tbuckley/cabot-search huggingface dataset:
A phase I clinical trial testing the safety of IL-21-expanded, off-the-shelf, natural killer cells for relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome.
Authors: Sumithira Vasu, Nidhi Sharma, Lynn Odonnell, Kevin Bosse, Dean Anthony Lee
Journal: Journal of Clinical Oncology (2020)

TPS7562 Background: Allogeneic transplantation (Allo-HCT) demonstrates the enduring and potent role of the immune system in the control and eradication of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, patients with relapsed, refractory (R/R) disease or comorbidities are not eligible for Allo-HCT. We sought to develop an allogeneic Natural killer (NK) cell-based immunotherapy approach to induce remission for these patients. The efficacy of haploidentical NK cells expanded ex vivo using a K562 feeder-cell line transfected with IL-21 and 41BBL has been established in R/R AML patients. However, haploidentical donor-derived NK cell manufacturing exceeds three weeks with the possibility of fulminant malignancy rendering patients ineligible for cellular therapy. To address this limitation we established a third-party NK cell bank derived from KIR and HLA-mismatched ‘ideal’ donors that allows scalable, affordable mass-production of large numbers of NK cells suitable for banking and immediate ‘off-the-shelf’ (OTS) administration to a broad population of recipients. Methods: This phase I study follows a 3+3 design to investigate the safety of mIL-21-expanded, third-party, OTS NK cells for treatment of R/R AML and MDS patients. Patients aged ≥18 or ≤80 years are enrolled into two cohorts: those &lt;60 years and able to tolerate intensive chemo will receive Fludarabine 30mg/m 2 /day (days -6 to -2) and Cytarabine 2g/m 2 /day (days -6 to -2). Patients &gt;60 years or &lt;60 years and unable/unwilling to tolerate intensive chemo will receive Fludarabine 30mg/m 2 /day (days -5 to -2) and Decitabine 20mg/m 2 /day (days -6 to -2). All patients subsequently receive a total of 6 infusions of NK cells administered thrice weekly for two weeks (between days 0-21) and will be followed up to day 56 from first NK cell infusion. Three NK cell dose-levels: 1x10 7 , 3x10 7 and 1x10 8 cells/kg/dose will be explored to determine maximum tolerated dose (MTD). 3-18 patients/cohort/dose may be enrolled for MTD determination plus an additional 10 patients/dose in an expansion phase (maximum 28/cohort = 56 total subjects). Primary objective is to determine safety and feasibility of NK cell infusions. Secondary objectives will explore rates of remission PFS, overall survival and measurable residual disease negativity, cell counts, infectious complications, and patients proceeding to transplant. Enrollment in dose level 1 has started. Clinical trial information: NCT04220684 .
Safety and efficacy of single-agent adjuvant trastuzumab in older women with early-stage breast cancer.
Authors: Cynthia Owusu, Seunghee P Margevicius, Heidi D. Klepin, Charles L. Vogel, Asrar Alahmadi, Sowjanya Vuyyala, Adam Brufsky
Journal: Journal of Clinical Oncology (2020)

528 Background: Older adults with multiple comorbidities and poor functional status may not be appropriate candidates for chemotherapy. We conducted a phase II trial to examine the safety and efficacy of single-agent Trastuzumab for older women with early stage Human Epidermal Growth Factor Receptor Type 2 (Her2)-positive breast cancer. Methods: This was a single-arm open label multi-institutional clinical trial of adjuvant single-agent Trastuzumab in women aged ≥ 60 years with stage I-III Her2-positive breast cancer who had either declined chemotherapy or were not chemotherapy candidates. Patients received Trastuzumab monotherapy, (8 mg/kg) for cycle 1 followed by (6 mg/kg) every 3 weeks for 12 months. The primary end point was one-year cumulative incidence of symptomatic congestive heart failure with reduced ejection fraction (HFrEF). Secondary endpoints were disease free survival (DFS) and overall survival (OS) at 5 years. Results: Fifty-six patients were enrolled across four centers with a median follow-up period of 5.0 years, (range 0-6.5). The median age was 72.5 years (range 60-90), 64% had stage I disease, 77% had estrogen-receptor positive disease and 82% had node-negative breast cancer. Only two patients had symptomatic congestive HFrEF with a one-year cumulative incidence of 3.6%; (95% confidence interval [CI], 0.09 to 13.8). Five patients had asymptomatic declines in ejection fraction with a one-year cumulative incidence of 9.1%; (95% CI, 3.9 to 20.1). The 5-year DFS was 86.4%; (95% CI, 73.6 to 93.3). Among seven relapses seen, two were due to distant metastatic breast cancer. The 5-year rate of overall survival was 90.2%; (95% CI, 78.1 to 95.8). Among five deaths, one was due to distant metastatic breast cancer. Conclusions: Among older women with stage I-III HER2-positive breast cancer who decline chemotherapy or are not chemotherapy candidates, treatment with her2 targeted therapy only without chemotherapy may offer a reasonable treatment option without an inordinate rate of cardiac toxicity. Clinical trial information: NCT00796978 .
Standardized management of patients with type 2 diabetes in Beijing Qinan community
Authors: Lili Bian, Wuzi Hou, Yuming Dong, Beibei Song, Hongying Zhao, Jing Li
Journal: BMJ (2018)

