tbuckley/cabot-search huggingface dataset:
Treatment-free interval (TFI) after first-line therapy (FLT) and disease control rate (DCR) on second-line therapy (SLT): Impact on overall survival (OS) in relapsed malignant pleural mesothelioma (MPM).
Authors: Maria G Viganò, Vanesa Gregorc, Domenico Ghio, Alessandra Bulotta, Gilda Rossoni, Claudio Sallemi, Scialini Colombi, Gloria Rossoni, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2013)

e18528 Background: Both TFI (the time elapsing from FLT completion to SLT initiation) and DCR (the rate of nonprogression at first tumor evaluation) have been found to predict OS in other tumor types. Methods: The impact on outcome of TFI after FLT and DCR on SLT was tested in an individual patient pooled analysis of 261 MPM patients (pts) who had radiologic progressive disease (PD) after a pemetrexed-based FLT before entering a ph 2 trial with single-agent NGR-hTNF (n=50) and a ph 3 trial with single-agent gemcitabine, vinorelbine or doxorubicin plus NGR-hTNF/placebo (n=211). In both trials, response to SLT was assessed every 6 weeks by MPM-modified RECIST. Progression-free survival (PFS) and OS were computed from SLT start. By ROC analysis, the cutpoint for estimating TFI in relation to OS was set at 6 months (AUC=0.59; p=.009). Results: After FLT, 60 pts (23%) had partial response (PR), 135 (52%) stable disease (SD), for a DCR of 75%, and 66 (25%) early PD. Median time to PD was 7.0 months (95% CI, 6.2-7.4) and median TFI was 4.4 months (3.8-5.0), with 97 pts (37%) having a TFI &gt; 6 months. Among baseline factors (age, sex, PS and histology) used in logistic regression, only younger age was related to higher odds to attain a TFI &gt; 6 months (OR=1.9; 95% CI, 1.2-3.3). A TFI &gt; 6 months (vs ≤ 6) was weakly related to DCR (Spearman's r=0.16; p=.01) and strongly associated with longer PFS and OS, with HR of 0.48 (0.36-0.65) and 0.59 (0.42-0.83), respectively. After SLT, 9 pts (3%) had PR, 130 (50%) SD, for a DCR of 53%, and 122 (47%) early PD. Of 60 pts responding to FLT, 23 (38%) progressed early on SLT, while of 66 pts progressing early during FLT, 32 (48%) experienced disease control on SLT. Baseline factors did not relate with DCR at week 6. On landmark analysis set at the 6-week time point, DCR (vs PD) was associated with OS benefit (HR=0.46; 0.32-0.65), which persisted after adjusting for baseline factors (HR=0.40; 0.27-0.57). Conclusions: With a smaller HR, an early-look measure such as 6-week DCR on SLT shows some advantage over TFI after FLT in predicting subsequent OS. In relapsed MPM, TFI as stratification factor and DCR as surrogate endpoint may be considered. Clinical trial information: NCT00484276-NCT01098266.
Three Public Health Interventions Could Save 94 Million Lives in 25 Years
Authors: Vasilis Kontis, Laura K. Cobb, Colin D. Mathers, Thomas R. Frieden, Majid Ezzati, Goodarz Danaei
Journal: Circulation (2019)

Preventable noncommunicable diseases, mostly cardiovascular diseases, are responsible for 38 million deaths annually. A few well-documented interventions have the potential to prevent many of these deaths, but a large proportion of the population in need does not have access to these interventions. We quantified the global mortality impact of 3 high-impact and feasible interventions: scaling up treatment of high blood pressure to 70%, reducing sodium intake by 30%, and eliminating the intake of artificial trans fatty acids.We used global data on mean blood pressure levels and sodium and trans fat intake by country, age, and sex from a pooled analysis of population health surveys, and regional estimates of current coverage of antihypertensive medications, and cause-specific mortality rates in each country, as well, with projections from 2015 to 2040. We used the most recent meta-analyses of epidemiological studies to derive relative risk reductions for each intervention. We estimated the proportional effect of each intervention on reducing mortality from related causes by using a generalized version of the population-attributable fraction. The effect of antihypertensive medications and lowering sodium intake were modeled through their impact on blood pressure and as immediate increase/reduction to the proposed targets.The combined effect of the 3 interventions delayed 94.3 million (95% uncertainty interval, 85.7-102.7) deaths during 25 years. Increasing coverage of antihypertensive medications to 70% alone would delay 39.4 million deaths (35.9-43.0), whereas reducing sodium intake by 30% would delay another 40.0 million deaths (35.1-44.6) and eliminating trans fat would delay an additional 14.8 million (14.7-15.0). The estimated impact of trans fat elimination was largest in South Asia. Sub-Saharan Africa had the largest proportion of premature delayed deaths out of all delayed deaths.Three effective interventions can save almost 100 million lives globally within 25 years. National and international efforts to scale up these interventions should be a focus of cardiovascular disease prevention programs.
Serum GPC3 combination with AFP Diagnostic value for primary liver cancer
Authors: Dexi Chen, Chun Huang, Huiguo Ding, Desheng Wang
Journal: Cancer Research (2008)

