tbuckley/cabot-search huggingface dataset:
Targeted therapies: How can CT imaging improve evaluations and help understand mechanism of drug action?
Authors: Hubert Beaumont, Antoine Iannessi, Emmanuel Chamorey, Nathalie Faye, Catherine Klifa, Chih-Yi Hsieh
Journal: Journal of Clinical Oncology (2020)

e13012 Background: We compared the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) by stratifying changes in tumor’s longest diameter (LD) and volume (VOL) per tumor location in patients with HER2+ metastatic breast cancer after trastuzumab therapy. Methods: We retrospectively analyzed the ASLAN001-003 double-arm trial (NCT02338245). We first tested the intra and inter-arm equivalence in number and size of tumors at each location of the disease.Second, we compared the inter-arm average changes in 1) tumor burden according to RECIST; 2) stratified tumor burden in summing, for each patient, the target lesions from the same organ locations; 3) tumors considered independent but grouped per organ location of the disease.Third, we tested the intra-arm differential responses of pairwise groups of tumor locations: breast-lung, breast-liver, breast-lymph nodes, lung-liver, lung-lymph nodes and liver-lymph nodes. A sensitivity analysis tested the robustness of our results. Results: We followed 74 tumors in 35 patients (14 VC; 21 LC) after 12 weeks of treatment. Primary breast tumors had a larger size than metastasis (p &lt; 0.002). Tumor proportions at each organ location of the disease were not significantly different. The inter-arm difference in changes of tumor burden yielded: p = 0.086 (LD) and p = 0.13 (VOL); in stratifying patients per breast tumors: p = 0.002 (LD) and p &lt; 0.001 (VOL); and for independent breast tumors: p = 0.001 (LD) and p &lt; 0.001 (VOL). We found differential responses in the LC arm for breast-liver (p = 0.007 (VOL)) and Liver-Lymph node (p = 0.06 (VOL)). After outlier’s removal, the inter-arm difference was confirmed for breast tumors (p = 0.004 (LD); p &lt; 0.001 (VOL)) and when considering all tumors as independent (p &lt; 0.01(LD); p = 0.04 (VOL)). The differential Breast-Liver response in the VC arm was confirmed p &lt; 0.05 (LD or VOL). Conclusions: Differential imaging responses were found across treatment arms and tumor locations. The stratification of changes provides new insights into responses of targeted therapies and more accurate drug comparisons. The stratification is a promising approach to better understand therapy mechanisms of action behind tumor heterogeneity.
Evaluation of combined specialist/generalist teaching rounds model in training of general practitioners
Authors: Haiqing Wang, Chunyan Zhao, Zhihong Zheng, Li'en Pan, Xiuhua Wang
Journal: BMJ (2014)

Objective
To evaluate the application of Combined Specialist/Generalist Teaching Rounds (CSGR) Model in training of general practitioners (GPs).


Methods
This study was based on the teaching rounds of hypertension. Eighty six GP trainees, who receive training courses from June to December 2012, were enrolled in the study. Forty seven trainees were randomly assigned to received CSGR model (study group) conducted by one cardiologist and one general practice mentor; while other 39 trainees were assigned to received the teaching round model (control group) conducted by one cardiologist. A comprehensive analysis was made based on a self-administered teaching rounds evaluation questionnaire and hypertension knowledge test among two groups after teaching rounds.


Results
Scores of 12 teaching rounds evaluation items in study group were significantly higher than those in control group, including inquiry of family factors, highlighting the importance of prevention and guidance of health education (Z=-2.668, -2.482, -2.269 respectively, all P<0.05). GPs in study group were more satisfied with general practice concept teaching than GPs in control group (χ2 =12.340, P<0.01). The average total score of hypertension knowledge in study group increased significantly after CSGR than before.(18.70±2.96 vs. 16.52±2.72, t=5.043, P<0.01); meanwhile there was no significant improvement in control group. 97.8%(44/45)GPs in study group identified with the cooperative, educational and medical value of CSGR model.


Conclusion
CSGR model takes the advantages of specialist and general practice, it can improve the quality and effectiveness of teaching rounds, enhance GP trainees clininical abilities and their clinical think of genernal practice.


