tbuckley/cabot-search huggingface dataset:
Bifidobacterium with mycosporin-like amino acid: A new model for oncogenesis.
Authors: Fatih Kose, Hüseyin Sancar Bozkurt, Cemile Karadeniz, Oguz Kara
Journal: Journal of Clinical Oncology (2018)

e24204 Background: The genus Bifidobacterium considered the gastrointestinal microbiota dominant once has an important role on immunologic,oncological and metabolic homeostasis of the host. Mycosporin-like Amino Acids (MAAs) had prebiotic effects and they modulated host immunity by regulating the proliferation and differentiation of intestinal epithelial cells, macrophage and lymphocytes. Also MAAs modulate immune system and oncogenesis. The safety of Bifidobacterium species is known; although they do not produce MAAs, their presence is required for immunological response continuity of intestine. Methods: The Bifidobacterium animalis subsp. lactis KLDS 2.0603 strain was demonstrated to have the highest survival rate and adhesion ability in simulated gastrointestinal tract treatments. The comparative genome analysis revealed that the KLDS 2.0603 has most similar whole genome sequence compared with BB-12 strain.Cyanobacterium is the source of MAAs and the genes of Cyanobacterium involved in MAAs biosynthesis could be transferred to the strain Bifidobacterium animalis subsp. lactis BB-12 Results: Bifidobacterium treatment decreased the upregulation of genes in the NF-κB activation pathway and downregulated genes associated with extracellular matrix remodeling in IL-1β-stimulated cells.Butyrate may play in mediating key processes in oncogenesis including genomic instability, inflammation,cell energy metabolism and bifidobacteria are the main source of butyrate production. Bifidobacterium may play in mediating key processes in modulation of Klf4 and Klf5 transcriptions factors’ expression Conclusions: Several oncological mechanisms link with gut microbiome alterations that potentially contribute to oncogenesis, including reduced SCFA production, chronic inflammation,alterated transcription factors and immune system. Creating Bifidobacteria species producing MAAs via genetic engineering could make better quality microbiota and more helpful to human health and these can be used not only as a probiotic, also as a pharmacological agent in intestinal and oncological disorders
Prognostic performance of lymph node staging systems in patients with resectable gastric cancer: Comparison of population-based nomograms.
Authors: Rui-hua Xu, Zi-xian Wang, Miao-zhen Qiu
Journal: Journal of Clinical Oncology (2016)

e15533 Background: Two ratio-based lymph node staging systems, the lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS), were proposed to refine the prediction of survival, but the use of these systems instead of the metastatic lymph node (MLN) number-based staging for survival prediction among patients with resectable gastric cancer (GC) is not widely accepted. We compared the prognostic performances of the nomograms based on MLN, LNR, and LODDS to predict the 5-year overall survival (OS) in patients with resectable GC. Methods: We analyzed 15320 patients with resectable GC in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2010 for nomogram development. Missing data were handled using multiple imputation. Factors affecting OS were identified by multivariate Cox analysis. When assessed as a continuous covariate, each MLN, LNR, and LODDS variable was incorporated into a nomogram with other significant prognosticators to predict the 5-year OS. The discriminatory abilities of the three nomograms were compared using the concordance indices (C-indices). An independent Chinese dataset (1595 cases) was used as an external validation set. Results: Negative lymph node count was included in the MLN-based nomogram as an independent favorable prognosticator (P < 0.001). The discriminatory abilities of the three nomograms were comparable in the SEER and Chinese datasets (C-indices for the MLN-, LNR-, and LODDS-based nomograms: 0.744, 0.741, and 0.744, respectively in the SEER set; 0.715, 0.712, and 0.713, respectively in the Chinese set; P > 0.152 for all multiple comparisons). The nomograms all showed significant predictive superiorities to the 7th American Joint Committee on Cancer TNM staging (C-indices: 0.713 in the SEER set, P < 0.001 for all; 0.693 in the Chinese set, P < 0.040 for all) and good calibration. The discriminatory abilities of the nomograms maintained comparable even within patients with node-negative GC or insufficient nodes harvested ( < 15 nodes) in both datasets. Conclusions: The MLN-, LNR-, and LODDS-based nomograms are equivalently effective to refine survival prediction for patients with resectable GC.
Abstract 16306: Characteristics of Left Ventricular Summit Ventricular Arrhythmias Ablation - The Inaccessible Peak
Authors: Jayasree Pillarisetti, Tulasi Annapureddy, Ravali Neeurmalla, Maruthsakhi Molugu, Mamatha Vodapally, Ryan Maybrook, Mousthapha Atoui, Madhu Reddy, Dhanunjaya Lakkireddy
Journal: Circulation (2015)

