tbuckley/cabot-search huggingface dataset:
Prevalence of white coat hypertension and its effect on left ventricular hypertrophy
Authors: 黄建凤, 吴海英, 谢晋湘, 刘力生
Journal: BMJ (2004)

目的 探讨确诊高血压患者中白大衣高血压(WCH)的发生率及白大衣效应与左室肥厚的关系.方法入选诊室舒张压水平在95～114 mm Hg(1 mm Hg=0.133 kPa)的高血压患者224例,监测其24 h动态血压,并进行心电图、超声心动图、血清脂质和血糖等检查.结果224例中WCH的发生率为10.3%.1级高血压患者中WCH发生率最高(19.4%),2级次之(10.1%),3级最低(1.6%),趋势P<0.01.WCH患者左室质量明显低于持续性高血压患者(P<0.05).在收缩压(或舒张压)水平已经确定的情况下,均未发现收缩期(或舒张期)白大衣效应与左室肥厚相关.结论在确诊高血压患者中,WCH的发生多见于年轻女性、轻型高血压患者.WCH患者发生左室肥厚的危险性低于持续性高血压患者,白大衣效应与左室肥厚无明显相关, 提示白大衣高血压可能是一种良性现象。
GRP78 expression and clinical outcomes in pancreatic cancer: A single institution review.
Authors: Brian Ernest Johnson, Anshu Hemrajani, Xianzhong Ding, Michael Wesolowski, Reginald Hill, Echo Zhang, Asha R. Dhanarajan
Journal: Journal of Clinical Oncology (2020)

e16767 Background: Pancreatic Ductal Adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers. Poor prognosis can be attributed in part to late detection and chemoresistance. Perioperative chemotherapy with or without radiation is the standard treatment for resectable PDAC, however recurrence rates remain high. GRP78 (HSPA5/BiP) is an endoplasmic reticulum (ER) chaperone protein involved in regulation of the ER stress response that leads to pro-survival pathway activation and chemoresistance in tumor cells. Prior studies of suppression of GRP78 expression in PDAC cell lines led to increased pancreatic cell apoptosis in response to gemcitabine. In vivo studies of human PDAC xenografts showed that tumors with higher GRP78 expression were associated with increased chemoresistance. Methods: We conducted a single institution retrospective review of 53 patients who underwent resection of PDAC from 1/1/2009-7/1/2016. Archived tumor tissue expression of GRP78 was assessed by immunohistochemistry (IHC) and scored as 0-3+. GRP78 IHC scores of 0-1+ were categorized as low and scores of 2-3+ as high. Corresponding clinical data were collected. Adjusted effects of GRP78 expression on the hazard of treatment failure or death were estimated using Cox proportional hazards models. Type III Wald Chi-square p-values are reported for the overall effect in each model. Results: GRP78 expression level demonstrated a significant effect on disease free survival (DFS) in unadjusted analyses (HR 2.00, p = 0.05), as well as after adjusting for performance status (p = 0.03), initial overall stage (p = 0.05), pathological tumor stage (p = 0.02), pathological node stage (p &lt; 0.01), resection margins (p = 0.05), and neoadjuvant therapy (p = 0.05) in separate models. In unadjusted analysis, high GRP78 expression showed a trend towards worsened overall survival (OS), but did not reach statistical significance (HR 1.8, p = 0.11). The effect on OS was significant when adjusting for pathological tumor stage (p = 0.04) and pathological node stage (p = 0.01). (575). Conclusions: Consistent with prior animal studies, our retrospective review revealed that high GRP78 expression was associated with worsened DFS in patients with resectable PDAC. When adjusting for pathological staging, high GRP78 expression had a similar impact on OS. These findings warrant further evaluation of the role of GRP78 in prognosis, response to therapy and as a potential treatment target.
Omitting chemotherapy in more patients with early breast cancer in the post-TAILORx era.
Authors: Christos Markopoulos, Zoi Andromahi Sariyanni, Dimitrios C. Ziogas, Zoh Antonopoulou, Nikolaos Tsoulos
Journal: Journal of Clinical Oncology (2020)

