tbuckley/cabot-search huggingface dataset:
Safety and clinical activity of atezolizumab (atezo) + radium-223 dichloride (r-223) in 2L metastatic castration-resistant prostate cancer (mCRPC): Results from a phase Ib clinical trial.
Authors: Michael J. Morris, Lawrence Fong, Daniel Peter Petrylak, A. Oliver Sartor, Celestia S. Higano, Lance C. Pagliaro, Ajjai Shivaram Alva, Leonard Joseph Appleman, Winston Tan, Ulka N. Vaishampayan, Raphaelle Porcu, Darren Tayama, Edward Ernest Kadel, Kobe Chi Yung Yuen, Asim Datye, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2020)

5565 Background: mCRPC patients (pts) tend to have a poor prognosis and limited treatment (tx) options, especially those with concomitant bone metastases (mets). We explored the ability of combination tx with atezo (anti–PD-L1) and r-223 (α-particle emitter) to stimulate anti-tumor immunity in mCRPC pts. Methods: This Phase Ib study evaluated the safety and tolerability of atezo + r-223 in pts with mCRPC and multiple bone mets, visceral mets and/or lymphadenopathy who progressed after androgen pathway inhibitor tx. The initial cohort phase evaluated the safety and tolerability of a concurrent dosing schedule (CDS), in which atezo and r-223 were administered on the same day. Following assessment of CDS, pts were randomized 1:1:1 to CDS or 1 of 2 staggered dosing schedules (atezo or r-223 introduced a full cycle before the other). This was followed by an expansion of enrollment (randomized 1:1:1). Pts got atezo 840 mg IV q2w and r-223 at 55 kBq/kg IV 6 times at 4-wk intervals until unacceptable toxicity or loss of clinical benefit. Exploratory measures of efficacy included investigator-assessed ORR (RECIST 1.1), PSA response rate, time to PSA progression, radiographic PFS (rPFS; PCWG2 criteria) and OS. Biopsy samples were collected at baseline and prior to cycle 2 to evaluate changes in the tumor microenvironment during tx. Results: As of Oct 4, 2019, 45 pts were enrolled and 44 had evaluable data. Baseline characteristics were generally similar across groups. All 44 evaluable pts had ≥ 1 all-cause AE; 23 (52.3%) had Gr 3-4 AE. Eight pts (18.2%) had Gr 5 AE as per protocol reporting of deaths; 4 (9.1%) were from disease progression. Median follow-up was 13.9 mo (range, 1.7–34.2). Confirmed ORR was 6.8% (95% CI: 1.43, 18.66). Confirmed PSA response rate was 4.5% and median time to PSA progression was 3.0 mo (95% CI: 2.8, 3.3). Median rPFS was 3.0 mo (95% CI: 2.8, 4.6) and median OS was 16.3 mo (95% CI: 10.9, 22.3). Changes in PD-L1 and CD8 IHC were consistent with the known mechanism of action of atezo, as were changes in alkaline phosphatase with radium. Conclusions: No dose-limiting toxicities, safety signals, or changes in serum biomarkers were observed beyond the known safety profiles of atezo and r-223. This Phase 1b study did not seem to show clinical benefit from combination tx. Ongoing subgroup and biomarker analyses may provide additional insights. Studies of PD-1/PD-L1 targeted therapies in combination with tumor-directed radiation in molecularly selected mCRPC pts are planned or underway. Clinical trial information: NCT02814669 .
Quality and Safety in Health Care, Part LXXI
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2020)

Abstract Peer review can be utilized to increase the quality of care for patients by upgrading the performance of all the providers by identifying learning opportunities. Peer review can identify providers whose care is below the standard of care and recommend actions to correct the situation. Peer review is also important to satisfy requirements of the government and The Joint Commission. Ongoing professional practice evaluation and focused professional practice evaluation have been required since 2008 to help insure that providers are rendering excellent care, and the results of these evaluation procedures are also utilized in privileging decisions.
2012年世界家庭医生组织亚太区会议精华
Authors: 邵隽一
Journal: BMJ (2012)