Introduction: Ventricular arrhythmias (VA) arising from the left ventricular (LV summit) are often inaccessible especially in the region superior to the coronary sinus (CS) and ablation at multiple sites may be required. We sought to define the procedural characteristics and outcomes in this group of patients. Methods: Consecutive patients who underwent ventricular premature beat (VPB) ablation at our academic center were obtained. Patients with VPBs arising from the LV summit were noted and their charts were reviewed for clinical and procedural characteristics. Results: There were a total of 110 patients who underwent VPB ablation between January 2012 to March 2015. Of these there were 13 patients whose VA site of origin was determined to be from the LV summit intra-procedurally. Mean age of the patients was 53±16 years with 85% whites and 54% males. Mean QRS duration was 117±33ms. 11 patients were on a beta-blocker, 1 on a class Ia agent and 2 on no medications. Mean EF pre and post procedure was 41±14% and 47±10%. Mean PVC burden was 26%. EKG morphology showed LBBB pattern pattern in V1 with transition in V3 (in 6 patients), RBBB pattern (7 patients) with inferior axis and negative lateral leads. Mean procedure and fluoroscopic times were 266±82 and 45±20 minutes respectively. Acute success was obtained in 69% (n=9) and partial success in 15% (n=2). Acute success was obtained by ablating in the CS alone in 3 patients, epicardially alone in 3 patients and endocardially in 1 patient. In the other 2 patients, epi and endocardial ablation was performed in 1 patient and endo, epi and CS ablation in the other patient to obtain acute success. In the 2 patients with partial success, epicardial and CS ablation in 1 patient and endocardial and CS ablation in the other was performed. In one patient no ablation was performed and in another patient ablation was performed in all 3 sites without any success. Long term recurrence &gt; 3 months occurred in 1 patient with acute success. A power of 30 to 50 watts was used in the CS, 30 to 45 watts in the epicardium and 30 to 50 watts in the endocardium. Conclusion: Epicardial or CS ablation alone was successful in terminating VPBS arising from the LV summit in about half of the patients with epicardial and/or endocardial and/or CS ablation required in few others.
Response status as predictor of survival after autologous hematopoietic cell transplant (AHCT), without or with consolidation (with bortezomib, lenalidomide (Len) and dexamethasone) and len maintenance (AM vs. ACM) versus tandem AHCT and len maintenance (TAM) for up-front treatment of patients (pts) with multiple myeloma (MM): BMT CTN0702-stamina (NCT01109004).
Authors: George Somlo, Marcelo C. Pasquini, Beth Blackwell, Steven Michael Devine, Siddhartha Ganguly, Yvonne Efebera, Sergio Giralt, Parameswaran Hari, John Koreth, Heather Jolie Landau, Brian L. McClune, Mussafar Quazilbash, Philip L. McCarthy, Nina Shah, David H. Vesole, Ravi Vij, Dan T. Vogl, Amrita Y. Krishnan, Edward A. Stadtmauer, Nancy Geller
Journal: Journal of Clinical Oncology (2017)

