tbuckley/cabot-search huggingface dataset:
Abstract 18617: Development of Aortic Root Dilation is Accompanied by Increased Vascular Expression of Proinflammatory Adhesion Molecules VCAM, ICAM and E-Selectin in Patients with Advanced Heart Failure Following Left Ventricular Assist Device Placement
Authors: Michael Lee, Shuiqing Yi, Hirokazu Akashi, Tomoko S Kato, Hiroo Takayama, Christina Wu, Katherine Xu, Elias Collado, Donna M Mancini, Yoshifumi Naka, Paul Christian Schulze
Journal: Circulation (2012)

Background Left ventricular assist devices (LVADs) are increasingly used for patients with advanced heart failure. Continuous flow LVADs (cfLVADs) have replaced older pulsatile LVADs (pLVADs); however, effects of attenuated pulse pressure waveforms are largely unknown. We compared vascular histomorphometric and molecular changes in patients on cfLVADs compared to pLVADs. Methods Clinical and echocardiographic data was collected from electronic medical records for 28 LVAD patients (12 pLVAD vs. 16 cfLVAD). Endothelial van Willebrand stores, markers of aortic wall thickness, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at LVAD placement and at explantation during heart transplant. Expression of adhesion molecules was quantified by Western blot. Results Age (55±13 vs. 62±9 yrs) and duration of LVAD support (279±191 vs. 201±114 days) were similar in both groups. Aortic root dilation was only observed in cfLVAD patients (change in root diameter: +0.32±0.29 in cfLVAD vs. -0.20±0.61 in pLVAD; p&lt;0.05). Decellularization of the aorta (tunica media and adventitia) was observed in cfLVAD patients (media: 22.8±7.1 vs. 48.0±8.0 cells/µm 2 in pLVAD; adventitia: 21.0±9.3 vs. 46.8±11.3 cells/µm 2 in pLVAD; both p&lt;0.01). Decreased media thickness developed only in cfLVAD patients (-0.44±0.01 vs. 0.047±0.006 µm/BMI in pLVAD; p&lt;0.05). Inflammation was higher in cfLVAD patients (T-cells: 5.2±3.2 vs. 8.2±4.2 cells/µm 2 in cfLVAD; macrophages: 5.2±2.6 vs. 6.86±3.3 cells/µm 2 in cfLVAD). Both device types showed an increase in vascular E-selectin, ICAM and VCAM levels following LVAD placement (E-selectin: +39.6% vs. +29.0% in pLVAD, ICAM: +24.42% vs. +19.6% in pLVAD, VCAM: +30.6% vs. +34.0% in pLVAD; all p&lt;0.05). Endothelial vWF stores were preserved in pLVAD patients with near complete depletion in cfLVAD patients. Conclusion LVAD implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on cfLVADs and associated with aortic media decellularization and endothelial vWF depletion. These findings help to explain the progressive aortic root dilation seen in patients following cfLVAD placement.
Use of bortezomib (BOR) pharmacogenomics (PG) to identify mechanisms of drug resistance and predict survival in multiple myeloma (MM) treated with total therapy 3 (TT3)
Authors: J. D. Shaughnessy, P. Qu, J. Haessler, J. Crowley, B. Barlogie
Journal: Journal of Clinical Oncology (2009)