Objective
To evaluate the effectiveness of standardized management for patients with type 2 diabetes in Beijing Qinan community.


Methods
Total 484 patients with type 2 diabetes in Qinan community were under standardized management. A cross-sectional study on the effectiveness of diabetes management was conducted in December 2016 based on the health records and clinic medical records.


Results
The mean age was(71.2±11.2)years, the duration of diabetes was(12.2±7.8)years, the mean BMI was(24.76±3.06)kg/m2 in 484 patients. The TC was(5.08±3.27)mmol/L and LDL-C was(2.72±0.78)mmol in 383 patients. The rate of achieving the target level of fasting blood-glucose was 51.96% (199/383); the rate of achieving glycosylated hemoglobin target was 60.08% (155/258); and the rate of achieving quick fasting blood-glucose target was 51.49% (52/101). There were 80.37% (389/484) patients with clinic blood pressure <140/90 mmHg(1 mmHg=0.133 kPa), 36.57% patients (177/484) had normal BMI; and 17.83% patients (46/258) with controlled clinic blood pressure, fasting blood glucose, glycosaylated hemoglobin and LDL-C. There were 53.79% patients with LDL-C<2.6 mmol/L and 23.24% with HDL-C ≥1.0 mmol/L. The patients with fasting glucose <7.8 mmol/L had lower LDL-C than the patients with fasting glucose ≥7.8 mmol/L, (F=4.42, P=0.04), The patients with fasting glucose <7.8mmol/L had higher HDL-C than the patients with fasting glucose ≥7.8 mmol/L (Z=-2.30, P=0.02). The rate of achieving glycosylated hemoglobin target was decreased with the increasing of disease duration (χ2=12.57, P=0.01).


Conclusion
The comprehensive target-reaching rate of type 2 diabetes patients with standardization management in Qinan community is relatively low. It is necessary to strengthen the control of blood lipid, body weight and blood pressure for improving the effectiveness of standardized management of diabetic patients.


Key words: 
Diabetes mellitus, type 2; Community health services; Cross-sectional studies; Case management
Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION interim analysis.
Authors: Andres Poveda, Stephanie Lheureux, Nicoletta Colombo, David Cibula, Kristina Lindemann, Johanne I Weberpals, Maria Bjurberg, Ana Oaknin, Magdalena Sikorska, Antonio Gonzalez Martin, Radoslaw Madry, Maria Jesus Rubio Pérez, Richard Davidson, Christopher Blakeley, James Bennett, Alan Barnicle, Erik Skof
Journal: Journal of Clinical Oncology (2020)

6057 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al. Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including those in the non-BRCAm subgroup. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al. Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 previous lines of platinum-based chemotherapy, we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and had responded to platinum-based chemotherapy. Pts initiated maintenance olaparib tablets (300 mg bid) until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed PFS (modified RECIST 1.1). Secondary endpoints included PFS by homologous recombination repair deficiency (HRD; assessed with the Myriad myChoice HRD plus test; HRD+ve: score ≥42) and somatic BRCA mutation (sBRCAm) status. An interim analysis was planned after ~135 PFS events. Results: 279 pts were enrolled from 17 countries (mean age: 64 yrs); 94.3% were confirmed non-gBRCAm by local testing. At data cut-off (Nov 15, 2019), the median PFS was 9.2 months (95% confidence interval [CI]: 7.6–10.9 months), with 152 PFS events (54.5% maturity). The Table presents PFS outcomes by key subgroups. The median exposure to olaparib was 8.1 months. Grade ≥3 adverse events (AEs) occurred in 72 (26%) pts. 19% of pts reported serious AEs. No deaths related to AEs were reported. AEs led to dose interruption, dose reduction and treatment discontinuation in 39%, 15% and 7% of pts, respectively. Conclusions: Maintenance olaparib demonstrated activity in non-gBRCAm PSR OC pts. There were no new safety signals. Clinical trial information: NCT03402841. [Table: see text]
腹膜后Castleman病二例并文献复习
Authors: 贾宗师, 周逢强, 高峰, 丁宝忠, 徐宏
Journal: BMJ (2006)