8010 Background: The Stamina trial primarily aimed to identify the best strategy among AM, ACM, and TAM, leading to longer PFS (LBA-1, ASH, 2016). Here we report on interim, exploratory results of the association between PFS and overall survival (OS) and baseline MM response, risk category, and treatments (Rx). Methods: Pts with MM, &lt; 71 years, &lt; 12 mos from diagnosis were randomized to melphalan 200mg/m 2 (mel) and AHCT (AM), tandem mel AHCT (TAM), or mel AHCT and 4 cycles of RVD ((ACM). Pts received Len till progression. Pts were stratified by high risk vs. standard ( del13q, del17q, t(4;14), t(14;16), t(14;20) and hypodyploid; high β2 microglobulin). Kaplan Meier estimates of PFS and OS were performed as a function of Rx and ≥ very good partial response (VPGR including CRs) vs. &lt; VGPR. Cox proportional hazard models explored associations between PFS or OS and risk category, Rx, and ≥ VPGR vs. &lt; VGPR. Results: Between 6/2010-11/2013, 758 pts (AM, N = 257; ACM, N = 254; TAM, N = 247) aged 20-70 years (median 57y) were enrolled (24% high-risk). Baseline ≥VGPR responses were 45.5- 49.8%. PFS at 38 months was similar. For &lt; VGPR, 38-mos PFS with TAM:55.8% (95%CI: 45.8%, 64.7%); ACM: 54.0% (44.7%, 62.5%); AM: 50.1% (40.6%, 58.9%); For ≥VGPR, 38-mos PFS with TAM: 57.1% (46.8%, 66.1%); ACM: 60.1% (50.1%, 68.7%); AM: 55.1% (45.1%, 64.0%). Analyzing response, risk category, and Rx revealed no association between baseline response and PFS (Baseline response &lt; VGPR, hazard ratio (HR): 1.21,95% CI: 0.97-1.52) or OS (baseline response &lt; VGPR, HR 1.02, 95%CI:0.70-1.48). High risk category had an adverse association for PFS (HR 1.62, 95% CI: 1.27-2.07) and OS (HR 1.51 (95% CI:1.01-2.26). Conclusions: In this analysis &lt; VGPR at baseline was not associated with PFS or OS. High-risk had an adverse association. Whether accomplishment of CR/minimal residual disease after AM, ACM,or TAM predicts for longer PFS and OS is the subject of ongoing analysis. Clinical trial information: NCT01109004.
Incidence of pneumonitis with use of PD-1 and PD-L1 inhibitors in non-small cell lung cancer: A systematic review and meta-analysis of trials.
Authors: Monica Khunger, Vinay Pasupuleti, Sagar Rakshit, Prantesh Jain, Peter J. Mazzone, James Stevenson, Nathan A. Pennell, Adrian V Hernandez, Vamsidhar Velcheti
Journal: Journal of Clinical Oncology (2017)

e20647 Background: PD-1/PD-L1 inhibitors show clinical activity in non-small cell lung carcinoma (NSCLC). However, these agents are sometimes associated with potentially fatal immune related pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis associated with PD-1 and PD-L1 inhibitors. In this meta-analysis, we sought to determine the overall incidence of pneumonitis, and differences by type of inhibitor and prior chemotherapy use. Methods:We systematically searched databases (PubMed-Medline, Embase, Scopus) and conference proceedings until December 2016 for clinical trials using PD-1/PD-L1 inhibitors. Rates of pneumonitis of any grade and grade 3 or higher from all phase I-III trials investigating nivolumab, pembrolizumab, atezolimumab, durvalumab and avelumab for NSCLC were collected. Only single agent PD-1/PDL-1 inhibitor trials were included. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors, as well as between treatment naïve and previously treated patients (pts). Results: 19 distinct published trials (12 with PD-1 inhibitors [n = 3232] and 7 with PD-L1 inhibitors [n = 1806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis as compared to PD-L1 inhibitors (3.6%, 95%CI 2.4%-4.9% vs 1.3%, 95%CI 0.8%-1.9%; p = 0.001). There was also a higher incidence of grade 3 or greater pneumonitis with PD-1 inhibitors (1.1%, 95%CI 0.6%-1.7% vs 0.4%, 95%CI 0%-0.8%, p = 0.02). Pts who received PD-1 or PD-L1 inhibitors in the front line setting experienced more grade 1-4 pneumonitis as compared to previously treated pts (4.3%, 95%CI 2.4%-6.3% vs 2.8%, 95%CI 1.7%- 4%, p = 0.03, however the rates of grade 3 or greater pneumonitis were not significantly different in treatment naïve and previously treated pts. Conclusions: Pneumonitis was more frequently associated with use of PD-1 inhibitors than PD-L1 inhibitors. There was a higher incidence of all grade pneumonitis with PD-1 inhibitors in treatment naïve patients as compared to previously treated patients.
Efficacy of Gastroplegia Patch on treating postoperative gastroplegia: A multicenter, double-blind, randomized controlled trial.
Authors: Tian Zhou, Qin Zhou, Yanbin Wang, Yingjiang Ye, Yantao Tian, Kaiwen Hu
Journal: Journal of Clinical Oncology (2017)