Key words: 
General practitioners; Teaching methods; Questionnaires
Incidence of large granular lymphocytosis (LGL) in patients with late cytopenias after allogeneic blood or marrow transplantation (AlloBMT).
Authors: Marcus Messmer, Laura Wake, Hua-Ling Tsai, Richard J. Jones, Ravi Varadhan, Nina D. Wagner-Johnston
Journal: Journal of Clinical Oncology (2020)

7544 Background: LGL - often called LGL leukemia - is a clonal disorder of T or NK cells often associated with cytopenias, autoimmunity, splenomegaly, and B symptoms. There are a limited number of studies of benign LGL expansion after alloBMT, some suggesting an association with improved transplant-related outcomes. In contrast, clinically significant LGL leukemia after alloBMT is only described in case reports. Methods: We cross referenced all patients receiving an alloBMT at Johns Hopkins since 2010 with patients who were evaluated for LGL expansion by peripheral blood (PB) flow cytometry (FC) since 2012. Results: There were 1930 alloBMTs from 1/1/10 to 7/1/19. PB FC for suspected LGL was sent on 153 unique patients after alloBMT, usually in the setting of cytopenias (97%). Median age was 59. 69 (45%) had LGL expansion (LGL+) at a median 194 days after alloBMT. Among LGL+, 53 (77%) had an absolute neutrophil count (ANC) &lt; 1500. The majority of the alloBMTs were non-myeloablative (NMA) (97%), related (88%), and haploidentical (89%), consistent with our center’s characteristics. Graft vs host disease (GVHD) prophylaxis was post-transplant cyclophosphamide (PTCy), mycophenolate mofetil, and tacrolimus or sirolimus. 64 (93%) cases were T cell LGL (T-LGL) and 5 were NK cell. Of those with T-LGL, 43 were assessed for T cell receptor clonality. 21% were clonal, 53% oligoclonal, 5% polyclonal, and 21% indeterminate. There were no significant demographic or transplant-related differences between LGL+ and LGL- in our 153 patient cohort. LGL+ were more likely to have had CMV viremia (75% vs 26%, p &lt; 0.0001), but not acute or chronic GVHD. LGL+ had higher lymphocyte counts (1520/cu mm vs 495, p &lt; 0.0001) and a trend toward more neutropenia (77% vs 63%, p = 0.07). There were no differences in overall survival, relapse, or non-relapse mortality. 29 (42%) of LGL+ received immunosuppressive therapy (IST) for cytopenias. First line treatment was corticosteroids for 24 (83%). 65% had normalization of ANC with first line treatment, compared to improvements in anemia in 15% and thrombocytopenia in 36%. 34% of those treated required ≥2 lines of treatment. Conclusions: In contrast to prior studies, where LGL after alloBMT was asymptomatic and associated with improved transplant outcomes, we identified a high rate of LGL with cytopenias and no improvement in transplant outcomes. Neutropenia was common in LGL+ and usually improved with IST.
Patterns of hepato-pulmonary metastasis and their impact on clinical outcomes in uveal melanoma.
Authors: Asad Javed, Abdullah S. Al Saleh, Matthew Stephen Block, Robert R. McWilliams, Yiyi Yan, Lisa A. Kottschade, Svetomir Markovic
Journal: Journal of Clinical Oncology (2020)

e22052 Background: Metastatic Uveal Melanoma (MUM) is a rare tumor with poor prognosis following development of liver metastasis. We hypothesized that patterns of metastasis in Uveal Melanoma correlate with clinical outcomes. Methods: We retrospectively reviewed patients with MUM at Mayo Clinic, Rochester from January 1999 to August 2019. Patients were stratified into two groups based on the pattern of hepatic and pulmonary metastasis at the time of diagnosis of metastatic disease: Group 1 (≤5 liver metastasis or lung metastasis) and Group 2 ( &gt; 5 liver metastasis without lung metastasis). Baseline characteristics were compared between both groups. Survival analysis was performed using the Kaplan Meier method. Univariate and multivariate analysis were performed for Overall Survival (OS). Results: 147 patients were included in the study (n = 67 Group 1; n = 80 Group 2). In Group 1, 49/67 patients presented with ≤5 liver metastasis and 18/67 had lung metastasis without liver metastasis. Median OS for Group 1 was significantly longer than Group 2 (38 vs. 15 months; p &lt; 0.0001) (Table). On univariate analysis, predictors for OS were: Pattern of Metastasis, ECOG PS &gt; 0, Time to metastasis &gt; 60 months, and Surgical metastatectomy. Pattern of Metastasis was an independent predictor for OS in a multivariate model that included these predictors (p = 0.0004). Group 1 patients were more likely to undergo surgical metastatectomy compared to group 2 (21.5% vs. 1.3%; p &lt; 0.0001). Interestingly, the median time to metastasis from diagnosis of UM was significantly longer for Group 1 as compared to Group 2 (67 vs. 24.5 months; p &lt; 0.0001). Conclusions: Limited (≤5) liver metastasis or lung metastasis (without liver metastasis) at diagnosis predict favorable clinical outcomes in MUM. The occurrence of such metastasis following a significantly longer time from primary diagnosis suggests the existence of a distinct sub-type of metastatic disease with relatively indolent behavior. [Table: see text]
澳大利亚社区卫生保健服务简介
Authors: 雷慧, 孔小清
Journal: BMJ (2004)

