tbuckley/cabot-search huggingface dataset:
Post-Transfusion Overall Survival for HLA- Alloimmunized Platelet Refractorythrombocytopenic Leukemia Patients
Authors: Maliha Khan, Courtney D. DiNardo, Denái R. Milton, Musa Yilmaz, Jorge E. Cortes, Hagop M. Kantarjian, Benjamin Lichtiger, Fleur M. Aung
Journal: Blood (2017)
The value of immunotherapy: Comparison of annual cost per patient receiving immunotherapy versus chemotherapy in patients with non-small cell lung cancer.
Authors: Monali K. Vasekar, Edeanya Agbese, Doug Leslie
Journal: Journal of Clinical Oncology (2020)

e19364 Background: Checkpoint Inhibitors (CPI) has revolutionized cancer treatment but financial toxicity can be incurred due to high cost. We performed a population-based analysis examining the cost of CPI vs. conventional chemotherapy (CT) in patients with NSCLC to capture the real-world value of CPI on an individual and community level. Methods: Population based claims database of privately insured individuals, MarketScan was interrogated. Pts in years 2015 and 2016 with ICD 9 or 10 diagnosis of lung cancer who were continuously enrolled in insurance plan for at least 12 months were included. CPT codes for CPIs and CT were used. Outcome Measure was Health Service Use ( surrogate for treatment related toxicity) such as Inpatient Admissions and Emergency Department Use. Cost Categories (US Dollars) noted were Total Costs,Total Out-of-Pocket Costs,Total Outpatient Infusion Costs, Outpatient Infusion Out-of-Pocket Costs, Inpatient Admissions Costs and Emergency Department Use Costs.Statistical tests “paired t tests” and “unpaired t tests” were used to compare the above variables using SAS software. Results: In 2015 of 22,193 with lung cancer 554 received CPI vs CT in 21,639. In 2016 of 22,810 pts 2478 received CPI vs CT in 20,332. Data for CPI vs. CT in years 2015 (a) and 2016 ( b) respectively. p value for each pair was &lt;0.0001 unless as noted below 1. Mean Total Cost: a) 228504 vs. 140,970 b) 202202 vs. 147801 2. Mean Total Out of Pocket Cost: a) 3381 vs. 3308 p=0.4829 b) 3500 vs. 3343 p=0.0021 3. Mean Total Outpatient Infusion Cost: a) 51158 vs. 18634 b) 60087 vs. 18999 4. Mean Total Out of Pocket Outpatient Infusion Cost: a)159 vs. 282 b) 359 vs. 263 5. Inpatient Admission rate: a) 33.75% vs. 59.40% b) 43% vs. 58% 6. Mean Inpatient Admission Cost: a) 53045 vs 69810 p =0.0025 b) 54124 vs 73903 7. ED Visit rate: a) 38.2% vs. 61.4% b) 50% vs. 61% 8. Mean ED Cost: a) 4117 vs. 5265 p=0.0379 b) 4947 vs. 6025 p=0.0001. Conclusions: Despite the higher individual total cost in pts receiving CPI vs CT; the cost of CPI could potentially be offset at healthcare level by lesser expenditure through lower ED visits and inpatient hospitalization. Though the out of pocket costs/patient was statistically different, the mean numerical difference was small between CPI vs CT. Future prospective trials of CPI should also incorporate costs to individual and healthcare systems in addition to evaluating the impact of CPI on Quality of life vs CT to understand the real “value” of CPI. This novel study can serve as a benchmark for future population based studies.
Outcomes of Pneumocystis juroveci pneumonia complicating treatment of solid tumors.
Authors: Andrew Peter Dean, Amy Rolston, Geena Kelly, Madeleine Seeley-Rogers, Shaun Ong
Journal: Journal of Clinical Oncology (2020)

