tbuckley/cabot-search huggingface dataset:
Improvement of Glucose Control and Reduction of Hypoglycemia Following Intravenous Immune Globulins in a Child With Type 1 Diabetes and High Levels of Insulin Antibodies
Authors: Lucien Marchand, Perrine Luigi, Jerome Place, Fabienne Dalla-Vale, Anne Farret, Eric Renard
Journal: Diabetes Care (2017)

Anti-insulin antibodies (AIA) usually have no impact on glucose control in type 1 diabetes (1). However, high titers of AIA with low/medium affinity for insulin may form unstable immune complexes resulting in high glucose variability (2). Corticosteroids, plasmapheresis, mycophenolate mofetil (3), and rituximab (4) have been tried to solve this issue. We report a case of interest owing to significant improvement following intravenous infusions of human immune globulins (IVIg).

A lean 8-year-old Caucasian boy was diagnosed with type 1 diabetes 3 years before being referred to our clinic. No autoantibodies against islet antigens, GAD, IA2, or zinc transporter 8 were detected, but testing for AIA was not done at onset and no GCK , HNF1A , HNF4A , HNF1B , ABCC8 , KCNJ11, or INS gene mutations were found. Under multiple daily insulin injections or an insulin pump, high glucose variability included uncontrollable postmeal hyperglycemia and recurrent severe hypoglycemia in fasting/nighttime periods. Despite a sensor-augmented …
Abstract 55: Detection of Atrial Fibrillation Using a Smartphone Camera
Authors: Oscar Maitas, Jinseok Lee, Dionyssios Robotis, Ki H Chon, David D McManus
Journal: Circulation Research (2012)

Introduction: Atrial fibrillation (AF) is the most common sustained dysrhythmia in the U.S. and is associated with significant morbidity and mortality. Although new AF treatment strategies have emerged over the last decade, a major challenge facing clinicians and researchers is the paroxysmal, often short-lived, and sometimes asymptomatic nature of AF. We hypothesized that a smartphone can detect AF based on its ability to record heart beat variability by placing a fingertip on the built-in camera. Methods: In this prospective clinical investigation, we recruited 33 participants at a tertiary care medical center who presented with persistent AF prior to elective cardioversion. We recorded 2-5 minutes of pulse readings from participants’ index finger using an iPhone 4S before (AF cases), and after, electrical cardioversion (Sinus rhythm controls). With heart beat interval time series obtained from changes in color signals of a fingertip recording, we compared the results of an AF detection algorithm using Root Mean Square of Successive Difference in combination with Shannon Entropy and Sample Entropy in comparison to the gold-standard of an electrocardiogram. Results: The AF detection accuracy was 97.67% (sensitivity of 96.08% and specificity of 99.97%) for each sample when a combination of the three signal processing techniques were applied compared to the gold-standard electrocardiographic recordings. All of the 33 AF episodes were detected. In addition, we tested on 29 healthy subjects and found that the accuracy (specificity) was 99.51%. Conclusions: In this paper, we show that a smartphone can accurately detect AF based on its ability to obtain RR time series. More accessible methods to accurately detect AF are necessary, and the use of existing smartphone technologies has potentially revolutionary clinical applications for in-home monitoring for AF.
A predictive test for therapeutic treatment outcomes of advanced gastrointestinal cancer patients (AGC)
Authors: N. B. Pandya, K. R. Tkaczuk, N. Tait, O. Ioffe, M. Tan, D. A. Van Echo, M. J. Sutula, S. A. Lesko, S. F. Deamond, P. O. Ts’o
Journal: Journal of Clinical Oncology (2009)

