tbuckley/cabot-search huggingface dataset:
Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality
Authors: Rachel K. Putman, Gunnar Gudmundsson, Gisli Thor Axelsson, Tomoyuki Hida, Osamu Honda, Tetsuro Araki, Masahiro Yanagawa, Mizuki Nishino, Ezra R. Miller, Gudny Eiriksdottir, Elías F. Gudmundsson, Noriyuki Tomiyama, Hiroshi Honda, Ivan O. Rosas, George R. Washko, Michael H. Cho, David A. Schwartz, Vilmundur Gudnason, Hiroto Hatabu, Gary M. Hunninghake
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although ILA have been associated with radiologic progression, it is not known if specific imaging patterns are associated with progression or risk of mortality.Objectives: To determine the role of imaging patterns on the risk of death and ILA progression.Methods: ILA (and imaging pattern) were assessed in 5,320 participants from the AGES-Reykjavik Study, and ILA progression was assessed in 3,167 participants. Multivariable logistic regression was used to assess factors associated with ILA progression, and Cox proportional hazards models were used to assess time to mortality.Measurements and Main Results: Over 5 years, 327 (10%) had ILA on at least one computed tomography, and 1,435 (45%) did not have ILA on either computed tomography. Of those with ILA, 238 (73%) had imaging progression, whereas 89 (27%) had stable to improved imaging; increasing age and copies of MUC5B genotype were associated with imaging progression. The definite fibrosis pattern was associated with the highest risk of progression (odds ratio, 8.4; 95% confidence interval, 2.7–25; P = 0.0003). Specific imaging patterns were also associated with an increased risk of death. After adjustment, both a probable usual interstitial pneumonia and usual interstitial pneumonia pattern were associated with an increased risk of death when compared with those indeterminate for usual interstitial pneumonia (hazard ratio, 1.7; 95% confidence interval, 1.2–2.4; P = 0.001; hazard ratio, 3.9; 95% confidence interval, 2.3–6.8;P < 0.0001), respectively.Conclusions: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.
RABL6A inhibits tumor-suppressive PP2A/AKT signaling to drive pancreatic neuroendocrine tumor growth
Authors: Shaikamjad Umesalma, Courtney A. Kaemmer, Jordan L. Kohlmeyer, Blake Letney, Angela M. Schab, Jacqueline A. Reilly, Ryan M. Sheehy, Jussara Hagen, Nitija Tiwari, Fenghuang Zhan, Mariah R. Leidinger, Thomas M. O’Dorisio, Joseph Dillon, Ronald A. Merrill, David K. Meyerholz, Abbey L. Perl, Bart J. Brown, Terry A. Braun, Aaron T. Scott, Timothy Ginader, Agshin F. Taghiyev, Gideon K. Zamba, James R. Howe, Stefan Strack, Andrew M. Bellizzi, Goutham Narla, Benjamin W. Darbro, Frederick W. Quelle, Dawn E. Quelle
Journal: Journal of Clinical Investigation (2019)

Hyperactivated AKT/mTOR signaling is a hallmark of pancreatic neuroendocrine tumors (PNETs). Drugs targeting this pathway are used clinically, but tumor resistance invariably develops. A better understanding of factors regulating AKT/mTOR signaling and PNET pathogenesis is needed to improve current therapies. We discovered that RABL6A, a new oncogenic driver of PNET proliferation, is required for AKT activity. Silencing RABL6A caused PNET cell-cycle arrest that coincided with selective loss of AKT-S473 (not T308) phosphorylation and AKT/mTOR inactivation. Restoration of AKT phosphorylation rescued the G1 phase block triggered by RABL6A silencing. Mechanistically, loss of AKT-S473 phosphorylation in RABL6A-depleted cells was the result of increased protein phosphatase 2A (PP2A) activity. Inhibition of PP2A restored phosphorylation of AKT-S473 in RABL6A-depleted cells, whereas PP2A reactivation using a specific small-molecule activator of PP2A (SMAP) abolished that phosphorylation. Moreover, SMAP treatment effectively killed PNET cells in a RABL6A-dependent manner and suppressed PNET growth in vivo. The present work identifies RABL6A as a new inhibitor of the PP2A tumor suppressor and an essential activator of AKT in PNET cells. Our findings offer what we believe is a novel strategy of PP2A reactivation for treatment of PNETs as well as other human cancers driven by RABL6A overexpression and PP2A inactivation.
Levels of Chlamydia pneumoniae Immunoglobulin E antibody in patients with asthma compared with non-asthma.
Authors: Jeffrey Loeffler, Yvonne Huang, Elliot Klein, Margaret R. Hammerschlag, Rauno Joks, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz
Journal: Journal of Allergy and Clinical Immunology (2019)
Established Prevention of Vaso-Occlusive Crises with Crizanlizumab Is Further Improved in Patients Who Follow the Standard Treatment Regimen: Post-Hoc Analysis of the Phase II Sustain Study
Authors: Darla K Liles, Rodolfo Cançado, Julie Kanter, Abdullah Kutlar, Andreas Bruederle, Michael Shi, Federico Campigotto, Kenneth I. Ataga
Journal: Blood (2018)
The feasibility of hepatectomy for the super-elderly patients with HCC.
Authors: Shogo Ohta, Shuichi Iwahashi, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saito, Shinichiro Yamada, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2019)

