tbuckley/cabot-search huggingface dataset:
Inhibition of PIM kinase with fractionated radiation and docetaxel in preclinical prostate cancer models.
Authors: Anne Rajkumar-Calkins, Vinay Sagar, Jian Wang, Shania Bailey, Philip Anderson, Sarki Abdulkadir, Austin Noah Kirschner
Journal: Journal of Clinical Oncology (2020)

e17534 Background: PIM kinases are highly expressed in high risk prostate cancer and are associated with aggressiveness and poor prognosis, presenting a therapeutic target. Methods: We studied PIM inhibition (PIMi) in both hormone-dependent (LNCaP) and -independent (DU145, 22Rv1) prostate cancer cell lines and mouse xenografts. We evaluated PIMi effects via Western blotting, immunofluorescence, and RNAseq of multiple relevant pathways, and performed radiosensitization analysis with colony formation assays. We also investigated xenograft tumor growth with PIMi +/- radiation (RT) or docetaxel. Results: Pretreating the cell lines with PIMi prior to RT caused marked changes in H2AX phosphorylation compared to no PIMi + RT, with most significant alteration in DU145. However, in colony formation assays, 22Rv1 showed greatest radiosensitization with colony survival reduced from 23% to 15% with PIMi. 22Rv1 xenografts were grown in castrated mice, which were randomized to 30 Gy in 15 treatments vs no RT over 3 weeks, -/+ PIMi on RT days. RT + PIMi eliminated gross tumor, compared to an average of 78% and 51% of initial tumor volumes remaining with PIMi alone and RT alone, respectively. Immunofluorescence and Western blotting of harvested tumors showed PIMi altered patterns in proteins involved with hypoxic response (COX-2), cell survival (MDM2), and androgen receptor and suggested interactions between RT and PIMi for both MDM2 and androgen receptor but not COX-2. RNAseq analysis of xenografts showed daily PIMi affected multiple pathways involved in metabolism, growth, and DNA repair. Finally, we tested PIMi -/+ docetaxel in castrated mice with hormone-sensitive (LNCaP) or -resistant (22Rv1) xenografts treated with PIMi -/+ docetaxel. With both xenografts, PIMi + docetaxel reduced tumor size best, with 22Rv1 xenografts most dramatically showing 74% volume reduction from baseline with PIMi + docetaxel compared to 50% and 25% reduction in volumes with PIMi alone and docetaxel alone, respectively. Conclusions: PIMi has multiple pathway effects in prostate cancer. PIMi significantly reduces disease burden, particularly in combination with RT or docetaxel. Our data provide rationale for testing PIMi in clinical trials for prostate cancer.
Hypophosphatemic osteomalacia caused by adefovir dipivoxil: case report and literature review
Authors: Maoling Yuan, Lei Wang, Jian Yu, Min Wu
Journal: BMJ (2018)

A 61-years male patients with chronic hepatitis B developed hypophosphatemic  following long-term use of   in our hospital. With adefovir dipivoxil and osteomalacia as the search terms, we searched Wanfang database and Chinese Biomedical bibliographic database since 2005, and retrieved 79 cases of  dipivoxil-induced hypophosphatemic osteomalacia. Of the 80 cases, there were 63 males and 17 females with a mean age of (52±11) years. The average duration of disease to first diagnosis made was 17 months, the average duration of   administration to the onset of the disease was 62 months, and the average duration of hepatitis B was 11 years. The most common clinical manifestation was progressive bone pain in all parts of the body (80/80 cases); the most common laboratory finding was decreased serum phosphorus (80/80 cases), followed by abnormal urine tests (55/56 cases) including increased urinary phosphorus, urinary protein and positive urinary occult blood. The X-ray, CT and MRI showed different degrees of decreased bone density, osteoporosis, and bone fracture in severe patients (76/77 cases). It is suggested that clinicians should pay attention to the renal damage during the treatment of  dipivoxil, and the renal function, electrolyte and bone density should be monitored regularly.


