tbuckley/cabot-search huggingface dataset:
Comparison of efficacy and safety of capecitabine and oxaliplatin (CAPOX) with epirubicin, oxaliplatin plus capecitabine (EOX) as first line treatment for advanced gastric cancer (AGC), a randomized clinical study.
Authors: Smita Kayal, Chinmaya kumar Pani, Dubashi Biswajit, Surendrakumar Verma, Sarath Chandra Sistla, Sunu Lazar Cyriac
Journal: Journal of Clinical Oncology (2015)

e15026 Background: Chemotherapy is the mainstay of treatment for AGC. There is no standard recommendation whether doublet or triplet chemotherapy is better. Hence our study aims to compare CAPOX with EOX as first line treatment for AGC. Methods: Patients with histologically proven AGC were randomly assigned to EOX (epirubicin 50mg/m2 on day1, capecitabine 625mg/m2 twice daily for 21 day and oxaliplatin 130mg/m2 on day1 three weekly for 8 cycle) or CAPOX (capecitabine 1gm/m2 /day twice daily for fourteen days and oxaliplatin 130 mg /m2 on day 1 in a three weekly cycle for 8 cycle). The primary end point was progression free survival (PFS) and secondary end points included overall survival (OS), overall response rate (ORR) and toxicity. Results: From December 2012 to December 2014, total of 69 patients were randomized; 34 in CAPOX arm and 35 in EOX arm. Median age at diagnosis was 55 years (18-70) and 57 (81.4%) patients had metastatic disease in the entire cohort. The baseline patients characteristics were similar in both groups except baseline weight (44.4±10.45 vs. 50±10.84, p-0.033) and hemoglobin (9.6±1.63 vs. 10.7±2.09, p=0.018), which were significantly higher in the EOX arm. The results are shown in table 1. Median follow up was 15.2 month. There were no toxic deaths. Conclusions: No statistically significant difference was observed between the two regimens with respect to response rate, PFS and OS . However toxicity profile favors the EOX group. Results with CAPOX versus EOX. Group A CAPOX(n=34) Group B EOX(n=35) P value Median no. of cycles (range) 6.5(3-8) 8(2-8) 0.236 ORR (CR/PR/SD) 18(54.5%) 25 (71.4%) 0.149 Median OS (months) 8.16 [95% CI( 2.5-13.8)] 10.93 [95% CI (6.7-15.1)] 0.298 1 year OS (%) 45.1% 49.4% 0.298 Median PFS (months) 5.56 [95% CI(5.004-6.12)] 8.36 [95% CI(6.7-10.02)] 0.06 1 year PFS (%) 17.9% 24.8% 0.06 Chemotherapy discontinuation toxicity(%) 15( 44%) 8 (22.9%) 0.061 Dose modification of any drug (%) 24(70.6%) 20(57.1%) 0.245 Grade III/IV neutropenia(%) 1 (2.9%) 8 (22.8%) 0.028 Grade III/IV vomiting(%) 8(23.5%) 0 0.011 Grade III/IV diarrhea(%) 6(17.6%) 0 0.002
Biochemical Urine Testing of Adherence to Cardiovascular Medications Reveals High Rates of Nonadherence in People Attending Their Annual Review for Type 2 Diabetes
Authors: Prashanth Patel, Pankaj Gupta, Angela Burns, Ali A. Suwaidan, Richard Cole, Dan Lane, Samuel Seidu, Kamlesh Khunti
Journal: Diabetes Care (2019)

