tbuckley/cabot-search huggingface dataset:
Quilt-3.064: An open-label phase I study of PD-L1 t-haNK in subjects with locally advanced or metastatic solid cancers.
Authors: Tara Elisabeth Seery, Mira Kistler, John H. Lee, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2020)

TPS3152 Background: Tumor cells can escape immunosurveillance through upregulation of PD-L1, which inhibits the proliferation and antitumor activity of T cells. T cells genetically altered to express chimeric antigen receptors (CARs) that recognize tumor-associated antigens have mediated potent responses in patients with hematologic cancers, but have shown limited efficacy in solid tumor cancers and can be associated with severe toxicity, ie, cytokine release syndrome (CRS). Like T cells, NK cells can be genetically modified to express CARs that can specifically recognize and lyse cancer cells. Unlike T cells, NK cell cytotoxicity does not require prior sensitization and is not HLA-restricted, making NK cells an attractive choice for clinical immunotherapy. In addition to their innate cytotoxicity, NK cells mediate antibody-dependent cellular cytotoxicity (ADCC) via expression of CD16. PD-L1 t-haNK is an off-the-shelf, human, allogeneic, NK cell line engineered to express a CAR targeting PD-L1. It can be easily and continuously expanded in culture and preclinical in vitro and in vivo studies have demonstrated effective PD-L1 CAR–mediated antitumor activity against PD-L1 + MDSCs. PD-L1 t-haNK has also been engineered to express the high-affinity variant of the Fcγ receptor (FcγRIIIa/CD16a 158V), and thus has enhanced CD16-targeted ADCC capabilities, particularly when combined with a monoclonal antibody. As such, a dual-targeted NK approach may be more effective at potentiating antitumor activity and reversing suppression in multiple cancers that express PD-L1 in the tumor microenvironment. Methods: This is a dose-escalation study of PD-L1 t-haNK in subjects with locally advanced or metastatic solid cancers, regardless of PD-L1 expression. Dose escalation will involve a standard 3 + 3 design. The primary objectives are to determine safety, maximum tolerated dose (MTD), and designate a recommended phase 2 dose. Secondary objectives include estimates of preliminary efficacy by objective response rate, progression-free survival, and overall survival. Subjects in Cohort 1 will receive ~2 × 10 9 PD-L1 t-haNK cells twice per week and assessed for dose-limiting toxicities (DLTs). If no DLTs occur, the dose may increase to ~4 × 10 9 cells twice per week in Cohort 2. Dose expansion will occur when the MTD has been determined. PD-L1 t-haNK is administered by IV infusion in an outpatient setting. Enrollment in Cohort 1 has been completed (N = 6, &gt; 100 doses total) without DLTs or CRS. Enrollment into Cohort 2 began December 2019. Clinical trial information: NCT04050709 .
Survey on psychological adaptability of medical undergraduate interns
Authors: Xin Li
Journal: BMJ (2012)

One hundred medical undergraduate interns were randomly selected to undergo a survey using self-designed questionnaire,95 students completed the questionnaire with a response rate of 95.0％.The results revealed that all interns receiving survey had psychological adaptability problems,57.9％ of the interns were not adaptive to life well,67.7％ had maladjustment of learning,63.2％ had social maladjustment,65.3％ had poor metal adaptability.The 47.4％ of the interns felt very heavy stress and 36.8 ％ felt stress,only 15.8 percent felt less stress.The stress sources included seeking employment and pursuing career for clinical practice or academic training.The results showed that psychological adaptability is a common problem for medical undergraduate interns and the social stress sources would intervene the clinical training and study for them.The medical educators should pay attention to this problem and psychological counseling and other measures should be taken for medical interns.

