tbuckley/cabot-search huggingface dataset:
Associations of functional, psychosocial, and medical factors with cognitive impairment in older, chemotherapy-naïve patients with early breast cancer.
Authors: Zev Nakamura, Allison Mary Deal, Kirsten A. Nyrop, Emily Damone, Hyman B. Muss
Journal: Journal of Clinical Oncology (2020)

12114 Background: Cognitive decline related to cancer and its treatments is a common concern among patients receiving treatment for cancer. Routine cognitive screening in oncology practice has been limited by the absence of a reliable, cancer-specific cognitive test. The Blessed Orientation Memory Concentration Test (BOMC) [1], has been incorporated in cancer-specific geriatric assessments, but there is no established cutpoint for cancer-related cognitive impairment. Recent research suggests that BOMC scores ≥ 5 may represent cognitive impairment in older patients with cancer. The purpose of this study was to identify cognitive impairment and associated characteristics in chemotherapy-naïve patients with breast cancer. Methods: Women with stage I-III breast cancer were recruited between 2009 and 2018. The BOMC (range 0-28, higher is worse function) was administered prior to chemotherapy. Associations between cognitive dysfunction (BOMC ≥ 5) and functional, psychosocial, medical variable were assessed using log binomial regression analysis. Results: In a sample of 331 women with breast cancer, the mean age was 65.2 years and 68.6% were 65 and older. Twenty-seven percent demonstrated cognitive impairment prior to treatment. Patients with Time Up and Go Test (TUG) ≥ 14 had increased risk of cognitive impairment compared to those with TUG &lt; 14 (44% vs. 23%, p = 0.0002). After controlling for demographic factors, the estimated increase in risk was 66% (RR: 1.66, 95% CI (1.20, 2.31), p = 0.002). For Medical Outcomes Survey (MOS) Physical Function, after controlling for demographic factors, each 1 point increase in physical function (range 0-20, higher is better function) was associated with a 5% decrease in risk of cognitive impairment (p = 0.0004). Conclusions: Using a newly proposed BOMC cutpoint of ≥ 5, our study identified cognitive impairment in over 25% of older, chemotherapy naïve women with breast cancer. This is similar to what has been reported using rigorous neuropsychological testing in comparable populations. Additionally, we found that this degree of cognitive dysfunction was associated with both patient-reported and clinician-assessed impairment in physical function, further supporting the clinical relevance of this new cutpoint. Reference: [1] Katzman et al. Am. J. Psychiatry. 140 (1983) 734–739.
Role of metabolic factors in formation of kidney stones and its non-surgical intervention
Authors: Chen Li, Yun Zhang
Journal: BMJ (2018)

The prevalence of kidney stone is increasing, and its recurrence risk is very high. This article reviews the current literature on causes of stone formation, its relation to metabolic factors, and dietary and medical intervention for kidney stones. It aims to emphasis the importance of comprehensive medical management based on the improvement of metabolic disorders, for treatment of kidney stone and reduction of its recurrence rate.


Key words: 
Kidney calculi; Urate lowering therapy; Nutritional and metabolic diseases
Biological predictors of third-line treatment outcomes in patients with advanced non-small cell lung cancer.
Authors: Antonios Vassias, Dimitrios Vassos, Dimitra Grapsa, Petros Bakakos, Nikoletta Rovina, Konstantinos N. Syrigos
Journal: Journal of Clinical Oncology (2020)