澳大利亚公民享受免费医院及社区医疗保障,其中社区卫生保健系统明显减少了患者入院率及病床占有率,减轻了医院的负担,而且从长远的角度促进了全民身心健康.社区卫生保健服务主要包括以下部分。
Enhanced Release of Glucose Into the Intraluminal Space of the Intestine Associated With Metformin Treatment as Revealed by [18F]Fluorodeoxyglucose PET-MRI
Authors: Yasuko Morita, Munenobu Nogami, Kazuhiko Sakaguchi, Yuko Okada, Yushi Hirota, Kenji Sugawara, Yoshikazu Tamori, Feibi Zeng, Takamichi Murakami, Wataru Ogawa
Journal: Diabetes Care (2020)

OBJECTIVE Positron emission tomography (PET)–computed tomography has revealed that metformin promotes the intestinal accumulation of [18F]fluorodeoxyglucose (FDG), a nonmetabolizable glucose derivative. It has remained unknown, however, whether this accumulation occurs in the wall or intraluminal space of the intestine. We here addressed this question with the use of [18F]FDG PET-MRI, a recently developed imaging method with increased accuracy of registration and high soft-tissue contrast. RESEARCH DESIGN AND METHODS Among 244 individuals with type 2 diabetes who underwent PET-MRI, we extracted 24 pairs of subjects matched for age, BMI, and HbA1c level who were receiving treatment with metformin (metformin group) or were not (control group). We evaluated accumulation of [18F]FDG in different portions of the intestine with both a visual scale and measurement of maximum standardized uptake value (SUVmax), and such accumulation within the intestinal wall or lumen was discriminated on the basis of SUVmax. RESULTS SUVmax of the jejunum, ileum, and right or left hemicolon was greater in the metformin group than in the control group. [18F]FDG accumulation in the ileum and right or left hemicolon, as assessed with the visual scale, was also greater in the metformin group. SUVmax for the intraluminal space of the ileum and right or left hemicolon, but not that for the intestinal wall, was greater in the metformin group than in the control group. CONCLUSIONS Metformin treatment was associated with increased accumulation of [18F]FDG in the intraluminal space of the intestine, suggesting that this drug promotes the transport of glucose from the circulation into stool.
心脏病患者的抑郁
Authors: 刘岚
Journal: BMJ (2009)

有报道,每3个心脏病发作患者中就有1人出现抑郁症状.女性,既往曾有过抑郁者,感觉孤独或缺乏社会、情感支持者,是心脏病发作后发生抑郁症的高危人群.患抑郁症后很难痊愈,但是可以治疗.治疗可使80%～90%的患者感觉更好。
Efficacy and safety of fixed combination of nitrendipine and atenolol in treatment for patients with mild to moderate essential hypertension and their optimal dosage matching
Authors: Gao-zhong Huang
Journal: BMJ (2010)

Objective To evaluate efficacy and safety of fixed combination of nitrendipine and atenolol in treatment for patients with mild to moderate essential hypertension and their optimal dosage matching.Methods Totally,275 patients with essential hypertension were selcted from seven hospitals in Shanghai,Nanjing and Suzhou,China and randomized into five groups with same proportional probability in a double-blind,double-dummy,parallel active-controlled,multi-center clinical trial,receiving fixed combination of nitrendipine and atenolol at three different dosage matching (nitrendipine/atenolol 5/12.5 mg,5/10 mg,5/7.5 mg for groups 1,2 and 3),and nitrendipine (10 mg for group 4) or atenolol (25 mg for group 5),respectively for eight weeks.Results Mean reduction of diastolic blood pressure (DBP)was (17±7) mm Hg,(18±9) mm Hg and (17±7) mm Hg for groupl,2 and 3,respectively from the baseline,significantly greater than that in groups 4 and 5[(13±7) mm Hg and (12±6) mm Hg,respectively].Mean reduction of systolic blood pressure (SBP) was (21 ±11)mm Hg,(24±12) mm Hg,(23±11) mm Hg,(19±13) mm Hg and (18±9) mm Hg,respectively for the five groups from the baseline,and the reduction in group 2 was significantly greater than that in group 5,with an overall efficacy of 94.4%,98.1% and 88.2% for groups 1,2 and 3,respectively,all statistically higher than that in group 5 (71.4%) with P＜0.01,eight weeks after treatment.The ratio of patients with increased dose of antihypertensive agents in week 5 was lower in group 2 than that in the other four groups,with mild adverse reaction only,no obvious change in laboratory biochemical examinations,and no needs in special management.Conclusions Fixed combination of atenolol and nitrendipine with an optimal doses of 5 mg and 10 mg respepctively was effective and safe for mild and moderate hypertension with good tolerance.