10110 Background: Postoperative gastroplegia is common in digestive cancer patients and there were no effective treatments. Gastroplegia Patch is an external-used Chinese Herbal Medicine recipe. It has been applied clinically for more than ten years, which showed good effect. We conducted this study to verify its safety and efficacy on the symptoms of postoperative gastroplegia. Methods: This clinical trial was designed as a multi-center, double-blind, superior effect, randomized controlled trial. It has been registered in ISRCTN (No.18291857) before initiation and was monitored by the third party. Patient inclusion criteria: 1. Gastroenterological cancer patient who was diagnosed as post-surgery gastroplegia, could not eat and need tube feeding (parenteral nutrition or with Jejunum nutrient canal); 2. The local identification of abdomen is cold pattern, which means this kind of patient prefers heat to cold, likes hot food and hates cold ones. Eligible participants were randomized into two arms, placebo arm and Patch arm, respectively. Beside the basic treatments (nutrition support, gastrointestinal decompression, promoting gastric dynamics medicine), placebo or Gastroplegia Patch was applied in control group or Patch group, respectively. Placebos or the patches were allocated at two acupuncture points ( Zhongwan and Shenque). The intervention course was 14 days or reached primary endpoint. The primary endpoint was able to eat without tube feeding. Results: All the 120 eligible participants (60 per arm) were recruited from four AAA hospitals in Beijing, China. Analysis was conducted based on intent-to-treat strategy. After the intervention, 68.33% of the participants in the Patch group were able to eat without tube feeding, which significantly higher than that of 41.67% in the control group (p = 0.003). It took 8 days on average in the Patch group to show effect, which significantly faster than that of 10 days in the control group (p = 0.017). The incidences of adverse events were compatible between the two arms (p = 0.244). Conclusions: Gastroplegia Patch is safe and effective in treating postoperative gastroplegia in gastroenterological cancer patients with cold syndrome. Clinical trial information: 18291857.
A phase 1b/2 study of napabucasin with weekly paclitaxel in advanced, previously treated non-squamous non-small cell lung cancer.
Authors: Carlos Becerra, Wahid Tewfik Hanna, Stephen Lane Richey, Gregory Michael Cote, Scott Andrew Laurie, Adrian Langleben, Yuan Gao, Wei Li, Youzhi Li, Matthew Hitron, Chiang Li
Journal: Journal of Clinical Oncology (2017)

9052 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, napabucasin plus weekly PTX was well tolerated. A phase II expansion cohort was opened for pts with advanced non-small cell lung cancer (NSCLC). Methods: Pts with metastatic non-squamous NSCLC were enrolled to confirm safety and preliminary anti-cancer activity. Prior platinum-based systemic therapy was required, and patients with an EGFR or ALK mutation required appropriately targeted therapy. Napabucasin was administered orally at a starting dose of 240 or 480 mg BID with PTX 80 mg/m2 IV weekly 3 of every 4 weeks. AEs were evaluated using CTCAE v4.03 and objective assessments were performed every 8 weeks per RECIST 1.1. Results: A cohort of 23 pts with advanced non-squamous NSCLC was evaluated. The median number of prior systemic treatment lines was 3, including taxane-based therapy in 100% and immune checkpoint inhibitor in 48% (n = 11). Treatment was well tolerated; related grade 3 AE included diarrhea (n = 4) and fatigue (n = 1). The objective response rate was 26% (6 partial responses [PR]) and the disease control rate (DCR; proportion with SD at 8 weeks plus PR per RECIST) was 70% (n = 16). Tumor regression, including PR, occurred in 35% (n = 8). The median progression-free survival (mPFS) was 5.4 months, and 43% (n = 10) of pts were alive and free of progression at the 24 week time-point or longer. The median overall survival (mOS) was 11.0 months, and 30% (n = 7) of pts were alive for 52 weeks or longer. Conclusions: Clinical safety and encouraging signs of anti-cancer activity were observed in pts with heavily pretreated non-squamous NSCLC who received napabucasin plus weekly paclitaxel. The objective response rate, progression free survival, and overall survival in this population warrant further clinical evaluation and a controlled phase 2/3 trial (CanStem43L) has been initiated. Clinical trial information: NCT01325441.
Abstract P017: Childhood Food Insufficiency and Adulthood Cardiometabolic Health Among a Population-based Sample of Elderly Adults in Puerto Rico
Authors: Amanda C McClain, Josiemer Mattei
Journal: Circulation (2018)