Key words: 
Anti-retrovviral agents; Adefovir dipivoxil; Osteomalacia; Fanconi syndrome; Hypophosphatemia
Heparin-induced thrombocytopenia leading to lower extremity arterial embolism and cerebral infarction in one case
Authors: Yuliang Ma, Xiaoqiang Li, Liming Tang, Guohua Wang, Hongliang Huang
Journal: BMJ (2016)

肝素诱导的血小板减少症(HIT)是与肝素有关的严重不良反应，可见于各临床科室且易被临床医师忽视，常造成漏诊。报道我院收治的1例下肢深静脉血栓患者发生HIT并发下肢动脉栓塞及脑梗死的诊治过程，提示临床医生应重视HIT的发生。
盆腔脓肿诊治28例分析
Authors: 孙选, 林峰
Journal: BMJ (2006)

盆腔脓肿是由于急性盆腔结缔组织炎未得到及时治疗化脓形成[1].妇科所指的盆腔脓肿主要包括输卵管脓肿、输卵管卵巢脓肿及卵巢脓肿.近年来盆腔脓肿的发病率有上升趋势,由于其临床表现复杂多样,诊断困难,误诊率较高.现对我院28例盆腔脓肿病例分析如下。
内分泌科临床精粹(四)
Authors: 李乃适, 朱惠娟
Journal: BMJ (2011)

一、诊断肥胖的目的和原则[1] 肥胖之所以被列入一种疾病,主要是其损害患者的身心健康,包括肥胖本身及肥胖相关疾病的影响.诊断肥胖并非为了设法让每个人都成为模特,而是要判断患者的预期寿命和生活质量是否受到影响。
Progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in advanced/recurrent gastric cancer (AGC) treatment: Individual-patient-data (IPD) based meta-analysis of randomized trials.
Authors: Koji Oba, Xavier Paoletti, Yung-Jue Bang, Olivier Bouché, Michel Ducreux, Stefan Michiels, Markus H. Moehler, Satoshi Morita, Yasuo Ohashi, Junichi Sakamoto, Mitsuru Sasako, Kohei Shitara, Eric Van Cutsem, Marc E. Buyse, Tomasz Burzykowski
Journal: Journal of Clinical Oncology (2020)

e16506 Background: In 2013, the GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research through International Collaboration) evaluated the surrogacy of PFS based on IPD of 4,069 patients from 20 randomized trials of AGC. Treatment effects on PFS and on OS were only moderately correlated, and we could not validate PFS as a surrogate endpoint for OS. More recent trials, with refined inclusion criteria and higher standards for evaluating progression, may allow for a more accurate estimate of the correlation. The 2 nd round of the GASTRIC sought to re-evaluate the surrogacy of PFS for OS in AGC. Methods: The GASTRIC database was updated with trials published after 2010 which used RECIST (Response Evaluation Criteria in Solid Tumors). Since the proportional hazards assumption was questionable for PFS, we primarily used mean-time ratio as a treatment effect measure, estimated by using the log-logistic model. Using the meta-analytic approach, correlations between PFS and OS at the individual level (R indiv ), and between treatment effects on PFS and on OS at the trial level (R trial ), were estimated using Spearman’s rank-correlation and estimation-error-adjusted regression, respectively. Surrogate threshold effect was estimated as well. Results: We analyzed 10,912 patient data (1 st round 4,069 patients from 20 trials and 2 nd round 6,843 patients from 17 trials). Overall, moderate correlations were found at the individual level (R indiv = 0.75, 95%CI = 0.75 to 0.76 in Hougaard copula) and at the trial level (R trial = 0.77, 95%CI = 0.32 to 1.00), respectively. Surrogate threshold effect was equal to 1.29, i.e., observing 29% increase in mean PFS time would predict a significant increase of the OS time. In the subgroup of patients with measurable disease in the 2 nd round dataset (4,866 patients), R trial was higher and equal to 0.93 (95%CI = 0.70 to 1.00), with STE equal to 1.21. These results were same for 1 st and 2 nd line trials. Conclusions: The meta-analysis indicates a strong correlation between treatment effects (expressed as log-mean-ratios) on PFS and OS in patients with measurable disease.
Therapeutic methods of gut microbiota modification in colorectal cancer management – fecal microbiota transplantation, prebiotics, probiotics, and synbiotics
Authors: Karolina Kaźmierczak-Siedlecka, Agnieszka Daca, Mateusz Fic, Thierry van de Wetering, Marcin Folwarski, Wojciech Makarewicz
Journal: Gut Microbes (2020)