Key words: 
Clinical clerkship;  Adaptability psychological
Clinical features of renal tubular acidosis patients with and without autoimmune disease
Authors: Ning-ning Gai, Wei-jun Gu, Jing-tao Dou, Jian-ming Ba, Zhao-hui L, Guo-qing Yang, Jin Du, Qing-hua Guo, Xian-ling Wang, Yi-ming Mu, Ju-ming Lu
Journal: BMJ (2010)

Objective To study clinical and immunological features of renal tubular acidosis (RTA) patients complicated with autoimmunity disease. Methods Data of 60 patients of RTA complicated with autoimmune disease and 40 without it during 1999 and 2009 were reviewed, including clinical features,immunological examinations and renal tubular function. Results Among 60 patients of RTA, 59 were type Ⅰ, one type Ⅱ, and 55 complicated with Sjogen's syndrome (92%), one with systemic lupus erythematosus, nine with autoimmune thyroid disease, and one with rheumatoid arthritis. Flaccid paralysis was manifested in 50 (83%) RTA patients complicated with autoimmune disease, polyuria in 28 (47%),polydipsia in 28 (47%) , bone disorder in 24 (40%) and arthralgia in 28 (47%) cases, but of those without autoimmune disease, bone disease only in eight (20%) and arthralgia in nine (22%) cases, with statistically significant difference ( P ＜0. 01 ). Serum level of parathyroid hormone increased noticeably, with prevalence of positive antinuclear antibody, anti-SSA antibody and anti-SSB antibody of 88 % (49/56),84% (47/56) and 43% (24/56), respectively in RTA patients with autoimmune disease, all significantly higher than those in the patients without it ( P ＜ 0. 05 ). Conclusions Sjogen' s syndrome is the most common and prevalence of bone disorder and arthralgia are significantly higher in patients of RTA complicated with autoimmune disease, which should be examined as early as possible for timely diagnosis and treatment.

Key words: 
Autoimmunity disease;  Renal tubular acidosis;  Sjogen's syndrome
Comparison of treatment costs of pembrolizumab versus nivolumab in head and neck squamous cell carcinoma.
Authors: Justin Yeh, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2020)

e19368 Background: Pembrolizumab and Nivolumab are PD-1 inhibiting immunotherapy agents approved for the treatment of metastatic or recurrent head and neck squamous cell carcinoma in patients previously treated with platinum-based chemotherapy. Both therapies have demonstrated similar survival benefits and adverse event profiles, but there is no published comparison of treatment cost and survival between the two agents. This study aims to analyze the cost-effectiveness of pembrolizumab compared to nivolumab through network meta-analysis techniques. Methods: Data published from the KEYNOTE-040 (pembrolizumab) and CheckMate 141 (nivolumab) studies were used to generate a model incorporating the cost of each drug in both the arms. The cost of treatment of side effects was extracted from previously published data and used for cost estimation in the model. Data from the standard of care arms (cetuximab, methotrexate, or docetaxel) in each study were adjusted to provide a common reference between the two studies. The number of years added in terms of overall survival was calculated for the entire experimental arm and the cost of each such year was calculated. All costs were adjusted for inflation. Results: Using published data from the KENOTE-040 trial, the average cost per patient adjusted for inflation over time, over 24 months in the pembrolizumab arm was $159,302, and similarly using data from the Checkmate 141 trial, the average cost per patient over 18 months in the nivolumab arm was $118,790. The cost of management of adverse effects was $18,728 vs $16,685 (pembrolizumab vs. nivolumab) during these time periods. Our model suggests that the adjusted total cost per month for patients on these drugs is very similar: $7417.91 vs. $7526.38. Assuming that the quality of life was similar in both groups and using an average OS for the standard of care arms, our model predicts that ICER for pembrolizumab is higher than nivolumab ($203,085 vs. 132,644). Conclusions: Both pembrolizumab and nivolumab improve survival benefit compared to their respective standard of care arms. However, the ICER for both medications is higher than the threshold set by many payers and health provider organizations. The model makes several assumptions which may render it less accurate to compare between trials but the cost of treatment for both drugs is not in the cost-effective range. To utilize these drugs in a cost-conscious practice, further research is needed to investigate lower doses at a slower frequency along with reduction of the price for each medication.
The prognosis valve of tumor regression grade in the same ypStage patients after neoadjuvant treatment in locally advanced rectal cancer: Post-hoc analysis of a prospective trial.
Authors: Jianwei Zhang, Yue Cai, Huabin Hu, Zehua Wu, Xiaoyu Xie, Jiayu Ling, Yanhong Deng
Journal: Journal of Clinical Oncology (2020)

