) vs. (77±13) beats/min, P<0.01] than the controls. Compared with normal heart rate recovery group, forced expiratory volume in one second as percentage of predicted (FEV1%pred) and exercise capacity decreased more significantly in abnormal heart rate recovery group(38±15 vs. 52±16, P<0.05 and 57±12 vs. 71±14, P<0.01). Heart rate recovery was significantly correlated with FEV1%pred and peak V·O2%pred (r=0.42, P<0.01 and r=0.52, P<0.01). Multivariate regression analysis showed that heart rate recovery and FEV1%pred could be used as independent predictors of exercise capacity in COPD patients.


Conclusion
In COPD patients, heart rate recovery is correlated with the degree of disease severity and it may be an independent predictor of exercise capacity.


Key words: 
Pulmonary disease, chronic obstructive; Heart rate; Exercise test
An intervention RCT-study aimed at improving mental health and increasing understanding of fertility preservation with Oncofertility! Psycho-Education And Couple Enrichment (O!PEACE) therapy.
Authors: Nao Suzuki, Tomoe Koizumi, Yodo Sugishita, Hiroshi Matsumoto, Tatsuro Furui, Manabu Futamura, Yasushi Takai, Kohei Sugimoto, Hiroko Nogi, Hideko Yamauchi, Akemi Kataoka, Shinji Ohno, Koichiro Tsugawa, Kiyotaka Kawai, Eisuke Fukuma
Journal: Journal of Clinical Oncology (2020)

12119 Background: Although ASCO revised Guidelines (2013) recommends referring to psychological professionals if cancer patients show concerns or anxiety about fertility, there is no evidence regarding the efficacy of psychotherapy. The aim of this study is to examine whether the Psycho-Education And Couple Enrichment (O!PEACE) therapy can reduce psychiatric symptoms and improve stress coping and marital relationship in breast cancer patients. Methods: Trial design: multicenter randomized controlled trial, pre-post design. Subjects were women aged 20–39 years with breast cancer before cancer treatment and their husbands. Couples were randomly assigned to receive O!PEACE therapy (n = 37) or not (usual care: n = 37). Assessments of PTSD symptoms, depression and anxiety were made as the primary end points at baseline and at the end of therapy before cancer treatment. Stress coping strategies, resilience, marital relationships, and marital communication were examined as secondary end points. Results: Four participants in O!PEACE therapy and one participant in the usual care withdrew from the trial. Intention-to-treat analyses were conducted using analysis of covariance after multiple imputation by R and SPSS. Series of ANCOVAs were integrated according to Rubin’s rule. A significant decrease was observed in the primary outcome of PTSD symptoms, from baseline to post-intervention, in women who participated in O!PEACE therapy (p = .011, η p 2 = .089). According to post-hoc analyses, for patients with a higher baseline IES-R-J score, O!PEACE therapy resulted in a significantly higher reduction in follow-up assessment IES-R-J score when compared with usual care (U = 172.80, p = .027, r = .258): 59.3% of the women in O!PEACE therapy showed a 5-point or greater reduction, whereas in usual care, 30.0% showed a 5-point or greater reduction. For husbands, the O!PEACE therapy also showed a significant improvement of giving up and blaming others as the stress coping strategy and escape-avoidance coping strategy in their marital communication. For breast cancer patients, the O!PEACE therapy significantly improved support from husbands and the patients’ knowledge level of oncofertility compared with those receiving usual care. Conclusions: Only two counseling sessions of O!PEACE therapy can reduce patients’ distress, improve their husbands’ coping style, and may build a better cooperative relationship for couples in terms of fertility preservation and cancer treatment. Clinical trial information: UMIN000017754 .