OBJECTIVE Liquid chromatography—tandem mass spectrometry (LC-MS/MS) is a new method to objectively and robustly detect nonadherence. We applied this technique to study nonadherence to cardiovascular medications in people with type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Routine urine samples, received at the time of the annual diabetes review from 228 people with T2DM in primary care, were assessed for adherence by LC-MS/MS. RESULTS A total of 28.1% patients (N = 64) were nonadherent to antidiabetic, antihypertensive, and/or lipid-lowering medications. Nonadherence to statins was the highest at 23.7%, and nonadherence to oral hypoglycemic agents was 9.3%. HbA1c, albumin-to-creatinine ratio, and lipid profiles were significantly higher in the patients who were nonadherent compared with those who were adherent to treatment. CONCLUSIONS This unique study shows that routine urine samples can be used for adherence testing screening by LC-MS/MS and has demonstrated high nonadherence rates especially to statins in people with T2DM. Future intervention studies using LC-MS/MS as a diagnostic/therapeutic tool may help to improve clinical outcomes.
Phase II study of sitravatinib in combination with nivolumab in patients undergoing nephrectomy for locally-advanced clear cell renal cell carcinoma (ccRCC).
Authors: Jose A. Karam
Journal: Journal of Clinical Oncology (2019)

TPS686 Background: Sitravatinib is a receptor tyrosine kinase inhibitor (RTKI) that targets multiple closely related RTK pathways including VEGFR, PDGFR, KIT, MET and the TAM receptors (TYRO3, AXL and MERTK) Nivolumab is a monoclonal antibody against PD-1 and releases PD-1-mediated inhibition of T-cell proliferation and cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment nivolumab’s efficacy. Mechanisms by which sitravatinib may augment an antitumor immune response include enhanced antigen presentation; depletion of immunosuppressive regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) via inhibition of split kinases VEGFR and KIT; and shifting tumor-associated macrophages from an immunosuppressive M2 to a pro-immunogenic M1 phenotype via inhibition of TAM RTKs. Each of these factors converge on promoting T effector cell expansion, tumor infiltration and an antigen-specific anti-tumor immune response. Methods: This open-label, non-randomized, preoperative window of opportunity Phase 2 study evaluates tolerability and clinical activity of sitravatinib in combination with nivolumab in pts with locally-advanced ccRCC undergoing nephrectomy. Study treatment consists of 2 weeks of sitravatinib monotherapy followed by 4 weeks of the combination. Sitravatinib is administered orally daily at 120 mg; nivolumab intravenously every 2 weeks at 240 mg. The primary objective is to evaluate clinical activity using percentage of pts achieving a presurgical point-in-time objective response. Secondary objectives include evaluation of safety and tolerability, and determination of the immune effects of sitravatinib monotherapy and the combination through serial tissue and blood collections (temporal changes in PD-L1 expression, selected cytokines and immune cell populations including MDSCs, Tregs and ratio of M1:M2 macrophages). The study is open for enrollment and recruitment is ongoing. Clinical trial information: NCT03680521.
Frequency of <i>CDH1</i> germline mutations in diffuse gastric cancer in Brazil.
Authors: Rodrigo Santa Cruz Guindalini, Fatima Solange Pasini, Ana Carolina Ribeiro Chaves De Gouvea, Priscila Abduch Branas, Marina Candido Visontai Cormedi, Simone Maistro, Maria Lucia Hirata Katayama, Giselly Encinas, Tauana Nagy, Maria Del Pilar Estevez-Diz, Adriana Vaz Safatle-Ribeiro, Ulysses Ribeiro, Maria A. A. Koike Folgueira
Journal: Journal of Clinical Oncology (2015)

