bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological and prognostic significance of survivin expression in renal cancer patients: a meta-analysis
Authors: Ma Chengquan , Lu Bingxin , Sun Erlin 
Published: August 2016

ABSTRACTBackgroundSurvivin has been reported to play a role in the diagnosis and prognosis of renal cell carcinoma (RCC); however, published data on this subject are conflicting.AimTo conduct a meta-analysis to evaluate the impact of survivin as a prognostic marker and its association with clinicopathological variables in patients with RCC.MethodComprehensive searches of electronic databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the Cochrane Library) were updated to June 2016 to retrieve eligible studies. The association strength was measured with relative risks (RRs) and pooled HRs with 95% CIs, which were extracted and pooled to determine the association between survivin expression and patient survival and clinicopathological features.ResultsTen studies with 1063 cases of RCC were included. Positive survivin expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07 to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The correlation between survivin expression and gender was not significant (pooled RR 0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found between survivin expression and overall survival for patients with RCC (pooled HR 1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17 (univariate model)).ConclusionsOur results indicate that survivin is of prognostic signiﬁcance in patients with RCC.
Paired Exome Analysis Reveals Clonal Evolution and Potential Therapeutic Targets in Urothelial Carcinoma
Authors: Lamy Philippe , Nordentoft Iver , Birkenkamp-Demtröder Karin , Thomsen Mathilde Borg Houlberg , Villesen Palle , Vang Søren , Hedegaard Jakob , Borre Michael , Jensen Jørgen Bjerggaard , Høyer Søren , Pedersen Jakob Skou , Ørntoft Torben F. , Dyrskjøt Lars 
Published: August 2016

Abstract
Greater knowledge concerning tumor heterogeneity and clonality is needed to determine the impact of targeted treatment in the setting of bladder cancer. In this study, we performed whole-exome, transcriptome, and deep-focused sequencing of metachronous tumors from 29 patients initially diagnosed with early-stage bladder tumors (14 with nonprogressive disease and 15 with progressive disease). Tumors from patients with progressive disease showed a higher variance of the intrapatient mutational spectrum and a higher frequency of APOBEC-related mutations. Allele-specific expression was also higher in these patients, particularly in tumor suppressor genes. Phylogenetic analysis revealed a common origin of the metachronous tumors, with a higher proportion of clonal mutations in the ancestral branch; however, 19 potential therapeutic targets were identified as both ancestral and tumor-specific alterations. Few subclones were present based on PyClone analysis. Our results illuminate tumor evolution and identify candidate therapeutic targets in bladder cancer. Cancer Res; 76(19); 5894–906. ©2016 AACR.
Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival in Patients with Metastatic Breast Cancer Receiving Taxane-Based Chemotherapy
Authors: Shachar Shlomit Strulov , Deal Allison M. , Weinberg Marc , Nyrop Kirsten A. , Williams Grant R. , Nishijima Tomohiro F. , Benbow Julia M. , Muss Hyman B. 
Published: August 2016

Abstract
Purpose: Severe skeletal muscle (SM) loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first-line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes.
Experimental Design: Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and density (SMD) were measured at the third lumbar vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) ≤ 41. Skeletal muscle gauge (SMG) was created by multiplying SMI × SMD. Fisher exact tests, t tests, the Kaplan–Meier method, and Cox regression modeling were used.
Results: MBC patients (N = 40), median age 55 (range, 34–80), 58% sarcopenic, median SMG 1296 AU (SD, 522). Grade 3–4 toxicity was found in 57% of sarcopenic versus 18% of non-sarcopenic patients (P = 0.02). Toxicity-related hospitalizations were also higher in sarcopenic patients (39% vs. 0%, P = 0.005) as were any adverse events—defined as any grade 3–4 toxicities, hospitalizations, dose reductions, or dose delay—(74% vs. 35%, P = 0.02). Low SMG was associated with grade 3–4 toxicity (P = 0.04), hospitalization (P = 0.01), and time to treatment failure (for progression or toxicity; P = 0.03). Low SMG had a borderline significant association with any adverse event (P = 0.06) and overall survival (P = 0.07).
Conclusions: SM measures are associated with toxicity outcomes and survival in MBC patients receiving first-line taxane-based chemotherapy. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and improve treatment planning. Clin Cancer Res; 23(3); 658–65. ©2016 AACR.
Association of AR-V7 and Prostate-Specific Antigen RNA Levels in Blood with Efficacy of Abiraterone Acetate and Enzalutamide Treatment in Men with Prostate Cancer
Authors: Qu Fangfang , Xie Wanling , Nakabayashi Mari , Zhang Haitao , Jeong Seong Ho , Wang Xiaodong , Komura Kazumasa , Sweeney Christopher J. , Sartor Oliver , Lee Gwo-Shu Mary , Kantoff Philip W. 
Published: August 2016