e12534 Background: The purpose of this analysis is to evaluate how many patients previously treated according to OncotypeDX Recurrence Score (RS) could have been spared of Chemotherapy if the TAILORx RS data had been taken into account in the clinical treatment decisions. Methods: A series of 182 patients, 34-74 years of age with early breast cancer, treated in our Breast Unit during the last 10 years, for whom treatment decisions were based on OncotypeDX RS. The Recurrence Scores of all these patients were obtained and the actual treatment decisions that were made based on the pre-TAILORx cut-offs of RS 18 and 31 were recorded. These decisions were then re-evaluated based on the after TAILORx cut-off scores, by taking also into consideration the patients’ age. Descriptive statistics were used as well as logistic regression models to estimate the potential change in treatment decisions based on the new Oncotype Dx cut-offs. Results: In the cohort of patients we analyzed that underwent Oncotype Dx testing, 34.1% (62/182) received Chemotherapy, based on the initial pre-TAILORX cut-offs of the RS. When utilizing the new cut-offs (after TAILORx results) in combination with age, we have estimated that, for the patients &gt; 50 years of age, a 12.7% was potentially over-treated and for those ≤50 years old, 9.1% was potentially over-treated since they have received chemotherapy with a RS below 16; additionally, 30.8% of the patients of that age that have RS between 16 and 20 have received chemotherapy even though the average chemotherapy benefit for this group is 1.6% and can go up to 6.7% if they have a high clinical risk as it was defined by the investigators of the TAILORx trial. Finally, 84,6% of patients ≤50 years old with RS between 21-25 received chemotherapy with a 6.5% potential benefit demonstrated in the TAILORx trial. Conclusions: Our analysis suggests that, by using the cut-offs of TAILORx trial, adjuvant chemotherapy could had been omitted in at least a further 11.5% of patients with early breast cancer, reassuring their quality of life without declining their prognosis.
Metastatic melanoma of the heart: A systematic review.
Authors: Alexander M. Balinski, Connor C. Kerndt, Nathan P. Parry, Rafey A. Rehman, Raymond Y. Yeow, Salim S. Hayek
Journal: Journal of Clinical Oncology (2020)

e22017 Background: Melanomas are highly aggressive tumors that can metastasize to a wide array of organs, including the heart. Cardiac metastasis is rare and most often diagnosed post-mortem. Here, we perform a systematic review evaluating patient demographics, characteristics, management, and outcomes of cardiac melanoma metastases. Methods: A comprehensive literature review was performed in Cochrane Library, PubMed, and EmBase databases. Study quality was determined based on study design and clinical endpoints using the Oxford Center for Evidence Based Medicine (OCEBM) Levels of Evidence categorization. Demographic data, patient symptomatology, imaging findings, management strategies, and patient outcomes were collected and analyzed. Results: Thirty studies, all case reports or case series, met inclusion criteria. In total, 33 patients with cardiac metastasis from melanoma were identified and histologically confirmed. All 30 studies included in this review received an evidence level of 4 based on OCEBM Levels of Evidence categorization. The most common presenting symptom at the time of diagnosis of cardiac metastasis was shortness of breath (36.4%) and the most common physical exam finding was tachycardia (24.2%). The most common site of cardiac metastasis was the left ventricle (41.9%), followed by the right atrium (35.5%). Notable echocardiogram findings included right ventricular inflow obstruction (27.6%) and valvular dysfunction (24.1%). Valvular dysfunction, classified as prolapse, regurgitation, or stenosis, always involved the tricuspid valve. Treatment strategies typically involved surgical intervention (66.7%), chemotherapy (39.4%), or chemotherapy with surgical intervention (15.2%). Of the 22 cases that reported outcomes, the majority (59.1%) were disease-free without evidence of recurrence. Two patients (9.1%) experienced recurrence within one year of treatment and eight patients (36.4%) expired within 12 months. Conclusions: When symptomatic, cardiac melanoma metastases typically present with shortness of breath and tachycardia, with a predilection for the left ventricle and right atrium. Surgical intervention is currently the mainstay of treatment for successful cardiac melanoma metastasis management. [Table: see text]
Survival analysis of the prospective randomized Cher-Lob study evaluating the dual anti-HER2 treatment with trastuzumab and lapatinib plus chemotherapy as neoadjuvant therapy for HER2-positive breast cancer (BC).
Authors: Valentina Guarneri, Maria Vittoria Dieci, Giancarlo Bisagni, Daniele Giulio Generali, Katia Cagossi, Samanta Sarti, Antonio Frassoldati, Lorenzo Gianni, Luigi Cavanna, Graziella Pinotti, Antonino Musolino, Federico Piacentini, Andrea Michelotti, Saverio Cinieri, Gaia Griguolo, Federica Miglietta, Gian Luca De Salvo, Pier Franco Conte
Journal: Journal of Clinical Oncology (2020)