·2012年世界家庭医生组织亚太区会议的主题更加强调初级医疗中的循证医学方法.·亚太区各地的全科医学发展存在较大差别,应该互相学习帮助.·全科医生是医生更是桥梁,其工作价值体现在很多方面,无人可以替代.·全科医生要理解临床指南的本质并学习指南,有效使用指南指导自己的医疗实践.·全科医生要懂得医学真谛,处理好以人为本和以病(医生)为本的平衡关系.·逐项强调未来对全科医生职责、核心职能和能力建设培训的内容.2012年5月24日至27日,世界家庭医生组织(WONCA)亚太区会议在韩国济州岛召开,今年会议的主题是:循证医学如何应用于全科医学。
Inotuzumab ozogamicin (INO) plus bosutinib (BOS) in R/R PH+ ALL or CML in lymphoid blast phase (CML LBP).
Authors: Nitin Jain, Abhishek Maiti, Farhad Ravandi, Marina Konopleva, Yesid Alvarado, Tapan M. Kadia, Nicholas James Short, Gautam Borthakur, Kiran Naqvi, Naveen Pemmaraju, Courtney Denton Dinardo, Naval Guastad Daver, Musa Yilmaz, Keyur P. Patel, Debra B Linderman, Rebecca Garris, Elias Jabbour, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2020)

7512 Background: Pts with R/R Ph+ ALL and CML LBP have poor outcomes. INO is an anti-CD22 antibody drug conjugate approved for R/R ALL. BOS is a 2 nd generation BCR-ABL TKI approved for CML. Methods: This was a phase I/II study of INO + BOS for R/R Ph+ ALL and CML LBP. Primary objective was to determine safety and the maximum tolerated dose (MTD) of the combination. Secondary objective was to assess efficacy. Pts with T315I mutation were excluded. Pts needed to have adequate organ function (Cr ≤2 gm/dL, total bilirubin ≤2 mg/dL, ALT &amp; AST ≤3xULN). BOS was dosed once daily starting on cycle 1 day 1, and 3 dose levels were evaluated (300, 400, 500 mg) in a standard 3+3 design. INO was given IV weekly during cycle 1 (0.8 mg/m 2 day 1; 0.5 mg/m 2 day 8; 0.5 mg/m 2 day 15). In responding pts, INO was subsequently administered at 1 mg/m 2 once every 4 weeks for a total of 6 cycles. Results: Between June 2015 and December 2019 we enrolled 18 R/R pts (16 Ph+ ALL, 2 CML LBP). The median age was 62 yrs (range 19-74), median no. of prior therapies was 1 (range 1-5) and 9 pts had ABL kinase domain mutations at screening. There were no early deaths (&lt;30 days). 3 pts were treated at BOS dose level 1; 6 pts at dose level 2; 9 pts at dose level 3. 1 pt had a DLT at dose level 2 - G3 skin rash, and 2 pts had a DLT at dose level 3 - both G3 skin rash. First 3 pts at dose level 3 did not receive ≥80% BOS doses during cycle 1 due to issues unrelated to adverse events (AE). As 2/6 DLT evaluable pts at dose level 3 had DLTs thus exceeding the MTD, the dose level 2 was identified as the MTD. Most frequent AE were diarrhea in 50%, rash in 50%, and nausea in 39%. Grade 3 AEs were rash (3), reversible ALT elevation (1) and hyponatremia (1). No pts had veno-occlusive disease. Pts have received a median of 3 cycles (range 1-8) with a median of 1 cycle to response (range 1-2). Responses are shown in Table. Median time to response was 1 months (mo, range 0.8-2.1), median time to negative MRD by flow cytometry (FCM) was 6.9 mo (range 3.4-18) and median time to complete molecular response (CMR) was 9.1 mo (range 3.4-18). After a median follow-up of 32 mo, the median overall survival was 15.4 mo and median event-free survival censored at stem-cell transplantation (SCT) was 6.1 mo. 6 pts underwent SCT, 8 pts relapsed, 10 pts are alive and 2 pts continue therapy. Conclusions: INO + BOS was well tolerated and showed promising activity in R/R Ph+ ALL and CML LBP. Clinical trial information: NCT02311998 . [Table: see text]
Evaluation of dietary quality by healthy eating index in type 2 diabetic patients CHEN Liang
Authors: Liang Chen, Lin-di Wang, Hui-qin Zhang
Journal: BMJ (2010)

