tbuckley/cabot-search huggingface dataset:
Impact of the timing and extent of debulking surgery on progression-free survival (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC): Single-center experience.
Authors: Muhieddine A-F Seoud, Alaa Husheimi, Iman Jaafar, Faek Jamali, Karam Hamed, Ali Khalil, Reem Abdallah
Journal: Journal of Clinical Oncology (2020)

e18060 Background: To evaluate the impact of timing and extent of cytoreduction on the survival of patients with EOC before (2002-2008) and after (2009-2018) the introduction of aggressive debulking. Methods: A retrospective review of 195 patients with Stages IIIC and IV EOC who underwent debulking between 2002-2018 (Group#1: G1:(2002-2008), and Group#2: G2:(2009-2018). Medical and surgical variables related to PFS and OS were analyzed. Results: Compared to patients in G1, more patients in G2 had neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) [56%(39/70 Vs. 76%(95/125) Vs), p = 0.003], had complete debulking (CD) [44%(31/71) Vs. 79%(103/131), P-value &lt; 0.001]including [diaphragmatic resection [6%(4/72) Vs. 48%(63/131) p &lt; 0.001], bowel ressection [15%(11/72) Vs. 37%(48/131), p = 0.001], peritnoectomy [11%(8/72) Vs. 62%(81/131) p &lt; 0.001], and lymph node dissection [8%(6/72) Vs. 26%(34/131) p = 0.003] .More patients in G2 received Bevacizumab than in G1 [59%(38/65) Vs. 14%(4/29), p &lt; 0.001]. More patients who had ACT and IDS had CD than optimal debulking (OD) than patients who had (PDS) (adjusted odds ratio (aOR) = 1.89, 95% CI: 0.98,3.6). After 2008, there was an increase in the number of patients with high tumor load and lower performance status who were referred for NACT and IDS. In patients with stage IIIC and IV, median PFS was longer in patients who had CD Vs. OD [in stage IIIC: 24 months, 95% CI: 21,27 Vs. 19 months, 95% CI: 17, 21, HR = 0.4, p = 0.006 respectively] [in stage IV: 18 months, 95% CI: 16,20 Vs. 14 months, 95% CI: 9,18, HR = 0.4, p = 0.1 respectively].Patients with stage IIIC who had PDS Vs. NACT and IDS had a non-statistically significant longer PFS [24 months, 95% CI; 20,27 Vs. 19 months, 95% CI: 17,21, HR = 0.8, p = 0.3]. Moreover, in stage IV, there was no difference in PFS in NACT and IDS Vs. PDS [16 months, 95% CI: 12,20 Vs. 17 months, 95% CI: 15,19 HR = 0.8, p = 0.7 respectively]. However, the timing and extent of the cytoreductive surgery did not significantly affect OS in both stages IIIC and IV. Conclusions: In Stage IIIC EOC, the extent but not timing of debulking surgery has the greatest impact on PFS. Longer follow-up is needed to assess the impact on OS.
Factors influencing professional relationship establishment between case managers and psychiatric patients in case management
Authors: Ling Yu, Yan Li, Yong Wang
Journal: BMJ (2016)

The records of 25 psychiatric patients (clients) who received case management from November 2009 to July 2010 were retrospectively analyzed. The factors related to the quality of professional relationship established between case managers and the clients were evaluated. The study revealed that timely supports, encourage and affirmation from case managers (40%), the successful coordinate service (40%), the active care for clients (24%) and helping to build up confidence and hope for clients (24%) were favourable factors for professional relationship establishment, while lack of desire to receive service and change from clients (24%) was adverse factor.