报告2例Castleman病患者,并对有关文献资料进行回顾性分析.从发病、病理、临床表现、实验室检查、诊断、鉴别诊断、治疗、预后等方面对Castleman病进行讨论.结果表明Castleman病的发病机制及临床表现复杂,治疗手段多样.临床医师应提高对该病的认识,早发现、早诊断、早治疗。
Early intervention of cognitive dysfunction
Authors: Min Xiong
Journal: BMJ (2018)

随着人口老龄化的加剧，认知功能障碍对家庭和社会的危害越来越严重，成为严重的医疗和社会问题。一旦发生痴呆，目前尚无有效的手段阻断疾病的进展，因此认知功能障碍的早期干预就显得至关重要。目前关于认知功能障碍的早期干预方法尚无统一的意见，但已有很多临床研究观察了各种针对认知障碍的早期干预方法，包括认知训练、认知康复、生活方式干预和药物干预等。这些方法的有效性尚存在争议，需要大规模的临床研究证实其疗效，从而为早期认知功能障碍提供有效的预防和治疗手段，以求减少痴呆的发生。
Improving provider practice patterns in ordering FDG PET/CT for breast cancer patients at a safety-net hospital.
Authors: Daria Abolghasemi, Tran Ho, Jennifer Short, Preeti Subhedar, Joel Okoli, Keerthi Gogineni, Jolinta Y Lin, David S. Yu, Teralyn Carter, Steven Yang, Sheryl G. A. Gabram
Journal: Journal of Clinical Oncology (2020)

e14027 Background: Accurate staging is critical in determining treatment strategies in the management of breast cancer (BC) patients. FDG PET/CT is used to identify the presence of metastatic disease. The criteria for FDG PET/CT utilization is variable, including in any patient with nodal positivity, any patients with systemic symptoms, to those with Stage III disease or higher.. This practice variation has results in different patterns of ordering FDG PET/CT. The preliminary results of a Quality Oncology Practice Initiative (QOPI) audit performed in our Cancer Center in 2017 prompted concern for the over utilization of FDG PET/CT in our BC patients. We performed an initial audit of these practices in 2017 and confirmed these findings. The goal of this study was to re-measure our adherence to NCCN guidelines in 2019 after an educational session complimented by use of a checklist. Methods: A retrospective review was conducted for all BC patients who had FDG PET/CT ordered as initial treatment planning from 1/2017-12/2017. This revealed a 33% rate of failure to meet NCCN guidelines. We then educated our team about the NCCN guidelines for initial PET/CT ordering during our weekly multi-disciplinary conferences, created a test ordering checklist and compared the effect of this education on the use of PET/CT in patients treated at our institution from 1/2019-12/2019. Results: 65 female BC patients had an FDG PET/CT ordered to assist in initial treatment recommendation in 2017. Overall, 66.2% (n = 43) of patients met NCCN indications while 33.8% (n = 22) did not. In comparison to 2017 data, 71 female breast cancer patients had an FDG PET/CT ordered in 2019. Overall, 67 patients (94.4%) met NCCN criteria indications for undergoing FDG PET/CT while only 5 patients (5.6%) did not. Conclusions: Review of FDG PET/CT scans ordered for initial treatment in 2017 revealed that about one third of scans were ordered outside of NCCN guideline recommendations. After an educational session and implementation of a test ordering checklist, we found a marked reduction in the use of FDG PET/CT outside of NCCN guideline recommendations. Although our study is limited by small sample sizes, we identified a practice area that deviated from national recommendations and were able to improve our internal compliance in national guidelines through education and system modification.
Montessori-based method for nursing care of elderly patients with dementia
Authors: Yanbing Zeng, Fengzhi Qin, Mengyang Yin, Ya Fang
Journal: BMJ (2016)

The nursing care is critical in preventing, eliminating or reducing symptoms and improving the quality of life for patients with dementia. Montessori-based method is a nursing care widely used in Western countries and has received good results. This article briefly introduces Montessori-based method and its operation guide, and current status of application in America and Australia, which would provide a reference for the nursing care of elderly patients with dementia in China.


