tbuckley/cabot-search huggingface dataset:
Utility of radiation after neoadjuvant chemotherapy for surgically resectable esophageal cancer.
Authors: Francis Igor Macedo, Kristin Kelly, Danny Yakoub, Dido Franceschi, Alan S Livingstone, Nipun B. Merchant
Journal: Journal of Clinical Oncology (2019)

172 Background: Neoadjuvant chemotherapy (NAC) is the gold standard approach for locally advanced esophageal cancer (EC), however the addition of radiation remains largely controversial. We sought to investigate the role of neoadjuvant radiation in resectable EC by comparing outcomes of patients who underwent neoadjuvant chemotherapy with (NACR) or without radiation (NAC) using a large nationwide cohort. Methods: National Cancer Data Base (NCDB) was queried for patients with non-metastatic EC between 2010 and 2014. Kaplan-Meier, log-rank and Cox multivariable regression analysis were performed to calculate overall survival (OS). Logistic regression was used to identify factors associated with 90-day mortality and complete pathological response (pCR). Results: A total of 12,546 EC patients who underwent neoadjuvant therapy were included: the majority were males (84%), Caucasians (90.3%), and had adenocarcinoma (81.1%), cT3 (60.6%) and cN1 (49.1%). 11,269 (89.8%) patients had NACR, whereas 969 (7.7%), NAC alone. pCR rate was 14.1% (19.2%, NACR vs. 6.3%, NAC, p &lt; 0.001). Neoadjuvant radiation was an independent predictor for improved pCR [HR 0.305, 95% CI 0.205-0.454, p &lt; 0.001], however OS was similar in patients undergoing NAC with or without radiation (35.9 vs. 37.6 months, respectively, p = 0.393). This persisted regardless of tumor staging. There was a trend towards worse 90-day mortality after radiation (8.2%, NACR vs. 7.7%, NAC; HR 1.410, 95% CI 0.975-2.038, p = 0.068). In Cox regression, controlling for patient and disease-related factors, neoadjuvant radiation was an independent predictor of worse OS (HR 1.322, 965% CI 1.177-1.485, p &lt; 0.001). Conclusions: This is the largest study comparing NACR versus NAC in resected EC. The addition of radiation to neoadjuvant chemotherapy is associated with improved pathological response rates, however it had deleterious effects in long-term and possibly, short-term survival. Our findings suggest that NAC without radiation may be the optimal neoadjuvant therapy in resectable EC, however further evidence with randomized clinical trials is warranted.
Landscape of Germline and Somatic Mitochondrial DNA Mutations in Pediatric Malignancies
Authors: Petr Triska, Kristiyana Kaneva, Daria Merkurjev, Noor Sohail, Marni J. Falk, Timothy J. Triche, Jaclyn A. Biegel, Xiaowu Gai
Journal: Cancer Research (2019)

Little is known about the spectrum of mitochondrial DNA (mtDNA) mutations across pediatric malignancies. In this study, we analyzed matched tumor and normal whole genome sequencing data from 616 pediatric patients with hematopoietic malignancies, solid tumors, and brain tumors. We identified 391 mtDNA mutations in 284 tumors including 45 loss-of-function mutations, which clustered at four statistically significant hotspots in MT-COX3, MT-ND4, and MT-ND5, and at a mutation hotspot in MT-tRNA-MET. A skewed ratio (4.83) of nonsynonymous versus synonymous (dN/dS) mtDNA mutations with high statistical significance was identified on the basis of Monte Carlo simulations in the tumors. In comparison, opposite ratios of 0.44 and 0.93 were observed in 616 matched normal tissues and in 249 blood samples from children without cancer, respectively. mtDNA mutations varied by cancer type and mtDNA haplogroup. Collectively, these results suggest that deleterious mtDNA mutations play a role in the development and progression of pediatric cancers. SIGNIFICANCE: This pan-cancer mtDNA study establishes the landscape of germline and tumor mtDNA mutations and identifies hotspots of tumor mtDNA mutations to pinpoint key mitochondrial functions in pediatric malignancies.
The interleukin-13 paradox in asthma: effective biology, ineffective biologicals
Authors: Parameswaran Nair, Paul M. O'Byrne
Journal: European Respiratory Journal (2019)

<b>IL-13 is involved in almost all aspects of asthma pathobiology, yet, anti-IL-13 mAb clinical trials, including the prednisone-sparing TROPOS study published in this issue of the <i>ERJ</i>, have been ineffective</b>http://ow.ly/ZMnd30n27VN
Treating Asthma Symptoms with Quick Relief Bronchodilators: Prescription or Over-The-Counter Inhalers
Authors: Marianna Sockrider, Maureen George
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