Key words: 
Disease management; Mentally ill persons
Risk of secondary hematologic malignancies in patients with ovarian cancer treated with PARP inhibitors: A combined meta-analysis of seven phase III randomized controlled trials.
Authors: Thura Htut, Somedeb Ball, Sriman Swarup, Anita Sultan, Myat M. Han, Yin Mon Myat, Fred L. Hardwicke, Lukman Aderoju Tijani, Kyaw Thein
Journal: Journal of Clinical Oncology (2020)

12076 Background: Ovarian cancer (OC) is a leading cause of death from gynecologic cancers in women worldwide. Poly adenosine diphosphate ribose polymerase (PARP) inhibitors prevent the repair of single-strand breaks and generate double-strand breaks in tumor cells and have recently shown survival benefits in OC. Yet, the impact on the risk of secondary hematologic malignancies (SHM) remains uncertain. We performed a combined meta-analysis of randomized controlled trials (RCT) to determine the risk of SHM in patients with advanced OC treated with PARP inhibitors. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through January 2020 were queried. Phase III RCTs utilizing PARP inhibitors maintenance in advanced OC were eligible. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with I 2 and Cochran's Q- statistic. Fixed effects model was applied. Results: A total of 4,445 patients with advanced OC from seven phase III RCTs were included. The study arm used olaparib or niraparib or rucaparib or veliparib or olaparib +bevacizumab while the control arm utilized placebo or bevacizumab. Randomization ratio was 2:1 in all studies. The I 2 statistic for heterogeneity was 0, suggesting some heterogeneity among RCTs. The overall SHM incidence was 0.80% in PARP inhibitors group vs 0.47% in control group (RR 1.45; 95% CI: 0.68 – 3.07, P = 0.34). In patients with newly diagnosed OC (n = 3,044), the incidence was 0.59% vs 0.09% in control group (RR 2.7; 95% CI: 0.7—10.37, P = 0.15). In recurrent OC subset (n = 1,401), 1.28% were reported in both study and control arms (RR 0.96; 95% CI: 0.38-2.46, P = 0.94). SHM was noted in 1.3% in the olaparib subgroup compared to 1% in the control with RR of 1.24 (95% CI: 0.46 –3.31, P = 0.67). SHM occurred in 0.7% in the niraparib subgroup compared to 0.47% in the control with RR of 1.28 (95% CI: 0.30-5.45, P = 0.74). Conclusions: Our study demonstrated that the risk of SHM was not significantly increased in patients who received PARP inhibitors compared to control arm, despite attaining survival benefits. Further studies and long term follow up are necessary to define the actual relation and definitive incidence.
Diagnosis of medically unexplained dyspnea
Authors: Min Peng
Journal: BMJ (2017)

功能性呼吸困难指有突出的呼吸困难症状，经过系统检查找不出器质性病因，同时伴有明显精神心理症状。功能性呼吸困难虽然没有器质性病理基础，但与精神障碍例如焦虑障碍、躯体化障碍、抑郁症的共患病率很高，尤其是其中的焦虑障碍。症状的发生可能与皮层对呼吸调节的异常有关。功能性呼吸困难的诊断主要根据典型的临床表现，结合实验室检查，在排除其他器质性疾病的前提下，做出临床诊断。临床特点为中青年男女为主、慢性病程伴急性发作、频繁门诊或急诊就医、起病前心因性诱因，典型症状包括呼吸渴求、胸部发紧、焦虑、肢体或面部麻木，系统体格检查无阳性发现，相关实验室检查结果正常。功能性呼吸困难一经诊断，在综合医院首选非药物治疗，比如呼吸行为治疗。对病情严重、焦虑突出而躯体症状不明显、自杀倾向的患者，建议转诊精神专科评估，需要精神专科干预的患者，建议在精神心理专科医师指导下进行。
Analytical study of community health services quality based on 5-gap model
Authors: Da-hong Gao, Rui Guo, Shi-bing Yang, Ya-dong Wang, Wan-nian Liang
Journal: BMJ (2010)

In the marketing theory, service disparity model is a simple effective tool, capable of figuring out the five clusters of reasons leading to service failure. This article applies it in the community health service domain. Through the efforts of healing the five gaps in service delivery, including Consumer expectation-management perception gap, Management perception-service quality specification, Service quality specifications-service delivery gap Consumer expectation-management perception gap and Service delivery-external communications gap, we hope to improve the community health service quality radically.