Abstract
Purpose: We evaluated the association of PSA and androgen receptor splice variant-7 (AR-V7) transcript levels in patients' blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate and/or enzalutamide treatment in castration-resistant prostate cancer (CRPC) patients.
Experimental Design: RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using droplet digital-PCR in retrospective cohorts treated with abiraterone acetate (N = 81) or enzalutamide (N = 51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses.
Results: PSA transcripts were detected in 57% of abiraterone acetate–treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95% confidence interval (CI) 1.26–4.10) and 2.60 (95% CI, 1.19–5.69); P = 0.006 and 0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P = 0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in enzalutamide cohort). In multivariable models, the association with TTF remained significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01–4.05; P = 0.048), but statistically insignificant in the abiraterone acetate cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS.
Conclusions: PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells. Clin Cancer Res; 23(3); 726–34. ©2016 AACR.
Systemic Ablation of MMP-9 Triggers Invasive Growth and Metastasis of Pancreatic Cancer via Deregulation of IL6 Expression in the Bone Marrow
Authors: Grünwald Barbara , Vandooren Jennifer , Gerg Michael , Ahomaa Kaarin , Hunger Annique , Berchtold Sonja , Akbareian Sophia , Schaten Susanne , Knolle Percy , Edwards Dylan R. , Opdenakker Ghislain , Krüger Achim 
Published: August 2016

Abstract
Matrix metalloproteinase 9 (MMP-9/Gelatinase B) is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and plays a central role in tumor cell invasion and metastasis. Here we complemented mechanistic insights in the cancer biology of MMP-9 and investigated the effects of specific long-term loss-of-function, by genetic ablation, of MMP-9 on PDAC initiation and progression in the well-established KPC mouse model of spontaneous PDAC. Tumor growth and progression were analyzed by histopathology and IHC. Invasive growth of PDAC cells was analyzed by both in vitro (proliferation, survival, migration, invasion assays) and in vivo (experimental metastasis assays) methods. Retroviral shRNAi was used to knockdown target genes (MMP-9, IL6R). Gene expression was analyzed by qRT-PCR, immunoblot, ELISA, in situ hybridization, and zymography. PDAC tumors from MMP-9–deficient mice were dramatically larger, more invasive, and contained more stroma. Yet, ablation of MMP-9 in PDAC cells did not directly promote invasive growth. Interestingly, systemic ablation of MMP-9 led to increased IL6 levels resulting from abrogation of MMP-9–dependent SCF signaling in the bone marrow. IL6 levels in MMP-9−/− mice were sufficient to induce invasive growth and STAT3 activation in PDAC cells via IL6 receptor (IL6R). Interference with IL6R blocked the increased invasion and metastasis of PDAC cells in MMP-9–deficient hosts. In conclusion, ablation of systemic MMP-9 initiated fatal communication between maintenance of physiological functions of MMP-9 in the bone marrow and invasive growth of PDAC via the IL6/IL6R/STAT3 axis.
Implications: Thus, the beneficial effects of host MMP-9 on PDAC are an important caveat for the use of systemic MMP-9 inhibitors in cancer. Mol Cancer Res; 14(11); 1147–58. ©2016 AACR.
Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover
Authors: Nührenberg Thomas , Amann Michael , Cederqvist Marco , Kleiner Pascal , Valina Christian M. , Trenk Dietmar , Neumann Franz-Josef , Hochholzer Willibald , Stratz Christian 
Published: August 2016

SummaryReticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all timepoints (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.Supplementary Material to this article is available online at www.thrombosis-online.com.
Acute migraine medication adherence, migraine disability and patient satisfaction: A naturalistic daily diary study
Authors: Seng Elizabeth K , Robbins Matthew S , Nicholson Robert A 
Published: August 2016

ObjectiveTo examine the influence of acute migraine medication adherence on migraine disability and acute medication satisfaction.MethodsAdults with migraine completed three months of daily electronic diaries assessing headache symptoms, acute medication taken, acute medication satisfaction, and daily migraine disability. Repeated measures mixed-effects models examined the effect of initial medication type [migraine-specific medication (MSM) vs. over-the-counter analgesic (OTC) vs. an opiate/barbiturate], the severity of pain at dosing, and their interaction with daily migraine disability and satisfaction with acute medication.ResultsParticipants (N = 337; 92.5% female; 91.1% Caucasian, non-Hispanic; 84.0% with episodic migraine) recorded 29,722 diary days. Participants took acute medication on 96.5% of 8090 migraine days. MSM was most frequently taken first (58%), followed by OTC (29.9%) and an opiate/barbiturate (12.1%). Acute medication was most frequently taken when pain was mild (41.2%), followed by moderate (37.7%) and severe pain (11.4%). Initially dosing with MSM while pain was mild was associated with the lowest daily disability [medication × pain at dosing F (4, 6336.12) = 58.73, p < .001] and highest acute medication satisfaction [medication × pain at dosing F (4, 3867.36) = 24.00, p < .001].ConclusionUsing an MSM (triptan or ergot) first was associated with the lowest migraine disability and highest acute medication satisfaction.
Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa
Authors: Lewandowski L B , Schanberg L E , Thielman N , Phuti A , Kalla A A , Okpechi I , Nourse P , Gajjar P , Faller G , Ambaram P , Reuter H , Spittal G , Scott C 
Published: August 2016