582 Background: The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete response (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. Here we report the results of survival analysis according to treatment arm and pCR. Methods: The CherLOB study randomized 121 HER2-positive, stage II-IIIA breast cancer patients to anthracyclines/taxane-based chemotherapy plus trastuzumab, lapatinib, or both. After surgery, patients received adjuvant trastuzumab for up to 1 year. The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib (Guarneri, J Clin Oncol 2012). Relapse-free survival (RFS) was calculated from randomization to breast cancer recurrence (locoregional or distant) or death from any cause, whichever first. Overall survival (OS) was calculated from randomization to death from any cause. Results: At a median follow up of 8.8 years, RFS rates at 5 years were: 85.8% in the trastuzumab + lapatinib arm, 77.8% in the trastuzumab arm, 78.1% in the lapatinib arm (log-rank p = 0.160). Patients treated with dual HER2 blockade (trastuzumab + lapatinib arm) experienced numerically better RFS as compared to patients treated with single HER2 blockade (trastuzumab arm and lapatinib arm combined): 5-yr RFS 85.8% vs 78.0%, log-rank p = 0.087; HR = 0.51, 95% CI 0.23-1.12, p = 0.093. The achievement of pCR was a strong prognostic factor. 5-yr RFS rate was 97.3% for pCR patients vs 72.9% for non-pCR patients (log-rank p &lt; 0.001, HR = 0.12, 95% CI 0.03-0.49, p = 0.003); similar significant results were observed in both the estrogen receptor-negative and estrogen-receptor positive subgroups. OS was also improved in pCR patients: 8-yr OS rates were 97.2% vs 80.0% for non pCR patients (log-rank p = 0.028, HR = 0.14, 95% CI 0.02-1.08, p = 0.060). Conclusions: In the Cher-LOB study, there was a not statistically significant signal for a better RFS for patients who received dual HER2 blockade with trastuzumab and lapatinib plus chemotherapy as compared to patients treated with single anti-HER2 agent (trastuzumab or lapatinib) plus chemotherapy. Patients achieving a pCR had longer RFS and OS as compared to non-pCR patients. Clinical trial information: NCT00429299 .
Linking insurance claims across time to characterize treatment, monitoring, and end-of-life care in metastatic breast cancer.
Authors: Jennifer Lee Caswell-Jin, Alison Callahan, Natasha Purington, Summer S. Han, Haruka Itakura, George W. Sledge, Nigam Shah, Allison W. Kurian
Journal: Journal of Clinical Oncology (2020)

7063 Background: Treatment and monitoring options for metastatic breast cancer (MBC) are increasing, but little is known about patterns or predictors of their use. Insurance claims are potentially informative, but tracking patient care timelines using episodic claims data has been cumbersome. Methods: We used an advanced cohort engine, implementing a temporal query language, to link IBM Marketscan claims over time for &gt; 125 million US individuals from 2007-2014. To select the most common MBC subtype (ER+, HER2-), our criteria were: ≥2 MBC ICD codes, ≥1 year of follow-up, and ≥1 CPT or medication code for endocrine therapy and 0 for HER2-targeted therapy. We defined aggressive MBC as ≥1 ICD code for visceral or central nervous system metastasis &lt; 1 year after the first MBC code. Geographic area was defined by 9 Census-Bureau designated regions. End-of-record was used as a surrogate for death in a Cox regression. We used multivariate logistic regression to determine correlation of factors, including disease aggressiveness and geography, with treatment, monitoring, and end-of-life events. Results: 7,335 women met criteria for ER+, HER2- MBC, with median age 59. Nearly half (46%) had aggressive disease, which correlated with shorter survival (hazard ratio (HR) 1.5 [1.4-1.6], P &lt; 0.001). Treatment: first-line was endocrine therapy for 64% versus chemotherapy for 36%. Monitoring: 79% were imaged mostly by CT versus 21% by PET-CT, with median between-scan interval of 81 days; 63% received CA 15-3 serum tumor markers. End-of-life: 10% had a hospice code, of whom 19% had an ICU stay and 34% chemotherapy in the prior 3 months. Correlates of care: Disease aggressiveness correlated with first-line chemotherapy (odds ratio (OR) 2.0 [1.8-2.2], P &lt; 0.001), PET/CT (OR 1.6 [1.4-1.8], P &lt; 0.001), more frequent scans (OR 2.3 [2.1-2.6], P &lt; 0.001), and chemotherapy &lt; 3 months pre-hospice (OR 1.2 [1.1-1.4], P &lt; 0.001), but not with CA 15-3 monitoring or ICU stay. Disease aggressiveness did not vary by region (χ2 P = 0.8), but region was significantly associated with treatment, monitoring, and end-of-life care (P &lt; 0.001). Conclusions: Approximately two-thirds of ER+, HER2- MBC patients receive first-line endocrine therapy and are monitored with CA 15-3 serum tumor markers; 10% had evidence of hospice use, a likely underestimate due to differential follow-up. MBC care patterns vary by geography while disease aggressiveness does not, suggesting that care is not optimally tailored to individuals. These insights from claims data can inform quality improvement for MBC care.
Helen Margaret James
Authors: John Eddy
Journal: BMJ (2020)