Key words: 
Community health services;  Total quality management
A precision medicine tool “Knowledge Frames” to explain poor results of STING agonist trials.
Authors: Al Blunt, Gerald L. Messerschmidt, Steve Gyorffy
Journal: Journal of Clinical Oncology (2020)

e15632 Background: STING activating cyclic-di-nucleotides result in the production of interferons, activating immune cells. We show that “Precision Medicine Knowledge Frames” (PMKF) are analyses inherently involving 2 processes: Frame 1 – Bench Science - biochemical functions of the experimental product, and Frame 2 - Human Organism Level - actions from product biochemical effects to tumor cell killing. Methods: STING agonists meet this PMK frame1 and activate STING (step 1) effectively. Activated STING binds TBK1 (step 2), then phosphorylates IRF3 (step 3), enters the nucleus (step 4), dimerizes (step 5) and binds specific regions of the DNA (step 6) for interferon transcription (step 7), which are secreted (step 8). Frame 2, the Human Organism Level - final common pathway requires many additional actions: Interferon must interact with immune cells (step 9) [within tumor or peripheral locations]. Very warm or hot tumors [contain functional immune cells] actively allow trafficking (homing) to the tumor (step 10) and infiltrating the tumor microenvironment (step 11). An activated immune cell can kill the tumor cell(s) (step 12). Cold tumors may not allow homing (step 10) to the tumor and/or infiltration (step 11) of the microenvironment. Results: PMKF modeling was applied to STING administration public data. Lack of efficacy was predicted if one of the critical pathway steps to tumor cell death are dysfunctional. Early steps (Frame 1) to interferon production and excretion into the environment occur within normal cells (antigen presenting cells) predictably. However, in the setting of malignancy, Frame 2 steps are often aberrant at the Organism Level. Cold tumors do not allow immune cell homing (step 10) and inhibit tumor infiltration (Step 11), tumor cell localization and killing of the tumor cell (step 12). Conclusions: STING Agonist are cutting edge therapies that perform PMKF Frame 1 well and increase interferon production. Application of the PMKF - Frame 2 demonstrate poor clinical activity may be explained by poor immune cell homing, infiltration and functional killing within the cold tumor microenvironment (dysfunctional steps 10, 11 and 12). Population selection may improve these results.
Prospective evaluation of <sup>18</sup>F-DCFPyL PET/CT in biochemically recurrent prostate cancer: Analysis of lesion localization and distribution.
Authors: Hong Song, Heying Duan, Caitlyn Harrison, Kip Guja, Negin Hatami, Benjamin Lewis Franc, Farshad Moradi, Carina Mari Aparici, Guido Davidzon, Sandy Srinivas, Andrei Iagaru
Journal: Journal of Clinical Oncology (2020)