e15079 Background: There are currently limited options for selecting an optimal treatment regimen for AGC patients. The Drug Response Indicator Test (DRIT) is a platform technology that provides a detailed profile of a patient's tumor response to commonly used chemotherapeutic drugs, as a basis for individualized treatment. Establishment of DRIT will allow physicians to choose effective drug treatments to improve the efficacy of cancer therapies on an individual basis. Methods: DRIT analysis is based on fluorescent dye-labeled monoclonal antibody staining followed by computer-assisted microscopy to measure expression levels in tumor sections. The interpretation of the Drug Response Indicator (DRI) expression levels result in classification of tumors as sensitive or resistant to treatment with a mechanistically related drug. Clinical outcomes are then analyzed with respect to the DRI data. This study utilized the following drug/DRI combinations: capecitabine, 5-flurouracil/thymidylate synthase; docetaxel, paclitaxel, abraxane/β-tubulin isoform III; gemcitabine/ribonucleotide reductase; platinum salts/ERCC-1; Irinotecan/Topoisomerase I. Results: DRIT retrospective studies were performed on a cohort of 33 consented patients (pts) receiving 55 treatments for AGC at UMGCC. This cohort included pts treated for rectal/colon, gastric, esophageal &amp; pancreatic cancers. DRIT sensitivity was 0.96, positive predictive value 0.84, negative predictive value 0.67 and overall predictive accuracy 83 %. DRI expression level cut-off points indicating sensitivity or resistance to a specific treatment were derived from previous retrospective breast cancer studies using similar drug complements (abstract 6075 San Antonio Breast Conference 2008). Conclusions: This study indicates that DRIT can provide accurate prediction of treatment outcomes for individual AGC patients. DRI expression level cut-off points indicating sensitivity or resistance to a specific treatment may be applied to both breast cancer &amp; AGC. DRIT will allow for tailoring of chemotherapy based on the specific biomarker expression within each patient's tumor tissue. [Table: see text]
A phase II trial of neoadjuvant metformin in prostatic adenocarcinoma with serum and tissue biomarker evaluation.
Authors: Anthony Michael Joshua, Sevan Evren, Vanessa E. Zannella, Barbara Bowes, Neil Eric Fleshner, Michael A. S. Jewett, Antonio Finelli, Andrew Evans, Marianne Koritzinsky, Joan Sweet, Michael N. Pollak
Journal: Journal of Clinical Oncology (2012)

e15118 Background: Metformin is an inhibitor of the complex 1 in the respiratory chain, and is widely used in diabetes due to its effect on reducing insulin resistance. It has also been recently described to have effects via AMPK on inhibiting the mTOR kinase. Significant preclinical and epidemiological studies suggest its role in chemoprevention. These actions provide significant rationale to evaluate its utility in prostate cancer. We conducted a phase II single centre study of neoadjuvant metformin in localised prostate cancer. Methods: Men were required to have histologically confirmed prostate cancer involving at least 20% of at least 1 unfragmented biopsy core. Exclusion criteria included patients who on initial assessment are found to be on treatment with any drug used for the treatment of any form of diabetes, or patients that begin treatment for any form of diabetes during the course of the study. Pts were treated with up to 500mg tid of metformin. Primary objectives were to demonstrate safety and tolerability of neoadjuvant metformin administration in men with prostate cancer and document changes in phospho-AKT signalling indices. Results: 24 patients were enrolled with 22 evaluable; median age was 64 yrs (range, 45-70 yrs). Baseline characteristics included median PSA 6 ng/mL (range, 3.22-36.11ng/mL). Median duration of drug treatment was 41 days (range 18-81). No grade 3 adverse events were reported, all patients underwent subsequent radical prostatectomy with adverse effects related to metformin. Final Gleason scores ranged form 6-8, and final stage ranged from pT2a-pT3b. Significant pre-and post changes were noted in serum IGF1 (p=0.02), fasting glucose (p=0.03), BMI (p&lt;0.01) and waist/hip ratio (p&lt;0.01). There was a trend for a PSA reduction (p=0.08), with 6/22 patients experiencing a PSA fall of greater than 20%. There were no correlations between any metabolic, morphometric or cancer-related serum indices.Tissue results are pending. Conclusions: Neoadjuvant metformin is well tolerated prior to radical prostatectomy. Data to date indicates promising effects on metabolic parameters, tissue results will be presented including proliferation indices and signaling pathway assessments.
Cost-effectiveness of HER-2 testing strategies to select women with metastatic breast cancer (MBC) for treatment with trastuzumab
Authors: G. Oster, T. E. Delea, A. Berger, P. Klein, G. Lieberman, V. E. Paton, A. Chawla
Journal: Journal of Clinical Oncology (2004)