A dietary survey was conducted with the 3-day dietary intake record in 167 type 2 diabetic patients in Nandan Community of Xujiahui Subdistric of Shanghai, the results were transferred to healthy eating index (HEI). The average score of HEI was 74. 0. According to the criteria of HEI, diet quality of 7. 8% patients was bad, that of 10. 8% patients was good and that of 81.4% patients was need improvement. In all components, the fruits consumption was the worst, especially for male patients.Patients with higher educational levels had better dietary quality and patients who were on working had better HEI score than who retired. The obese and overweight patients consume more grains, meat and total fat than those with normal body weight.

Key words: 
Diabetes mellitus;  type 2;  Diet surveys
Phase II study of gedatolisib for small-cell lung cancer (SCLC) patients (pts) with genetic alterations in PI3K/AKT/mTOR pathway based on a large-scale nationwide genomic screening network in Japan (EAGLE-PAT/LC-SCRUM-Japan).
Authors: Hibiki Udagawa, Takaya Ikeda, Shigeki Umemura, Haruko Daga, Ryo Toyozawa, Daijiro Harada, Jun Sakakibara-Konishi, Masahiro Morise, Noboru Yamamoto, Toshiaki Takahashi, Terufumi Kato, Masato Shingyoji, Ryota Ushio, Satoshi Hara, Saori Takata, Shogo Nomura, Shingo Matsumoto, Seiji Niho, Akihiro Sato, Koichi Goto
Journal: Journal of Clinical Oncology (2020)

9064 Background: Development of targeted therapy for SCLC based on a large-scale genomic screening is an innovative challenge. Gedatolisib is a highly potent dual inhibitor of PI3K/mTOR and is expected to have an effect for tumors with PI3K/AKT/mTOR pathway alterations. SCLC harboring this pathway alterations is rare. Thus, we conducted a phase II study based on a nationwide genomic screening network in Japan (LC-SCRUM-Japan) to develop novel targeted therapies. Methods: SCLC pts with targetable genetic alterations were screened at 154 institutions in Japan. A multicenter, single-arm phase II study was conducted to evaluate the efficacy and safety of gedatolisib in advanced SCLC pts with genetic alterations in the PI3K/AKT/mTOR pathway. The primary endpoint was objective response rate (ORR). The planned sample size was 19 (threshold and expected ORR of 20% and 50%, one-sided alpha of 5%, and power of 80%). Results: 930 SCLC pts were screened from July 2015 to January 2020. Targetable genetic alterations were identified in 148 pts (16%), including 53 PI3K/AKT/mTOR (6%), 81 MYC family (9%), 10 EGFR (1%) and 15 KRAS (2%). A total of 12 pts with genetic alterations in the PI3K/AKT/mTOR pathway (5 PIK3CA, 6 PTEN, and 1 AKT1 mutation) were enrolled in the phase II study. The median age was 67 years (range 58-79), 7 pts were male and 5 pts received 2 or more prior chemotherapy (range 1-4). The ORR was 0% and disease control rate was 25%. The median progression-free survival (PFS) was 0.9 months (95% CI, 0.4 to 3.0). The median overall survival was 5.8 months (95% CI, 1.1 to NR). Treatment-related G3 adverse events (hypertension, hypoalbuminemia, oral mucositis, ALT increased and creatinine increased) were observed in 4 pts. One patient with PTEN I8fs mutation had a long duration of stable disease (PFS; 6.7 months). Conclusions: This Large-scale nationwide genomic screening network was effective to identify rare targetable genetic alterations and had a potential role to develop targeted therapies in SCLC. This phase II study didn’t show promising clinical benefit of gedatolisib for advanced SCLC pts with genetic alterations in the PI3K/AKT/mTOR pathway. The safety profile of gedatolisib was similar to that reported previously. Clinical trial information: UMIN000020585.
Value of heart-type fatty acid binding protein in the clinical diagnosis of early acute myocardial infarction
Authors: Jian Wang, Qiu-mei Cao, Yan Fu
Journal: BMJ (2012)