5556 Background: 18 F-DCFPyL, a promising PET agent targeting prostate specific membrane antigen (PSMA), is prospectively evaluated in a single academic center for detecting recurrent lesions in prostate cancer patients with biochemical recurrence (BCR). Methods: We prospectively enrolled 150 men (51-91 years old, mean ± SD: 70.3±7.5) with biochemical recurrence (PSA median 2.38 ng/mL, range 0.12 to 698.4) after primary definitive treatment with prostatectomy (65%), radiotherapy (35%) or both (19%). The 18 F-DCFPyL positive lesions compatible with prostate cancer were evaluated by two independent readers. Impact of 18 F-DCFPyL PET/CT on patient management was recorded from clinical chart review. Results: 18 F-DCFPyL PET/CT had an overall positivity rate of 83% (125 scans), which increased with higher prostate specific antigen (PSA) levels (ng/mL): 63% (PSA &lt; 0.5), 75% (0.5≤PSA &lt; 1), 91% (1≤PSA &lt; 2), 95% (2≤PSA &lt; 5) and 98% (PSA≥5), respectively. In the cohort who underwent prostatectomy, 18 F-DCFPyL PET/CT had higher positivity rate in patients with shorter PSA doubling time (PSAdt) (94% in PSAdt 0-3 months vs. 53% in PSAdt &gt; 12 months, P&lt; 0.01). No difference of 18 F-DCFPyL positivity rate was observed in post-radiation patients with different PSAdt, nor were there differences between patients with low grade (Gleason 6) or higher-grade prostate cancer (Gleason 7-10). 20 patients (13%) had lesions in the prostate bed only and 41 patients (27%) had oligometastatic disease (1-3 lesions), making them candidates for locally targeted therapy. We identified a total of 1455 18 F-DCFPyL positive lesions, including 51 lesions in the prostate bed, 271 pelvic and 463 extra-pelvic lymph nodes, approximately 585 osseous lesions, including 5 patients with diffuse osseous metastases, and 85 lesions in other organs (most commonly in the lungs). 91 out of 150 patients (61%) had change in treatment after 18 F-DCFPyL PET and, most noticeably, 48 of these patients (32% total) had lesions only localized on 18 F-DCFPyL PET/CT despite negative conventional imaging. Conclusions: 18 F-DCFPyL PET/CT holds great potential to be a “one-stop shop” diagnostic tool in the work-up of BCR prostate cancer, with high (61%) impact on the management of these patients. Clinical trial information: NCT03501940 .
Alterations in STK11 to limit response to immune checkpoint inhibitors in lung cancer.
Authors: Jeremy Fricke, Isa Mambetsariev, Rebecca Pharaon, Angel Ray Baroz, Dan Zhao, Erminia Massarelli, Marianna Koczywas, Ravi Salgia
Journal: Journal of Clinical Oncology (2020)

e21503 Background: The use of immune checkpoint inhibitors (ICIs) drastically transformed the treatment of lung cancer. However, a variety of response rates have been observed in patients due to intrinsic or acquired resistances. STK11 mutated patients represent a subgroup of lung cancer patients with diminished outcomes when given ICIs, with some of these patients developing hyperprogressive disease (HPD). Methods: In this study, a retrospective cohort of 384 lung cancer patients previously treated with ICIs was identified from the City of Hope Thoracic Registry (THOR) with a cutoff date of November 11, 2018. Next-generational sequencing (NGS) was performed on 246 patients. 24 of these patients were harboring an alteration in STK11. Data was collected on these patients until December 31, 2019. HPD was exclusively defined by time-to-treatment failure (TTF) &lt; 2 months (TTF is defined as the time from the start of treatment with ICI to ICI discontinuation for any reason, including progression, patient preference, toxicity, or death). Overall survival (OS) and progression free survival (PFS) was started from the initiation of ICI therapy. OS and PFS was calculated between 2 groups (HPD vs non-HPD) using the Mantel-Cox Log-rank test. Results: Almost half (11/13; 45.8%) of the patients with STK11 developed HPD. There was a significant difference between HPD and non-HPD patients in median OS (2 vs 23 months; p = 0.0013) and median PFS (1 v 9 months; p &lt; 0.0001). The median age was 66 (range, 41-90) years old with the majority of patients female (14/24; 58.3%). Most of the patients are deceased (16/24; 66.7%). 91.7% of STK11 patients histologically were adenocarcinoma and 91.7% were smokers with a median pack year history of 40 (range, 4-90). All of the patients had metastatic disease presenting with stage IV disease (21/24; 87.5%). ICI therapies used were pembrolizumab (11/24; 45.8%), Atezolizumab (8/24; 33.3%), nivolumab (4/24; 16.7%), and durvalumab (1/24; 4.2%). PD-L1 expression varied: negative (8/24; 33.3%), 1%- &lt; 50% (7/24; 29.2%), ≥50% (4/24; 16.7%), and not reported (5/24; 20.8%). The most commonly occurring co-mutations were found in TP53 (14/24; 58.3%), KRAS (12/24; 50.0%), SMARCA4 (9/24; 37.5%), PRKDC (8/24; 33.3%) and LRP1B (8/24; 33.3%). Three patients had a pathological co-mutation that is targetable (1 ALK rearrangement, 1 EGFR exon 19 deletion, and 1 RET fusion). Conclusions: STK11 patients who developed HPD had worse OS and PFS compared to STK11 patients without HPD. These results are preliminary and additional analysis is needed to compare differences between various cohorts.
Geriatric assessment-driven intervention (GAIN) on chemotherapy toxicity in older adults with cancer: A randomized controlled trial.
Authors: Daneng Li, Can-Lan Sun, Heeyoung Kim, Vincent Chung, Marianna Koczywas, Marwan Fakih, Joseph Chao, Leana Chien, Kemeberly Charles, Simone Fernandes Dos Santos Hughes, Monica Trent, Elsa Roberts, Enrique Soto Perez De Celis, Reena Jayani, Vani Katheria, Jeanine Moreno, Cynthia Kelly, Mina S. Sedrak, Arti Hurria, William Dale
Journal: Journal of Clinical Oncology (2020)