274 Background: We previously reported the feasibility of hepatectomy for HCC patients who were above 80 years old (Yamada S, Shimada M, et al. Hepatology Res. 2012). However, there was the manuscript that it was important to assess the preoperative co-morbidity on hepatectomy in elderly patients. The aim of this study is to investigate the feasibility of hepatectomy in super-elderly patients over 85 years old focused on the postoperative complications. Methods: Two hundred twenty-nine patients with HCC who underwent primary hepatectomy from April 2004 to October 2016 were enrolled in this study. Patients were divided into three groups; above 85 years old (super-elderly, n=6), between 75 and 85 years old (elderly, n=54) and below 75 years old (non-elderly, n=169). All of patients in this study did not underwent neither preoperative treatment nor additional splenectomy. Clinicopathological data and outcomes after hepatectomy were compared between three groups. Results: There were no significant differences between the super-elderly group and other two groups in the patients’ backgrounds and tumor factors. Regarding as the rate of total postoperative complications, there was no difference between three groups However, in super-elderly group, the mortality was higher compared with other two groups (super-elderly 16.7%, elderly 0%, non-elderly 1.2%: p&lt;0.01 One-way ANOVA, Turkey’s test). There was the one patient of liver failure in the super-elderly group, and he died due to the liver and respiratory failure. In long-term outcomes, there was no significant difference between the super-elderly group and other two groups. Conclusions: The long-term outcome of super-elderly patients was similar to that of non super-elderly, however, the careful attention to the liver failure might be paid on super-elderly hepatectomy patients. Therefore, hepatectomy might be justified for selected super-elderly patients.
Impact of Ga-68 DOTATATE imaging on clinical management of neuroendocrine tumor patients: Post-FDA-approval analysis of first 200 clinical patients.
Authors: Aman Chauhan, Riham Khouli, Mark Evers, Elizabeth Oates, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2019)

238 Background: Gallium 68 dotatate (Ga-68 DOTA) provides physiologic imaging and assists in the localization of disease in somatostatin (SSA) receptor positive neuroendocrine tumor (NET) patients. Questions regarding the value of Ga-68 DOTA imaging in the FDA post-approval era for NET patients include: usefulness in disease monitoring, correlation of Ga-68 DOTA avidity to Ki-67 index and its impact on clinical decision making. We present our experience with 200 Ga-DOTATATE scans performed at University of Kentucky. Methods: A retrospective review of the first 200 patients who had undergone Ga-68 DOTA imaging at the Markey Cancer Center from Dec 2016 to Dec 2017 was conducted. Results: 59.5% were females and the median age was 62 (30-84 years). Primary tumor sites included: small bowel 37.5%, pancreas 18.5%, bronchial 14%, colon 3.5%, rectum 2%, appendix 1.5%, adrenal 0.5%, prostate 0.5%, others 3% and unknown primary 19%. Ga-68 DOTA scan influenced clinical decisions in 39% (n = 78) patients. Ga-68 DOTA imaging identified primary tumors in 17 of 38 patients who were classified as NET of unknown primary based on CT imaging. Subgroup analysis of mean standardized uptake value (SUV) for hepatic metastatic lesions revealed 37.3 for G1 (n = 20) as compared to 32.3 for G2 (n = 37) and 17.46 for G3 (n = 4). Mean hepatic SUV of the lesion with the greatest radiolabel uptake in 96 patients was similar irrespective of exposure to SSA LAR; 31.3 versus 27.8 for SSA versus the no SSA cohorts. Conclusions: Ga-68 DOTA imaging impacted clinical decision making in 39% of NET patients (n = 200) and identified the primary site in 17 of 38 patients with unknown primary. Systemic exposure to long acting SSA does not seem to impact quality of Ga-68 DOTA scan.
The impact of infectious complications on long-term prognosis after curative resection for gastric cancer.
Authors: Yukio Maezawa, Toru Aoyama, Hiroshi Tamagawa, Tsutomu Sato, Takashi Ogata, Haruhiko Cho, Takashi Oshima, Norio Yukawa, Takaki Yoshikawa, Yasushi Rino, Munetaka Masuda
Journal: Journal of Clinical Oncology (2019)