"Treating Asthma Symptoms with Quick Relief Bronchodilators: Prescription or Over-The-Counter Inhalers." American Journal of Respiratory and Critical Care Medicine, 199(4), pp. P7–P8
Icatibant Treatment of Acute Attacks in Pediatric Patients With Hereditary Angioedema: Findings from the Icatibant Outcome Survey
Authors: Irmgard Andresen, Hilary Longhurst, Werner Aberer, Laurence Bouillet, Teresa Caballero, Anete S. Grumach, Marcus Maurer, Jaco Botha, Andrea Zanichelli
Journal: Journal of Allergy and Clinical Immunology (2019)
Microscopic heterogeneity in ulcerative colitis: implications for microscopic measurement of disease activity
Authors: Noam Harpaz, Samuel Ballentine, Jean-Frederic Colombel, Bruce E Sands, Huabin Mabel Ko
Journal: Gut (2019)

Growing interest in histological measurements of inflammatory  activity to determine therapeutic efficacy and endpoints in IBD has been accompanied by progress in developing and validating scoring instruments for this purpose.1–5 Four histological grading instruments, the Geboes score, Nancy index, Robarts Histological Index (RHI) and modified Riley score, have recently demonstrated responsiveness to clinical changes based on data from a phase II trial of ozanimod.6 Further refinement of the operating characteristics of these instruments and definition of threshold values for remission can be expected.7 

Less attention has been given to pre-analytical factors which might affect the histological assessment of disease activity and the definition of therapeutic endpoints, such as biopsy sampling density and target selection. Clinical consensus guidelines have thus far provided only empirical guidance. The European Crohn’s and Colitis Organisation (ECCO) guidelines for initial IBD diagnosis recommend two forceps biopsies from each of five sites in the colorectum and terminal ileum and separate biopsies from endoscopically distinct regions8 but do not address sampling density and target selection in other clinical situations. Likewise, uniform standards for biopsy sampling in therapeutic drug trials are lacking. One study has reported good endoscopic concordance between the rectosigmoid and proximal colon at baseline …
Impact of renal function on the efficacy and safety of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer.
Authors: Satoshi Kobayashi, Makoto Ueno, Gakuto Ogawa, Akira Fukutomi, Masafumi Ikeda, Takuji Okusaka, Tosiya Sato, Yoshinori Ito, Tomohiro Kadota, Tatsuya Ioka, Kazuya Sugimori, Naohiro Sata, Shoji Nakamori, Kyoko Shimizu, Nobumasa Mizuno, Hiroshi Ishii, Junji Furuse
Journal: Journal of Clinical Oncology (2019)

301 Background: S-1 is an oral agent consisting of a mixture of tegafur which is a prodrug of 5-fluorouracil (5-FU), 5-chloro-2,4-dihydroxypyrimidine (DHP) and potassium oxonate. Serum concentration of 5-FU increases in case of renal dysfunction due to decrease of DHP excretion into urine. The aim of this study was to evaluate the influence of renal function to the efficacy and safety of S-1 with concurrent radiotherapy (RT) for locally advanced pancreatic cancer (LAPC). Methods: This study was an integrated exploratory analysis of JCOG1106 and LAPC- S1RT, in which pts with LAPC received RT (50.4Gy/28 fr over 5.5 weeks) and concurrent S-1 (40 mg/m 2 /dose, bid. on the day of irradiation). Eligibility criteria for this study were pts who received both irradiation and S-1 at least once without induction chemotherapy, and who had creatinine clearance (CCr) ≥ 50 ml/min at the time of registration. We assigned pts into high (≥ 80 ml/min) and low (&lt; 80 ml/min) CCr groups. The primary endpoint was the incidence of ≥ Grade 3 adverse reactions (ARs). Secondary endpoints were the incidence of ≥ Grade 2 gastrointestinal ARs (GI-ARs) defined as anorexia, nausea, vomiting, diarrhea and mucositis oral, relative dose intensity of S-1, CA19-9 response, progression-free survival, and overall survival. Results: Fifty and 59 pts were included in this study from JCOG1106 and LAPC-S1RT, respectively. Median age was 65 years old (range: 31–80), and 57 pts were male. Median CCr was 80.4 ml/min. High CCr group included 57 pts and the median was 97.5 ml/min (range 80.0–194.6), and low CCr group included 52 pts and the median was 64.4 ml/min (range 50.0–78.3). Low CCr group tended to have more ≥ Grade 3 ARs and ≥ Grade 2 GI-ARs compared to high CCr group (30.8% vs. 15.8% and 51.9% vs. 36.8%). However, no evident tendencies were observed in other secondary endpoints. Multivariable analysis showed risk ratio of low CCr group for ≥ G3 ARs was 1.493 [95% CI: 0.710–3.145], although risk ratio of females was 2.486 [95% CI: 1.043–5.924]. Conclusions: Our study indicated that renal dysfunction may increase adverse reactions in the treatment of S-1 with concurrent RT for LAPC, and we should pay attention to renal function and consider for dose reduction.
Neoadjuvant therapy duration and outcome of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC).
Authors: Safi Shahda, Susan Perkins, Harvey M Cramer, Michael Garrett House, Attila Nakeeb, Nicholas J Zyromski, Eugene P Ceppa, Amikar Sehdev, Fatih Akisik, Jingmei Lin, Christian Schmidt, Susannah G. Ellsworth, Nina O'Neil, Kristen Link, Bert O'Neil
Journal: Journal of Clinical Oncology (2019)