e19104 Background: Pneumocystis Juroveci Pneumonia (PJP) is a life threatening infection by an opportunistic pathogen historically affecting those with HIV and patients with immunosuppression from multiple lines of cytotoxic therapy, with mortality rates often &gt; 50%. We previously reported data showing that PJP can affect patients early in the course of treatment, even during 1st line treatment. We analysed our outcomes from PJP occurring in these patients. Methods: Electronic database records were searched to identify PJP, chemotherapy, lines of therapy and survival. Results: 12 patients were identified who contracted PJP whilst undergoing chemotherapy for solid tumours, 4 during first line therapy and 5 during second line therapy. Age ranged from 33 to 84. 3 of 12 patients died within 1 week of diagnosis, one during first line therapy with erlotinib, 1 after 5 lines of chemotherapy and 1 after 7 lines of chemotherapy. 1 patient who survived had received 10 lines of therapy. Those who survived the initial infection had received between 1 and 10 lines of therapy and survival ranged from 2 to 25 months with a median survival of 11.5 months. Patients contracting PJP during 1-3 lines of therapy had the highest likelihood of survival with median survival of 11 months. Conclusions: PJP had a mortality rate in our series of 25% and was not exclusive to those with multiple lines of chemotherapy. Early recognition of infection resulted in good outcomes with ultimate prognosis being related to underlying malignancy rather than PJP.
Triple-negative and non–triple-negative breast cancer in a south Indian cohort.
Authors: Narayanankutty Edavalath Warrier, Uma V Sankar, Sreedharan P S, Ajmal Sherif
Journal: Journal of Clinical Oncology (2020)

e13110 Background: The heterogeneity of breast cancer explains in part the differences in the morbidity and mortality of this disease. Triple-negative breast cancer (TNBC) is a specific subset of tumors characterized by the absence of the 3 most commonly targeted biomarkers considered for breast cancer treatment: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). TNBC accounts for 15% to 20% of all breast cancer diagnoses and usually has a more aggressive clinical course, with worse evolution within the first 3 to 5 years after diagnosis; early and higher rates of distant recurrences, typically visceral; and poor survival. Methods: To analyze the clinical, pathological, and sociodemographic aspects between triple-negative breast cancer (TNBC) and non-TNBC in a Kerala cohort and identify potential prognostic factors. This hospital-based retrospective cohort study (From January 2017 till December 2018) included 465 women with breast cancer treated at MVR Cancer Centre &amp; Research Institute in North Kerala. Overall and disease-free survival was compared; prognostic factors were evaluated. Results: Triple-negative breast cancer corresponded to 16.3% of breast cancer diagnosis and was more prevalent among rural women. The patients with TNBC tended to present with stage III cancer, high p53 expression, lymphocytic infiltration, and multifocality and treated with radical surgery and chemotherapy. The 2-year overall and disease-free survival were 52.1% and 43.5% for TNBC and 83.8% and 73.4% for non-TNBC, respectively ( P &lt; .001). The TNBC recurrence was associated with multicentricity, whereas lymph node involvement increased the risk of both recurrence and death. Non-TNBC worse clinical course was associated with rural women, younger age, lymph node involvement, and advanced stage. Conclusions: Triple-negative breast cancer exhibited a more aggressive behavior, earlier and more frequent recurrence, and worse survival compared with non-TNBC. While biological and social variables were associated with poorer prognosis in non-TNBC, only lymph node involvement and multicentricity were correlated with worse clinical outcomes in TNBC.
Attach importance to identification and prevention of anxiety and depression disorders in general hospitals and community health institutions
Authors: Li Qingwei
Journal: BMJ (2016)

焦虑障碍与抑郁障碍是综合医院和社区卫生医疗机构就诊患者中常见的精神障碍，患病率高，与躯体疾病共病多，常以躯体症状就诊，识别率和治疗率低，严重影响患者生命质量，占用大量医疗资源。应整合专科和非专科、尤其是全科医师等多方面力量，加强焦虑障碍和抑郁障碍的识别和防治。
Mutational landscape of <i>AKT1/2/3</i> in Chinese patients with solid tumors.
Authors: Hui Kong, Weijia Fang, Haibo Mou, Feng Xiao Chen, Lingxiang Liu, Jia Wei, Shiyun Cui, Yongzhong Wei, Juming Li, Juan Du, Qi Ling, Xiaofeng Tang, Yigang Qian, Songfeng Yu, Liang Xue, Ting Wang, Min Xiao, Qiuyue Pan, Shiyue Zhang, Lin Zhang
Journal: Journal of Clinical Oncology (2020)