8538 Background: The prognosis of patients with MM is best captured by gene expression profiling (GEP) analysis of CD138-purified plasma cells (PC), distinguishing a high-risk group of 15% with dismal survival using a 70-gene baseline risk model (BLR). Translational research in TT3 was designed to investigate whether short-term BOR-induced GEP alterations could advance our understanding of BOR's novel mechanism of action. Methods: PG studies were performed as part of two TT3 trials (TT3a, n=303; TT3b, n=177), obtaining PC prior to and 48hr after a BOR test-dose (1.0mg/m2), which was accomplished in 142 patients in TT3a (training set) and 127 in TT3b (test set). Among 1051 genes significantly altered post-BOR in TT3a, 80 were identified as being significantly associated with EFS. A continuous risk score was calculated and an optimal cut-point for EFS separation determined. The independent prognostic power of the binary risk score was tested in TT3b. Multivariate analyses (MV) were employed to determine post-BOR risk (PBR) in relationship to standard prognostic variables and BLR. Results: The discriminatory power in TT3a (3-yr OS: 95% v 45%, p&lt;0.0001; 3-yr EFS: 90% v 35%, p&lt;0.0001) was confirmed in TT3b (18-mo OS: 100% v 65%, p=0.0004; 18-mo EFS: 95% v 45%, p&lt;0.0001). Evaluating PBR in the context of BLR, 12/26 in TT3a and 7/21 in TT3b deemed as having low BLR had high PBR; conversely, 8/126 in TT3a and 14/106 in TT3b deemed as having high BLR had low PBR. In the context of our 8 molecular subgroup model, high PBR was over-represented in the Proliferation (PR) subgroup (7/15 in TT3a, 8/18 in TT3b) and absent in the Low Bone disease (LB) group (0/28). On MV, PBR was an independent adverse variable for both OS and EFS in TT3a (OS: HR=3.17, p=0.006, R2=55%; EFS: HR=4.40, p&lt;0.001, R2=48%) and in TT3b (OS: HR=13.00, p=0.002, R2=48%; EFS: HR=15.57, p&lt;0.001, R2=55%). Proteasome genes ranked first among those differentially up-regulated by BOR. Conclusions: PG identified a powerful 80-gene PBR model with unprecedented prognosis-discriminating power, dispelling BLR from MV analysis by altering BLR designation mainly from low to high risk. High PBR (18%) could be traced to up-regulation of proteasome genes, the target of BOR. [Table: see text]
Prognostic Implications of Long-Chain Acylcarnitines in Heart Failure and Reversibility With Mechanical Circulatory Support
Authors: Tariq Ahmad, Jacob P. Kelly, Robert W. McGarrah, Anne S. Hellkamp, Mona Fiuzat, Jeffrey M. Testani, Teresa S. Wang, Amanda Verma, Marc D. Samsky, Mark P. Donahue, Olga R. Ilkayeva, Dawn E. Bowles, Chetan B. Patel, Carmelo A. Milano, Joseph G. Rogers, G. Michael Felker, Christopher M. O’Connor, Svati H. Shah, William E. Kraus
Journal: Journal of the American College of Cardiology (2016)
Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Nigeria, 2015
Authors: Daniel KW Chu, Jamiu O Oladipo, Ranawaka APM Perera, Sulaiman A Kuranga, Samuel MS Chan, Leo LM Poon, Malik Peiris
Journal: Eurosurveillance (2015)

Evidence of current and past Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels slaughtered at an abattoir in Kano, Nigeria in January 2015, was sought by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and serology. MERS-CoV RNA was detected in 14 (11%) of 132 nasal swabs and antibody in 126 (96%) of 131 serum samples. Phylogenetic analyses demonstrate that the viruses in Nigeria are genetically distinct from those reported in the Arabian peninsula.
Quantitative total bone imaging (QTBI) in patients with metastatic castration-resistant prostate cancer (CRPC) using NaF PET/CT.
Authors: Glenn Liu, Scott Perlman, Tim Perk, Stephanie Harmon, Kelly Simmons, Mary Jane Staab, Robert Jeraj
Journal: Journal of Clinical Oncology (2015)

180 Background: CRPC is frequently associated with the development of osseous metastases. While imaging allows treatment response determination in soft tissue metastasis, its application in bony metastasis is limited to staging. Methods: QTBI is an innovative tool that allows extraction of comprehensive functional information in all osseous metastases, as well as treatment response in individual lesions, using 18 F-Sodium Fluoride (NaF) PET/CT. We completed a multi-center trial assessing the performance characteristics (test-retest) and responsiveness of QTBI as an imaging biomarker of treatment response in men with metastatic CRPC to bone treated with either a taxane-based or androgen-signaling pathway directed therapy. Results: 54 patients have been enrolled from three academic centers. Potential imaging biomarkers of treatment response have been identified. Here we present initial data regarding the inter-lesional response heterogeneity and implications. Conclusions: Changes in SUVmax, SUVtotal, and SUVmean reflect quantifiable PET measurements that are complementary, but may have different meaning depending on the treatment administered (cytotoxic vs cytostatic). Relying on one measure alone can be misleading, particularly when assessing treatment response. For example, some lesions may experience a decrease in SUVmax, while simultaneously having an increase in SUVtotal. This implies that the therapy decreased the max functional activity of the lesion, but the overall functional burden of the lesion increased analogous to “slowing down” progression. This is in contrast with lesions that decrease (increase) in both SUVmax and SUVtotal, which would imply decreased activity and burden (increased activity and burden). We will show data representative of the above along with clinical outcomes in support of this conclusion, as well as the implications of treatment response heterogeneity in the clinical outcome. In summary, QTBI provides a unique tool in understanding the dynamics of treatment response, allowing newer trial designs that can explore combination, sequence, and the issue of continuing treatment beyond progression with existing therapies. Clinical trial information: NCT01516866.
Women doctors' use of hormone replacement therapy
Authors: E. Banks, B. Crossley, R. English, A. Richardson
Journal: BMJ (1996)