436 Background: Neoadjuvant chemotherapy (NA CT) may improve surgical selection for resectable (R) PDAC, and margin negative resection in borderline resectable (BR) PDAC. Optimal duration of NA CT is unknown, as is the role of XRT with modern chemotherapy. We compared survival outcomes by duration of NA CT and NA CT + XRT. Methods: Patients with R or BR PDAC who underwent NA CT with or without XRT and followed by curative resection were included in this analysis. Data was extracted from an IRB approved pancreatic cancer database at Indiana University. Disease Free (DFS) and Overall (OS) survival were calculated from the surgery date and compared between: 1) &lt; 3 v ≥ 3 months NA CT and 2) NA CT with/without XRT. Results: Between Summer 2008 and Summer 2018, 116 patients received NA CT with or without XRT and completed surgical resection. Median (range) age was 63 years (36, 84), stages were R=47%, BR=53%. Most patients received modified FOLFIRINOX or FOLFIRINOX (59 %), or gemcitabine/nab-paclitaxel (13%) and 24% received XRT. There were four (3 %) pathologic complete responders, all in the ≥ 3 mo NA CT + XRT group. Percent node positive was lower in NA CT + XRT versus NA CT only (median 0% vs 7.4%, p &lt; 001), but did not differ by duration of NA CT. With a median (range) follow-up time of 13.7 mo (0.7, 83.0), median OS was 22.5 mo (19.5, 29.8) with &lt; 3 mo NA CT versus 16.3 (12.2, 18.9) with ≥ 3 mo NA CT (p = 0.02) and was 22.6 mo (17.0, 82.9) with NA CT + XRT versus 19.5 (13.1, 22.5) in NA CT only (p = 0.03). There was no difference in DFS by duration of NA CT or XRT. Conclusions: In this study, patients who received a shorter course of chemotherapy and radiation had improved mOS when calculated from the surgery date. While this unexpected results could reflect selection bias of therapy, further analysis will account for tumor stage at diagnosis, perioperative complications and use propensity score adjustment to examine/adjust for possible treatment selection bias.
The correlation between the proportion of patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and overall survival between 2004 and 2015.
Authors: George Molina, Akhil Chawla, Thomas E. Clancy, Jiping Wang
Journal: Journal of Clinical Oncology (2019)

395 Background: Neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is associated with improved overall survival (OS), and this has led to its rising use. The aim of this study was to evaluate the correlation between use of NAT and OS among patients with PDAC. Methods: This population-level study evaluated the Spearman correlation between the annual proportion of patients receiving NAT and the annual 1-year and 5-year OS, respectively, using the 2004-2015 National Cancer Database. Annual 1-year and 5-year OS was calculated from year of diagnosis using Kaplan-Meier survival analysis. All patients with a confirmed diagnosis of PDAC (histology code 8500), without any metastasis, and who underwent an R0 or R1 resection were included. Results: A total of 18,852 patients (median age 67 (IQR 60–74); 49.4% female) with PDAC underwent an R0/R1 resection from 2004 to 2015. Among these patients, there was a significantly positive correlation between the proportion of patients who received NAT (12.1%; n = 2,133) and 1-year OS (Spearman’s rho = 0.9091; P = 0.0001) and 5-year OS (Spearman’s rho = 0.7833; P = 0.01), respectively. Patients who underwent R0 resection (n = 14,547; median age 67 (IQR 60-74); 49.9% female) had a significantly positive correlation between those who received NAT (13.1%; n = 1,773) and 1-year OS (Spearman’s rho = 0.8818; P = 0.0003) and 5-year OS (Spearman’s rho = 0.7333; P = 0.02), respectively. Among 9,142 patients who had upfront resectable disease with R0 resection margin status (median age 68 (IQR 60–75); 49.8% female), there was a significantly positive correlation between proportion of patients who received NAT (9.1%; n = 781) and 1-year OS (Spearman’s rho = 0.7273; P = 0.01) and 5-year OS (Spearman’s rho = 0.8000; P = 0.0096), respectively. Conclusions: Between 2004 and 2015 there has been an increase in the use of NAT for patients with PDAC. Concurrently, the OS has also increased during this time period. This study demonstrates that there is a statistically significant and positive correlation between the proportion of patients with R0/R1 resected PDAC who received NAT and 1-year OS and 5-year OS, respectively.
Abstract 16576: Intravenous Infusion of Cardiosphere-Derived Cells and their Exosomes Improve Dystrophin-Deficient Cardiomyopathy in mdx Mice
Authors: Russell G Rogers, Mario Fournier, Mark A Aminzadeh, Kenneth Gouin, Lizbeth Sanchez, Eduardo Marban
Journal: Circulation (2017)

Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disease caused by genetic lesions in the Dmd gene. Patients not only experience skeletal muscle weakness and pulmonary insufficiency, they also develop severe cardiomyopathy - one of the main causes of premature death. Secondary to the loss of dystrophin, the heart exhibits chronic inflammation, oxidant stress, fibrosis, and cardiomyocyte loss, which directly contribute to the pathogenesis of the disease. There is no cure for DMD, and nothing has been proven to slow the progression of cardiomyopathy. Cardiosphere-derived cells (CDCs) are cardiac progenitor cells with anti-inflammatory, anti-oxidant, anti-fibrotic, and regenerative properties, making them a logical therapeutic candidate. Previous work has demonstrated that CDCs are efficacious in treating dystrophic cardiomyopathy in mdx mice when injected directly into the myocardium, which motivated the ongoing HOPE-Duchenne clinical trial. Here, we sought to explore the efficacy of CDCs to tre...
Pre-treatment pulmonary function testing as a predictor of cardiopulmonary toxicity in esophageal cancer patients treated with trimodality therapy.
Authors: Na Lu Smith, Christopher Leigh Hallemeier, Grant M. Spears, Thorvardur Ragnar Halfdanarson, Michelle A. Neben-Wittich, William S. Harmsen, Amit Mahipal, Shanda H Blackmon, Michael G. Haddock, Kenneth Merrell
Journal: Journal of Clinical Oncology (2019)

121 Background: We evaluated the role of pre-treatment pulmonary function testing (PFT) in predicting the likelihood of cardiac and/or pulmonary toxicity for esophagus cancer patients receiving trimodality therapy. Methods: From 2007 to 2013, 64 patients with esophageal cancer received trimodality therapy at a single tertiary center with pre-treatment PFTs. The odds ratio of pre-treatment PFT as a predictor of cardiopulmonary toxicity was assess with univariate analysis (UVA). FEV1 (forced expiratory volume in 1 second) and DLCO (diffusion capacity for carbon monoxide) were assessed per 0.5-unit decrease. Percent FEV1 and DLCO predicted were assessed per 10% decrease. Results: The median age was 62 years (range, 41-79) with 88% male patients. A total of 70% of patients had adenocarcinoma with 66% having stage 3 disease. Most patients were former (43%) or current smokers (32%) and 18% had COPD. One or more cardiac comorbidities were observed in 54% of patients. The median RT dose was 50 Gy and the most frequent concurrent chemotherapy was cisplatin/5FU (53%). The median pre-treatment FEV1 and DLCO was 2.8 liters (range, 1-4.9) and 22.5 mL/min/mmHg (range, 17.2-25.5), respectively. This correlated to a median percent predicted value for FEV1 and DLCO of 85% (range, 30-124%) and 81.5% (range, 49-119%), respectively. The overall rate of any cardiac and pulmonary toxicity was 35% and 50%, respectively. Percent predicted value of both FEV1 and DLCO was statistically associated with pulmonary but not cardiac toxicity (Table). Conclusions: Patients with compromised pre-treatment pulmonary function are at higher risk of developing post-treatment pulmonary toxicities. Pulmonary function testing should be routinely performed prior to initiation of trimodality therapy for patient risk stratification. [Table: see text]
Phase 1/2 Trial of Durvalumab and Lenalidomide in Patients with Cutaneous T Cell Lymphoma (CTCL): Preliminary Results of Phase I Results and Correlative Studies
Authors: Christiane Querfeld, Jasmine M. Zain, Devin L. Wakefield, Tijana Jovanovic-Talisman, Sung Hee Kil, Renee Estephan, James Sanchez, Joycelynne Palmer, Steven T Rosen
Journal: Blood (2018)
Abstract 18337: Adenylate Cyclase Type 9 Inactivation Protects Against Atherosclerosis Only in Mice Without Cholesterol Ester Transfer Protein
Authors: Yohann Rautureau, Vanessa Deschambault, Marie-Ève Higgins, Mélanie Mecteau, Daniel Rivas, Kurunradeth Uy, Géraldine Miquel, Geneviève Brand, Samaneh Samami, Gaétan Mayer, Éric Rhéaume, Jean-Claude Tardif
Journal: Circulation (2017)

