tbuckley/cabot-search huggingface dataset:
Disease and Patient Characteristics, Patterns of Care, Toxicities, and Outcomes of Chronic Lymphocytic Leukemia (CLL) Patients Treated with Venetoclax: A Multicenter Study of 204 Patients
Authors: Anthony R. Mato, Constantine S. Tam, John N. Allan, Danielle M. Brander, John M. Pagel, Chaitra S. Ujjani, Brian T. Hill, Nicole Lamanna, Frederick Lansigan, Ryan Jacobs, Mazyar Shadman, Alan P Skarbnik, Jeffrey J. Pu, Paul M. Barr, Alison R. Sehgal, Bruce D. Cheson, Clive S Zent, Hande H. Tuncer, Stephen J. Schuster, Peter V. Pickens, Nirav N Shah, Allison M. Winter, Kaitlin Kennard, Krista Isaac, Colleen Dorsey, Alexandra Marie Vandegrift, Arun K Singavi, Annalynn Williams, Christina Howlett, Hanna Weissbrot, Naveed Ali, Sirin Khajavian, Andrea Sitlinger, Eve Tranchito, Joanna Rhodes, Erica Bharat Bhavsar, Neil Bailey, Bhavisha Patel, Timothy F. Burns, Melissa Yacur, Mansi Malhotra, Sasanka Handunnetti, Jakub Svoboda, Richard R. Furman, Chadi Nabhan
Journal: Blood (2017)
Development of the Mitochondrial Intermembrane Space Disulfide Relay Represents a Critical Step in Eukaryotic Evolution
Authors: Sandra Backes, Sriram G Garg, Laura Becker, Valentina Peleh, Rudi Glockshuber, Sven B Gould, Johannes M Herrmann
Journal: Molecular Biology and Evolution (2019)

The mitochondrial intermembrane space evolved from the bacterial periplasm. Presumably as a consequence of their common origin, most proteins of these compartments are stabilized by structural disulfide bonds. The molecular machineries that mediate oxidative protein folding in bacteria and mitochondria, however, appear to share no common ancestry. Here we tested whether the enzymes Erv1 and Mia40 of the yeast mitochondrial disulfide relay could be functionally replaced by corresponding components of other compartments. We found that the sulfhydryl oxidase Erv1 could be replaced by the Ero1 oxidase or the protein disulfide isomerase from the endoplasmic reticulum, however at the cost of respiration deficiency. In contrast to Erv1, the mitochondrial oxidoreductase Mia40 proved to be indispensable and could not be replaced by thioredoxin-like enzymes, including the cytoplasmic reductase thioredoxin, the periplasmic dithiol oxidase DsbA, and Pdi1. From our studies we conclude that the profound inertness against glutathione, its slow oxidation kinetics and its high affinity to substrates renders Mia40 a unique and essential component of mitochondrial biogenesis. Evidently, the development of a specific mitochondrial disulfide relay system represented a crucial step in the evolution of the eukaryotic cell.
Targeting the Tumor Microenvironment in Radiation Oncology: Proceedings from the 2018 ASTRO–AACR Research Workshop
Authors: Heather M. McGee, Dadi Jiang, David R. Soto-Pantoja, Avinoam Nevler, Amato J. Giaccia, Wendy A. Woodward
Journal: Clinical Cancer Research (2019)