Key words: 
Dementia, aged; Nursing care; Montessori; Prevention
An analysis of test results of in-service training for stomatological professionals in Beijing community health service
Authors: Gang Liu, Guang-liang Niu, Dong Zeng
Journal: BMJ (2009)

In this paper we analyzed examination results of the Beijing Community Dentistry Professional Post Assessment and related factors, also discussed the measures for improving the quality of the post assessment. In 325 examinees 244 passed with a pass rate of 75.1%. There significant differences among examinees, educational background and academic training were most influential

Key words: 
Community health services;  Inserviee training
GAIN-2: Neo-/adjuvant phase III trial to compare intense dose-dense chemotherapy (CT) to tailored dose-dense CT in patients (pts) with high risk early breast cancer (EBC): Results on safety and interim invasive disease-free survival (iDFS).
Authors: Volker Moebus, Hans-Joachim Lueck, Ekkehart Ladda, Peter Klare, Marcus Schmidt, Andreas Schneeweiss, Michael Untch, Frederik Marmé, Jens Bodo Huober, Elmar Stickeler, Mattea Reinisch, Theresa Link, Bruno Valentin Sinn, Jenny Furlanetto, Toralf Reimer, Christine Solbach, Sabine Schmatloch, Julia Rey, Nicole Burchardi, Sibylle Loibl
Journal: Journal of Clinical Oncology (2020)

516 Background: GAIN-2 (NCT01690702) compared efficacy and safety of intense, dose-dense epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) vs dose-dense, dose-tailored epirubicin/ cyclophosphamide followed by dose-dense, dose-tailored docetaxel (dtEC-dtD) as adjuvant or neoadjuvant CT for node-positive or high risk node-negative EBC. Here, we report safety results and interim analysis (IA) of the primary endpoint iDFS. Methods: Pts (luminal A ≥N2; luminal B N+; HER2+ and TNBC) were randomized between iddEnPC (E 150 mg/m2, nP 330 mg/m2, C 2000 mg/m2, all q2w x 3) or dtEC-dtD (dtEC q2w x 4 followed after 1 week rest by dtD q2w x 4). Primary objective was to compare iDFS. 797 events are needed to detect a hazard ratio of 0.819 with a 2-sided log-rank-test with 80% power and α=0.05. The IA of iDFS was planned after 50% of the events have occurred. Safety and compliance were secondary objectives. Results: Between 10/2012 and 09/2018, 2887 pts were randomized and 2857 started treatment (iddEnPC 1429; dtEC-dtD 1428). Median age was 51 (range 18-75) years. Overall, 18.1% were luminal A, 31.5% luminal B/HER2-, 18.8% hormone-receptor (HR)+/HER2+, 8.5% HR-/HER2+ and 23.2% TNBC. Overall, 88.1% of pts completed all treatment in both arms. 66.8% with iddEnPC vs 58.8% with dtEC-dtD delayed CT dose (p&lt;0.001). Grade 3-4 non-hematological adverse events (AEs) were more frequent with iddEnPC (iddEnPC 50.8% vs dtEC-dtD 45.1%, p=0.002). Grade 3-4 leukopenia, neutropenia, febrile neutropenia, arthralgia, and peripheral sensory neuropathy were significantly higher with iddEnPC. There were 1464 serious AEs (iddEnPC 870 vs dtEC-dtD 594) and 26 (9 vs 17) predefined AEs of special interest (anaphylaxis, any AE affecting cranial nerves, macula edema). Two deaths occurred during dtEC-dtD. After a median follow-up of 45.8 months, there was no difference in iDFS between arms (log-rank p=0.9102, hazard ratio iddEnPC vs dtEC-dtD 1.01, 95% CI 0.83-1.23). Conclusions: No new safety concerns were observed. Use of both iddEnPC and dtEC-dtD appears feasible in the (neo)adjuvant treatment of high risk EBC. Clinical trial information: NCT01690702 .
Increased prevalence of BRCA1/2 mutations in women with macrotextured breast implants and anaplastic large cell lymphoma of the breast
Authors: Mintsje de Boer, Michael Hauptmann, Nathalie J. Hijmering, Carel J. M. van Noesel, Hinne A. Rakhorst, Hanne E. J. Meijers-Heijboer, Jan Paul de Boer, René R. W. J. van der Hulst, Daphne de Jong, Flora E. van Leeuwen
Journal: Blood (2020)
Population genetic screening for hereditary breast and ovarian cancer in at-risk patients: A novel testing and prevention model for community hospitals reveals high mutation rates rurally.
Authors: Charles Hendrix Shelton, Leigh Boehmer, Christine B. Weldon, William C. Guenther, Julia Rachel Trosman, Antonio Ruiz
Journal: Journal of Clinical Oncology (2020)