A total of 115 patients with acute chest pain under the suspicion of acute myocardial infarction (AMI) were selected.By the onset time of chest pain,they were divided into two periods of ＜3 h and 3 -6 h respectively. Heart-type fatty acid binding protein (H-FABP)and such traditional cardiac biochemical markers as cardiac troponin T (cTnT),creatine kinase isoenzyme (CK-MB) and myoglobin (MYO) were tested to compare the sensitivity and specificity in the early diagnosis of AMI.The sensitivity of H-FABP was significantly higher than those of cTnT,CK-MB and MYO (P =0.026,0.005,0.048 ) ; the specificity of H-FABP was lower than those of cTnT,CK-MB in the diagnosis of AMI ( P ＞ 0.05 ).The sensitivities of H-FABP were 81.6％ and 78.1％ in the ST-elevation myocardial infarction (STEMI) and nonST elevation myocardial infarction (NSTEMI) groups respectively ( P =0.095 ).Regardless of the onset of chest pain at ＜ 3 h or 3 -6 h,the combination of H-FABP and cTnT had a higher sensitivity than those of cTnT,CK-MB and MYO in the early diagnosis of AMI (P =0.005,0.028).In the early and rapid diagnosis of AMI patients,H-FABP has a high sensitivity and a poor specificity.And it has some reference value.

Key words: 
Heart-type fatty acid binding protein; Myocardial infarction
Preliminary report of a multi-center study of bronchial asthma control in Beijing suburb
Authors: Yongxiang Zhang, Chunxiao Yu, Fucheng An, Xiangxin Li, Wanku Guo, Xiuhong Jin, Jianhua Liu, Zhenyang Xu, Chunhong Wang, Xisheng Chen, Qingrong Nie
Journal: BMJ (2015)

Objective
To investigate the control level of bronchial asthma and related factors in Beijing suburb.


Methods
A face-to-face questionnaire survey with patients with bronchial asthma was conducted by 11 Beijing regional medical centers from January 15th to May 15th 2014. The contents of survey included the demographic data, diagnosis, treatment, control level, asthma control test(ACT) scores and the related factors.


Results
Total 321 patients with bronchial asthma participated in the questionnaire survey and 315 completed survey with a response rate of 98%. In the aspect of treatment, inhaled corticosteroids(ICS) combined with long-term beta 2 receptor agonist(LABA) accounted for 72.4%(228/315), and medication containing ICS(265/315) for 84.1%. After treatment, the rates of complete control, partial control and no control were 16.8%(53/315), 65.1%(205/315)and 18.1%(57/315), respectively. Among 115 patients with ACT<20, the main affecting factors of asthma control are poor adherence(92 cases, 80.0%), concomitant diseases(32 cases, 27.8%)and unreasonable treatment plan(28 cases, 24.3%).


Conclutions
ICS and LABA are the main drugs in treatment of bronchial asthma. The complete control rate plus partial control rate of bronchial asthma in Beijing suburb is satisfactory, but the complete control rate is still low. The main factors affecting asthma control are treatment compliance and rationality of the treatment plan.


Key words: 
Asthma; Questionnaire; Control level
双坐骨结节巨大滑囊炎引起坐骨神经受压一例
Authors: 张功林, 葛宝丰, 杨荣华, 陈克明
Journal: BMJ (2009)

患者女,71岁.因左下肢疼痛、麻木、无力两月余,于2006年8月10日入院.患者5年前无明显诱因渐觉双坐骨部不适,因不影响正常生活未引起重视,也未行特殊检查.近两个月来,逐渐出现左下肢疼痛、麻木、无力。
Correlation between nucleated red blood cell count and perinatal asphyxia in neonates
Authors: Ning Tan, Huabao Peng, Shulan Fei, Yonghong Wang, Wenyuan Shi, Guizhen Xu
Journal: BMJ (2014)