e16129 Background: The ypStage after neoadjuvant treatment was an important prognosis factor in locally advanced rectal cancer (LARC). pCR or ypStage 0 showed best prognosis, while ypStage II-III showed poor prognosis and further adjuvant chemotherapy with FOLFOX was recommended. Tumor regression grade (TRG) was another factor to evaluate the response to neoadjuvant treatment. Even in the same ypStage, the TRG could be different. Here, we tried to analyze the prognosis valve of TRG in the same ypStage after neoadjuvant treatment in LARC from a prospective trial (FOWARC study). Methods: Patients with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil plus radiotherapy followed by surgery and seven cycles of infusional fluorouracil as adjuvant treatment, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). Survival analysis was performed on different ypStage and TRG (WHO classification) group. Results: In total, 495 patients were randomly assigned to different neoadjuvant treatment. 444 patients received surgery with a median follow-up of 45.2 months. The 3-year disease free survival (DFS) in ypStage 0, ypStage I, ypStage II and ypStage III was 95.8%, 89.2%, 71.7% and 55.1%, respectively (P &lt; 0.0001). In TRG 0, 1, 2 and 3, the 3-year DFS was 93.3%, 83.2%, 68.4% and 63.6%, respectively (P &lt; 0.0001). In ypStage I subgroup, TRG was not an independent prognosis factor, the 3-year DFS for TRG 1, 2 and 3 was 90.0%, 90.7% and 76.2%, respectively (P = 0.277). In ypStage II population, the 3-year DFS for TRG 1, 2 and 3 was 78.6%, 70.3% and 64.7%, respectively (P = 0.184). The ypStage III group showed great heterogeneity, the 3-year DFS for TRG 0-3 was 60.0%, 70.0%, 41.8% and 59.5%, respectively (P = 0.067). Conclusions: Both ypStage and TRG was strong prognosis factor for rectal cancer after neoadjuvant treatment. However, TRG was not an independent prognosis factor in the same ypStage after neoadjuvant treatment. Clinical trial information: NCT01211210 .
Relationship between caregiver burden and psychological distress among stem cell transplant (SCT) recipients prior to transplant.
Authors: Carlisle Topping, Ashley Nelson, Jamie M. Jacobs, Joseph A. Greer, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2020)

12120 Background: SCT is a potentially curative therapy for patients with hematologic malignancies that involves prolonged hospitalization, intensive follow-up, and a considerable risk of morbidity and mortality. Family and friends caring for SCT recipients experience substantial caregiving burden as they prepare for SCT. Previous research demonstrates caregiver distress is highest pre-transplant and is comparable to or higher than patient-reported distress. However, the extent of this distress and its relationship to certain domains of quality of life (QOL) and caregiving burden is currently unknown. Methods: We conducted a secondary analysis of cross-sectional data from two supportive care studies focused on caregivers of SCT recipients. Caregivers completed the Hospital Anxiety and Depression Scale (HADS) and the CareGiver Oncology QOL questionnaire to assess their psychological distress and QOL prior to SCT. Scores &gt;8 on the HADS anxiety and depression subscales indicated clinically significant symptoms. We selected eight domains from the CareGiver Oncology QOL questionnaire including social support, physical wellbeing, self-efficacy, coping, leisure time, financial stability, private life concerns, and caregiving burden. Multivariate regression models adjusted for age, sex, caregiver relationship, and SCT type were used to examine associations between these domains and caregivers’ anxiety and depression symptoms. Results: A total of 193 caregivers (age M= 57 years, 70% female, 52% allogeneic transplant) were enrolled with a majority caring for their spouse (80%), parent (8%) or child (5%). Overall 47% and 16% of caregivers reported clinically significant anxiety and depression symptoms, respectively. Low social support, physical well-being, coping and leisure time as well as high caregiver burden, private life concerns and financial distress were associated with both caregiver anxiety and depression symptoms (p &lt; .05). Low self-efficacy was associated with higher anxiety symptoms (p &lt; .05). Conclusions: Caregivers of SCT recipients experience substantial anxiety and depression symptoms prior to SCT. Impairments across multiple QOL domains are associated with caregiver’s psychological distress. Psychosocial interventions designed to improve coping, reduce caregiving burden, and enhance QOL are needed for caregivers prior to transplant.
Diagnostic value of B-type natriuretic peptide in patients with acute dyspnea
Authors: 刘纪改, 刘晓红, 杨宏丽, 穆伟
Journal: BMJ (2005)