e12535 Background: Although hereditary diffuse gastric cancer syndrome is a rare condition its contribution to gastric cancer burden in Brazil is unknown. The aim of this study was to examine the frequency of CDH1 germline mutations in a population-based series of diffuse gastric cancer (DGC) in Brazil, which is considered a middle/high-incidence country for gastric cancer. Methods: From October 2013 to October 2014 a total of 64 unrelated and consecutive patients attending a Brazilian public hospital with DGC were enrolled and all CDH1 exons and intronic boundaries were sequenced. Clinico-pathological features were extracted from electronic medical records. Recruitment for this study is still ongoing. Results: Of 64 patients, 57.8% were female and the mean age at gastric cancer diagnosis was 46.6 years (range 21-76); 17% reported family history of gastric cancer in first- or second-degree relatives, 39% were diagnosed ≤ 40 years old, and none of them fulfilled the original 1999 International Gastric Cancer Linkage Consortium criteria for genetic testing. The majority of the tumors were poorly differentiated (84%), and located in the middle and distal-third of the stomach (70%). One germline deleterious mutation (c.1849G>A, p.A617T) was identified in 2 unrelated female patients with DGC (42 years and 47 years) and without family history of gastric cancer (Table 1). The overall frequency of germline CDH1 mutations was 3.1% (2/64) for DGC. Conclusions: To our knowledge, this is the largest population-based study investigating the contribution of CDH1 germline mutations in DGC cancer in Brazil. For a middle/high-incidence country, mutation frequency was higher than expected. This finding warrants further validation in larger cohort studies. Clinical characteristics of CDH1 mutation carriers. Age Sex Stage Part Grade Mucinous Hp Fam hist 42 yo F IV body Poorly differentiated yes N/A no 47 yo F IIb pylorus Poorly differentiated no positive no Abbreviations: F, female; Hp, Helicobacter pylori; Fam hist, family history of gastric cancer in first- or second-degree relatives; N/A, not available; yo, years old.
A dyadic partner-schema model of relationship distress and depression: Conceptual integration of interpersonal theory and cognitive-behavioral models
Authors: Jesse Lee Wilde, David J.A. Dozois
Journal: Clinical Psychology Review (2019)

Difficulties in romantic relationships are a prominent part of the disorder for many individuals with depression. Researchers have called for an integration of interpersonal and cognitive-behavioral theories to better understand the role of relational difficulties in depression. In this article, a novel theoretical framework (the dyadic partner-schema model) is presented. This model illustrates a potential pathway from underlying "partner-schema" structures to romantic relationship distress and depressive affect. This framework integrates cognitive-behavioral mechanisms in depression with research on dyadic processes in romantic partners. A brief clinical case example is presented to illustrate the utility of the dyadic partner-schema model in conceptualizing the treatment of depression. The implications of the model are discussed, and areas for future research are explored.
Abstract 12019: Durable Infarct Size Reduction Due to Allogeneic Mesenchymal Stem Cell Therapy Regulates Whole-Chamber Left Ventricular Remodeling
Authors: Adam R Williams, Viky Y Suncion, Fredric McCall, Danny Guerra, Jacques Mather, Decio Carvalho, Juan P Zambrano, Alan W Heldman, Joshua M Hare
Journal: Circulation (2012)

Background: Myocardial infarction (MI) leads to left ventricular remodeling, characterized by progressive chamber enlargement and geometric change from an elliptical to a spherical configuration. A...
Mass balance study of TAS-102 using <sup>14</sup>C labeling analyzed by accelerator mass spectrometry.
Authors: James J. Lee, Jabed Seraj, Kenichiro Yoshida, Milind Narurkar, Hirokazu Mizuguchi, Sandra Strychor, Jillian Fiejdasz, Tyeler Faulkner, Laura Pollice, Scott Mason, Weijing Sun, Edward Chu, Marie Croft, James Nguteren, Charles Tedder, Jan Hendrik Beumer
Journal: Journal of Clinical Oncology (2015)