768 Background: In the pivotal trial of trastuzumab (Herceptin) (N=469), Herceptin in combination with chemotherapy improved survival when administered as first-line therapy to women with MBC who were HER-2+ by immunohistochemistry (IHC). In a retrospective analysis of data from this trial, the benefits of Herceptin were found to be greatest in patients who were HER-2+ by fluorescence in-situ hybridization (FISH). Despite higher costs, primary FISH testing to identify women who may benefit from Herceptin may be economically justified. Methods: A decision-analytic model was developed to evaluate the cost-effectiveness of five strategies for identifying women with HER-2+ MBC. These strategies used IHC only, IHC and FISH, or FISH only: (1) treat if IHC 2+ or 3+, (2) treat if IHC 3+; IHC then FISH, (3) FISH if IHC 2+, treat if IHC 3+ or FISH+, (4) FISH if IHC<3+, treat if IHC 3+ or FISH+; FISH alone (5) treat if FISH+. FISH+ patients were assumed to be HER-2+. Probabilities of progression, death, and cardiac dysfunction were estimated from the Herceptin pivotal trial. Time to death conditional on disease progression was assumed to be independent of treatment and HER-2 status. Other probabilities and costs were estimated from published sources. For each strategy, expected costs, life-years (LYs), and cost-effectiveness were calculated over a five-year period. Results: Expected costs per patient tested ranged from $12,861 (Strategy 2) to $17,548 (Strategy 1). Expected LYs ranged from 1.527 (Strategy 2) to 1.544 (Strategies 4 and 5). Strategy 5 dominated Strategies 1, 3 and 4. The cost-effectiveness of Strategy 5 vs 2 was $63,375 per LY saved. In probabilistic sensitivity analyses, Strategies 2 and 5 were repeatedly identified as preferred, with ∼90% probability that the cost-effectiveness of Strategy 5 vs 2 is <$100,000 per LY saved. Conclusions: Primary FISH testing to identify women with MBC who should receive Herceptin is cost-effective relative to other testing strategies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech
Cross-Platform Comparison of Four Leading Technologies for Detecting <i>EGFR</i> Mutations in Circulating Tumor DNA from Non-Small Cell Lung Carcinoma Patient Plasma
Authors: Ting Xu, Xiaozheng Kang, Xiaofang You, Liang Dai, Dequan Tian, Wanpu Yan, Yongbo Yang, Hongchao Xiong, Zhen Liang, Grace Q. Zhao, Shengrong Lin, Ke-Neng Chen, Guobing Xu
Journal: Theranostics (2017)

Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available.Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients.Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison.Fifteen EGFR mutations across twenty NSCLC patients were identified.Firefly NGS, cobas-ARMS and ddPCR all displayed superior sensitivity while ADx-ARMS was better suited for the qualitative detection of EGFR mutations with allele frequency higher than 1% in plasma and tissue samples.We observed high coincidence between the plasma and tissue EGFR mutational profiles for three driver mutations (L858R, exon 19 deletion and G719X) that are known targets of first generation EGFR-TKI therapies among patients who relapsed.Discrepancies between tissue and plasma EGFR mutational profiles were mainly attributable to spatial and temporal tumor heterogeneity, mutation inhibition due to therapy response and drug resistance (T790M).This study illustrates the challenges associated with selection of a technology platform for EGFR ctDNA analysis in the context of treatment evaluation and drug resistance detection.
Ranking therapies for clinical trial selection based on somatic mutation profiles.
Authors: Christopher S. Potter, Sara E. Patterson, Xing Yi Woo, Grace A. Stafford, Gregory J. Tsongalis, Susan M. Mockus
Journal: Journal of Clinical Oncology (2015)