12010 Background: Geriatric assessment (GA) can predict chemotherapy (chemo) toxicity in older adults (age ≥65) with cancer. However, evidence regarding the effect of GA-driven intervention (GAIN) on the incidence of chemo toxicity has been limited. Therefore, we conducted a randomized controlled trial evaluating the impact of GAIN vs. standard of care (SOC) on chemo toxicity in older adults with cancer. Methods: Patients (pts) age ≥65, diagnosed with a solid malignancy, and starting a new chemo regimen at City of Hope were eligible (NCT02517034). In a 2:1 ratio, 600 pts were randomly assigned to either GAIN (n = 398) or SOC (n = 202) arms. All pts completed a baseline GA prior to chemo. In the GAIN arm, a multidisciplinary team led by a geriatric oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist, reviewed GA results and implemented interventions based on predefined triggers built into the GA’s various domains. In the SOC arm, GA results were sent to treating oncologists to use at their discretion. Pts were followed until either end of chemo or 6 months after start of chemo, whichever occurred first. The primary endpoint was incidence of grade 3-5 chemo-related toxicity (NCI CTCAE v.4.0). Secondary endpoints included advance directive (AD) completion, emergency room (ER) visits, hospitalizations, and average length of stay (ALOS). Chi-square and Fisher’s exact tests were used to compare the categorical outcomes, and Kruskal-Wallis test was used to compare the ALOS between arms. Results: Pt characteristics were balanced between arms. Median age was 71 (range 65-91). Cancer types included: 33% gastrointestinal, 23% breast, 16% lung, 15% genitourinary, and 13% other. Most (71%) had stage IV disease. The incidence of grade 3-5 chemo-related toxicity was 50.5% (95% CI: 45.6-55.4%) in the GAIN arm and 60.4% (95% CI: 53.7-67.1%) in the SOC arm (p = 0.02). Compared to SOC, the GAIN arm had a reduction of 9.9% (95% CI: 1.6-18.2%) in chemo-related toxicity. At the end of study, AD completion increased 24.1% in the GAIN arm vs. 10.4% in the SOC arm (p &lt; 0.001). No significant differences in ER visits (27.4% vs. 30.7%), hospitalizations (22.1% vs. 19.3%), or ALOS (median 4.8 vs. 5.0 days) were observed between the GAIN and SOC arms, respectively. Conclusions: Integration of multidisciplinary GA-driven interventions reduced grade 3-5 chemo-related toxicity and improved AD completion in older adults with cancer. GA-driven interventions should be included as a part of cancer care for all older adults. Clinical trial information: NCT02517034 .
Pharmaco-economic assessment of subcutaneous compared to intravenous trastuzumab in HER2-positive breast cancer patients: A single institution experience.
Authors: Shereef Ahmed Elsamany, Mohamed Jafal, Fayza Hassanin
Journal: Journal of Clinical Oncology (2020)