The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients’ overall survival is also discussed.
Real-world evidence: Molecular subtype and its prognostic implications of Lung-molGPA in EGFR-mutated adenocarcinoma.
Authors: Feng-Che Kuan, Chung-Sheng Shi, Wei-Hsun Yang, Hung-Yi Lai, Chun-Chieh Huang, Cheng-Ta Yang
Journal: Journal of Clinical Oncology (2020)

e21621 Background: EGFR mutations are heterogenous but all carry the same weight in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Methods: Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 256 patients were included with a median overall survival (OS) of 17.2months. Patients with Lung-molGPA scores of 1, 1.5-2.0, 2.5-3.0, and 3.5-4.0 had median OS of 5.9,11.5, 17.2, and 23.4months, respectively (p &lt; 0.001). In multivariate analysis of OS, only age (³70 versus &lt; 70 years, HR:1.71, 95% CI:1.25-2.35, p &lt; 0.001), KPS ( &lt; 70 versus ³70, HR:1.71, 95% CI:1.26-2.31, p &lt; 0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p = 0.037) remained statistically significant. In patients with a Lung-molGPA score £2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.9vs 12.8vs 4.5months, p = 0.021) and prognostic implications (Leu858Arg versus exon 19 deletions, HR: 1.85, 95% CI: 1.20-2.84, p = 0.005; other versus exon 19 deletions, HR:2.18, 95% CI:1.11-4.26, p = 0.023). Conclusions: Different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.
系统性红斑狼疮患者胃肠道受累21例临床分析
Authors: 江涛, 胡大伟, 李挺, 王晓栋, 顾越英
Journal: BMJ (2007)

收集整理21例系统性红斑狼疮(SLE)合并胃肠道受累患者的临床资料.10例患者行小肠CT及增强扫描,其中8例发现肠壁不同程度增厚.2例B超提示肠段肠壁水肿、增厚.SLE的胃肠道受累是SLE常见的临床表现;小肠CT、B超检查均为可靠、有价值的检查手段;有胃肠道症状并有其他脏器受累者应排除有无SLE。
Evaluation on community clerkship of general practice for medical students
Authors: Yi Xu, Hong Chen, Qinghuan Zhou
Journal: BMJ (2014)

A questionnaire survey was conducted in 114 medical students of 4th year in eight-year program before and after community clerkship of general practice. The survey showed that there were significant differences in the awareness of the function and features of community health service, the doctor-patient relationship and the difference with large hospitals before and after community clerkship (P 0.05). 85.1% students (97/114) thought that the community health service center had a harmonious doctor-patient relationship, 65.0% (74/114) thought thatfull communication between general practitioners and patientswas an important factor to build a harmonious doctor-patient relationship, 66.6% (76/114) feltsatisfied, and 72.8% (83/114) gained a lot in the clerkship. The results indicate that the community clerkship of general practice is conducive for students to understand theory, knowledge of general practice.


Key words: 
General practice; Teaching
Racial disparities in pancreatic resection and survival among elderly patients: A SEER database analysis.
Authors: Seojin Park, Dexter Waters, Karen Walsh, Nathan Handley, Harish Lavu
Journal: Journal of Clinical Oncology (2020)

e16784 Background: For localized pancreatic cancer treatment, surgical resection is the only potentially curative option. Currently, little is known about whether racial disparities exist in elderly patients’ access to resection and outcomes after resection. This study aims to understand the relationship between race/ethnicity and both resection rate and survival after surgery in elderly patients. Methods: The analysis included patients aged ≥65 years diagnosed with locoregional resectable (stage I and II according to the 6th AJCC TNM staging system) pancreatic cancer between 2007 and 2016 in the Surveillance, Epidemiology, and End Results database. Patients without complete surgical or survival data were excluded from the analysis. Multiple logistic regression was used to assess the association between race/ethnicity and receipt of resection. The effect of resection on 6-month and 5-year overall survival (OS) was evaluated using multivariate Cox proportional hazards regression, controlling for other clinical and demographic factors, such as sex, age, martial status, residence region, tumor location, tumor size, and year of diagnosis. Results: Of 12,829 patients, 4,310 (46.0%) received resection and 5,062 (54.0%) did not. Median follow-up among resected patients was 16 months (1-60 months), and 6-month and 5-year OS was 62.83% and 4.54%, respectively. The majority of the patients were white (73.1%), followed by Hispanic (9.3%), black (9.1%), and other (American Indian, Asian/Pacific Islander) (8.6%). Black (OR 0.69; 95%CI 0.60-0.80) and Hispanic patients (OR 0.78; 95%CI 0.68-0.90) were less likely to receive resection compared to white patients. While Hispanic patients had worse 6-month OS compared to white patients (HR 1.43; 95%CI 1.19-1.72), 5-year OS was not significantly different across the racial/ethnic groups. Other factors significantly worsened 5-year OS were being age 75 years or older, living in South region, and having tumor size greater than 50mm. Conclusions: Our findings support that racial disparities exist in resection rate in elderly populations. However, no racial difference was seen in the long-term survival after pancreatic resection. This may suggest that improving the access to resection for minorities with pancreatic cancer may improve their health outcomes. [Table: see text]
Non-medical use of prescription pain reliever among high school students in China: a multilevel analysis
Authors: 郭蓝, 许燕, 邓剑雄, 何源, 高雪, 李鹏声, 吴虹, 周金华, 卢次勇
Journal: BMJ (2015)