To explore the correlation between nucleated red blood cell (NRBC) count and perinatal asphyxia in neonates.Full-term newborns born from May 2011 to November 2012 were recruited and divided into perinatal asphyxia (n=40) and normal (n=30) groups.Apgar score was recorded immediately at delivery.The umbilical arterial blood was also collected into anticoagulant-treated tube and NRBC was counted by Japan OlympusCX41 biological microscope.NRBC count for perinatal asphyxia group [(10.70±2.61)/100 WBC] was significant higher than that for normal group [(2.67±0.35)/100 WBC]. A statistically significant negative correlation existed between NRBC and umbilical arterial blood pH, Apgar score at 1 min, BE value (r=-0.802, P<0.05; r=-0.639, P<0.05; r=-0.566, P<0.05). Associated with perinatal asphyxia in neonates, NRBC may be used as a simple index for assessing the severity of neonatal perinatal asphyxia.


Key words: 
Asphyxia neonatorum; Erythrocyte count
Reflection rounds to facilitate resilience in hematology/medical oncology fellows.
Authors: Erica C. Nakajima, Joseph Christopher Murray, Jacquelyn W. Zimmerman, Marcus Messmer, Najeff Waseem, Emily Nizialek, Ramy Sedhom, Arjun Gupta, Ross C. Donehower, Kristen Marrone
Journal: Journal of Clinical Oncology (2020)

11019 Background: Given the prevalence of burnout among medical oncologists (40-60% in the literature), education on burnout risk factors, recovery, and prevention are needed urgently in training curricula for medical oncology fellows. Care of patients with cancer is increasingly complex, and often can seem overwhelming to new trainees. Debriefing as a resiliency skill to develop self-reflection and identify coping strategies may provide a durable way to navigate these complexities. Optimization of fellowship Reflection Rounds (RR) was selected as a fellow-led quality improvement (QI) project for the current academic year. Methods: A QI team including the APD and representatives from all levels of fellowship training was assembled. Feedback regarding previously unstructured, monthly, hour long faculty-facilitated RR for first year fellows was reviewed. Topics with associated readings were selected and paired with fellow-nominated faculty based on the most common recurring themes. The QI team administered the Stanford Professional Fulfillment Index (PFI) to all fellows at the midway point of the academic year. RR were re-structured to include a chaplain with trainee communication expertise and a chief fellow to participate the sessions to assess changes in trainee engagement. Repeat assessment of the Stanford PFI is planned for the end of the academic year. Results: Topics identified for discussion included handling bias, futile care, patient communication, end of life care, and work-life balance. 26 fellows completed the Stanford PFI including nine 1 st year fellows, 13 2 nd year fellows, and 6 3 rd year fellows. Survey results revealed emotional and/or physical fatigue as areas of greatest need for improvement in fellow well-being with 27% of fellows reporting “moderate” emotional or physical exhaustion. Conclusions: RR provides a safe and effective forum to develop peer debriefing and self-refection as resiliency skills within hematology/medical oncology fellowship training. Optimization of RR will continue as fellows become more involved in planning and implementation of curricular improvements to promote resiliency and enhance wellness.
Modulating tumor immune microenvironment by the <i>STK11</i>/LKB1 <i>signaling</i> in breast cancer.
Authors: Hui-Ping Hsu, Chih-Yang Wang, Yao-Lung Kuo, Kuo-Ting Lee, Pai-Sheng Chen, Chun Hei Antonio Cheung, Che-Hung Shen, Chih-Peng Chang, Yi-Ling Chen, Ming-Derg Lai, Meng-Ru Shen
Journal: Journal of Clinical Oncology (2020)