4446  Objective: To evaluate novel tumor serum marker- GPC3(glypican-3)combination with AFP in diagnosis for primary liver cancer(PHC). methods: Fifity-four patients with PHC and 15 patients with liver cirrhosis were studied. GPC3 was quantitaviely measured using ELISA, AFP was detected using automated electrochemiluminescence immunoassay. The diagnosis value of serum GPC3 alone and combination with AFP for primary liver cancer was analysed using ROC curve (receiver operator characteristic curve). Results: Serum GPC3 in patients with PHC (317.89±206.02pg/ml) were higher than cirrhotic patients(240.8±110.140 pg/ml).No statistical significance was observed.The area under the ROC curve(AUC) of GPC3+AFP(0.822,95%CI:0.726-0.928)> AFP(0.795, 95%CI: 0.682-0.908)>GPC3(0.607,95%CI:0.467-0.747).The sensitivity and specificity of GPC3 was in 31.5% and 93.3%, when the cutoff point was 400pg/ml, respectively. Postive diagnosis in AFP-negative patients with PHC(
Re: Ming-Jun Shi, Xiang-Yu Meng, Philippe Lamy, et al. APOBEC-mediated Mutagenesis as a Likely Cause of FGFR3 S249C Mutation Over-representation in Bladder Cancer. Eur Urol 2019;76:9–13
Authors: Alexander Yang, Vincent L. Cannataro, Jeffrey P. Townsend
Journal: European Urology (2019)
Second Line Systemic Treatments Including Extracorporeal Photopheresis Among Patients with Chronic Graft Versus Host Disease (cGVHD) in the United States, 2009-2016
Authors: Namita Joshi, Linlin Luo, Xingyue Huang, Ghaith Mitri, Belinda Lovelace, An Pham, Xin Gao
Journal: Blood (2017)
Ursodeoxycholic acid in pregnancy?
Authors: Elsemieke de Vries, Ulrich Beuers
Journal: Journal of Hepatology (2019)

The case of a 34-year-old woman with primary biliary cholangitis (PBC) before, during and after pregnancy is described. The use of ursodeoxycholic acid (UDCA) during and after pregnancy is discussed. UDCA has not been approved by the drug regulatory authorities as a pregnancy-safe drug; therefore, the reluctance of clinicians to prescribe UDCA during pregnancy is understandable. This Grand Round aims to provide a detailed analysis of the current evidence, safety data and clinical experience with UDCA (and alternative drugs) during pregnancy and lactation. Based on this analysis, advice for clinicians regarding the use of UDCA during pregnancy and lactation is given.
Prognostic value of BRAF<sup>V600</sup> mutations in melanoma patients after resection of metastatic lymph nodes.
Authors: Philippe Saiag, Stephanie Moreau, Philippe Aegerter, Daphne Bosset, Christine Longvert, Zofia Helias-Rodzewicz, Cristi Marin, Frederique Peschaud, Sophie Chagnon, Ute Zimmermann, Thierry Clerici, Jean-François Emile
Journal: Journal of Clinical Oncology (2012)