目标
考虑到普通中学学生与职业中学学生的差异，本研究调查中学生处方止痛药非医疗目的使用率，并从学校水平和个体水平同时探讨了中学生非医疗目的使用处方止痛药的相关因素。


方法
本研究采用横断面研究的方法，于2012年调查了重庆市11 906名普通中学及职业中学学生。采用自填式问卷的方法收集信息，并采用二水平logistic回归的方法探索非医疗目的使用处方止痛药独立的影响因素。


结果
中学生非医疗目的使用处方止痛药的总使用率为11.3%，其中职业中学学生的使用率明显高于普通中学学生(职业中学为15.8%，普通中学为9.8%)。最终的logistic回归模型结果显示职业中学学生更有可能参与非医疗目的使用处方止痛药中[校正比值比(AOR)＝1.64, 95%可信区间(CI)＝1.42～1.89]。有关个体层面的影响因素的研究结果显示低于一般水平的家庭经济状况与非医疗目的使用处方止痛药呈负相关关系(AOR＝ 0.77, 95% CI＝ 0.60～0.98)，以及有较多零花钱的学生越有可能有使用处方止痛药的行为。除此，家庭关系较差的学生，师生或同学关系较差的学生，父母或同学使用处方药的学生，考虑或尝试过自杀的学生均更有可能参与非医疗目的使用处方止痛药。


结论
中学生非医疗目的使用处方止痛药受许多因素的影响，本研究发现了职业中学学生是使用处方止痛药的高危人群，以及强调了后续应开展有关预防和干预青少年非医疗目的使用处方止痛药的研究。
Cannabidiol: Assessing preclinical safety in ovarian and endometrial carcinoma cell lines.
Authors: Shannon Rush, Arvinder K Kapur, Manish S. Patankar, Lisa Marie Barroilhet
Journal: Journal of Clinical Oncology (2020)

e24130 Background: Cancer patients use cannabidiol (CBD) for chemotherapy and cancer symptoms, though research of CBD safety and efficacy for these conditions are ongoing and mixed. We sought to determine endometrial (ECC1) and epithelial ovarian cancer (Kuramochi) cell proliferation when exposed to different concentrations of CBD, for the broader goal to establish if CBD can safely be utilized to treat the symptoms of cancer, including those caused by chemotherapy. Methods: ECC1 and Kuramochi cells were kept in media (RPMI with 10% bovine serum and 1% penicillin/streptomycin). We passaged cells when &gt; 90% confluent by adding tryspin-EDTA, incubating at 37C for 3 minutes, then spinning down with media to harvest the cell pellet. Cells were re-suspended in media, counted and apportioned to 96 well plates. Plates were incubated at 37C x 24 hours. CBD (from Cayman Chemical) was suspended in DMSO per manufacturer instruction then used to treat cells x72 hours at different concentrations (2.5-50uM). MTT was added to cells, cells incubated at 37C x 3 hours, media and MTT were removed and DMSO was added. Optical depth (OD) was calculated for plates using SoftMaxPro version 6.2.2. ODs were used to calculate inhibitory concentration for 50% cell death (IC50). Results: Kuramochi and ECC1 demonstrated decreased cell proliferation when exposed to CBD for 72hours. ECC1 IC50 fell between 2.5-5uM. Kuramochi IC50 fell between 15-20uM. Nearly all ECC1 growth was inhibited at concentrations 10uM or greater. Kuramochi proliferation was 15% that of controls at concentrations of 40 and 50uM CBD. Conclusions: ECC1 and Kuramochi cells demonstrated decreased proliferation in the presence of CBD. This bodes well for future studies of concurrent exposure to CBD and cytotoxic chemotherapy. Further preclinical research needed on CBD effects in endometrial and ovarian cancer, as patients turn to CBD for symptomatic relief from cancer and chemotherapy side effects. [Table: see text]
TCR clonality and Treg frequency as predictors of outcome in stage III NSCLC treated with durvalumab.
Authors: Sally CM Lau, Shirin Soleimani, Stephanie WY Wong, Stephanie Pedersen, Ben X Wang, Arielle Elkrief, Devalben Patel, Aline Fusco Fares, Kevin Jao, Nathalie Daaboul, Taiki Hakozaki, Penelope Ann Bradbury, Geoffrey Liu, Natasha B. Leighl, Ming-Sound Tsao, Pamela S Ohashi, Trevor John Pugh, Bertrand Routy, Frances A. Shepherd, Adrian G. Sacher
Journal: Journal of Clinical Oncology (2020)