2563 Background: TAS-102 is composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 2:1 ratio. FTD is a thymidine analog, and is degraded to inactive trifluoromethyluracil (FTY) by thymidine phosphorylase (TPase). TPI inhibits degradation of FTD by TPase, increasing systemic exposure to FTD. TAS-102 demonstrated improvement in overall survival in patients with metastatic colorectal cancer refractory to standard therapies. Although the metabolism of FTD has been reported, the metabolic fate and excretion of TAS-102 is unknown. Methods: Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0-1) enrolled. Group A (N = 4) received 60 mg TAS-102 with 200 nCi [14C]-FTD, and group B (N = 4) received 60 mg TAS-102 with 1000 nCi [14C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h, and were analyzed for 14C by accelerator mass spectrometry and for components of TAS-102 by LC-MS/MS. Results: FTD: Approximately 10% of plasma 14C AUC is accounted for by FTD (7%) and FTY (3.5%). The long half-life of 14C in plasma (>300 h) is in line with the moderate recovery of FTD-related 14C in the excreta over the 168 h collection period. 14C was mostly excreted in urine, and only very little was in feces and expired air, suggesting good absorption and limited metabolism of the pyrimidine ring. TPI: Approximately 36% of plasma 14C AUC is accounted for by TPI. 14C was mostly excreted in feces likely due to poor absorption of TPI. The majority of absorbed 14C was excreted into urine. Conclusions: The mass balance of FTD and TPI as part of TAS-102 was successful. The majority of the 14C-TPI dose was recovered in feces. Approximately 60% of the 14C-FTD dose was recovered, largely in urine. The current data with the ongoing hepatic and renal dysfunction studies will provide a better understanding of the TAS-102 dispositional profile. Clinical trial information: NCT02031055. FTD Plasma AUC (h*ng/mL) 14C recovery (%) 14C FTD FTY Urine Feces Expired CO2 Overall #1 63000 4640 2870 57.3 3.01 1.75 62.0 #2 64900 4020 2370 54.1 2.65 2.57 58.8 #3 92700 6200 1830 54.3 2.12 2.27 58.5 #4 127000 11600 4930 53.4 2.82 4.34 59.9 TPI 14C TPI - Urine Feces Expired CO2 Overall #5 901 216 24.5 62.4 - 86.8 #6 437 171 18.8 17.5 - 36.3 #7 509 268 27.0 58.3 - 85.3 #8 965 269 37.9 60.8 - 98.7
Comparison of initial diagnosis and treatment for Hepatocellular Carcinoma (HCC) between Veterans Affairs (VA) and SEER populations.
Authors: Sandra Patricia Susanibar Adaniya, Eric R Siegel, Rangaswamy Govindarajan
Journal: Journal of Clinical Oncology (2015)

e15123 Background: VA subjects undergo regular HCC screening. Our hypothesis is that VA subjects with HCC are diagnosed at earlier stages and tend to receive more loco-regional treatment than the SEER population. Methods: VA patients with HCC were identified from tumor-registry data from the VISN 16 network from 2007 to 2012. Stage, treatment characteristics and survival data were collected. VA data were compared to a published result from the SEER population spanning from 1998 to 2008. Disease stages were classified as local (AJCC stages I, II, IIIA, IIIB), regional (AJCC stages IIIC and IVA), and distant/unknown (AJCC stages IV, IVB, and unknown). Results: 1035 VA patients with HCC were identified. 53.1% cases had biopsy confirmation. The median age was 60 years (range 43-93); 99.4% were male; 63.4% Caucasian, 34.6% African-American. 76.4% had history of alcohol use; 47.3% were positive for Hepatitis C, 2.1% for Hepatitis B, and 1.1% for both. At diagnosis, 74.4% had local, 7.2% regional and 7.6% distant disease. 30.5% received loco-regional treatment at first [5.7% surgical resection, 1.2% ethanol ablation, 22.2% only trans-arterial chemoembolization (TACE), 1.5% other local tumor-destruction therapies]. Sorafenib was used in 19.2% patients. Median overall survival (OS) of all subjects was 12 months (interquartile range 3.5-33.4 months) and 16.6, 6.0 and 2.9 months for local, regional and distant disease, respectively. Survival benefit was seen with TACE (p < 0.001) and ethanol injection (p = 0.005). When compared to the SEER population, VA subjects had more local disease at diagnosis (74.4% vs 41.3%, p < 0.0001) and received more loco-regional therapy (32.4% vs 22.6 %, p < 0.0001). See table below. Conclusions: Veterans with HCC are diagnosed at earlier stages and receive more loco-regional therapy than SEER subjects with HCC. TACE and ethanol injection prolonged OS significantly in veterans with HCC. Regular screening appears to have a beneficial effect. Staging VA SEER p-value Local (%) 74.4 41.3 < 0.0001 Regional (%) 7.2 28.0 Distant/Unknown (%) 18.4 30.6 Loco-regional treatment (%) 30.5 22.6 < 0.0001
Single‐Irradiation Simultaneous Dual‐Modal Bioimaging Using Nanostructure Scintillators as Single Contrast Agent
Authors: Qiang Ju, Shouhua Luo, Chunxiao Chen, Zhenlan Fang, Shengkai Gao, Gong Chen, Xueyuan Chen, Ning Gu
Journal: Advanced Healthcare Materials (2019)