e19409 Background: Traditionally, trastuzumab is given through intravenous (IV) administration. Recently, subcutaneous (SC) trastuzumab formulation has been developed showing similar efficacy and safety with shorter administration time. This study aims to assess the pharmaco-economics of SC compared to IV trastuzumab in patients with HER2-positive breast cancer treated in a single institution in Saudi Arabia. Methods: We checked the average number of trastuzumab doses, both IV and SC, given per year in King Abdullah Medical City, Saudi Arabia. One-year pharmaco-economic analysis of either trastuzumab forms were performed separately. This analysis included direct medication price based on hospital purchasing in addition to costs of drug preparation kits, nursing administration utilities and staff working time, based on average duration of drug preparation/ administration in chemotherapy unit records. IV trastuzumab dose was calculated based on an average body weight of 80 kg. Results: On average, the total number of trastuzumab doses, both IV and SC, were 1000 doses per year. We calculated the overall cost of 1000 doses of IV compared to SC trastuzumab separately. The average costs of one dose of IV and SC trastuzumab were 2,099 and 1,619 USD, respectively. This is translated to 2,099,000 and 1,619,000 USD per year for IV and SC trastuzumab, respectively. Other costs of trastuzumab administration were 24,933 and 2,666 USD per year of IV and SC trastuzumab, respectively. IV and SC trastuzumab administration needed 2,000 and 83 working hours per year, respectively, resulting in 1,917 saving in nursing working hours per year. This is translated to 18,106 USD saving per year based on average nursing salary. IV and SC trastuzumab pharmacy preparation needed 333 and 33 working hours per year, respectively, corresponding to annual saving of 300 hours in pharmacist- working time and 10,106 USD of pharmacist salary. The overall cost of IV trastuzumab per year was 2,153,667 compared to 1,623,236 USD for SC trastuzumab which corresponds to 2,153 and 1,623 USD per dose for IV and SC trastuzumab, respectively. This is translated to 24.6% overall cost reduction with the SC formulation. Conclusions: SC trastuzumab is associated with favorable pharmaco-economic profile with considerable cost saving compared to the IV counterpart. This is coupled with significant reduction of administration time and improved convenience.
遗传性非息肉病性大肠癌合并一穴肛原癌一例
Authors: 孙学军, 姜燕
Journal: BMJ (2008)

先证者男性,51岁,因大便习惯性改变半年,右腹部包块2个月于2007年1月4日入院.半年前出现大便习惯改变,有时便血,近2个月症状加重,并发现右腹部有一鸡蛋大包块,活动.查体:腹平软,右下腹麦氏点处可触及一5 em×5 em包块,质硬,活动.纤维肠镜检查见:距肛缘约5 em处一巨大不规则隆起,占2/4周,表面充血,有糜烂、出血,质硬,管腔狭窄,回盲部见2/3周占位,溃疡型肿物,质硬.入院诊断:多原发大肠癌(直肠癌,回盲部结肠癌)。
加速康复外科在结直肠外科中的应用
Authors: 钱群, 江从庆, 丁召
Journal: BMJ (2010)

外科手术仍是治疗结直肠疾患的主要手段,但标准选择性结直肠切除术的并发症发生率大约为20%～30%,术后住院日期平均为8～12 d[1].如何更好地预防或减少术后并发症的发生,促进患者早日康复,尽快回归社会,越来越受到临床医师的关注.随着微创、术后镇痛等新技术、新理念在临床的应用,一种新的外科治疗模式即加速康复外科(fast-track surgery,FTS)正在悄然兴起。
Exploration and practice of " combination of general practice with specialties" model in community health service institutions
Authors: Yunfeng Yang, Liping Xu, Wenqin Gu
Journal: BMJ (2018)

Community health service is an important part of the health system reform in the new period in China, the community health service institutions play important roles in promoting the health reform and the development ofthe national medical and health service. Shanghai Fenglin Subdistrict Community Health Service Center has integrated general practice with specialist care for the patients in community health service, this article summarizes the exploration and practice of the combination of general practice with specialties model in the community health service in order to provide reference for relevant medical institutions.


Key words: 
Community health service; General medicine; Medical model