3050 Background: Novel blood-based biomarkers evaluating T-cell receptor (TCR) clonality as well as the frequency/activation of immune populations hold significant potential for predicting response and elucidating the biology of anti-tumor immunity in stage 3 NSCLC treated with durvalumab. In this study, we sought to characterize clinical and immunologic predictors of durable response to therapy with a specific focus on TCR clonality and peripheral immune populations. Methods: Stage 3 NSCLC patients undergoing chemoradiation (CRT) and durvalumab were prospectively recruited and underwent baseline and serial blood collections. TCR repertoire analysis was performed on cfDNA using hybrid-capture TCR sequencing and TCR diversity estimated using Shannon’s entropy index. Viably preserved peripheral blood mononuclear cells (PBMC) were analyzed by high-dimensional flow cytometry using validated panels to evaluate T/B/NK-cell, Treg and myeloid populations. Correlations between cell populations were examined using linear and cox regression. Results: 134 stage 3 NSCLC patients who received durvalumab had a median PFS was 15.4 months, with worse PFS in patients with PD-L1 1-49% (HR 2.4, p = 0.03) and PD-L1 &lt; 1% (HR 2.6, p = 0.03). Smoking and EGFR/ALK mutations were not predictors of PFS. Immune profiling was performed in a pilot of 19 patients. Baseline TCR diversity did not associate with clinical factors or outcome. However, lack of clonal expansion after CRT indicated by a higher Shannon’s index was significantly associated with increased frequency of Tregs after durvalumab (p &lt; 0.05). In turn, this elevation in Tregs was associated with significantly reduced PFS in EGFR/ALK wt patients (p = 0.03) and a trend towards reduced PFS in the overall cohort (HR 5.2, p = 0.1). Conclusions: Clonal expansion of T cells after CRT may influence the likelihood of an anti-tumor immune response following PD-L1 blockade in stage 3 NSCLC. Similarly, expansion of peripheral Treg populations is associated with increased likelihood of disease recurrence. Further characterization of TCR clonality, minimal residual disease and T cell subpopulations using serially collected blood is ongoing.
Effects of alkaline water intake on gastritis and miRNA expression (miR-7, miR-155, miR-135b and miR-29c) in the Amazon population.
Authors: Juliana Ramos Chaves, Carolina Rosal Teixeira de Souza, Antonio André Conde Modesto, Fabiano Cordeiro Moreira, Eliel Barbosa Teixeira, Jonathan Souza Sarraf, Thaís Suellen Ramos Allen, Taíssa Maíra Thomaz Araújo, Andre Salim Khayat, Luis Eduardo Werneck De Carvalho
Journal: Journal of Clinical Oncology (2020)

e16544 Background: It is known that abnormal expression of miRNAs in the gastric cancer (GC) contributes to its carcinogenesis. Therefore, ingestion of commercial (usual) water on a daily basis may be a contributing factor for the occurrence of alterations in the gastric mucosal. In this study, it was evaluated the expression of the miRNAs miR-29c, miR-7, miR-155, and miR-135b in the gastric tissue of patients with gastritis before and after the consumption of alkaline water (pH range from 8.0 to 10.0), as well as the clinic pathological characteristics. Methods: 50 subjects from the Amazon region, diagnosed with gastritis that routinely used commercial (usual) water with a pH lower than 5.0, were enrolled to change the consume water to a pH of 8.5 to 10.0 for 5 months. Results: Endoscopic findings of gastritis were such different (less severe disease), p = 0.024; in 43% diagnosed with moderate gastritis upfront esophagogastroduodenoscopy (EGD) presented mild gastritis after the consumption of alkaline water, according to study methods; there were no worsening gastritis and there were a significant increase in the expression of miR-135b (p = 0.039) and miR-29c (p = 0.039). Conclusions: Modified pH range water (from 8.0 to 10.0) ingested for 5 months was able lead to a less severe gastritis according to the Sidney classification system, suggesting that this lifestyle change represented a clinical benefit in patients with gastritis on the Amazon region. In addition, higher expression of miR-135b and miR-29c was observed after the consumption of alkaline water for 5 months. [Table: see text]