8540 Background: Prognosis of AJCC stage III melanoma is heterogeneous. BRAF V600 mutations are frequent in melanomas. BRAF V600 -targeted therapy has dramatic, but often transitory, efficacy in stage IV patients (pts). We aimed to determine for the first time the prognostic value of BRAF V600 mutations and other known prognostic criteria in stage III pts with sufficient nodal invasion. Methods: We searched all pts with cutaneous melanoma who had radical lymphadenectomy in our institution between 1/1/00 and 15/6/10 and included those with a nodal deposit &gt;2 mm. BRAF V600 mutations were detected by DNA sequencing and pyrosequencing in formalin-fixed nodal samples containing &gt;60% melanoma cells. Samples were considered mutated when &gt;15% of DNA was positive. Endpoints were overall survival (OS) and distant metastasis free survival (DMFS). 92 patients had to be included to demonstrate a doubling of OS in patients without (40 months (m)) and with BRAF V600 mutation (20 m). Log-rank test and multivariate Cox proportional hazards regression model were used. Results: 105 consecutive pts were included, with 72% prospectively followed-up pts. BRAF V600 mutations (E: 83%; K: 14% of pts) were detected in 40% of pts. Median follow-up was 19 m (range: 3-139). Death occurred in 83% and 60% of pts with and without BRAF mutations, respectively, with median OS of 1.4 and 2.8 years. Pts’ age, primary melanoma ulceration, number of invaded nodes, AJCC staging, and BRAF status influenced OS and DMFS in the univariate analysis. The multivariate analysis showed the major prognostic role of BRAF status and of the number of invaded nodes (table). Conclusions: Provided our findings are independently replicated, BRAF V600 status should be used to stage melanoma pts with nodal metastasis. Our results also help to plan adjuvant trials with BRAF V600 -targeted therapy in such patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies. [Table: see text]
Abstract 13290: GDF-15 at One Month After an Acute Coronary Syndrome is Associated With Increased Risk of Major Bleeding - A PLATO Biomarker Substudy
Authors: Daniel Lindholm, Emil Hagström, Stefan K James, Richard C Becker, Christopher P Cannon, Anders Himmelmann, Steen Husted, Hugo A Katus, Gerald Maurer, Jose Lopez-Sendon, Philippe Gabriel Steg, Robert F Storey, Agneta Siegbahn, Lars Wallentin
Journal: Circulation (2015)

Introduction: Levels of Growth Differentiation Factor-15 (GDF-15) are associated with major bleeding events in acute coronary syndromes (ACS), when measured at the time of initial presentation. We hypothesized that an additional measurement of GDF-15 at 1 month after ACS provides additional information regarding risk of major bleeding. Methods: In the PLATO trial, levels of GDF-15 were determined in 4049 ACS patients at both baseline and at 1 month, using an immunoassay (Roche). The primary endpoint was non-CABG related major bleeding. A 1-month landmark analysis was performed, in relation to GDF-15 elevation status at baseline and 1 month, using a cutoff of 1800 ng/L. The relation between GDF-15 at 1 month and the primary endpoint from 1 month onward was evaluated using a Cox proportional hazards model; adjusting for baseline GDF-15, age, anemia (hemoglobin &lt;130 g/L in men, &lt;120 g/L in women), impaired renal function (eGFR &lt;50 mL/min/1.73m2), and history of gastrointestinal bleeding. Results: In the unadjusted analysis, patients with GDF-15 &gt;1800 ng/L at 1 month had increased bleeding rates during follow-up, irrespective of the baseline value. Patients with GDF-15 ≤1800 ng/L at 1 month had lower bleeding risk regardless of initial level (see figure). In the adjusted analysis, GDF-15 &gt;1800 ng/L at 1 month was independently associated with the outcome, hazard ratio 3.39 (95% CI 1.89-6.09). Conclusions: The level of GDF-15 at 1 month after ACS is related to the risk of bleeding during dual antiplatelet treatment. Assessment of GDF-15 level at 1 month provides additional information on the subsequent bleeding risk, regardless of the patient’s index GDF-15 level in the acute phase, and may therefore be helpful for decision-making on continued dual antiplatelet treatment.
Post-Transplantation Cyclophosphamide Versus Low Doses ATG Fresenius As Part of Two Immunosuppression Regimens for Graft Versus Host Disease Prophylaxis: Low Severe Graft Versus Host Disease (GVHD) Incidence and y Similar Gvhd-Free and Relapse-Free Survival (GRFS)
Authors: Cristina Fernández Martínez, Arancha Bermúdez, Sara García Ávila, Borja San Pedro, Almudena Cabero Martínez, Lucrecia Yáñez, Mónica López Duarte, Mercedes Colorado, Sonia González de Villambrosia, Joan Manuel Mora, Yolanda Gonzalez Romero, David Gomez, Sara Fenandez Luis, Irati Ormazabal, Andrés Insunza, Iñigo Romon, Jose Luis Arroyo, Eulogio Conde, Carlos Richard
Journal: Blood (2018)
MicroRNA profiles (including 370 miRNAs) in lymphomas.
Authors: Semra Paydas, Arbil Acikalin, Melek Ergin, Hikmet Celik, Basak Yavuz, Kahraman Tanriverdi
Journal: Journal of Clinical Oncology (2013)