Helen Margaret James was educated at Llanelli grammar school and received the J P Morgan prize for the highest A level result in Carmarthenshire. She had a scholarship to Westminster and qualified with honours and a distinction in applied pharmacology and therapeutics. She then did the professorial, medical, and urology resident pathologist jobs. She went to West Middlesex Hospital as medical registrar and passed her royal …
过敏性支气管肺曲霉病二例并文献复习
Authors: 姚国忠, 曾力强, 张晋芝
Journal: BMJ (2006)

回顾分析武警上海总队医院近年来诊断的2例过敏性支气管肺曲霉病资料,探讨过敏性支气管肺曲霉病的临床表现、诊断、治疗方法,以期引起临床医生重视.并复习国内1994年至2005年相关文献,发现国内明确诊断的病例与国外相比极少,仅有5例。
A survey on perceptions of two-way referral system and career development among health practitioners in Beijing communities
Authors: Yue Sha, Chao-ying Qu, Xiao-ming Huang, Yang Jiao, Xue-jun Zeng, Qiang Shen, Gui-li Cao, He-ping Ji
Journal: BMJ (2013)

To assess the perceptions on two-way referral system and career development of community health practitioner, a cross section questionnaire survey was conducted among health practitioners in Dongcheng and Gaobeidian community health service centers of Beijing from April, 2009 to July, 2009. There are 306 practitioners who finished the survey. 51.31% of the practitioners had experience of referring patients to tertiary hospitals while 31.37% of them had received the patients referring back from tertiary hospitals. The reasons of referring to tertiary hospital were severity of diseases (46.50%) or tests not available in the community (48.41%). The reasons of referring back from hospital were common diseases with confirmed diagnosis (87.25%) or patients in convalescence (80.72%). 57.84% practitioners took the poor communication between community and hospital as the major barrier for the two-way referral, while they thought unsmooth process (47.39%) and poor communication between themselves and the hospital doctors (32.35%) were the major risks during the two-way referral. 63.72% practitioners thought they would have difficulties to accept patients referring back from hospital, but less than 7% thought themselves now incompetent for their patients needs. 77.78% of them believed that their workload was more than that they could bear. Only 21.89% of them could get enough job satisfaction, 27.78% of them held positive opinion on their future career path. After all, to achieve smooth two-way referral, motivating the health practitioners in community to give better medical services, building better communication between practitioners in communities and in hospitals, were as important as improving referral policy and referral procedure.


Key words: 
Community health service; Questionnaires; Two-way referral
Transient elastography in diagnosis of non-alcoholic fatty liver disease
Authors: Xiuzhen Yang, Li Xiao, Jianchun Xian, Lili Zhang, Wei Wang, Aiwen Geng
Journal: BMJ (2018)

Clinical data of 113 patients with non-alcoholic fat liver disease (NAFLD) diagnosed by liver biopsy from January 2015 to January 2017 in Taizhou People′s Hospital were retrospectively reviewed. Patients all underwent transient elastographic (TE) examination and the values of fat attenuation index (FAI) were obtained. The hepatocyt fatty changes in pathological examination were scored as 0 ( 66%, n=18). There were significant differences in AST, Glu, TC and FAI among patients with hepatocyte fatty change scores 0, 1, 2 and 3, and the FAI was significantly correlated with the degree of fatty liver disease. The areas under the ROC curve (AUCs) of FAI in patients with hepatocyte fatty change scores 1, 2 and 3 were 0.78, 0.90 and 0.96, respectively. Logistic regression analysis showed that FAI was correlated with TG, TC and BMI. The results suggest that FAI in TE can be a non-invasive, rapid and objective evaluation method for patients with NAFLD.