Abstract The rising demand for clinical diagnosis tools has led to extensive research on multimodal bioimaging systems. Unlike single‐modal detection, multimodal imaging not only can provide both function and structure information but also can address the issue of sensitivity, depth, and cost. Despite enormous efforts, conventional step‐by‐step procedures for obtaining multimodal imaging pose a significant constraint on their practical applications. In this work, X‐rays as highly penetrating radiation is proposed as a single‐irradiation resource, while lanthanide‐based nanostructure scintillators are employed as the single contrast agent to attenuate and convert X‐rays, achieving computer tomography (CT) and optical dual‐modal imaging at the same time. In other words, CT and optical dual‐modal imaging are simultaneously produced via single radiation combined with single contrast agent. The function and structure information of targeted tumors in a mouse model can be clearly provided with large penetration and high sensitivity, indicating that this strategy is a simple but promising route for multimodal imaging of molecular disease and preclinical applications.
Combined chemotherapy and gene therapy of esophageal cancer with human adenoviral p53 administered by endoscopic injection combined with chemotherapy.
Authors: Hongli Cui, Xiaochun Shen, Dongfeng Chen
Journal: Journal of Clinical Oncology (2015)

e15097 Background: Conventional management of esophageal cancer with radiotherapy, chemotherapy, surgery and combination thereof, remains to have limited efficacy. In this study, we sought to evaluate the clinical curative effect of gene therapy with a recombinant human adenovirus-p53 (rAd-p53) vector combined with chemotherapy in the treatment of middle- to advanced stage esophageal cancer patients. Methods: The gene therapy plus chemotherapy group (GT+CT) consisting of 30 patients was treated with a combination of a rAd-p53 gene therapy vector, which was administered directly to the tumor via endoscopic injection, and with chemotherapy consisting of tegafur, gimeracil and oteracil potassium (Shandong New Era, China). The control group (CT) also consisted of 30 patients and were treated with chemotherapy only. In the GT+CT group, the patients were treated by endoscopic injection of 1×1012 viral particles (VP) of rAd-p53 at a frequency of one injection per week for 4 consecutive weeks. All patients in both GT+CT and CT groups received the same chemotherapy orally at a dose of 50 mg twice per day, d1-14×6. Results: The comparisons between two groups showed that the curative effect of patients with esophageal cancer chemotherapy has improved obviously in the GTCT group (P < 0.05). For the GTCT group, after the injection treatment for 4 weeks, the tumor had averagely shrunk to 71% ± 18%and 49% ± 23%. After the treatment for 12 weeks, the tumor had averagely shrunk to 80% ± 16% and 68% ± 17%. 24 cases of the GTCT group in the process of treatment had got self-limiting fever, while others had no obvious toxic and side effect. Conclusions: The treatment of RAd-p53 combined with chemotherapy for esophageal cancer has good curative effect and slightly side effect, is also safe in clinic use.
More than a third of CCGs and trusts fail to show value for money, says public spending watchdog
Authors: Susan Mayor
Journal: BMJ (2019)

Many clinical commissioning groups and hospital trusts are failing to show that the money they spend is good value, the parliamentary public spending watchdog has said.

It has called for greater transparency from all public bodies that provide local services and said that the government must demand more so that citizens can hold their services to account.