Key words: 
Hypertension; Antihypertensive agents; Atenolol; Nitrendipine
Inspiration from UK experience in chronic non-communicable diseases management
Authors: Xiaomin Peng
Journal: BMJ (2017)

慢性非传染性疾病(NCD)已经成为威胁人类身体健康的主要疾病。文章介绍英国NCD管理的经验特色，以及在制度、信息、时间、效果四大保障体系的有力支撑下NCD取得的成效，并比较上海和英国在NCD管理方面的差异，提出针对性改革建议。
CSNK2 in cancer: Pathophysiology and translational applications.
Authors: Scott Strum, Laszlo Gyenis, David W Litchfield
Journal: Journal of Clinical Oncology (2020)

e15594 Background: Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase whose expression levels are frequently elevated in solid and hematologic malignancies. CSNK2 has been discovered to hold prognostic and therapeutic significance across multiple cancers and is an excellent target for oncology research. This systematic review summarizes the current knowledge from in vitro and in vivo studies on the biology of this kinase in cancer alongside pre-clinical/clinical investigations from 24 different human cancer types. Methods: PRISMA methodology was used to generate a study protocol and building-block search strategy, from which a total of 796 publications in PubMed were retrieved across 24 human cancers. 245 of these publications met both screening and inclusion criteria. Data was then systematically extracted, including information about CSNK2 subunit mRNA/protein/activity levels, phosphorylation targets, phenotypic changes, in vivo studies, and prognostic/therapeutic data. The data was thereafter summarized and analyzed. Results: Five targets phosphorylated by CSNK2 were identified in at least 4 cancers: AKT, STAT3, RELA, PTEN, and TP53. The most heavily cited was AKT, identified in 15 cancers. Phenotypically, behaviors influenced by CSNK2 that were reported in 11 or more cancers included: evasion of apoptosis, enhancement of proliferation, enhancement of invasion/metastasis, and cell cycle control. Interestingly, these pathways correlated heavily with the most commonly cited CSNK2 targets. From a clinical perspective, CSNK2 held prognostic significance in 17 of the cancers. Additionally, xenograft experiments were found to have been performed in 13 cancers where CSNK2 inhibition resulted in a positive response to treatment. Lastly, early studies have shown promising results through the clinical application of CSNK2-specific inhibitors, with several clinical trials now underway for further assessment. Conclusions: Overall, our analysis supports CSNK2 as an attractive target for cancer therapy and points to specific areas where additional investigation is critical to advance our understanding of CSNK2 biology. The design of targeted therapies by exploiting the pathophysiology of CSNK2 has the potential to generate impactful treatment strategies across a wide range of cancers, promising exciting new discoveries scientifically and clinically.
Significance of stem cell transcription factor Nanog expression in hepatocellular carcinoma
Authors: Xie-wu Qiu, Cong-hui Yu, Jun-bo Yao, Chao Nai
Journal: BMJ (2012)

From August 2007 to April 2011,hepatocellular carcinoma (HCC) (n =40),paraHCC tissues (n =10),seminoma (n =10) and cavernous hemangioma (n =10) were selected.And the method of immunohistochemical streptavidin-perosidase was applied to detect the protein expression of Nanog.The expression ratios of Nanog were 17/40 (42％),1/10,0/10 and 5/5 in HCC,para-HCC tissues,seminoma and cavernous hemangioma respectively.Its expression showed no significant correlation with the patient gender,age,serum alpha fetoprotein (AFP),hepatitis B surface antigen (HBsAg),differentiation,Child grade and TNM stage ( P ＞ 0.05 ).It may be used as a surface marker of liver cancer stem cell.