目的 探讨B型钠尿肽(B-type natriuretic peptide)对充血性心力衰竭患者急性呼吸困难的鉴别诊断意义.方法选择130例急性呼吸困难患者,根据临床资料及左室射血分数分为充血性心力衰竭组78例、非充血性心力衰竭组52例.采用干式快速免疫荧光定量分析法检测血浆中的B型钠尿肽浓度.结果充血性心力衰竭组血浆B型钠尿肽浓度为(732±53) ng/L,高于非充血性心力衰竭组的(71±34) ng/L(P 500 ng/L常预示猝死发生.结论血浆B型钠尿肽水平对于充血性心力衰竭的诊断具有较高的敏感性、特异性和准确性,对于鉴别呼吸困难是否为心源性具有重要参考意义。
Pembrolizumab (P) or P + chemotherapy (C) versus EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): analysis of KEYNOTE-048 by disease state.
Authors: Danny Rischin, Kevin Joseph Harrington, Richard Greil, Denis Soulieres, Makoto Tahara, Gilberto Castro, Amanda Psyrri, Neus Baste, Prakash C. Neupane, Åse Bratland, Thorsten Fuereder, Brett Gordon Maxwell Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Jianxin Lin, Burak Gumuscu, Ramona F. Swaby, Barbara Burtness
Journal: Journal of Clinical Oncology (2020)

6530 Background: In the phase 3 KEYNOTE-048 trial ( NCT02358031 ) in R/M HNSCC (N = 882), 1L P vs E showed superior OS in PD-L1 CPS ≥20 and CPS ≥1 populations, noninferior OS in the total population, no PFS benefit, and favorable safety; 1L P+C vs E showed superior OS in CPS ≥20, CPS ≥1, and total populations, no PFS benefit, and comparable safety. Results of P or P+C vs E in incurable recurrent only, metastatic only, and R/M subgroups are shown. The metastatic only and R/M subgroups were combined and classified as metastatic. Methods: Patients with incurable recurrent (local and/or regional node recurrent disease) or metastatic HNSCC were randomly assigned 1:1:1 to P, P+C, or E. OS and PFS were estimated using the Kaplan-Meier method. Hazard ratios and 95% CIs were based on a Cox regression model with Efron’s method of tie handling with treatment as a covariate stratified by ECOG performance status, HPV status, and PD-L1 status. Data cutoff: Feb 25, 2019. Results: In the incurable recurrent only subgroup (n = 252), median OS was 11.5 vs 12.1 mo (P vs E) and 13.0 vs 11.1 mo (P+C vs E). In the metastatic subgroup (n = 620), median OS was 11.4 vs 9.7 mo (P vs E) and 13.0 vs 10.1 mo (P+C vs E). Median follow-up, OS, and PFS are shown in Table. Treatment-related adverse events (TRAE) in the incurable recurrent only subgroup: 49.4% (P), 94.7% (P+C), and 97.8% (E); grade 3-5 TRAEs rates: 16.0%, 78.7%, and 73.3%, respectively. TRAE rates in the metastatic subgroup: 61.6% (P), 96.4% (P+C), and 96.4% (E); grade 3-5 TRAEs rates: 17.6%, 69.5%, and 67.0%, respectively. Conclusions: P and P+C vs E were efficacious in the metastatic subgroup; in the relatively smaller subgroup of patients with incurable recurrent only HNSCC, the effect was less pronounced. Consistent with the total study population and regardless of disease state, the safety profile was favorable with P vs E and comparable with P+C vs E. These data further support use of 1L P or P+C in patients with R/M HNSCC. Clinical trial information: NCT02358031 . [Table: see text]
儿童单纯肥胖症的行为矫正和膳食指导
Authors: 蒋竞雄, 姜民慧
Journal: BMJ (2009)