The development of cancers and their response to radiation are intricately linked to the tumor microenvironment (TME) in which they reside. Tumor cells, immune cells, and stromal cells interact with each other and are influenced by the microbiome and metabolic state of the host, and these interactions are constantly evolving. Stromal cells not only secrete extracellular matrix and participate in wound contraction, but they also secrete fibroblast growth factors (FGF), which mediate macrophage differentiation. Tumor-associated macrophages migrate to hypoxic areas and secrete vascular endothelial growth factor (VEGF) to promote angiogenesis. The microbiome and its byproducts alter the metabolic milieu by shifting the balance between glucose utilization and fatty acid oxidation, and these changes subsequently influence the immune response in the TME. Not only does radiation exert cell-autonomous effects on tumor cells, but it influences both the tumor-promoting and tumor-suppressive components in the TME. To gain a deeper understanding of how the TME influences the response to radiation, the American Society for Radiation Oncology and the American Association of Cancer Research organized a scientific workshop on July 26-27, 2018, to discuss how the microbiome, the immune response, the metabolome, and the stroma all shift the balance between radiosensitivity and radioresistance. The proceedings from this workshop are discussed here and highlight recent discoveries in the field, as well as the most important areas for future research.
Dysgeusia Is Associated with Higher Melphalan Pharmacokinetic Levels and Results in Poorer Caloric Intake and Worse Symptom Burden after Autologous Stem Cell Transplantation for Multiple Myeloma
Authors: Michael Scordo, Gunjan L. Shah, Elaina V. Preston, Natasia Rodriguez, Andrew Lin, Molly Maloy, Brooke Mastrogiacomo, Dean Carlow, Ryan Schofield, Andrea Knezevic, Sean M Devlin, Heather J. Landau, David J. Chung, Jonathan U. Peled, Marissa L. Buchan, Sergio Giralt
Journal: Blood (2018)
Timeliness and completeness of routine childhood vaccinations in young children residing in a district with recurrent vaccine-preventable disease outbreaks, Jerusalem, Israel
Authors: Chen Stein-Zamir, Avi Israeli
Journal: Eurosurveillance (2019)

Background Childhood vaccination schedules recommend vaccine doses at predefined ages. Aim We evaluated vaccination completeness and timeliness in Jerusalem, a district with recurrent vaccine-preventable disease outbreaks. Methods Vaccination coverage was monitored by the up-to-date method (vaccination completeness at age 2 years). Timeliness of vaccination was assessed in children (n = 3,098, born in 2009, followed to age 48 months, re-evaluated at age 7 years) by the age-appropriate method (vaccine dose timeliness according to recommended schedule). Vaccines included: hepatitis B (HBV: birth, 1 month and 6 months); diphtheria, tetanus, acellular pertussis, polio, Haemophilus influenzae b (DTaP-IPV-Hib: 2, 4, 6 and 12 months); pneumococcal conjugate (PCV: 2, 4 and 12 months); measles-mumps-rubella/measles-mumps-rubella-varicella (MMR/MMRV: 12 months) and hepatitis A (HAV: 18 and 24 months). Results Overall vaccination coverage (2014 cohort evaluated at age 2 years) was 95% and 86% for MMR/MMRV and DTaP-IPV-Hib4, respectively. Most children (94%, 91%, 79%, 95%, 92% and 82%) were up-to-date for HBV3, DTaP-IPV-Hib4, PCV3, MMR/MMRV1, HAV1 and HAV2 vaccines at 48 months, but only 32%, 28%, 38%, 58%, 49% and 20% were vaccinated timely (age-appropriate). At age 7 years, the median increase in vaccination coverage was 2.4%. Vaccination delay was associated with: high birth order, ethnicity (higher among Jews vs Arabs), birth in winter, delayed acceptance of first dose of DTaP-IPV-Hib and multiple-dose vaccines (vs MMR/MMRV). Jewish ultra-Orthodox communities had low vaccination coverage. Conclusions Considerable vaccination delay should be addressed within the vaccine hesitancy spectrum. Delays may induce susceptibility to vaccine-preventable disease outbreaks; tailored programmes to improve timeliness are required.
Peutz–Jeghers Syndrome
Authors: Shreya Sengupta, Sayantan Bose
Journal: New England Journal of Medicine (2019)