122 Background: Several studies have reported that postoperative complications such as anastomotic leakage affect long-term prognosis after gastric cancer surgery. This study aimed to determine whether or not long-term outcomes were affected by the postoperative inflammatory complications in patients who underwent curative resection for gastric cancer. Methods: The patients were retrospectively selected from the medical records of consecutive patients who underwent curative gastrectomy with nodal dissection for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015. Inflammatory complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) was compared between postoperative inflammatory complications (IC) and no-complication (NC) groups. Results: A total of 2,254 patients were eligible for inclusion in the present study. One hundred seventy-five patients had IC group, while 2,079 patients had not. Operation time (p &lt; 0.001), blood loss (p &lt; 0.001) was significantly greater in the IC group. The incidence of postoperative inflammatory complication grade 2 or higher was 8.5% in which, pancreatic fistula (2.8%), anastomotic leakage (1.8%) were occurred. The mortality rate was 0.18%. The five-year OS rates of the IC and NC groups were 74.9% and 83.2%, respectively. The difference was statistically significant (p = 0.015). Multivariate Cox’s proportional hazard analyses demonstrated that the postoperative inflammatory complications were a significant prognostic factor for OS. Conclusions: Postoperative inflammatory complications have an obvious impact on the OS in curatively resected gastric cancer patients. It is necessary to reduce the incidence of postoperative complications.
Common risk factors for heart failure and cancer
Authors: Wouter C Meijers, Rudolf A de Boer
Journal: Cardiovascular Research (2019)

Cardiovascular (CV) disease and cancer are the leading causes of death.1,2 Over the last decades, it has been appreciated that both CV disease and cancer are more common in individuals in whom risk factors for disease development accumulate, and preventative measures have been extremely important in driving down the incidence of disease.3-6 In general, the field of epidemiology, risk reduction, and preventative trials is divided into health care professionals who have an interest in either CV disease or cancer. As a result, the medical literature and medical practice has largely focused on the one disease, or the other. However, human individuals do not behave according to this dogma. Emerging data clearly suggest that identical risk factors may lead to CV disease in the one individual, but may cause cancer in another, or even both diseases in the same individual. This overlap exists between risk factors that are historically classified as 'CV risk factors' as these factors do equally strong predict cancer development. Therefore, we propose that a holistic approach might better estimate actual risks for CV disease and cancer. In this review, we summarize current insights in common behavioural risk factors for heart failure, being the most progressed and lethal form of CV disease, and cancer.
NEUROMUSCULAR KNEE JOINT CONTROL IN ADOLESCENTS WITH AND WITHOUT GENERALISED JOINT HYPERMOBILITY DURING LANDING IN THE SINGLE LEG HOP FOR DISTANCE TEST
Authors: T Junge, B Juul-Kristensen, J Bloch Thorlund, J Søgaard, N Wedderkopp
Journal: British Journal of Sports Medicine (2014)

Background Knee injuries often occur due to biomechanical factors such as knee joint laxity. Individuals with Generalised Joint Hypermobility (GJH) frequently have knee joint hypermobility. Thus, GJH has been proposed as an intrinsic risk factor for knee injuries in adults and adolescents. To potentially compensate for reduced passive joint stability, adequate neuromuscular knee joint control is required before and during loading of the lower extremities. Objective To determine whether there is a difference in the neuromuscular pre and post activation landing patterns of the knee in adolescents with GJH and without GJH (NGJH) in the Single leg Hop for Distance test. Design Case-control study with groups matched on age and sex. Participants 54 adolescents (10–15 years), 25 with GJH and 29 with NGJH. GJH inclusion criteria were Beighton score ≥5/9 and hypermobility of at least one knee, and no current pain in the lower extremities. Main outcome measurements EMG of Vastus Medialis (VM), Vastus Lateralis (VL), Biceps Femoris (BF), Semitendinosus (ST), Gastrocnemius Medialis (GM) and Lateralis (GL) of the most hypermobile knee for the GJH group was used to determine pre- and post impact activation levels in % MVE before and during landing of the Single leg Hop for Distance test. Results Age and sex-adjusted analysis showed that GJH pre-activated ST 30% less compared with NGJH (22.1 (±12.6) vs 31.4 (±16.6.), P = .02). Conversely, GJH had a 28% higher GM pre-activity level than NGJH (32.5 (±14.8) vs 23.2 (±15.6), P = .02). There was no difference in performance (P=.67). Conclusions Lower ST but higher GM pre-activation levels were found in adolescents with GJH and knee joint hypermobility compared with NGJH. This latter is likely a compensatory strategy to enhance joint stability. For adolescents with GJH and knee joint hypermobility, intensive knee injury preventive training could be important, focusing among others on the ST.
Influence of radiation field on safety and efficacy for stage II/III esophageal cancer treated with definitive chemoradiotherapy: An exploratory analysis of JCOG0909.
Authors: Azusa Komori, Shuichi Hironaka, Ryunosuke Machida, Yoshinori Ito, Hiroya Takeuchi, Gakuto Ogawa, Ken Kato, Masakatsu Onozawa, Keiko Minashi, Tomonori Yano, Kenichi Nakamura, Takahiro Tsushima, Hiroki Hara, Isao Nozaki, Takashi Ura, Keisho Chin, Haruhiko Fukuda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2019)