1575 Background: Genetic testing for at risk non-cancer patients continues to increase (Guo F, et al Cancer 2020). We identified a high risk of familial breast and ovarian cancer in rural eastern North Carolina, and created a systematic approach for genetic screening, counseling and testing. Methods: A family history questionnaire was designed to assess for the risk for hereditary breast and ovarian cancer (HBOC) using NCCN guidelines, and used at key intake points within the unaffected population to determine eligibility for genetic testing. First it was offered at the time of all mammograms. Second, we offered it in the primary gynecology care setting to capture younger patients not participating in screening mammography. Patients meeting HBOC criteria were sent a letter and two phone calls to schedule genetic counseling. Analysis via descriptive statistics. Results: 3000 rural women screened using our systematic approach to genetic risk assessment. 22.4% (673/3000) of female patients met NCCN criteria for HBOC panel testing. All offered consultation and counseling. With a backlog to see patients due to higher than expected accrual, 217 patients have completed pre-test genetic counseling, 201 completed local 19-gene panel test, and 201 had post-test counseling. Germline mutations (=&gt;1) that predict for genetic susceptibility to cancer(s) occur in 7.8% of our screened and tested population. Currently 1 in 400 patients screened in our unaffected population carry a BRCA mutation, and 1 in 200 carry some pathogenic mutation that increases risk for HBOC. Conclusions: This rural model of screening and prevention of at risk patients for HBOC is successful at detecting pathogenic mutations in unaffected patients before they are diagnosed with cancer. Interestingly, the rate of positivity in the unaffected population (meeting criteria) is as high as the known breast cancer population rate of germline mutations (5-10%), validating the use of testing guidelines with our model. Discovering this susceptibility before a cancer diagnosis resulted in appropriate high risk management with prevention and risk reduction strategies. We plan to expand this model to the male screening population in 2021, and streamline genetic assessment and testing for the larger population at risk by engaging more rural primary care clinics over time to increase testing compliance. We also plan to consider broader gene panels as newer mutations become linked to HBOC. Clinical trial information: UMCIRB 19-001052.
Former smokers as the most frequent smoking status in patients with lung cancer in Brazil.
Authors: Guilherme Jorge Costa, Maria Julia Gonçalves Mello, Carlos Gil Ferreira, Anke Bergmann, Luiz Claudio Santos Thuler
Journal: Journal of Clinical Oncology (2020)

e13597 Background: Lung cancer is the principal cause of death from cancer worldwide. However, little is known of the clinic and histological profile from former smokers patients with lung cancer. Objectives: To characterize the clinical and histological profile and to identify independent factors associated with smoking status (former versus current) in patients with lung cancer in Brazil between 2010 and 2016. Methods: An ecological study was conducted using data from Brazilian hospital-based cancer registries between 2010 and 2016. Data with p-value &lt; 0.20 in the univariate analysis were included in the logistic regression analysis by using the stepwise forward method, in order to control for potential confounders. Results: This study evaluated 23,462 patients with lung cancer diagnosed between 2010 and 2016 in Brazil. In general, the average age of all patients was 63.7 + 10.7 years old. Never smokers, former smokers and current smokers corresponded to 18.9 %, 35.2% and 45.9% of cases in the moment of the diagnosis, respectively. Current smokers were the most frequent smoking status, albeit its frequency decreased significantly during the period. Male and female former smokers had its frequency increasing over the period and male former smokers became more frequent than males current smokers since 2015. In multivariate analysis, comparing former versus smokers, the follow variables were statistically significant: former drinkers, older age group, higher schooling, married or living married, from non-public (private) health system insurance, living in region North, Northeast and West Center and more recent year of diagnosis. Conclusions: Recently, former smokers with lung cancer is increasing and became the most frequent smoking status, as a result of the very effective policies against to smoking in Brazil since 1990’s. The increase in that specific population discloses some interesting challenges and opportunities in clinical and translational settings.