We have shown that the clinical effects of the cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DAL) on cardiovascular events and atherosclerosis (ATH) imaging are determined by the...
Focal 123I-MIBG Uptake in the Medial Segment of the Normal Liver
Authors: Yohji Matsusaka, Tadaki Nakahara, Yu Iwabuchi, Yasuhiro Minami, Masahiro Jinzaki
Journal: Clinical Nuclear Medicine (2019)

An 84-year-old man with parkinsonism was referred for I-MIBG scintigraphy. Abnormal uptake in the right upper abdomen was incidentally seen in planar image, and SPECT revealed focal uptake in the medial segment (S4) of the liver. Subsequent triple-phase contrast-enhanced CT showed no evidence of hepatic tumors, although in the arterial phase, there were an enhanced region corresponding to the uptake area and the enhanced vein of Sappey that flowed into S4. In this case, the focal I-MIBG uptake would be attributable to hemodynamic change in the liver.
Scurvy Outbreak Among South Sudanese Adolescents and Young Men — Kakuma Refugee Camp, Kenya, 2017–2018
Authors: Mija Ververs, Jesse Wambugu Muriithi, Ann Burton, John Wagacha Burton, Allison Oman Lawi
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Scurvy is a relatively rare micronutrient deficiency disease that can occur among refugees dependent on food aid (1). Inadequate access to fresh fruits and vegetables in refugee camps can result in scurvy (2,3). Kakuma Refugee Camp in Kenya's Turkana District is home to 148,000 refugees, mostly from Somalia and South Sudan, who receive food assistance. In August 2017, a number of South Sudanese adolescent and young adult male refugees were evaluated at a health clinic in the camp for calf pain, chest pain, and gingival swelling. Because the symptoms were nonspecific, no diagnosis was made, and some patients received antibiotics and analgesics. All were managed as outpatients, but symptoms did not improve. During subsequent months, more young men with similar symptoms were reported. On January 20, 2018, the United Nations High Commissioner for Refugees (UNHCR) was informed and conducted clinical examinations. Signs and symptoms included lower limb pain and swelling (in some cases involving joints), lethargy, fatigue, gingival swelling and pain, hyperkeratotic skin changes, and chest pain. Based on these clinical findings, micronutrient deficiency, particularly vitamin C deficiency (scurvy), was considered a possible diagnosis, and an investigation of a possible outbreak was conducted. The suspected scurvy cases all occurred in young men from South Sudan who were living and cooking together in one geographic section of the camp. All patients who received treatment with vitamin C noted improvement of symptoms within <1 week. Patients were provided with food and cash assistance, the latter to allow dietary diversification (i.e., fresh fruits and vegetables). However, both forms of assistance were inadequate to allow access to sufficient amount of calories and the dietary diversification needed for intake of micronutrients, such as vitamin C. It is important to consider these needs when determining the amount of food or cash assistance provided to adolescents and young adult male refugees.
Age-related Gene Expression and Histologic Changes in Human Nasal Polyps
Authors: Seong Ho Cho, Ara Jo, Lydia A. Suh, Roderick G. Carter, David B. Conley, Robert C. Kern, Bruce K. Tan, Anju T. Peters, Leslie C. Grammer, Robert P. Schleimer, Richard F. Lockey
Journal: Journal of Allergy and Clinical Immunology (2019)
2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk
Authors: Robert H. Eckel, John M. Jakicic, Jamy D. Ard, Janet M. de Jesus, Nancy Houston Miller, Van S. Hubbard, I-Min Lee, Alice H. Lichtenstein, Catherine M. Loria, Barbara E. Millen, Cathy A. Nonas, Frank M. Sacks, Sidney C. Smith, Laura P. Svetkey, Thomas A. Wadden, Susan Z. Yanovski
Journal: Journal of the American College of Cardiology (2013)