A 45-year-old man presented with abdominal pain and vomiting. He had abdominal tenderness and hyperpigmented macules on the lips, oral mucosa, and nose. Emergency laparotomy revealed jejunojejunal intussusception and multiple polyps. A diagnosis of the Peutz–Jeghers syndrome was made.
Abstract 19700: Comparison of AQUACEL® Ag Silver Dressing With Micro-contour Technology to Traditional Silverlon® Silver-impregnated Dressing for Prevention of Cardiac Implantable Electronic Device Infection: A Randomized Open Label Study
Authors: Mohammad-Ali Jazayeri, Venkat Vuddanda, Madhav Lavu, Roshni Jain, Valay Parikh, Mohit K Turagam, Sudharani Bommana, Donita Atkins, Rhaguveer Dendi, Martin P Emert, Rhea Pimentel, Seth H Sheldon, Loren Berenbom, Madhu Reddy, Dhanunjaya R Lakkireddy
Journal: Circulation (2017)

Introduction: Silver-impregnated dressings have shown utility for wound healing and infection prevention in a variety of procedures, including cardiac implantable electronic device (CIED) implantat...
Deception and Study Participation—Unintended Influences and Ramifications for Clinical Trials
Authors: Marlene P. Freeman
Journal: JAMA Network Open (2019)

Holly Fernandez Lynch, JD, MBE; Steven Joffe, MD, MPH; Harsha Thirumurthy, PhD; Dawei Xie, PhD; Emily A. Largent, JD, PhD, RN
Survival outcomes comparable between endoscopic resection and surgical resection for T1b esophageal adenocarcinoma.
Authors: Samit Kumar Datta, Geoffrey Belini, Maharaj Singh, Wesley Allan Papenfuss, Lyndon Hernandez, Federico Augusto Sanchez, James L. Weese, Aaron Chevinsky, Nalini Guda
Journal: Journal of Clinical Oncology (2019)

100 Background: Current guidelines recommend esophagectomy for submucosal T1b esophageal cancer. Data regarding efficacy of endoscopic resection (ER) of T1b esophageal cancer are limited. Our goal was to compare survival outcomes of ER as opposed to conventional surgical resection (SR) in a large cohort of patients with T1b cancers from a large national database. Methods: Data were obtained from the large national database maintained by the Commission on Cancer. Patients with T1b esophageal cancers with clinical stage 1A and 1B who underwent ER and SR between 2010 and 2014 were identified using the American Joint Committee on Cancer (AJCC Version 7). Patients undergoing ER and SR were identified. Patients who underwent neoadjuvant therapy or had incomplete survival data were excluded. The primary outcome was survival for age and Deyo-Charlson comorbidity index. We also evaluated 30-Day and 90-Day Mortality outcomes. Results: There were 1071 patients with T1b esophageal cancer with complete mortality data. After selecting and excluding patients above, 141 patients were identified who underwent EET and 286 who underwent esophagectomy. Average age was 71.5 years in the ER group and 64.5 years in the SR group (p &lt; 0.001). In the group, 30-Day mortality after surgery was 1/134 (0.8%, 7 missing) compared to surgery with 30-Day mortality of 6/283 (2.1%, 3 missing) (P = 0.308). 90-Day mortality after surgery for the ER group was 3/134 (2.2%, 7 missing) compared with the surgery with 90-Day mortality of 11/281 (3.9%, 5 missing) (P = 0.377). Adjusted for age and Deyo-Charlson comorbidity index, there was a HR of 1.051 (95% CI 0.695-1.589, p = 0.815) for mortality associated with surgery compared with ER. Mean follow-up of 42.6 months for the ER group and 55.7 months for surgery group. Conclusions: Based on the data from a large national cancer data base ER seems to be comparable to SR in terms of short term (30 day and 90 day) mortality. Overall survival seems to be similar in both groups Prospectively done randomized studies comparing ER versus SR are desirable.
Dynamics of T helper 9, T helper 22, and regulatory T helper cells in minor &amp; major trauma
Authors: Surbhi Khurana, Purva Mathur, Nidhi Bhardwaj, Minu Kumari, Sushma Sagar, Subodh Kumar, Amit Gupta, Richa Aggarwal, Kapil Dev Soni, Rajesh Malhotra
Journal: Journal of Allergy and Clinical Immunology (2019)
Long-term outcome of preoperative docetaxel with cisplatin plus S-1 therapy for advanced gastric cancer with extensive nodal metastasis (JCOG1002).
Authors: Shinji Morita, Seiji Ito, Takeshi Sano, Daisuke Takahari, Hiroshi Katayama, Junki Mizusawa, Mitsuru Sasako, Yoichi Tanaka, Takahiro Kinoshita, Masanori Terashima, Atsushi Nashimoto, Hiroki Yamaue, Norimasa Fukushima, Makoto Yamada, Yoshiyuki Fujiwara, Yutaka Kimura, Atsuki Ikeda, Tsunehiro Yoshimura
Journal: Journal of Clinical Oncology (2019)