MPs on the Public Accounts Committee found that more than 20% of local public bodies, including local authorities and fire and police services as …
Sustained Remission of Eosinophilic Esophagitis Following Discontinuation of Dietary Elimination in Children
Authors: Assaf Hoofien, Alexandra Papadopoulou, Carolina Gutiérrez-Junquera, Maria José Martínez Gómez, Gloria Domínguez-Ortega, Johanna Oudshoorn, Eleftheria Roma, Jorge Amil Dias, Salvatore Oliva, Luba Marderfeld, Noam Zevit
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract P086: Significant Association of House Collapse With High Urine Na/K Ratios Among 24,580 Coastal Residents Who Survived the Great East Japan Earthquake
Authors: Takahiro Mikami, Kozo Tanno, Ryohei Sasaki, Nobuyuki Takanashi, Yuka Kotozaki, Atsushi Hozawa, Mana Kogure, Shinichi Kuriyama, Ichiro Tsuji, Mamoru Sato, Jiro Hitomi, Kiyomi Sakata, Makoto Sasaki
Journal: Circulation (2019)

Introduction: There is an association between dietary sodium/potassium intake and the pathogenesis of hypertension and cardiovascular disease. Some reports have indicated a correlation between psychological distress and high sodium intake. Victims who are affected by natural disasters tend to consume an unbalanced diet, with high sodium and low potassium levels, which may stem partly from high psychological distress due to natural disasters. Hypothesis: We tested the hypothesis that house collapse was associated with high urine Na/K (UNa/K) ratios in victims of the Great East Japan Earthquake. We also hypothesized that psychological distress could modify the relationship between house collapse and UNa/K ratio. Methods: We analyzed complete data collected from 24,580 coastal residents who did not take anti-hypertensive medications, were 20 to 74 years of age, and were enrolled in the Tohoku Medical Megabank Project Community-based Cohort (TMM CommCohort) Study. Participants were recruited between 2013 and 2015 at municipality-specific health checkup sites in the Iwate and Miyagi Prefectures. UNa/K ratios were assessed using spot urine samples. Participants were classified into four groups according to the extent of house collapse: total collapse (TC, n=4206); half collapse (HC, n=2825); partial collapse (PC, n=5964); and no damage (ND, n=11585). Using a covariance analysis, the multivariate-adjusted geometric means of the UNa/K ratios according to the group of house collapse were calculated, with adjustments for sex, age, systolic blood pressure, estimated glomerular filtration rate, HbA1c level, low-density lipoprotein cholesterol level, Kessler Psychological Distress Scale (K6) score, current alcohol consumption, current smoking habits, and daily exercise. In addition, after stratification according to K6 score (9/10), the multivariate-adjusted geometric means of the Una/K ratios were calculated according to house collapse group. Results: The multivariate-adjusted geometric means (95% confidence intervals) of UNa/K ratios of those whose houses underwent TC, HC, and PC were 3.33 (3.28-3.39), 3.37 (3.30-3.44), and 3.34 (3.30-3.40), respectively, all of which were significantly greater than the value of 3.23 (3.20-3.27) that was observed for the ND group. In analysis stratified by K6 score, the same tendencies were observed in both groups of K6&lt;10 and K6≥10. Conclusions: House collapse was significantly associated with high UNa/K ratios, and psychological distress did not modify this association.
Combining Brentuximab Vedotin with DHAP as Salvage Treatment in Relapsed/Refractory Hodgkin Lymphoma: The Phase II HOVON/LLPC Transplant BRaVE study
Authors: Anton Hagenbeek, Josée M Zijlstra, Wouter J Plattel, Franck Morschhauser, Petronella J Lugtenburg, Pauline Brice, Martin Hutchings, Thomas Gastinne, Roberto D Liu, Coreline N Burggraaf, Marcel Nijland, Sanne H Tonino, Harm van Tinteren, Marta I Lopez Yurda, Marie José Kersten
Journal: Blood (2018)