# High prevalence of use is not confined to doctors {#article-title-2}

EDITOR,—A J Isaacs and colleagues report high rates of use of hormone replacement therapy among a sample of women doctors.1 They note the relative paucity of information regarding the prevalence of use and remark that this high rate among female doctors may “presage more widespread use in the general population.”

We carried out a survey of use of hormone replacement …
Upper Respiratory Infections during Infancy and Childhood Aeroallergen Sensitization and Asthma
Authors: Leilanie Perez Ramirez, Heepke Wendroth, Jocelyn Biagini-Myers, Grace K. LeMasters, Patrick Ryan, James E. Lockey, David I. Bernstein, Gurjit K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2016)
A phase III study of Æ-941 with induction chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non-small cell Lung cancer (NSCLC) (NCI T99–0046, RTOG 02–70, MDA 99–303): An interim report of toxicity and response
Authors: C. Lu, R. Komaki, R. S. Herbst, W. K. Evans, J. J. Lee, M. Truong, C. A. Moore, H. Choy, A. Bleyer, M. J. Fisch
Journal: Journal of Clinical Oncology (2005)

7144 Background: Æ-941(Neovastat, Aeterna Laboratories) is a standardized shark cartilage extract with antiangiogenic properties (inhibition of VEGF signaling and MMP activity, induction of endothelial cell apoptosis). An ongoing placebo-controlled trial is testing Æ-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria include performance status (PS) < 2, weight loss < 10%. Subjects receive one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) x 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) x 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) x 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) x 2 cycles. Æ-941 or placebo (120 ml orally twice daily) is started with IC and continued after CRT as maintenance therapy. Planned sample size: 756. Results: A data safety board review of the first 40 patients who completed CRT was performed in 4/02. Excess or differential toxicity between the Æ-941 and placebo arms was not observed. Between 6/00 and 11/04, 341 subjects have been randomized. Blinded overall toxicity data are available on 179 and 172 subjects during IC and CRT, respectively. Subject characteristics (N=179): 60% male, median age 62 years (range 41–81), 47% PS 0, 54% stage IIIB. Grade 3 or 4 hematologic toxicities (IC/CRT) included: granulocytopenia (22%/1%), leukopenia (2%/4%), thrombocytopenia (1%/3%), anemia (1%/0%), neutropenic fever (5%/2%). The most common grade 3 or 4 non-hematologic toxicities during IC were fatigue (4%), hyperglycemia (3%), and dyspnea (2%). The most common grade 3 or 4 non-hematologic toxicities during CRT were esophagitis (17%) and dyspnea/pneumonitis (5%). The following blinded response data after IC and CRT are available for 233 and 214 subjects, respectively (IC/CRT): PR+CR 35%/39%, SD 57%/48%, PD 8%/13%. Conclusions: Interim overall toxicity observed in this trial appears acceptable. Accrual to this NCI-sponsored intergroup study continues. No significant financial relationships to disclose.
Salt-inducible Kinase (SIK1) regulates HCC progression and WNT/β-catenin activation
Authors: Chao Qu, De He, Xiaoling Lu, Lihua Dong, Yuekun Zhu, Qin Zhao, Xin Jiang, Pengyu Chang, Xinping Jiang, Lizhe Wang, Yuyu Zhang, Lirong Bi, Jian He, Yi Peng, Jing Su, Heng Zhang, He Huang, Yan Li, Sufang Zhou, Yaqin Qu, Yongxiang Zhao, Zhiyong Zhang
Journal: Journal of Hepatology (2016)
Distinct Requirements for Vacuolar Protein Sorting 34 Downstream Effector Phosphatidylinositol 3-Phosphate 5-Kinase in Podocytes Versus Proximal Tubular Cells
Authors: Madhusudan Venkatareddy, Rakesh Verma, Anne Kalinowski, Sanjeevkumar R. Patel, Assia Shisheva, Puneet Garg
Journal: Journal of the American Society of Nephrology (2016)