e15185 Background: Standard treatment for breast cancer patients includes surgery, chemotherapy, radiotherapy, target and endocrine therapy. Immune checkpoint inhibitors are newly developing medications. The theoretical basis of immunotherapy is the interaction between cancer cells and tumor-infiltrating immune cells. Cancer cells secrete cytokines and create a specific tumor immune microenvironment (TIME) to attract or modulate immune cells. Further, genetic mutations or copy-number variations in cancer cells contribute to immunosuppression. Liver kinase B1 (LKB1) protein ( STK11 gene) is the upstream of AMP activated Protein Kinase (AMPK)/mammalian Target of Rapamycin Complex 1 (mTORC1) signaling pathway. STK11/LKB1 is one of the possible pathways modulating TIME. Methods: Twenty-seven breast cancer patients who developed recurrence within postoperative 24 months and 22 control cancer patients without recurrence were enrolled from National Cheng Kung University Hospital in Taiwan. Targeted deep sequencing was performed to assess the mutations among individuals with breast cancer using a panel of 143 cancer-associated genes. Bioinformatics and public databases were used to predict the protein functions of the STK11 genes. Immunohistochemical staining of LKB1 protein was performed in clinical specimens. Immune-related molecules were analyzed by RNA sequencing and cytokine array after suppression of STK11. Results: Mutations of STK11 gene were detected in recurrent patients and associated with poor prognosis of patients. From immunohistochemical study, the patients with low LKB1 expression had a worse survival. We utilized CRISPER/Cas9 system to transfect sgRNA into three mouse cell lines, including M158, NF639 and PY8119. RNA sequencing was performed in parental and Stk11-sgRNA cells. Immune-related pathways were ranked in the top 10 networks. Increased mRNA expression of Csf3 (protein G-CSF), Cxcl5, and Ccl2 was detected. The results are confirmed by cytokine array. The expression of G-CSF (gene Csf3) and CXCL5 (gene Cxcl5) proteins was increased in Stk11-sgRNA cells. The results were similar with RNA sequencing. Conclusions: Our findings suggest that suppression of STK11/LKB1 is correlated with early recurrence of breast cancer patients and contributes to modulate TIME. The STK11/LKB1 and downstream AMPK/mTORC1 pathways may be potential targets for immunotherapy.
盐酸吉西他滨单药联合伽玛刀治疗晚期胰腺癌的疗效观察
Authors: 潘德键, 王标, 周锡建, 王东林, 李相勇, 范晓强, 周仁贵, 唐新宇
Journal: BMJ (2007)

对22例晚期胰腺癌患者采用盐酸吉西他滨(健择)单药与伽玛刀联合治疗,健择为1000 mg/m2、每周期第1、8天静脉滴注,伽玛刀在第1个化学治疗(化疗)周期的第2天开始,等剂量曲线为55%～70%,单次周边剂量肿瘤≤5 cm为4.0～5.5 Gy,肿瘤＞5 cm为3.0～4.0 Cy,治疗总剂量为32.0～48.0 Gy.全组22例共完成118个周期化疗,治疗开始后3个月CT检查,完全缓解4例(18%),部分缓解5例(23%),稳定12例(55%),进展1例(5%),中位生存期11.6个月(4～28个月),临床受益反应阳性17例.主要毒性反应是白细胞、血小板下降.提示健择单药联合伽玛刀治疗不能手术的晚期胰腺癌具有较好的耐受性和疗效。
大面积深度烧伤后期畸形的整形外科治疗
Authors: 黄书润, 李小毅, 王浩, 张勇
Journal: BMJ (2009)

大面积深度烧伤导致全身多部位瘢痕挛缩、畸形严重,需要进行整形手术,但因自体皮源匮乏,给治疗带来极大困难.我院自1994年1月至2008年5月收治大面积烧伤后期整形病例31例,总结如下。
改良吻合血管游离腓骨移植术治疗股骨头坏死
Authors: 张长青, 李鸿帅, 张开刚, 眭述平, 曾炳芳
Journal: BMJ (2006)

股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种治疗困难且致残率高的疾病,多发于30～50岁的青壮年[1].对于老年患者,常选用人工关节置换术[2,3];对于青年患者,选择保存患者股骨头(简称保头)治疗还是人工关节置换仍有较大争议[4].大量文献报道,保头治疗是有效的[5-7]。