141 Background: Neoadjuvant chemotherapy (NAC) with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis based on the results of JCOG0405. In JCOG1002, we added docetaxel to CS (DCS) to further improve the long-term outcome. However the primary endpoint, clinical response rate (RR), did not meet the expected level (Ito S, Gastric Cancer. 2017). Herein we report the long-term survival. Methods: Patients with BN and/or PAN metastasis received two or three cycles of DCS therapy (docetaxel at 40 mg/m 2 and cisplatin at 60 mg/m 2 on day 1, S-1 at 40 mg/m 2 twice daily for 2 weeks, were administered every four weeks) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. Results: Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% of patients had both PAN and BN metastasis, and remaining patients had either PAN (26.4%) or BN (56.6%) metastasis. The clinical response rate (RR) was 57.7 % as assessed by RECIST v1.0, and the R0 resection rate was 84.6%, which did not exceed those in JCOG0405 (64.7% and 82.3%, respectively). The pathological RR defined as residual tumor corresponding to less than one-third the size of the original tumor was 34.6% in 52 eligible patients, which was slightly higher than in JCOG0405 (28.6%). Among all eligible patients, 5-year overall survival was 54.9% (95% confidence interval 40.3–67.3%) at the date cut-off of May 2018. Among 44 eligible patients with R0 resection, 5-year progression-free survival was 47.7% (95% confidence interval 32.5–61.5%). These were similar to the results of JCOG0405 (52.8% and 50.0%). Twenty patients developed cancer recurrence. The most frequent site of recurrence was lymph nodes (50.0% of all recurrences). Conclusions: Adding docetaxel to CS in NAC for extensive lymph node metastasis did not improve not only short-term outcomes but also long-term survival. NAC with CS followed by D2 + PAN dissection and postoperative S-1 remains standard for patients with extensive nodal metastasis. Clinical trial information: UMIN000006069.
Methodology Flaws and Implications of a Complementary Medicine Study
Authors: Ozan Bahcivan
Journal: JAMA Oncology (2019)

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Comprehensive genomic profiling in metastatic pancreatic adenocarcinoma, correlation with early death versus prolonged survival.
Authors: Mandana Kamgar, Gregory Dyson, Anthony Frank Shields, Anteneh A. Tesfaye, Philip Agop Philip, Mohammed Najeeb Al Hallak
Journal: Journal of Clinical Oncology (2019)