e21597 Background: The introduction of molecularly-guided targeted therapies and immunotherapy in routine oncology practice has led to significant survival increases in a subset of patients with advanced-stage non-small cell lung cancer (NSCLC). Nevertheless, the ultimate prognosis of these patients remains grim, and their overall therapeutic management challenging, particularly beyond the first-line treatment setting. We herein aimed to assess outcomes of third-line treatment in real-world patients with NSCLC, and to investigate potential correlations of clinicopathological and laboratory fearures with survival data. Methods: The medical records of 111 patients with advanced NSCLC, diagnosed and treated at the Oncology Unit of Sotiria Athens General Hospital between January 1, 2015 and December 31, 2018, were retrospectively reviewed. Eligible patients were those who had received more than two cycles of third-line treatment. Clinicopathological and laboratory features of patients, including baseline levels of complete blood count parameters evaluated immediately before administration of third-line therapy, were recorded and correlated with progression-free and overall survival. Results: The majority of patients had lung adenocarcinoma (54.1%) and stage IV disease (64,9%). Progression-free survival rates at 3 and 6 months were 59% and 20, respectively. Risk of disease progression was 35% lower in adenocarcinoma, as compared to other histological subtypes. Increased haematocrit and reduced white blood cell count levels were independently correlated with decreased risk of disease progression [HR (95% CI): 0,95(0,91-1,00); p = 0,044 and HR (95% CI):.1,05(1,00-1,11); p = 0,048, respectively]. Furthermore, higher white blood cell count and platelet count levels were independent predictors of decreased survival [HR (95% CI): 1,05 (1,01-1,1); p = 0,018 and HR (95% CI): 1,02(1-1,04); p = 0,018, respectively]. Conclusions: Haematocrit, white blood cell count and platelet count, recorded immediately before initiation of third-line therapy, may represent independent predictors of survival parameters in patients with advanced NSCLC.
Risk factors and comprehensive interventions for stroke
Authors: Lin Zhao
Journal: BMJ (2008)

In May 2005,269 patients with cnnfirmed stroke were enrolled in this studv and completed questionnaire survey or interview to explore the risk factors of the disease.Our results showed that Hypertension,tobacco smoking,alcohol intake,hyperlipidemia and diabetes mellitus were significant risk factors of stroke for patients.An earlier onset trend seemed to be found.According to these results.we proposed some effective interventions and standardized management to reduce the recurrence rate of stroke.

Key words: 
Cerebrovascular accident;  Risk factors
Pandemrix:why was the public not told of vaccine warning signs?
Authors: Doshi Peter, 王岳, 宋奇繁
Journal: BMJ (2019)

在大流行性流感爆发后的第8年，一项控告葛兰素史克公司生产的疫苗导致嗜睡症的诉讼，揭露了内部报告存在安全隐患的现象。Peter Doshi询问：在突发公共卫生事件期间，透明度意味着什么？
One-step treatment of low anal fistula plus mixed hemorrhoids with automatic ligation
Authors: Guoqiang Zhang, Maohe Jin, Jiangang Tang
Journal: BMJ (2018)

Sixty two patients with low anal fistula were treated by anal fistulectomy (fistula group) and 82 patients with mixed hemorrhoids were treated by automatic ligation of hemorrhoids (RPH group) and 38 patients with anal fistula plus mixed hemorrhoids were treated by the RPH and anal fistulectomy (fistula plus RPH group), the clinical data of patients were retrospectively analyzed.The complication rate, the degree of pain and, the urination disorders, the postoperative recurrent rate, scar area and the anal functions were observed and compared.There were no differences in pain degree at d1 and d3 among three groups(P>0.05). There was significant difference in urination disorders between the fistula group and anal fistula plus RPH group (8% vs. 32%, P 0.05). There were significant differences in scar area and the anal functions between anal fistula group and anal fistula plus RPH group(P<0.05). There were no postoperative massive hemorrhage, proctenclisis and infection in all three groups.


Key words: 
Rectal fistula; Hemorrhoids; Digestive system surgica procedures; Automatic ligation of hemorrhoids; Phase Ⅰ
Pain medication use in patients with HR+, HER2-neg advanced breast cancer treated with endocrine therapy and a CDK 4/6 inhibitor: A U.S. FDA pooled analysis.
Authors: Jennifer J Gao, Bellinda King-Kallimanis, Christine Hodgdon, Joyce Cheng, Mallorie Fiero, Pradeep Bandaru, Andrew Girvin, Christy Osgood, Gwynn Ison, Laleh Amiri-Kordestani, Richard Pazdur, Julia A. Beaver
Journal: Journal of Clinical Oncology (2020)