e15566 Background: As a central component of PI3K/AKT pathway, AKT serves as an attractive target of anti-cancer strategy with various AKT inhibitors, which show great promise in phase I/II clinical trials. This study aimed to investigate AKT1/2/3 status in different types of cancers by using next generation sequencing (NGS). Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10,010 Chinese patients with solid tumors and subjected to next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations, tumor mutational burden (TMB) values, and microsatellite instability (MSI) status were assessed with a mean coverage of 1000X, including single base substitutions, short and long insertion/deletions, copy number variations, gene fusions, and rearrangements. Genomic data and immune checkpoint inhibitors (ICIs) treatment outcome of a cohort of 1610 patients with solid tumors were derived from cBioPortal (MSKCC, Nat Genet. 2019). Results: AKT1/2/3 were found to be mutually exclusive with each other and accounted for 3.4% in this cohort. The frequencies of AKT1/2/3 variations were 1.1%, 1.6%, and 0.8%, respectively. The most common co-altered genes associated with AKT1/2/3 variations were TP53 (69.4%), PIK3CA (19.3%), KRAS (19%), CCNE1 (18.4%), CDKN2A (16.6%), and 11q13 (6.5%). AKT1/2/3 variations were significantly associated with higher TMB, and independent of MSI status. Outcome data from the MSKCC cohort showed that patients with AKT1/2/3 variations had a remarkable clinical benefit to ICIs treatment compared to patients with wild-type AKT1/2/3 in overall survival (OS) (NA vs 18 months, p = 0.009). Furthermore, AKT1/2/3 variations were independent risk factors of OS (HR: 0.55, 95%CI: 0.34-0.87, p = 0.012). Conclusions: The prevalence of AKT1/2/3 somatic alterations across different types of solid tumors in China was 3.4%. AKT1/2/3 variations were associated with an increased TMB and favorable response to ICIs, suggesting that A KT1/2/3 variations may be biomarkers for guiding anti-AKT agents and ICI treatment.
Mechanism of sensitivity to TPF chemoagents and its potential alternative of erbB2 in oral cancer with GDF15 overexpression.
Authors: Lai-Ping Zhong, Tong-chao Zhao, Wu-tong Ju, Si-yuan Liang, Li-zhen Wang, Jiang Li, Dong-wang Zhu, Zhi-yuan Zhang
Journal: Journal of Clinical Oncology (2020)

e18542 Background: To explore the mechanism of sensitivity to docetaxel, cisplatin, and 5-fluorouracil (TPF) chemoagents in patients with oral squamous cell carcinoma (OSCC) and growth differentiation factor 15 (GDF15) overexpression recruited in a TPF induction chemotherapy trial; and to explore potential alternative agents for patients who might not benefit from TPF induction chemotherapy. Methods: GDF15-overexpression and silenced OSCC cells were used to investigate sensitivity to TPF chemoagents in vitro and in vivo. Immunoprecipitation combined with mass spectrometry was used to screen out the possible receptor for GDF15, and associated signaling pathways were detected after intervention with the possible receptor of GDF15. The efficacy of an inhibitor of the phosphorylation of the possible GDF15 receptor was evaluated by treatment of GDF15-overexpression OSCC cells in vitro and in vivo. Results: Overexpression of GDF15 in OSCC cell lines and xenografts lead to an increase of chemotherapeutics sensitivity on apoptosis effects induced by docetaxel, cisplatin and 5-fluorouracil, through a caspase -dependent pathway. Immunoprecipitation combined with mass spectrometry revealed that the erbB2 protein was a potential binding protein of GDF15, as verified by coimmunoprecipitation. When GDF15 was overexpressed, the phosphorylation of erbB2 and downstream PI3K/AKT and MAPK/ERK pathways was significantly upregulated, but was downregulated when GDF15 expression was interfered. The erbB2 phosphorylation inhibitor CI1033 significantly inhibited the proliferation and colony-forming ability of GDF15-overexpression OSCC cells as well as the growth of xenografts. CI1033 might be used as a potential targeted drug or alternative of TPF chemoagents for OSCC patients with GDF15 overexpression. Conclusions: OSCC with GDF15 overexpression exhibit sensitivity to TPF chemoagents through a caspase-dependent pathway. ErbB2 phosphorylation inhibitors might be used as potential targeted drugs or an alternative of TPF chemoagents for OSCC patients with GDF15 overexpression.
Allogeneic hematopoietic stem cell transplantation for primary myelofibrosis: A single-center experience.
Authors: Taner Demirer, Guldane Cengiz Seval, Sinem Civriz Bozdag, Selami Kocak Toprak, Meltem Kurt Yuksel, Pervin Topcuoglu, Gunhan Gurman, Osman Ilhan, Meral Beksac, Muhit Ozcan
Journal: Journal of Clinical Oncology (2020)