282 Background: PDAC has a very poor prognosis and around 50% of the patients die within two months of their diagnosis and around 10% live beyond one year. In this study we sought to find biomarkers differentiating patients with early death from those with more prolonged survival. Methods: Tumors from our patients with PDAC were examined using NexGen sequencing (evaluating somatic mutations in 592 genes), immunohistochemistry, and in-situ hybridization (Caris Life Sciences). Tumor mutational burden, microsatellite instability, copy number variation, and gene fusion assessment were done in a subset of samples. Extremes in clinical outcome were defined as death in &lt; 4 months and &gt; 12 months from metastasis diagnosis. Fischer’s exact tests were used to associate the categorical clinical data and genomic factors with the extremes of clinical outcome. A t-test was used to associate the continuous clinical factors with the extreme outcomes. Hierarchical clustering using the Ward amalgamation and binary distance metric was used to define cluster based upon the genomic factors. Results: From October 2014 to August 2018, we evaluated 115 patients. 15 patients with PDAC died &lt; 4 months and 39 died &gt; 12 month from the time of metastasis diagnosis. Compared to the patients with prolonged survival, patients with an early death were significantly older (Average 67.5 vs. 60.5 years old, P = 0.03) and had significantly higher neutrophil counts (average 9.6 vs. 5.1, P = 0.001) and monocyte counts (average 1 vs. 0.6, P = 0.01). No genomic alteration differentiated the groups with extreme outcomes. None of the clusters defined upon the genomic factors differentiated the two outcome groups. Using classification model to predict early death vs prolonged survival, no factor evaluated by the genomic profiling was discriminatory between the groups. Conclusions: We did not find a pattern of genomic alteration difference in PDAC patients between the short-term versus the long-term survivals using Next Generation Sequencing. The short-term survivals were older and had higher neutrophil and monocyte counts at the time of metastatic disease diagnosis.
Durable Responses in Fit Elderly Patients with Chronic Lymphocytic Leukemia (CLL) in a Randomised, Fludarabine-Based, Immunochemotherapy Dose De-Escalation Study - Long-Term Follow-up By Treatment Arm and Mutational Status
Authors: Stephen P. Mulligan, Devinder Gill, Gavin Cull, Leanne Berkahn, David Simpson, Philip Campbell, Rosemary Anne Harrup, Naomi J. Mackinlay, Constantine S. Tam, Xavier Badoux, Oliver Giles Best, Bryone Jean Kuss
Journal: Blood (2018)
Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study
Authors: Youssef A Elnabawi, Amit K Dey, Aditya Goyal, Jacob W Groenendyk, Jonathan H Chung, Agastya D Belur, Justin Rodante, Charlotte L Harrington, Heather L Teague, Yvonne Baumer, Andrew Keel, Martin P Playford, Veit Sandfort, Marcus Y Chen, Benjamin Lockshin, Joel M Gelfand, David A Bluemke, Nehal N Mehta
Journal: Cardiovascular Research (2019)

The use of biologic therapy has increased over the past decade well beyond primary autoimmune diseases. Indeed, a recent trial using an anti-IL-1beta antibody reduced second myocardial infarction (MI) in those who have had MI. Psoriasis is a chronic inflammatory disease often treated with biologics when severe, is associated with increased risk of MI, in part driven by high-risk coronary plaque phenotypes by coronary computed tomography angiography (CCTA). We hypothesized that we would observe a reduction in inflammatory-driven phenotypes of coronary plaque, including non-calcified coronary plaque burden and lipid-rich necrotic core in those treated with biologic therapy after one-year compared with non-biologic therapy.In a prospective, observational study, 290 participants were recruited from 1 January 2013 through 31 October 2018 with 215 completing one-year follow-up. Of the 238, 121 consecutive participants who were biologic treatment naïve at baseline were included. A blinded reader (blinded to patient demographics, visit and treatment) quantified total coronary plaque burden and plaque subcomponents (calcified and non-calcified) in the three main coronary vessels >2 mm using dedicated software (QAngio, Medis, Netherlands). Psoriasis patients were middle-aged [mean (standard deviation) age, 50.5 (12.1) years], mostly male (n = 70, 58%) with low cardiovascular risk by Framingham score [median (interquartile range, IQR), 3 (1-6)] and had moderate to severe skin disease at baseline [median (IQR) Psoriasis Area Severity Index, PASI, 8.6 (5.3-14.0)]. Biologic therapy was associated with a 6% reduction in non-calcified plaque burden (P = 0.005) reduction in necrotic core (P = 0.03), with no effect on fibrous burden (P = 0.71). Decrease in non-calcified plaque burden in the biologic treated group was significant compared with slow plaque progression in non-biologic treated (Δ, -0.07 mm2 vs. 0.06 mm2; P = 0.02) and associated with biologic treatment beyond adjustment for traditional cardiovascular risk factors (β = 0.20, P = 0.02).In this observational study, we demonstrate that biologic therapy in severe psoriasis was associated with favourable modulation of coronary plaque indices by CCTA. These findings highlight the importance of systemic inflammation in coronary artery disease and support the conduct of larger, randomized trials.
Impact of tumor growth rate during preceding treatment on tumor response to nivolumab or irinotecan in advanced gastric cancer.
Authors: Kyoko Kato, Toshiki Masuishi, Kunihiro Fushiki, Shintaro Nakano, Takeshi Kawakami, Yasuyuki Kawamoto, Yukiya Narita, Takahiro Tsushima, Hiroshi Nakatsumi, Shigenori Kadowaki, Akiko Todaka, Satoshi Yuki, Masahiro Tajika, Nozomu Machida, Yoshito Komatsu, Kei Muro, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2019)