e24145 Background: Pain medications (PMs) are commonly used to treat pain in patients (pts) with advanced/metastatic breast cancer (MBC). We examined PM usage patterns in pts receiving CDK 4/6 inhibitor (CDKI) based treatment. Methods: We pooled data from seven phase 3 randomized, controlled trials of CDKI + endocrine therapy in pts with hormone receptor positive, human epidermal growth factor receptor-2 negative MBC. PM were categorized as opioid (includes codeine-containing), NSAID, or other (i.e. bone-directed, antiepileptic, topical PMs). All analyzed pts received at least 1 dose of CDKI/placebo and had concomitant PM with a documented start date. Medications prescribed during hospitalizations were not included. We evaluated percent PM by demographic factors and pts with bone mets, and liver/lung mets. Results: 2416 pts met the inclusion criteria, of which 928 pts started a PM before the study and 1488 pts did not start PM before the study. Of the 1488 pts not on a PM before the study, 739 started a PM after study started, and 749 did not receive any PM at any time. Of the 739 pts who started a PM only after study start, overall, 59% were prescribed only an NSAID, 10% were prescribed only opioid, 17% were prescribed both an NSAID and opioid, and 14% were prescribed other PMs. The PM use by percent in demographic subgroups in the 1488 pts who took none or more PMs only after study start are presented in the table. Conclusions: To our knowledge, this is the first analysis of PM usage patterns in pts with MBC receiving CDKI or placebo with hormonal therapy on clinical trials. NSAID use was higher than opiates in all prespecified subgroups. Future analyses will examine the benefit of different classes of pain medications in treating symptoms of pain and whether there are differences between study treatment arms Percent PM Use by Class (Patients Who Took None or More PM Only After Study Start). [Table: see text]
Prostate-specific antigen levels in diabetics and non-diabetics
Authors: Jian-yang Lü, Lin Chen, Jian-ming Chang, Chen-bo Liu
Journal: BMJ (2013)

A retrospective analysis was conducted for male Han patients aged 46 years or above undergoing serum test of total prostate specific antigen (tPSA) at our hospital from 2007 to 2009. Among them, there were 109 patients with complete clinical data (including a history of hypertension and dyslipidemia), including 36 type 2 diabetics and 73 non-diabetics. For type 2 diabetes and non-diabetes groups, the median values (lower quartile, upper quartile) of serum tPSA test results were 1.01 (0.44, 3.43) μg/L and 2.26 (1.04, 5.48) μg/L (t=-2.65, P<0.01) respectively. The serum level of tPSA in type 2 diabetics was significantly lower than that in non-diabetics.


Key words: 
Diabetes mellitus, type 2; Prostate-specific antigen
Long Range Endocrine Delivery of Circulating miR-210 to Endothelium Promotes Pulmonary Hypertension
Authors: Jingsi Zhao, Jonathan Florentin, Yi-Yin Tai, Stéphanie Torrino, Lee Ohayon, Tomasz Brzoska, Ying Tang, Jimin Yang, Vinny Negi, Chen-Shan Chen Woodcock, Michael G. Risbano, Seyed Mehdi Nouraie, Prithu Sundd, Thomas Bertero, Partha Dutta, Stephen Y. Chan
Journal: Circulation Research (2020)