Objective: Childhood food insufficiency is associated with poor physical health and psychosocial development in children, but less is known about long-term health implications. The objective of this study was to elucidate the association of childhood food insufficiency with cardiometabolic risk factors and health outcomes in later life among a sample of elderly adults. Methods: We conducted cross-sectional analysis of data from the Puerto Rican Elderly: Health Conditions Project (n=2,712), a longitudinal, population-based sample of elderly adults (&gt;60 y) living in Puerto Rico. Participants reported childhood food insufficiency at wave 2. Prevalence of cardiometabolic health outcomes was self-reported at wave 1 or 2, and included hypertension, diabetes, and cardiovascular disease (heart attack, heart disease, and stroke). Obesity was assessed at wave 2 using objective measurements. Multivariate-adjusted complex survey logistic regression models tested the associations of childhood food insufficiency with each condition, as well as with total number of cardiometabolic conditions (0-6). Findings: Nearly a third (31.8%) of the sample reported childhood food insufficiency; 71.0% reported hypertension, 33.0% reported diabetes, 34.3% reported cardiovascular disease, and 29.5% had obesity. Over half (55.2%) had two or more cardiometabolic conditions. In models adjusted for age, sex, childhood socioeconomics and health factors, and current socioeconomic status and smoking status (current/former/never), childhood food insufficiency was associated with increased odds of hypertension (Odds Ratio (OR), 95% Confidence Intervals (CI): 1.65 (1.03, 2.63)) and of having 1 (2.52 (1.36, 4.67)), 2 (2.38 (1.35, 4.20)), or 3 or more (2.36 (1.34, 4.17)) cardiometabolic conditions compared to no cardiometabolic conditions. Childhood food insufficiency was not significantly associated with cardiovascular disease (1.19 (0.82, 1.74)), diabetes (1.33 (0.92, 1.93)), or obesity (0.82 (0.54, 1.26)). Conclusions: Childhood food insufficiency may increase the likelihood of having hypertension or multiple cardiometabolic conditions in adulthood, independent from socioeconomic factors. Creating strategies to prevent and reduce food insufficiency in childhood may be a way to prevent eventual cardiovascular-related diseases.
Stereotactic body radiotherapy (SBRT) as an alternative to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).
Authors: Eli Sapir, Yebin Tao, Neehar D. Parikh, Latifa Bazzi, Pauline Devlin, Paula M. Novelli, Kyle Clifford Cuneo, Theodore Steven Lawrence, Matthew J Schipper, Mary Feng
Journal: Journal of Clinical Oncology (2016)

4087 Background: TACE is a standard treatment for patients (pts) with HCC. SBRT is a newer, noninvasive therapy. There have been no comparative studies to date. Thus, we examined TACE and SBRT outcomes. Methods: After IRB approval, institutional HCC and radiotherapy databases were queried for pts receiving TACE or SBRT for 1-2 tumors and combined with a diagnosis and billing code query for HCC, TACE, and SBRT. Pts with main branch portal venous (PV) involvement, extrahepatic spread, and Child Pugh C cirrhosis were excluded, since they are not candidates for TACE. Inverse probability weighting, via a propensity score, was used to adjust for imbalances between treatment groups. Local control (LC), overall survival (OS), and toxicity were compared. LC for was defined as no tumor growth within or immediately adjacent to the TACE cavity or original tumor. Results: From 2006-2014, 84 pts with 114 tumors were treated with TACE and 125 pts with 173 tumors with SBRT. Median follow-up was 28 months (1.8-103) and 16 months (0.2-98) for pts treated with TACE or SBRT, respectively (p<0.001). Pts treated with TACE were younger (61 vs 65 yrs, p=0.01) and had slightly larger tumors (2.9 vs 2.3 cm, p<0.001). In propensity adjusted analysis, 1- and 2-yr LC favored SBRT: 97% and 91% for SBRT and 41% and 18%, for TACE (HR 18.8, 95% CI 6.7-52.7, p<0.001). Increasing tumor size (HR 1.2 per cm, 95% CI 1.05 - 1.23, p<0.001) and partial PV tumor thrombus (HR 7, 95% CI 2.73 - 15.2, p<0.001) predicted for worse LC in pts treated with TACE, but not with SBRT. Grade 3+ toxicity occurred after 14% and 7% of TACE and SBRT treatments, respectively (p=0.05). From HCC diagnosis, SBRT was initiated a mean of 9 months later than TACE (p<0.001), and more patients underwent liver transplantation after TACE (18% vs. 8%, p=0.01). After adjustment for baseline liver function and transplantation, overall survival was not significantly different (HR = 0.73, 95% CI 0.48 – 1.12, p =0.15). Conclusions: SBRT is a safe alternative to TACE for 1-2 tumors, and provides better LC, with no difference in OS. Prospective comparative trials of TACE, SBRT, and other ablative therapies are warranted.