84 Background: Although nivolumab (NIVO) and irinotecan (IRI) are recognized as standard third-line and further treatments for patients (pts) with advanced gastric cancer (AGC), the drug that should be administered first remains unclear. Conversely, tumor growth rate (TGR) during preceding treatment was associated with tumor response to regorafenib or trifluridine/tipiracil in colorectal cancer. Methods: We retrospectively evaluated 212 pts with AGC treated with NIVO or IRI for the first time between January 2015 and June 2018 at three institutions. The main inclusion criteria were ECOG PS of 0–2, prior use of fluoropyrimidines and taxanes, and no prior use of NIVO or IRI. Pts were classified into slow- (SG) and rapid- (RG) growing groups according to TGR and presence or absence of new lesions (NL) during preceding treatment. TGR = (D 1 − D 0 )/100D 0 (CT 1 − CT 0 ), where CT 1 is the date of CT at PD during preceding treatment, CT 0 is the date of CT before CT 1 , and D n is the sum of target lesion diameters at CT n . SG and RG were defined as NL− with low TGR and NL− with high TGR or NL+, respectively. TGR cut-off value was defined as a median TGR of 0.30%/day. Results: A total of 117 pts (RG/SG, 72/45; NIVO/IRI, 32/85) were eligible. Almost all baseline characteristics were similar between the NIVO and IRI groups among the RG or SG, whereas the proportion of pts with peritoneum metastases was higher in the NIVO group than in the IRI group among the RG. The response rate (RR) was significantly higher with NIVO than with IRI [31% vs. 3%, odds ratio (OR): 13.8, p = 0.01; adjusted OR (aOR): 52, p = 0.002] among the SG, whereas it was comparable between both drugs (5% vs. 8%, OR: 0.68, p = 0.73; aOR: 0.94, p = 0.96) among the RG. PFS was longer with NIVO than with IRI [median PFS (mPFS) 4.2 vs. 1.9 months (m), hazard ratio (HR): 0.50, p = 0.10] among the SG, whereas it was shorter with NIVO than with IRI (mPFS 1.6 vs. 2.1 m, HR: 1.37, p = 0.28) in the RG. Conclusions: RR was higher with NIVO than with IRI among slow growing tumors, whereas it was comparable between both drugs among rapid growing tumors. TGR during preceding treatment might be helpful for drug selection in pts with AGC who are considered for treatment with NIVO or IRI.
Neutropenia-Associated Mutations Differentially Impact Developmental Cell-States
Authors: David Muench, Kyle Ferchen, Giang Pham, Somchai Chutipongtanate, Pankaj Dwivedi, Stuart Hay, Kashish Chetal, Jayati Mookerjee-Basu, Kejian Zhang, Kasiani C. Myers, Kristopher Nazor, Kenneth D Greis, Dietmar J Kappes, Sing Sing Way, Nathan Salomonis, H. Leighton Grimes
Journal: Blood (2018)