Rationale: Unproven theories abound regarding the long-range uptake and endocrine activity of extracellular blood-borne microRNAs into tissue. In pulmonary hypertension (PH), microRNA-210 (miR-210) in pulmonary endothelial cells promotes disease, but its activity as an extracellular molecule is incompletely defined. Objective: We investigated whether chronic and endogenous endocrine delivery of extracellular miR-210 to pulmonary vascular endothelial cells promotes PH. Methods and Results: Using miR-210 replete (wild-type [WT]) and knockout mice, we tracked blood-borne miR-210 using bone marrow transplantation and parabiosis (conjoining of circulatory systems). With bone marrow transplantation, circulating miR-210 was derived predominantly from bone marrow. Via parabiosis during chronic hypoxia to induce miR-210 production and PH, miR-210 was undetectable in knockout-knockout mice pairs. However, in plasma and lung endothelium, but not smooth muscle or adventitia, miR-210 was observed in knockout mice of WT-knockout pairs. This was accompanied by downregulation of miR-210 targets ISCU (iron-sulfur assembly proteins)1/2 and COX10 (cytochrome c oxidase assembly protein-10), indicating endothelial import of functional miR-210. Via hemodynamic and histological indices, knockout-knockout pairs were protected from PH, whereas knockout mice in WT-knockout pairs developed PH. In particular, pulmonary vascular engraftment of miR-210–positive interstitial lung macrophages was observed in knockout mice of WT-knockout pairs. To address whether engrafted miR-210–positive myeloid or lymphoid cells contribute to paracrine miR-210 delivery, we studied miR-210 knockout mice parabiosed with miR-210 WT; Cx3cr1 knockout mice (deficient in myeloid recruitment) or miR-210 WT; Rag1 knockout mice (deficient in lymphocytes). In both pairs, miR-210 knockout mice still displayed miR-210 delivery and PH, thus demonstrating a pathogenic endocrine delivery of extracellular miR-210. Conclusions: Endogenous blood-borne transport of miR-210 into pulmonary vascular endothelial cells promotes PH, offering fundamental insight into the systemic physiology of microRNA activity. These results also describe a platform for RNA-mediated crosstalk in PH, providing an impetus for developing blood-based miR-210 technologies for diagnosis and therapy in this disease.
Survival differences between smokers and nonsmokers with EGFR mutated non-small cell lung cancer.
Authors: David Macari, Oluwatoyin Ibironke, Sruthi Jinna, Michael J. Stender, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2020)

e21509 Background: Patients with epidermal growth factor receptor (EGFR) mutated lung cancer have an excellent prognosis compared to other non-small cell lung cancer (NSCLC) with no driver mutation, however, there is a wide range of survival between even a cohort with an EGFR driver mutation. Given that many patients with EGFR mutations are never smokers, it is possible that those with a smoking history have tumors with other oncogenic mutations and therefore as their tumors are less dependent on the EGFR driver, they may derive less benefit from targeted therapy. Methods: Pathology specimens of NSCLC sent for EGFR testing between January 1 2012 and December 31 2016 at Beaumont Hospital, Michigan were reviewed. If a tumor harbored a targetable EGFR mutation, the chart was queried. Inclusion criteria were EGFR exon 19 or 21 mutations, stage IV disease, at least 2 time points of follow up. Exclusion criteria included small cell histology, negative EGFR test, or inadequate information in the chart. The primary endpoint of the study was median survival. Results: Out of 329 cases identified, 40 were positive for EGFR exon 19 or 21 mutations. Of the 40 positive cases, 26 fit all inclusion criteria. Median duration of follow up was 14 months (range 0-80). Smokers represented 13/26 (50%) of cases. Death occurred in 9/13 (69%) of smokers vs 7/13 (54%) in non-smokers. Median survival was 8 mo (0-26) vs 20 mo (1-80) respectively for smokers vs non-smokers. Conclusions: This data suggests there may be a clinically relevant difference in the survival between smokers and nonsmokers who have NSCLC with an EGFR driver mutation. This may be due to the relatively low burden of alternative driver oncogene mutations in the nonsmoker’s tumors resulting in a lower likelihood of an escape mechanism for the tumor to survive. Further analysis of larger datasets with complete molecular analysis of the tumors would be informative in exploring this hypothesis. This would aid in risk stratifying patients more effectively for future clinical trials targeting the EGFR mutation and refining the prognosis in this otherwise good prognosis group.
Metabolism of tumor cell in tumor micro environment assist immune escape.
Authors: Ning He, Jianfei Wang, Lingyu Wang, Ge Jin, Rongbo Lin, Yadong Yang
Journal: Journal of Clinical Oncology (2020)