e19512 Background: MicroRNAs (miRNAs) are small noncoding RNAs and they control the expression of protein-coding genes. Deregulation of miRNAs has been found to be associated with the pathogenesis and prognosis of various diseases including malignant tumors. In this study cancer related 370 miRNAs, which are most commonly related with cancer, have been explored in 88 cases with diffuse large B cell lymphoma (DLBCL) and 32 cases with Hodgkin’s lymphoma (HL). Sixty samples taken from cases with reactive lymphadenopathy have been used as control. Quantitative miRNA results were compared with lymphoma entities and also with controls. Methods: Samples taken from 88 cases with DLBCL and 32 cases with HL were used as study material. QPCR method was used to profile 370 miRNAs. Biogazelle qbasePLUS 2.0 software was used for analysis of the results. Global mean normalization method used for normalization of the individual miRNA expression levels. Mann-Whitney U test was used and p&gt;0.05 was evaluated as statistically important. Results: miR -41-5p, miR-494, miR-10a-5p, 340-5p, miR-155-5p, miR-500a-5p, miR-148b-3p, miR-330-3p, miR-191-5p, miR-193b-3p, miR-92a-3p, miR-34a-5p, miR-99b-5p, miR-671-3p were found to be increased in cases with DLBCL as compared with controls. miR-370, miR-155-5p, miR-372, miR-93-5p, miR-324-3p, miR-34a-5p were found to be increased in cases with HL as compared with controls. miR-320a, miR-889, miR-126-3p, miR-370, miR-138-5p, miR-29a-3p, miR-339-3p, miR-93-5p, miR-324-3p, miR-345-5p were found to be increased in cases with DLBCL as compared with HL. Conclusion: miRNA profile of DLBCL has been previously studied. However there is limited information about miRNA profile of HL. Our method for miRNA profiling is qPCR and it is the gold standard for miRNA profiling currently. Studies which has comprehensive numbers of miRNAs are mostly microarray based studies. Becuase of short sequence of miRNAs, microarray method doesn’t perform as good as in gene expression studies especially in low expressed miRNAs. In our best knowledge our study is the most comprehensive qPCR miRNA profiling study in HL and NHL. In further step we would like to compare miRNA profile and clinic-prognostic parameters.
Low-dose interleukin-2 therapy in refractory systemic lupus erythematosus: an investigator-initiated, single-centre phase 1 and 2a clinical trial
Authors: Jens Y Humrich, Caroline von Spee-Mayer, Elise Siegert, Martina Bertolo, Angelika Rose, Dimas Abdirama, Philipp Enghard, Bruno Stuhlmüller, Birgit Sawitzki, Dörte Huscher, Falk Hiepe, Tobias Alexander, Eugen Feist, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten
Journal: The Lancet Rheumatology (2019)
Endocrine responses during CPAP withdrawal in obstructive sleep apnoea: data from two randomised controlled trials
Authors: Sira Thiel, Sarah R Haile, Mirko Peitzsch, Esther I Schwarz, Noriane A Sievi, Salome Kurth, Felix Beuschlein, Malcolm Kohler, Thomas Gaisl
Journal: Thorax (2019)

The aim of this investigation was to elucidate the effect of CPAP withdrawal on neurometabolic and cardiometabolic markers in patients with obstructive sleep apnoea. We evaluated 70 patients (mean age 61±10 years, 82% men) treated with CPAP in two 2-week, parallel, randomised controlled trials. CPAP withdrawal resulted in elevated 3,4-dihydroxyphenylglycol, norepinephrine and cortisol after 2 weeks of CPAP withdrawal; however, no statistically significant changes of the renin–angiotensin–aldosterone system (RAAS) determinants were documented. In summary, CPAP withdrawal may be more prominently linked to short-term increases in sympathetic activation than hypothalamic–pituitary–adrenal axis or RAAS activation. ClinicalTrials.gov Identifier: NCT02493673 and NCT02050425 .
Efficacy and safety of over-the-scope clips for gastrointestinal bleeding: a systematic review and meta-analysis
Authors: Viveksandeep Thoguluva Chandrasekar, Madhav Desai, Muhammad Aziz, Harsh K. Patel, Venkata Subhash Gorrepati, Ramprasad Jegadeesan, Tarun Rai, Anjana Sathyamurthy, Alberto Murino, Cesare Hassan, Alessandro Repici, Prateek Sharma
Journal: Endoscopy (2019)