104 Background: JCOG0909, a single-arm confirmatory trial of definitive chemoradiotherapy (dCRT) including salvage treatment, demonstrated promising efficacy and safety for cStage II/III (UICC-TNM 6th) esophageal cancer (EC) (Ito Y, ASCO 2018). Radiation (RT) fields included the elective regional lymph node during initial 41.4 Gy, such as bilateral supraclavicular fossae and superior mediastinal lymph nodes for upper thoracic (Ut), and mediastinal and perigastric lymph nodes for middle thoracic (Mt)/lower thoracic (Lt) EC. It is unclear whether the safety and efficacy are associated with the tumor location in patients with cStage II/III EC treated with dCRT. Methods: Patients who were enrolled in JCOG0909 and underwent dCRT were analyzed. Patients were categorized into three groups according to primary tumor location (Ut/Mt/Lt). We compared adverse events during dCRT, complete response (CR) rate, progression-free survival (PFS) and overall survival (OS) among groups. Results: Ninety-four patients (Ut/Mt/Lt: 16/59/19) were analyzed. The proportions of cStage IIA/IIB/III were 31%/44%/25% in Ut group, 20%/42%/37% in Mt group, and 21%/32%/47% in Lt group, respectively. The summary of safety and efficacy was listed in Table 1. Grade 3-4 leukopenia, neutropenia and thrombocytopenia were more frequently observed in Mt and Lt groups than in Ut group. CR rate was 63% in Ut, 63% in Mt, and 42% in Lt, respectively. 3-year PFS in Ut/Mt/Lt was 60%/59%/47% and 3-year OS was 73%/78%/58%, respectively. Conclusions: The RT field by the tumor location might be associated with efficacy and safety of dCRT for cStage II/III esophageal cancer. [Table: see text]
Abstract B014: Simulating prostate cancer stem cell dynamics to predict patient-specific sensitivity or resistance to intermittent androgen-deprivation therapy
Authors: Renee Brady, John Nagy, John Nagy, Heiko Enderling
Journal: Cancer Research (2018)

Abstract Intermittent androgen suppression is an attractive treatment approach for biochemically recurrent locally advanced prostate cancer to delay evolution of treatment resistance (PMID: 16783817). We developed a mathematical model of prostate cancer stem cell dynamics during therapy as a plausible mechanism of resistance evolution. We simulate division dynamics of cancer stem cells, non-stem cancer cells, and PSA concentration and generate highly accurate model fits to the longitudinal data of 55 patients undergoing 2-4 cycles of intermittent androgen suppression. We analyze model dynamics to identify cancer stem cell proliferation patterns that correlate with patient outcomes, and score model predictive power to accurately forecast evolution of resistance in individual patients. The presented framework may contribute to identifying patients who do and do not develop resistance to intermittent androgen suppression. The obtained predictive power on a retrospective data set warrants prospective evaluation in a clinical setting. Citation Format: Renee Brady, John Nagy, John Nagy, Heiko Enderling. Simulating prostate cancer stem cell dynamics to predict patient-specific sensitivity or resistance to intermittent androgen-deprivation therapy [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B014.
Impact of rotavirus vaccination on rotavirus genotype distribution and diversity in England, September 2006 to August 2016
Authors: Daniel Hungerford, David J Allen, Sameena Nawaz, Sarah Collins, Shamez Ladhani, Roberto Vivancos, Miren Iturriza-Gómara
Journal: Eurosurveillance (2019)