e15181 Background: Tumor cell’s metabolism has been identified assisting immune evasion in tumor micro environment (TME), and it is very different from that of immune cells. Previous studies mostly focus on bulk or cell lines transcriptome; we aim to find the specific metabolic model of tumor cell based on vast single cell RNA-seq data. Methods: Public transcriptome of 7186 cells (SMART-Seq2) from 33 melanoma tumors in Benjamin’s study were collected from Single Cell Portal of Broad Institute, and metabolic genes were obtained from Human Metabolome Database (HMDB). Raw count data was preprocessed and analyzed using Seurat R package. Statistical analysis and data visualization were all carried out using R software. Results: Metabolic signature genes of malignant cells (Mals), CD8 + T cells, CD4 + T cells, B cells, natural killer (NK) cells, macrophages, cancer associated fibroblasts (CAFs), and endothelial cells (Endos) were extracted using Seurat. Mals, CAFs, Endos and macrophages shared similar metabolism patterns (high-level glycolysis, pyruvate metabolism, purine metabolism and specific proteoglycans profile compared to immune cells, p &lt; 0.01). Glutathione metabolism activity in Mal was higher than that in immune cell, especially GPX1, GPX4 and GSTO1 genes were highly expressed in Mal ( fc &gt; 2, p &lt; 0.01). Compared to immune cells, genes participate in glycolysis, PFKL, ADH5, ENO2, G6PC3, PGM1, ALDH1B1, PFKM, ALDH7A1, GAPDHS, TPI1, PGK1, LDHA, GPI, PKM, LDHB, ENO1, ALDOA and GAPDH were highly expressed in Mals, CAFs and Endos ( fc &gt; 2, p &lt; 0.01). Noteworthily, LGALS1, an inducer of T-cell apoptosis, was highly expressed in Mals and CAF ( fc &gt; 2, p &lt; 0.01). Otherwise, proteoglycans (PGs) in cancer, which contribute to cancer pathogenesis, exhibited high variation from immune cells. Conclusions: We firstly highlight the differential metabolism between tumor and immune cells in TME. Mals, CAFs, endothelial cells and macrophages can assist in evading immune surveillance through reshaping their metabolic patterns at cell level. This study is helpful for exploring new target of metabolic based anti-cancer immunotherapy.
以晕厥起病的左心房黏液瘤一例
Authors: 李尊波, 刘建军
Journal: BMJ (2012)

患者女,45岁,因反复头晕伴短暂性意识不清6年,再发1个月于2008年10月6日以晕厥待查人院.患者6年前某日由坐位起立时突感头晕、黑矇、站立不稳,旋即跌倒于地,意识不清,约1 min自醒,无四肢抽搐及二便障碍.此后在活动中有3次类似发作,每次发作不足1 min,病后面色苍白,曾行头颅CT未见明确异常,未予特殊治疗.既往否认癫痫、高血压、糖尿病等病史,家族中无类似患者. 关键词：晕厥
FDA analysis: Impact of BMI on efficacy outcomes in multiple myeloma trials.
Authors: Rachel Ershler, Laura L Fernandes, Bindu Kanapuru, Thomas Gwise, Paul Gustav Kluetz, Marc Robert Theoret, Nicole Gormley, Richard Pazdur
Journal: Journal of Clinical Oncology (2020)