The over-the-scope clip (OTSC) has been increasingly utilized for the management of gastrointestinal (GI) bleeding. Limited efficacy data are currently available from large-scale studies.An electronic database search was conducted for eligible articles using OTSCs for hemostasis in GI bleeding. The primary outcome was the rate of definitive hemostasis after primary hemostasis and without rebleeding at follow-up. Secondary outcomes were: primary technical success, primary clinical success, rebleeding, and failure rates. Pooled rates were expressed as proportions of patients with events over total patients, 95 % confidence limits (CI) with heterogeneity, and P values of < 0.05 for significance.A total of 21 studies (n = 851) were analyzed (62.2 % males), with a median patient age of 69.7 years. The definitive hemostasis rate was 87.8 % (95 %CI 83.7 % - 92 %) after a median follow-up of 56 days. The OTSC was successfully deployed in 97.8 % of patients (95 %CI 96.7 % - 98.9 %) and the primary clinical success rate was 96.6 % (95 %CI 95.1 % - 98.2 %). Rebleeding was seen in 10.3 % of patients (95 %CI 6.5 % - 14.1 %). The failure rate of OTSCs was 9 % (95 %CI 5.2 % - 12.8 %) when used as first-line treatment and 26 % (95 %CI 16.1 % - 36.0 %) when used as second-line treatment.This systematic review showed high rates of definitive hemostasis, technical success, and clinical success, along with low rebleeding rates when OTSCs were used for the treatment of GI bleeding. The lack of randomized controlled trials of OTSC vs. other therapies makes comparison with conventional treatment difficult.
MRI based radiomic signature to predict treatment response to intraventricular natural killer (NK) cell infusion therapy for recurrent/refractory pediatric brain tumors.
Authors: Soumen Khatua, Tagwa Idris, Aikaterini Kotrotsou, Sumit Gupta, Wafik Tharwat Zaky, Vidya Gopalakrishnan, Dean Anthony Lee, Rivka R. Colen
Journal: Journal of Clinical Oncology (2019)

e21511 Background: NK cell therapy is a novel immunotherapeutic strategy used in cancer therapy. We conducted first-in-human, loco-regional infusion of autologous ex-vivo expanded NK cell directly into the brain in children with recurrent medulloblastoma (MB) and ependymoma (EP). Radiomics is considered an emerging method to predict treatment response as well as evaluate prognosis and tumor milieu. This is the first study evaluating the ability of radiomics to predict response to intraventricular infusions of NK cell in children with recurrent/refractory posterior fossa malignant brain tumors. Methods: We evaluated 7 patients (5 males: 2 females; mean age 11.8 years) with refractory/recurrent MB or EP (MBs = 3, EPs = 4), who were enrolled on a Phase-1 trial (NCT02271711) and received 3 cycles of intraventricular NK cell infusions. Patients were categorized based on their clinical response into responders (N = 2) and non-responders (N = 5). After semiautomatic segmentation of the tumor, 3,660 radiomic features were extracted from the baseline (before treatment) MRI scan. The least absolute shrinkage and selection operator regression was used for feature selection, and the radiomics signature was built using the unsupervised anomaly detection algorithm. The performance of the radiomics model was assessed using leave-one-out cross-validation. Results: The radiomic signature/model was comprised of 6 radiomic features and demonstrated high discriminatory performance in predicting response to NK cell therapy with an area under the curve, sensitivity, and specificity of 100% ( P = 0.09486). In addition, patients clustered into responders and non-responders using unsupervised hierarchical clustering. Conclusions: To our knowledge, this is the first study to identify the ability of radiomics to predict those who will likely benefit from NK cell therapy. Though this small study did not attain statistical significance, the robust discriminatory results warrant larger prospective studies, evaluating radiomics as a potential tool to identify responders to NK cell therapy at diagnosis.
Lessons learned from animal models: adverse effects of electronic cigarettes
Authors: Laimute Taraseviciene-Stewart
Journal: European Respiratory Journal (2019)

We thank R. Emma and colleagues for their interest in our preclinical study to investigate the effects of e-cigarettes on the lung. Our study was initiated from clinical observations that children exposed to second-hand e-cigarette vapour at home and undergoing surgery have a longer recovery and healing time than children from a non-smoking environment. For this reason, our animals underwent whole body (or so called second-hand smoke) exposure to e-cigarette vapour. Electronic cigarettes have a signature of harm in the lung that challenges the concept that switching from cigarettes to e-cigarettes is a healthier alternative <http://bit.ly/2Z3Ahdu>