Key words: 
Carcinoma,hepatocellular;  Transcription factors Nanog
Integrating pharmacogenomics panel testing for supportive care medications in patients with solid tumors.
Authors: Adrijana Kekic, Mahesh Seetharam, Parminder Singh, Katie Kunze, Michael A Golafshar, Cindy Azevedo, Sydney Welp, Anne Bofferding, Tyler Koep, Jason Ross, Eric Nelson, Christopher Grilli, Jewel Samadder
Journal: Journal of Clinical Oncology (2020)

e24114 Background: Pharmacogenomics (PGx) testing is used increasingly in cancer supportive care for drug and dose selection, and side effects prediction with antidepressants, antiemetics, and pain medications. Genetic variants in genes that encode for drug metabolizing enzymes (CYPs), transporters (SLC6A4) and drug receptors (HTR2A, OPRM1, etc) are well known for these medications. They contribute to inter-individual differences in medication safety and efficacy. We report on their frequency and effect on supportive care drugs in patients with solid tumors. Methods: Between 06/06/19 and 12/18/19, solid tumor cancer patients at Mayo Clinic Arizona were enrolled in a PGx prospective study. They were genotyped using a multi-gene panel, OneOme RightMed. The panel assessed 27 genes, including CYP2C9, CYP2C19, CYP2D6, CYP3A4, COMT, OPRM1, GRIK4, HTR2A, SLC6A4, associated with pain medications, antidepressants, and antiemetics. PGx pharmacist provided medication recommendations and dose adjustments based on PGx test results and concurrent medications. Results: 200 patients were swabbed and 196 patients were genotyped. The results were available within 5 days. All patients were also assessed for pheno-conversion (drug-drug-gene interactions) by a pharmacist. Recommendations were made based on predicted phenotype. Various solid tumor types were represented, including prostate (19.9%), colorectal (17.9%), melanoma (14.8%), and others (47.4%). Median age was 65 with 59.2% patients being male and 40.85% female. All had at least one actionable polymorphism related to these medications. The most significant findings were related to CYP2C19 and CYP2D6 genes. Of 196 patients, a total of 132 (67.3%) had other than normal CYP2D6 metabolizer phenotype and 112 (57.1%) had other than normal CYP2C19 metabolizer phenotype. Based on these genotypes, alternatives to pain medications were recommended for 37 patients, to ondansetron in 9 patients, and to anti-depressants in 51 patients. Conclusions: Genetic variants were commonly found that affect supportive care medications used in oncology practice and contribute to inter-individual differences associated with increased risk of adverse drug effects and reduced efficacy. PGx guided recommendation may help physicians in individualizing medication treatment outcomes for patients with different cancer types and with polypharmacy. PGx trained pharmacist can serve as a valuable asset in optimizing personalized medication management.
Use of a patient-preferences shared-decision-making encounter tool in clinical practice for patients with non-Hodgkin’s lymphoma.
Authors: Debra Wujcik, Amitkumar N. Mehta, Rachel Corona, Felice Cook, Matthew Dudley, William Dudley
Journal: Journal of Clinical Oncology (2020)

e24192 Background: Non-Hodgkin lymphoma (NHL) is the fourth leading cause of cancer in the United States with 77,240 new cases and 19,940 deaths annually. Treatment options are numerous and driven by patient’s molecular profile, risk, preferences/goals, and ability to tolerate treatment. Aligning physician-patient goals of care and integrating patient preferences into a shared-decision making (SDM) model allows patients and providers to select treatment consistent with medical science and personalized to each patient. This project evaluates feasibility of a patient preferences (PP) SDM encounter tool using technology to facilitate SDM at treatment decision (TD) for patients with NHL. Methods: To date, 45 patients with NHL at a TD making point were recruited from two sites to complete a tablet-based PPSDM encounter tool. The tool includes questions about needs, decision making preferences, values and goals of care. Results are reviewed by the provider and used to facilitate SDM in treatment selection during the clinical encounter. Patients also completed measures to assess satisfaction with the TD, patient activation, and perceived achievement of desired role in SDM at 3 weeks and 3 months post TD. Results: Participants are mean age 66 years (range 23-86), 53% male, and 98% white. 47% (n = 45) preferred that their doctor share responsibility with them when deciding which treatment was best for them. 69% said they would like to make the TD together with family and close friends and 69% agreed that their spouse was the most important person in helping make a TD. 51% said spirituality did not play a part in their TD. When asked how they liked to get medical information, 67% said they wanted all the facts, but not the prognosis. 87% said they had identified a medical surrogate to make decisions, yet 31% had an advanced directive on file. 64% agreed their cancer was curable and 84% agreed that a treatment goal was to get rid of all cancer. 73% of providers used the PPSDM results in conversation with the patient and 53% indicated their patient management changed based on the PPSDM results. There was 24% concordance between patient and provider perception of how TD were made. Conclusions: Collecting patient preferences, values, and care goals prior to the clinical visit using technology is feasible in busy clinics. Although most providers used the PPSDM results and over half changed their management plan, there was low concordance between patient and provider perceptions. Final analysis will include 3 week and 3 month measures of patient activation and satisfaction.