8543 Background: Obesity has been implicated as a risk factor for the development of certain types of cancers, including multiple myeloma. Previous studies in other tumor types suggest that overweight subjects may have better outcomes, however, in relapsed/refractory multiple myeloma (RRMM), it is unknown whether body weight affects outcomes to therapy. Methods: We conducted a retrospective analysis of 13 RRMM clinical trials submitted to the FDA between 2012-2018. Patients were divided into four groups, underweight (BMI &lt; 18.5 kg/m 2 ), normal weight (BMI 18.5- &lt; 25 kg/m 2 ), overweight (BMI 25.0- &lt; 30 kg/m 2 ) and obese (BMI &gt; 30.0 kg/m 2 ). A multivariate analysis for progression free survival (PFS) and overall survival (OS), stratified by study and adjusted for age, cytogenetic risk group (Standard, High, Unknown), immunoglobin subtype (IgG Y/N), ECOG status (0-1, &gt; 1, UNK), sex (M/F) was used to estimate the HR. Results: A total of 5898 patients were included in this analysis. The median age was 65 years (range 30-91 years). A total of 87(1.5%) patients were underweight, 1853 (31%) were normal weight, 2212 (38%) were overweight, 1332 (23%) were obese, and 414 (7%) had missing BMI. The results of the multivariate analysis of PFS and OS are shown in the Table. Conclusions: Exploratory analysis of patients with RRMM found that patients who were overweight and obese had a trend towards slightly improved PFS and OS when compared to normal weight patients. Similar trends were observed in the analyses of overall response rate and BMI (not presented in the abstract). These results are consistent with previous studies in other malignancies. Limitations include the lack of adjustment for multiple testing, the small sample of patients in the underweight category, and heterogeneity in the treatment regimens and PFS assessments in the clinical trials included in the analysis. Future studies are needed to evaluate safety and impact of treatment regimens on efficacy outcome measures based on body weight. [Table: see text]
Correlation of gene expression profile to identify tumors with extreme sensitivity to the alkylating agent LP184.
Authors: Umesh Kathad, Aditya Kulkarni, Kishor Bhatia, Kerry Barnhart, Panna Sharma
Journal: Journal of Clinical Oncology (2020)

e21021 Background: Lantern Pharma is advancing LP184, a next generation alkylating acylfulvene class prodrug. LP184 damages DNA that is subject to preferential repair by Transcription-Coupled Nucleotide Excision Repair. LP184 efficacy in 35 cell lines from solid tumor origin with known transcriptomic profiles identifies gene expression patterns that strongly correlate with response in cell lines. This gene expression profile allows the interrogation of clinical transcriptomics datasets to identify tumors that would potentially be highly responsive to LP184. Methods: LP184 cytotoxicity in cell lines was tested in a concentration range from 14 nM to 10 uM. Cell viability readout using CellTiter Fluor reagent was measured 72h post drug addition, and IC50 value was generated using GraphPad Prism. Bioinformatic analyses were run using the Morpheus tool from the Broad Institute. CCLE microarray expression data were used for gene signature findings and TCGA patient data were used for gene signature validation. Results: LP184 showed broad anti-tumor cytotoxicity in solid tumor cell lines including liver, NSCLC, prostate, ovarian, kidney and thyroid cancers (median IC50: 358.9 nM). Across this spectrum, LP184 sensitivity was found to be most highly correlated with high transcript levels of PTGR1, and with low transcript levels of KDM4A. Analysis of top 10 sensitive cell lines showed that NSCLC cell lines had the highest representation (5 of 10). Differential sensitivity and gene expression pattern analyses on NSCLC cell lines correlated with high relative expression of PTGR1, CASP6, NAMPT, SMARCD3 and GLRX genes along with low relative expression of KMD4A, HPGD, PTPRF and KRT14 genes in the highly sensitive cell lines. The oxidoreductase activity of PTGR1 is likely involved in bioactivation of LP184 and CASP6 mediates drug-induced apoptosis. HPGD acts upstream of PTGR1 in the prostaglandin metabolism pathway in turn modulating the turnover of endogenous PTGR1 substrate. Assessing relative expression of these genes in selected clinical NSCLC data indicates that around 37% of such tumors would potentially respond with high sensitivity to LP184. Conclusions: Overall, LP184 is a novel alkylating agent with nanomolar potency in solid tumor cell lines, especially NSCLC, and can serve as a molecularly guided therapy option in multiple tumors. The correlated genes KDM4A/ HPGD that impart high sensitivity at low expression levels, suggest potential synergistic combinations of their respective inhibitors in development PKF118-310/ ML147 with LP184.