蒋竞雄:从20世纪80年代中期到21世纪,儿童肥胖在我国呈逐渐上升的趋势,已经成为比较严重的儿童健康问题. 肥胖的发生和社会发展、家庭环境及人们生活水平的变化有很大关系.独生子女在很多家庭尤其在城市里,常受到来自父母、祖父母以及亲戚朋友等多方面的关爱,受传统习俗的影响,很多情况下用食物作为载体来表达关爱;孩子的进食习惯与行为也多从家庭、父母那儿学到,所以孩子的饮食习惯与家长的饮食行为关系密切,饮食量过多及不良饮食习惯均可使儿童发生肥胖。
Clinical analysis of the extracellular vesicle-fingerprint score blood test to refine the prediction of clinically significant prostate cancer and avoid prostate biopsy.
Authors: Adrian S. Fairey, Robert J Paproski, Desmond Pink, Deborah L Sosnowski, Catalina Vasquez, Bryan Donnelly, M. Eric Hyndman, Armen G. Aprikian, Perrin Beatty, John D Lewis
Journal: Journal of Clinical Oncology (2020)

5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]
Analysis of the prognostic factors of triple-negative breast cancer and the clinical efficacy of postoperative radiotherapy in early cases.
Authors: XT Cheng, Y Zhang, XX Zuo, J Yang, ML Dong, K Liu, Y Mi, Yg Shi
Journal: Journal of Clinical Oncology (2020)

e12502 Background: To explore the prognostic value of pretherapeutic peripheral blood parameters and breast imaging-reporting and data system (BI-RADS) classification of triple-negative breast cancer (TNBC) and the effect of postoperative radiotherapy in early cases. Methods: A total of 278 TNBC patients’ medical records between January 2013 and December 2018 were retrospectively collected, including white blood cells, neutrophils, lymphocytes, platelets, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum tumor markers, BI-RADS classification, TNM staging and therapeutic methods. We used the log-rank test and Kaplan-Meier curves to assess the progression-free survival (PFS) of enrolled patients. Multivariate prognostic analysis was performed by the Cox regression model. Results: The median PFS of all 278 patients was 20 months (4-72 months) at the end of follow-up. Operable patients who obtained adjuvant chemotherapy had a better median PFS (20 vs 18.5 months, P= 0.018, HR = 5.943, 95% CI: 1.36-25.92) than those without. Lymph node metastasis (52%) and chest well relapse (28%) were the critical failure forms followed by other metastases (12% lungs, 9.3% bones, 4% liver and 2.7% brain) with p value less than 0.001. Multivariate analysis indicated that platelet counts &gt; 113.5×10 9 /L (p = 0.024), PLR ≤ 111.7 (p = 0.036) and CA15-3 ≤ 8.4 U/mL (p = 0.003) were significantly associated with the favourable prognosis of PFS in TNBC patients. Furthermore, BI-RADS of grade 2-4 had a better median PFS compared with grade of 5-6(20 vs 17.5 months, p = 0.008, HR = 2.154, 95% CI: 1.219-3.805). In subgroup analysis, forty-three early cases with pN1 stage earned additional benefits from postoperative radiotherapy in terms of low risk of distant metastasis and recurrence (p = 0.014). Residual tumor after surgery was another important factor of poor prognosis (p = 0.029). Conclusions: Adjuvant chemotherapy improved median PFS for operable TNBC patients and pretherapeutic platelets, PLR, CA15-3 and BI-RADS were the independent prognostic factors of survival. Lymph node metastasis and chest well relapse were the main patterns of treatment failure. Radiotherapy could reduce the risk of disease progression for postoperative patients with N1 stage.
Relationship between serum 1, 25(OH)2D3 and oxidative stress in patients with diabetic nephropathy
Authors: Xiaojun Li, Yingying Zhang, Lu Fang, Hualin Qi, Shougang Zhuang
Journal: BMJ (2014)

To explore the relationship between serum 1, 25(OH)2D3 and oxidative stress in patients with diabetic nephropathy (DN). The serum levels of 1, 25(OH)2D3 in DN patients were significantly lower than those in DM and healthy controls. And the 1, 25(OH)2D3 level was negatively correlated with advanced oxidation protein products (AOPP), reactive oxygen species (ROS) and positively correlated with superoxide dismutase (SOD) in DN patients. 1, 25(OH)2D3, low density lipoprotein-cholesterol (LDL-C), body mass index (BMI), serum creatinine and age were associated with the level of oxidative stress in DN patients. With the progression of CKD, the serum levels of AOPP and ROS increased significantly while those of SOD and 1, 25(OH)2D3 decreased markedly.


Key words: 
Diabetic nephropathy; Oxidative stress