Key words: 
Fatty liver, non-alcoholic; Ultrasonograph; Elasticity imaging techniques
Effect of administration of systemic steroids on survival benefit associated with immunotherapy-induced skin toxicity.
Authors: Nicholas Gulati, Douglas M. Donnelly, Yingzhi Qian, Una Moran, Paul Johannet, Anna C. Pavlick, Judy Zhong, Iman Osman
Journal: Journal of Clinical Oncology (2020)

e22046 Background: Immune checkpoint inhibition (ICI) improves progression-free survival (PFS) and overall survival (OS) for patients with metastatic melanoma (MM), but treatment may cause serious immune-related adverse events (irAEs) that require the use of immunosuppressive steroids. Skin toxicity (ST), the most common side effect, has been reported to be associated with better response to ICI in some studies but not others. Herein, we tested the hypothesis that the portended survival benefit associated with ICI-related ST reaches a threshold in MM patients, dependent on the severity of the ST. Methods: We analyzed MM patients enrolled prospectively in a clinicopathological database with protocol-driven follow up and treated with ICI at NYULH. The patient and/or physician reported the ST, and an immunologist-dermatologist independently confirmed the event was ICI-related. Severe ST was defined as a skin event that required treatment with systemic steroids. Other site-specific toxicities were recorded using the CTCAE v5.0. We tested the associations between ST and PFS and OS, stratified by no, mild, and severe ST, adjusting for age, gender, number of metastatic sites, LDH, and ECOG score at treatment initiation. Results: The cohort included 256 MM patients (387 lines of ICI treatments). ST was the most common irAE (34%), and was significantly associated with development of endocrine toxicity (P = 0.007). Of the ST events (n = 130), 66% were mild and 34% were severe. Compared to none, mild ST was significantly associated with improved PFS (adjusted hazard ratio [aHR] = 0.58 [0.38, 0.89], P = 0.01), and a similar trend was observed with OS (aHR = 0.68 [0.45, 1.03], P = 0.06). However, the positive effect was reduced to insignificant (PFS P = 0.53; OS P = 0.25) in patients who developed severe ST irAEs that required systemic steroids. Conclusions: Our data demonstrate that ICI-induced ST is a complex phenomenon and might explain the discordance of reported data. While the worse outcome in patients with severe ST compared to mild may stem from steroidal immunosuppression, a threshold may also exist wherein severe ST itself might contribute to a relative reduction in ICI efficacy. More research is needed to elucidate the mechanisms that link ST and response to ICI in order to better characterize and treat skin irAEs without systemically suppressing anti-tumor immunity.
Validation of an immunomodulatory gene signature algorithm to predict response to neoadjuvant immunochemotherapy in patients with primary triple-negative breast cancer.
Authors: Toshiaki Iwase, Lajos Pusztai, Kim Blenman, Xiaotong Li, Robert Seitz, Tyler J Nielsen, Brock L Schweitzer, David Richard Hout, Dan B Bailey, Xiang Zhang, Yichao Shen, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2020)

3117 Background: A 101-gene algorithm established as a molecular subtyping method for triple-negative breast cancer (TNBC) includes assignment of an immunomodulatory (IM) subtype based on genes active in immune cell processes. Recently, we isolated the IM concept to an independent 27-gene algorithm and its predictive ability for immunotherapy response was demonstrated in lung cancer. The objective of this study was to validate the predictive accuracy of the IM subtype as determined by the 27-gene algorithm for pathological complete response (pCR) compared with PD-L1 immunohistochemistry (IHC) staining in TNBC. Methods: We obtained RNA sequencing data from pretreatment core needle biopsies in 55 patients with stage I-III primary TNBC who received neoadjuvant immunotherapy (durvalumab with weekly nab-paclitaxel followed by ddAC) in phase I/II trial (NCT02489448). The 27-gene algorithm was used to determine IM positivity using a cutoff point previously validated from 71 lung cancer biopsy patients treated with immunotherapy. Results from the algorithm and PD-L1 IHC (antibody, SP263) were compared with pCR. Predictive accuracy of both methods was determined by diagnostic indicators. In cases positive for the IM subtype and pCR, we analyzed the immune microenvironment by deconvoluting the immune infiltration using a computational algorithm. Results: Of the 55 patients, 25 (45%) had pCR. Compared with previous subtyping methods, the 27-gene algorithm showed stronger predictive value (odds ratio, 4.125; 95% CI, 1.36-13.47; P &lt; 0.015). For PD-L1 IHC, the odds ratio was 2.63 (95% CI, 0.82-9.21; P = 0.11). The positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for PD-L1 IHC were 0.55, 0.68, 1.43, and 0.54, respectively. For the 27-gene algorithm, these metrics were 0.65, 0.69, 2.09, and 0.51, indicating its superior accuracy for predicting pCR. The computational algorithm showed that the IM subtype and pCR were negatively associated with a macrophage-enriched microenvironment. CD4+ T cells and dendritic cells were significantly increased among the baseline immune cell population in IM-positive patients. Conclusions: We conclude that 27-gene algorithm is a clinically applicable and a possible predictive marker for response to neoadjuvant immunochemotherapy for patients with primary TNBC. Our immune microenvironment results suggest that antigen-presenting immune cells have a crucial role in immunochemotherapy response.