e22089 Background: Clinical utility of NGS assays for therapy selection in clinical trials is challenging due to the lack of consistency across clinical reports and the ambiguity of gene mutations reported in the literature. A therapy selection method insuring consistency and addressing the lack of mutational specificity is required for creating a simplified clinical report based on a complex assay. Methods: DNA from 56 FFPE solid tumors was subjected to the JAX Cancer Treatment Profile, a 358-gene next-generation sequencing assay. Actionable mutation profiles with matched therapies were identified to compile a clinical report for each patient sample. A 25-tier ranking system was developed and implemented to score the strength of efficacy evidence for each patient’s actionable variant/therapy combination for clinical trial selection. A statistical analysis was conducted to compare clinical reports before and after the implementation of the ranking system and to graphically represent strength of efficacy evidence data for therapies from high to low. Results: 3.16 ± 1.15 actionable variants were found per patient sample. Means of associated therapies included 1.36 ± 1.63 FDA approved therapies, 8.52 ± 5.42 FDA approved in other indications, and 12.07 ± 9.01 investigational therapies. Efficacy evidence of variant/therapy combinations produced an average ranking of 2.73 (high) for FDA approved, 16.97 for FDA approved in other indications, and 19.5 for investigational therapies with an average of 72.68 ± 43.01 clinical trials per report. The mean for reports scored before the ranking system was 19.6 with a variance of 34.9, while after the use of the ranking system the mean was 16.7 with a variance of 59.3 and comparison between before and after was statistically significant (p < .00005). Conclusions: We have developed a ranking system to score the strength of evidence supporting somatic mutations and therapy combinations. Statistical analysis demonstrated that the ranking not only serves as a quality control across multiple report writers, but also provides an evidence-based method for the selection of clinical trials most likely to benefit patients who have exhausted standard-of care options.
Human infections with recently-emerging highly pathogenic H7N9 avian influenza virus in China
Authors: Fuchun Zhang, Yuhai Bi, Jian Wang, Gary Wong, Weifeng Shi, Fengyu Hu, Yang Yang, Liuqing Yang, Xilong Deng, Songfeng Jiang, Xi He, Yingxia Liu, Chibiao Yin, Nanshan Zhong, George F. Gao
Journal: Journal of Infection (2017)
Prognostic impact of orotate phosphoribosyl transferase (OPRT) activity in resectable colorectal cancers (CRC) treated by 5-FU-based adjuvant chemotherapy
Authors: T. Ochiai, M. Sugitani, K. Nishimura, H. Noguchi, T. Okada, M. Oouchi, M. Yamada
Journal: Journal of Clinical Oncology (2004)

3574 Background: Dihydropyrimidine dehydrogenase and thymidylate synthase are 5-FU metabolism and target enzyme, and has been studied as prognostic factors in CRC. Meanwhile, phosphoribosylation of 5-FU is an essential step leads to tumor growth inhibition and OPRT is the main enzyme that involves in this conversion of 5-FU to FUMP. The aim of this study was to evaluate the prognostic relevance of OPRT activity in CRC patients treated by 5-FU-based adjuvant chemotherapy. Methods: Surgical specimen was obtained from resectable CRC patients who were subsequently treated by 5-FU-based adjuvant chemotherapy. OPRT activity in the extract of tumor tissue was determined by the method of Laskin et al. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier estimate. Results:During 1999 to 2003, tumor tissue was collected from 124 CRC patients and then the patients were followed for 3.7 years (Median). Patients were divided into 2 groups by the cut-off value of tumor OPRT (0.147 nmol/min/mg protein) determined by maximal χ2 method (high group (≥0.147): n=102, low group (<0.147): n=22). There were no significant imbalances in T and N value between 2 groups. 5-year DFS for high and low group were 75.7% and 56.9% (p=0.05, log-rank test) and OS were 84.6% and 58.4% (p=0.01), respectively. Conclusions: Lower OPRT activity in tumor tissue was associated with poor survival in resectable CRC patients treated by 5-FU-based adjuvant chemotherapy and this research clarified that OPRT assay is indispensable for the determination of 5-FU-based adjuvant chemotherapy indication. Thus, the application of OPRT assay to routine clinical practice should be considered prior to 5-FU-based adjuvant chemotherapy. No significant financial relationships to disclose.
Clinical characteristics of melanoma patients with non-V600E/K <i>BRAF</i> mutations.
Authors: Sasan Nowroozi, Zhuang Zuo, Keyur Patel, Sapna Pradyuman Patel, Rajyalakshmi Luthra, Mark Routbort, Alexander J. F. Lazar, Michael A. Davies, Hassan Hasanein, Nicholas E. Papadopoulos, Wen-Jen Hwu, Agop Y. Bedikian, Scott Woodman, Patrick Hwu, Kevin Kim
Journal: Journal of Clinical Oncology (2013)