The mechanisms by which the glomerular filtration barrier prevents the loss of large macromolecules and simultaneously, maintains the filter remain poorly understood. Recent studies proposed that podocytes have an active role in both the endocytosis of filtered macromolecules and the maintenance of the filtration barrier. Deletion of a key endosomal trafficking regulator, the class 3 phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology and podocyte dysfunction. We recently showed that the vacuolation phenotype in cultured Vps34–deficient podocytes is caused by the absence of a substrate for the Vps34 downstream effector PtdIns 3-phosphate 5-kinase (PIKfyve), which phosphorylates Vps34-generated PtdIns(3)P to produce PtdIns (3,5)P2. PIKfyve perturbation and PtdIns(3,5)P2 reduction result in massive membrane vacuolation along the endosomal system, but the cell-specific functions of PIKfyve in vivo remain unclear. We show here that the genetic deletion of PIKfyve in endocytically active proximal tubular cells resulted in the development of large cytoplasmic vacuoles caused by arrested endocytic traffic progression at a late-endosome stage. In contrast, deletion of PIKfyve in glomerular podocytes did not significantly alter the endosomal morphology, even in age 18-month-old mice. However, on culturing, the PIKfyve-deleted podocytes developed massive cytoplasmic vacuoles. In summary, these data suggest that glomerular podocytes and proximal tubules have different requirements for PIKfyve function, likely related to distinct in vivo needs for endocytic flux.
Post interventional local bleeding within the mediastinal lymph nodes - A rare complication during EBUS procedure
Authors: Andreas Schlesinger, Constanze Steiner, Kappauf Lena
Journal: European Respiratory Journal (2013)

According to the Aquire registry EBUS is a safe and efficient procedure established in pulmonary medicine. Complications during EBUS procedure are rare and not associated with death. We describe an unexpected incident in our unit; a center that preforms this procedure over 200 times a year.  EBUS was preformed in a 36 year old male patient with mediastinal lymphadenopathy under topical anesthesia and conscious sedation. The lymph node position 4, 10 and 7 were aspirated with a 22 GA needle system for pathological verification of sarcioidosis. One hour after the procedure the patient suffered of severe chest pain localized behind his sternum. Myocardial infarction was excluded although CK and LDH levels were elevated. The ct scan of the thorax showed in lymphnode position 7 left a consecutive swelling double sized the former status (-6cm) due to a local bleeding. A thoracotomy was considered but under monitoring conditions and supplement of pain reliever the thoracal symptoms vanished. The ct scan documented within the intervall of 16 hours a complete reduction of the local swelling of the lymph node to the size before the intervention. No further problems were reported and the patient was dismissed.  Local bleeding in a punctured lymph node region during EBUS procedure without receiving antiplatlet therapy is a rare complication with a spontaneous reconvalescence within 16 hours. Intensive monitoring should be considered.
The effect of laparoscopic sleeve gastrectomy (LSG) on glycemic control in morbidly obese patients
Authors: Amit Gaur, C.S. Naidu, P.P. Rao, Sanjay Sharma, A.K. Singh, V. Trehan, S.V. Kulkarni, Nishant Pathak, Amit Singh, Balram Goyal
Journal: International Journal of Surgery (2016)
Timeliness of code status documentation in terminally ill cancer patients admitted to a general oncology ward.
Authors: A. Caissie, L. W. Le, C. Zimmermann
Journal: Journal of Clinical Oncology (2010)