e19522 Background: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a well-established treatment modality for patients with Myelofibrosis (MF) and still remains the only potentially curative therapy. The aim of this study was to determine overall outcomes of myelofibrosis patients treated with allo-HSCT in our center. Methods: This is a retrospective single-center analysis of 26 patients (female/male: 8/18) suffering from MF who underwent allogeneic HSCT at our center between 2002-2019. Forty-two percentages of the patients were at least MF intermediate-2 status based on DIPSS score (calculated at the time of transplantation). Results: All patients were in chronic phase of PMF at the time of the transplant. The median age at diagnosis was 48.2 years (range, 32-63 years). Median follow up of the patients were 15 months (range, 3-213 mo) and median time from diagnosis to HSCT was 25 months. Three of the patients had splenectomy before allo-HSCT. Splenomegaly was found in 20 patients and resolved completely in 6 patients. Myeloablative and RIC regimens were used for 8 (36.4%) and 18 (69.2%) of the 26 transplant procedures. All patients experienced engraftments of neutrophil and platelet except the five who died in aplasia period. Neutrophil and platelet engraftments occurred at median of 16 days (12-39 d) and 20 days (range, 11-78 d). There were no statistically significant differences in engraftment time between the types of conditioning regimens. Acute GVHD occurred with 11 of 26 transplanted allografts, with 6 of these being grade 3-4 acute GVHD. Chronic GVHD was seen 7 (26.9%) of the patients and 3 of these being extensive. A total of 26 out of the 11 patients died and 9 of the these 15 patients were alive and GVHD free at the end of our study. Relapse occurred in 3 patients after a median of 12 months and was treated with DLI in one case. The probability of 3-year progression free survival (PFS) and overall survival (OS) in all patients were 86.2%±9.1% and 58.7±11.4%, respectively. No statistical significance was observed for mean estimated 3-year OS in terms of the conditioning regimens. Conclusions: Despite the small number of patients, our results suggest that allo-HSCT may provide a curative treatment for patients with PMF.
Health economic analysis of doublet chemotherapy with and without bevacizumab for first-line treatment of RAS mutant metastatic colorectal cancer based on real-world data.
Authors: Koen Degeling, Hui-Li Wong, Amanda Pereira-Salgado, Suzanne Kosmider, Rachel Wong, Jeanne Tie, Greg Stefanou, Louise M. Nott, Jeremy David Shapiro, Gary Edward Richardson, Peter Gibbs, Maarten J. IJzerman
Journal: Journal of Clinical Oncology (2020)

e16048 Background: Bevacizumab remains the dominant biologic treatment option for RAS mutant (RASmt) metastatic colorectal cancer (mCRC). While the health economic impact of bevacizumab in the RASmt subpopulation may deviate from its use in the general mCRC population, this has never been investigated. This study uses the power of real-world data to assess the cost-effectiveness of doublet chemotherapy with compared to without bevacizumab (ChemBev and ChemOnly, respectively) for first-line treatment of RASmt mCRC, while accounting for subsequent treatment in second and third line. Methods: Data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was analyzed to populate a discrete event simulation of three treatment lines, surgery of primary tumor and metastases, hospitalizations following serious adverse events, and best supportive care. Imbalance in baseline patient and disease characteristics was corrected for in all analyses using inverse probability weights. Costs were included from an Australian public payer perspective in Australian dollars (AUD). All health and economic outcomes were discounted at 5% per year. Results: Of the 507 included RASmt mCRC patients that started first-line treatment in the 2010 – 2017 time period, 345 received ChemBev and 162 ChemOnly. The corrected median time on first-line treatment was 7.1 months (95% confidence interval: 6.4 – 8.0) for ChemBev and 4.1 months (3.5 – 5.1) for ChemOnly. Time on second- and third-line treatment was comparable between the groups. Corrected overall survival was 22.6 months (21.7 – 24.0) for ChemBev and 14.3 months (12.1 – 21.7) for ChemOnly. In terms of the health economic impact, mean life years were 1.9 for ChemBev and 1.5 for ChemOnly, and mean costs were AUD 93,025 and AUD 44,929 per patient, respectively. The resulting incremental cost-effectiveness ratio (ICER) of ChemBev compared to ChemOnly was AUD 149,317 per life-year gained (LYG). Conclusions: In contrast to results from clinical trials, overall survival was substantially longer for patients who received bevacizumab, which can possibly be attributed to an imbalance between groups despite correction for known prognostic factors. At an ICER of AUD 149,317 per LYG, the economic burden of upfront treatment with bevacizumab was found to be substantial and consistent with estimates for the general mCRC population. This is mainly caused by the duration of first-line treatment, which was significantly longer for ChemBev.
Clinical impact of early progression among patients (Pts) with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs) in first-line (1L) setting: IMPACT RCC real-world study.
Authors: Thomas E. Hutson, Frank Xiaoqing Liu, Shivani Pandya, Christopher Dieyi, Ruth Kim, Stan Krulewicz, Vijay Kasturi, Abhijeet Bhanegaonkar
Journal: Journal of Clinical Oncology (2020)