Introduction Rotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence. Aim We assessed the vaccine’s impact on rotavirus genotype distribution and diversity 3 years post-vaccine introduction. Methods Epidemiological and microbiological data on genotyped rotavirus-positive samples between September 2006 and August 2016 were supplied by EuroRotaNet and Public Health England. Multinomial multivariable logistic regression adjusting for year, season and age was used to quantify changes in genotype prevalence in the vaccine period. Genotype diversity was measured using the Shannon’s index (H′) and Simpson’s index of diversity (D). Results We analysed genotypes from 8,044 faecal samples. In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year. In the vaccine era, G1P[8] prevalence declined each season (35%, 231/654; 12%, 154/1,257; 5%, 34/726) and genotype diversity increased significantly in 6–59 months old children (H’ p &lt; 0.001: D p &lt; 0.001). In multinomial analysis, G2P[4] (adjusted multinomial odds ratio (aMOR): 9.51; 95% confidence interval (CI): 7.02–12.90), G3P[8] (aMOR: 2.83; 95% CI: 2.17–3.81), G12P[8] (aMOR: 2.46; 95% CI: 1.62–3.73) and G4P[8] (aMOR: 1.42; 95% CI: 1.02–1.96) significantly increased relative to G1P[8]. Conclusions In the context of reduced rotavirus disease incidence, genotype diversity has increased, with a relative change in the dominant genotype from G1P[8] to G2P[4] after vaccine introduction. These changes will need continued surveillance as the number and age of vaccinated birth cohorts increase in the future.
The prognostic value of systemic inflammatory factors in BRAF (V600E) mutant metastatic colorectal cancer (mCRC).
Authors: Nieves Martinez Lago, Marta Covela Rúa, Elena Brozos Vazquez, Ana Fernandez Fernandez Montes, Juan Cruz de la Cámara Gómez, Carlos Méndez Méndez, Mónica Jorge Fernández, Antia Cousillas Castiñeira, Begoña Graña Suárez, Guillermo Alfonso Quintero Aldana, Sonia Candamio Folgar, Mercedes Salgado Fernandez, Maria Luz Pellon Augusto, Paula Gonzalez Villarroel, Elena Gallardo Martin, Marta Carmona Campos, Francisca Vazquez Rivera, Carlos Grande Ventura, Alberto Carral Maseda, Margarita Reboredo Lopez
Journal: Journal of Clinical Oncology (2019)

622 Background: Multiple studies have reported prognostic association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLT) and albumin levels including patients with early and advanced metastatic colorectal cancer. However, it is unknown the prognostic impact in patients with BRAF (V600E) mutant metastatic colorectal cancer (mCRC). Methods: We conducted an observational, retrospective, multicentric study of patients with BRAF V600E-mt mCRC treated at nine university Spanish hospitals belonging to GITuD (Galician Research Group on Digestive Tumors). Demographic, clinic, pathological characteristics, overall survival (OS) and progression free survival (PFS) data were retrospectively analyzed. Results: Data from 65 pts. treated between November 2010 to June 2018 were recorded. Median age was 62.8 years (range 30-83), 55.4 % female, 75.4% ECOG PS0-1, 49.2% right-sided, 35.2% high grade, 69.2% synchronous presentation, 66.2% primary tumor resection and median metastatic locations was 2 (range 1-5). With a median follow up of 64.6 months, median OS was 12.9 months (95% CI, 9.8-16.0) and first line PFS was 4.1 months (95% CI, 2.7-5.5). NLR (HR 2.294; p = 0.004), PLR (HR 6.329; p = 0.028) and albumin levels (HR 2.575, p = 0.011) were independent prognostic factors for OS. Patients with higher NLR (&gt; 3 vs. &lt; 3): had a significantly lower OS 6.8 versus 17.5 months (HR 2.294; 95% CI 1.3-4.1, p = 0.004), which was also true for patients with higher PLR (&gt; 200 vs. &lt; 200): with OS 6.3 versus 14.5 months (HR 1.879; 95% CI 1.1-3.3, p = 0.028), while patients with low albumin had lower OS 6.8 versus 13.4 months (HR 2.575; 95% CI 1.2-5.5, p = 0.011). NLR was positively associated with PLR (p &lt; 0.001). Neither NLR (p = 0.190) or PLR (p = 0.327) were associated with low albumin levels. A Systemic Inflammation Score (assigning one point for each factor) was predictive of survival: OS 0/1/2/3 factors were 17.7 versus 8.7 versus 9.7 versus 5.0 months (p &lt; 0.001). Patients with Systemic Inflamation Score = 0 had significantly higher OS: 17.7 versus 8.2 months (HR 0.357; 95% CI 0.2-0.7, p = 0.001). Conclusions: NLR, PLR and albumin levels are significant prognostic factors in patients with BRAF V600E-mt mCRC.