e19519 Background: Code status (CS) discussions are important to avoid unwanted or futile invasive interventions. This study assessed CS documentation and timeliness thereof in terminally-ill patients on a general oncology ward. Methods: A retrospective chart review was performed of consecutive patients who died on the general oncology ward of the Princess Margaret Hospital, Toronto, Canada (admission January 2007-February 2009). Data retrieved included details of admission, CS, consults to the intensive care unit (ICU) and death. CS was classified as timely (documentation ≤24 hours of admission) or not timely (documentation >24h of admission). Outcomes of ICU consultations, attempts at CPR and ICU admission were compared between these two groups. Fisher's exact test and Wilcoxon test were used for statistical analysis. Results: The 150 patients (71 males, 79 females) had a mean age of 62 years (SD 13). All patients had recurrent or spread disease (lymph nodes or distant), with exception of 7 locally advanced (1 esophageal, 3 head & neck, 3 gynecologic) and 4 intracranial primaries. The mean time to death was 16 days (SD 21). Of 150 patients, 68 (45%) did and 82 (65%) did not have timely CS documentation. The 68 timely CS were initially 6 full codes and 62 do-not-resuscitate (DNR). CS was eventually documented in 70 of the 82 without timely CS (1 full code and 69 DNR); in 12 patients, CS was never documented. Compared to patients with a timely CS, those without timely CS had significantly more ICU consults (32 vs. 4, p<0.00001) and more attempts at CPR (11 vs. 1, p = 0.006); all 11 attempts in the patients without timely CS were futile. There were 4 ICU stays in the group without timely CS, compared to one stay in the timely CS group (11 vs. 4 days in ICU, p = 0.26). Conclusions: In this study of general oncology ward deaths, the majority of patients had CS documentation more than 24 hours after admission. The group without timely CS had more ICU consults and more futile attempts at CPR. Better knowledge with respect to CS documentation may help guide policy and improve patient care. No significant financial relationships to disclose.
Study of association between changes in pain, fatigue, satisfaction and independent predictors of fatigue after one week (wk) of cancer pain management (CPM)
Authors: S. S. Hwang, V. T. Chang, S. Srinivas, Y. Alejandro, P. Osenenko, B. Kasimis
Journal: Journal of Clinical Oncology (2004)

6150 Background: Pain has been identified as an important factor for cancer fatigue. We studied the association between changes in pain, fatigue, satisfaction and identified independent predictors of worse fatigue outcome and of clinically relevant fatigue (CRF) (usual fatigue ≥ 3/10) after 1 wk of CPM. Methods: 141 pts with worst pain ≥ 4/10 completed the Brief Pain Inventory, Brief Fatigue Inventory, and satisfaction at day 1, wk 1 and were screened for laboratory abnormalities on day 1. The presence of other symptoms and self-rated perception of changes in pain severity (SRPC) were assessed at wk 1. Raw changes in pain severity (RCPS), fatigue severity (RCFS) and satisfaction (RCSAT) were calculated; Spearman correlation, oneway ANOVA and multivariate logistic analysis were performed. Results: The median (M) age was 68 (44–87) with M Hemoglobin 11.6 g/dL (6.5–16.3). By SRPC, worse pain was found in 13 pts (9%), no changes in 33 (23%) and better in 95 (68%), (a little bit in 38, moderate in 23 and very much in 34). SRPC correlated significantly with RCPS (p<0.0001), RCFS (p=0.03) and RCSAT (p<0.001). Pts with moderate and much better SRPC had M 3 points decrease in pain severity. Three fatigue outcome groups (FOGs) were defined based on RCFS: better in 64 (46%), no changes in 30 (21%) and worse in 47 (33%); CRF was present in 103 pts (73%). There were significant differences in pain severity (p=0.04), RCPS (p=0.004) and satisfaction (p=0.02) among 3 FOGs by oneway ANOVA. In a multivariate logistic model with known fatigue predictors and pain outcome (RCPS ≥ 3 vs < 3), independent predictors of worse fatigue outcome were presence of drowsiness, poor pain outcome (PPO) and older age (p= 0.006, 0.009 & 0.03 respectively). In addition to drowsiness (p=0.002) and PPO (p=0.05), feeling nervous (p=0.02), sedation (p=0.07) and feeling irritable (p=0.07) predicted CRF independently. Conclusions: Perceived better pain outcome was reported in 68% pts and SRPC correlated significantly with RCPS, RCFS and RCSAT. Although 45% had better RCFS, 73% of pts had CRF. The PPO was predictive of worse fatigue outcome and CRF. (VAHSR&D PCC98068). Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration VA HSR&D
TLR-7 activation enhances IL-22–mediated colonization resistance against vancomycin-resistant enterococcus
Authors: Michael C. Abt, Charlie G. Buffie, Bože Sušac, Simone Becattini, Rebecca A. Carter, Ingrid Leiner, James W. Keith, David Artis, Lisa C. Osborne, Eric G. Pamer
Journal: Science Translational Medicine (2016)

A synthetic TLR-7 agonist restores immune defenses to an antibiotic-resistant pathogen lost due to antibiotic use.