e17079 Background: Previous research has indicated a high burden of illness among mRCC pts who progressed to second line (2L) systemic therapy, suggesting benefits to delaying 1L progression. This study examined the clinical impact of early vs delayed disease progression among mRCC pts treated with 1L TKI monotherapies followed by 2L therapy in the US Veterans Health Administration (VHA) database. Methods: Newly diagnosed mRCC pts treated with 1L TKIs followed by 2L therapy were identified between OCT2013-MAR2018 within the VHA database (1L start date = index date). Eligible pts were required to have continuous enrollment for ≥6 months post-2L therapy initiation unless the pt died. A Kaplan-Meier (KM)-derived median time to 2L therapy initiation was used as the cut-off to categorize pts into early (≤median) and delayed ( &gt; median) progression cohorts. KM analysis and Cox proportional hazards models were used to compare and assess the impact of predictive factors on clinical outcomes including overall survival (OS), time to 2L discontinuation (index date to 2L discontinuation or death), and time to 3L treatment initiation (index date to 3L start or death) among pts in the early vs delayed progression cohorts. Results: Among 289 mRCC pts, the mean age was 67.4 years and the median time to 2L initiation was 6.1 months. Pt characteristics were similar between the early (n = 145) and delayed (n = 144) progression cohorts. During follow-up, the delayed progression cohort had better clinical outcomes than the early progression cohort did (Table below). Conclusions: Early progression is associated with worse clinical outcomes, confirming the need to delay disease progression among mRCC pts with effective 1L treatment strategies. Results indicate the need for use of more efficacious therapies, e.g. immuno-oncology-based combinations, in 1L that can delay disease progression and have potential to reduce disease burden. [Table: see text]
地震灾害现场急救与处理的原则
Authors: 刘晓伟, 刘志
Journal: BMJ (2008)

5·12汶川大地震给当地人民群众的生命财产造成了巨大损失.地震发生后,灾难性医疗需求瞬间剧增,时间就是生命,广大基层医务人员在第一时间第一现场展开专业而规范的现场救护非常重要.地震灾害具有突发紧急性、危重灾难性和环境复杂性等特点,往往造成大规模伤亡,伤员病情重、变化快,伤情可彼此掩盖又相互作用,加上条件所限,现场急救工作量大,任务艰巨[1]。
Cervical human papillomavirus infection and cervical lesions in postmenopausal women
Authors: Huiling Zhu, Yan Gao, Longmei Jin, Xiaohua Zhang, Huibin Yang, Linlin Zhang, Jing Cao
Journal: BMJ (2019)

The status of human papillomavirus (HPV) infection and cervical lesions was analyzed among 20 420 postmenopausal women who participated in gynecological disease screening in Shanghai Minhang district 2017. The infection rate of HPV in postmenopausal women was 8.37%(1 710/20 420), and the infection of high-risk HPV 52,58,16,18 accounted for 95.26%(2 029/2 130). The HPV infection rate was 7.37% in women aged ≥65 years,and that was 8.62% in women aged 0.05). The study suggests that HPV genotyping should be taken into account in gynecological disease screening,and the subjects with high-risk HPV infection should be closely followed up; meanwhile,the age limits of screening population should be appropriately extended.


Key words: 
Postmenopausal; Human papillomavirus; Cervical lesion