e20036 Background: BRAF mutations are found in ~50% of melanoma. V600E/K substitutions are the most common and well-characterized. We analyzed the clinical characteristics of patients with non-V600E/K BRAF mutations. Methods: We identified 38 melanoma patients whose tumor contained a non-V600E/K BRAF mutation and reviewed the clinical characteristics. The sequencing analysis was performed with either pyrosequencing or next generation sequencing assay. Results: 38 patients were identified with non-V600E/K BRAF mutations. Mutations detected in more than 1 patient included V600R (n=14, 37%), K601E (5, 13%), G469E (3, 8%); L597S (3, 7%), D594G (2, 5%); 11 other mutations were identified in single patients. Median age was 57 yrs; 82% were men; 95% were white. The common primary subtypes were nodular (26%), superficial spreading (24%), unknown primary (21%); no one were acral, mucosal or uveal melanomas. Ten (26%) of 27 with known ulceration status had ulceration, and 3 (7%) of 22 with known mitosis status had &lt; 1 mitosis /mm 2 . The sites of primary melanoma were located mostly in the head/neck and the trunk (63%), extremities (16%) and unknown primary (21%). The stage at diagnosis was I /II (29%), III (40%), IV (18%) and unknown (13%). Among 33 (87%) patients who ultimately developed distant metastases, 23(67%) had metastasis in the soft tissue/nodes, 21 (63%) in the lung, 9 (24%) in the brain, 7 (21%) in the liver, 6 (16%) in the bone, and 5 (15%) in the adrenal gland. Among patients (n=25) with initial stage I-III melanoma who later developed distant metastasis, the median duration between the time of initial diagnosis and distant metastases was 36 months. Among the 32 (84%) of the patients who developed stage IV melanoma, the median survival from the time of stage IV diagnosis was 18 months. Five patients received vemurafenib treatment, and 2 patients (K601E; T599_V600ins2) had stable disease and 2 patients (L597Q; G466E) had disease progression and 1 lost to follow up. Conclusions: Unexpectedly higher proportion of the patients with non-V600E/K mutant-melanoma had unknown primary melanoma and higher mitotic rate. In a small number of patients who received vemurafenib, the clinical response appears to be low.
Interventions for Anxiety and Depression in Conflict-Affected Areas—Reply
Authors: Atif Rahman, Mark van Ommeren, Saeed Farooq
Journal: JAMA (2017)

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Physical health and depression as predictors of fatigue in women with breast cancer undergoing chemotherapy
Authors: K. A. Shimabukuro, K. L. Clark, W. A. Bardwell, J. E. Mortimer
Journal: Journal of Clinical Oncology (2006)

8591 Background: Fatigue is common in breast cancer patients undergoing systemic chemotherapy and is also linked with depression. We evaluated the importance of physical health and depression in the fatigue reported by women with early-stage breast cancer undergoing adjuvant chemotherapy. Methodology: 75 women treated for Stage I-II breast cancer were assessed within 1mo after initiating chemotherapy (‘baseline‘) and at 2, 6 and 12mo. Scales included the Profile of Mood States (POMS) &amp; SF36 quality of life (QOL) survey. The POMS contains fatigue and depression subscales (higher scores, worse mood symptoms). The SF36 is comprised of 4 physical and 4 mental health subscales (higher scores, better QOL). Results: 26 Stage I (46.4%) and 30 (53.6%) Stage II breast cancer patients provided baseline data (median age 53yrs; range 28–82 yrs). Fatigue decreased significantly from baseline to 12mo (p&lt;0.01). Using Pearson correlations, worse physical health summary scores (r= −0.55, p&lt;0.01) and higher depression scores (r=0.55, p&lt;0.01) were independently linked with fatigue at baseline. In partial correlations controlling for depression, the relationship between physical health and fatigue remained significant (p&lt;0.01), but was reduced in strength by 27%, although, the influence of depression on fatigue diminished over time. Similar patterns were observed for 3 of the SF36 physical health subscales. However, the relationship between fatigue and bodily pain was unchanged when controlling for depression (p&lt;0.01), suggesting a strong independent relationship. In linear regression models, depression predicted fatigue at all time points and was the strongest predictor at baseline and 2mo; however physical health subscales assumed increasing importance in accounting for fatigue at 6 and 12mo. Conclusion: Depression is the strongest predictor of fatigue during chemotherapy, however, over time physical health variables become increasingly important at predicting fatigue in women with early stage breast cancer. Conducted at Washington University, supported by NIH CA72554–02 No significant financial relationships to disclose.