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.
When Terminal Illness Is Worse Than Death: A Multicenter Study of Health-Care Providers’ Resuscitation Desires
Authors: Chavez Luis O. , Einav Sharon , Varon Joseph 
Published: August 2016

Purpose: To investigate how a terminal illness may affect the health-care providers’ resuscitation preferences. Methods: We conducted a cross-sectional survey in 9 health-care institutions located in 4 geographical regions in North and Central America, investigating attitudes toward end-of-life practices in health-care providers. Statistical analysis included descriptive statistics and χ2 test for the presence of associations ( P < 0.05 being significant) and Cramer V for the strength of the association. The main outcome measured the correlation between the respondents’ present code status and their preference for cardiopulmonary resuscitation (CPR) in case of terminal illness. Results: A total of 852 surveys were completed. Among the respondents, 21% (n = 180) were physicians, 36.9% (n = 317) were nurses, 10.5% (n = 90) were medical students, and 265 participants were other staff members of the institutions. Most respondents (58.3%; n = 500) desired “definitely full code” (physicians 73.2%; n = 131), only 13.8% of the respondents (physicians 8.33%; n = 15) desired “definitely no code” or “partial support,” and 20.9% of the respondents (n = 179; among physicians 18.4%; n = 33) had never considered their code status. There was an association between current code status and resuscitation preference in case of terminal illness ( P < .001), but this association was overall quite weak (Cramer V = 0.180). Subgroup analysis revealed no association between current code status and terminal illness code preference among physicians ( P = .290) and nurses ( P = .316), whereupon other hospital workers were more consistent ( P < .01, Cramer V = .291). Conclusion: Doctors and nurses have different end-of-life preferences than other hospital workers. Their desire to undergo CPR may change when facing a terminal illness.
MR Parametric Mapping as a Biomarker of Early Joint Degeneration
Authors: Chang Eric Y. , Ma Yajun , Du Jiang 
Published: August 2016

Context: Osteoarthritis (OA) is a common, worldwide disorder. Magnetic resonance (MR) imaging can directly and noninvasively evaluate articular cartilage and has emerged as an essential tool in the study of OA. Evidence Acquisition: A PubMed search was performed using the keywords quantitative MRI and cartilage. No limits were set on the range of years searched. Articles were reviewed for relevance with an emphasis on in vivo studies performed at 3 tesla. Study Design: Clinical review. Level of Evidence: Level 4. Results: T2, T2*, T1 (particularly when measured after exogenous contrast administration, such as with the delayed gadolinium-enhanced MR imaging of cartilage [dGEMRIC] technique), and T1ρ are among the most widely utilized quantitative MR imaging techniques to evaluate cartilage and have been implemented in various patient cohorts. Existing challenges include reproducibility of results, insufficient consensus regarding optimal sequences and parameters, and interpretation of values. Conclusion: Quantitative assessment of cartilage using MR imaging techniques likely represents the best opportunity to identify early cartilage degeneration and to follow patients after treatment. Despite existing challenges, ongoing work and unique approaches have shown exciting and promising results.
MedLink: A mobile intervention to improve medication adherence and processes of care for treatment of depression in general medicine
Authors: Corden Marya E , Koucky Ellen M , Brenner Christopher , Palac Hannah L , Soren Adisa , Begale Mark , Ruo Bernice , Kaiser Susan M , Duffecy Jenna , Mohr David C 
Published: August 2016

Background Major depressive disorder is a common psychological problem affecting up to 20% of adults in their lifetime. The majority of people treated for depression receive antidepressant medication through their primary care physician. This commonly results in low rates of recovery. Failure points in the process of care contributing to poor outcomes include patient non-adherence to medications, failure of physicians to optimize dose and absence of communication between patients and physicians. Objective This pilot study evaluated the feasibility of a systemic digital intervention (MedLink) designed to address failure points and improve treatment of depression in primary care among patients during the first eight weeks of initiating a new course of antidepressant therapy. Methods Participants were provided with the MedLink mobile app that provided dose reminders, information and surveys of symptoms and side effects. A cellularly enabled pillbox monitored antidepressant medication adherence. Reports were provided to physicians and participants to prompt changes in medication regimen. Study outcomes were assessed via self-report and interview measures at baseline, week 4 and week 8. Results Medication adherence detected by the MedLink system was 82%. Participants demonstrated significant decreases in depressive symptoms on the patient health questionnaire-9 (PHQ-9) ( p = 0.0005) and the Quick Inventory of Depressive Symptomatology ( p = 0.0008) over the eight-week trial. Usability was generally rated favorably. Conclusions The MedLink system demonstrated promise as an intervention to address failure points in the primary care treatment of major depressive disorder. Current findings support the further development of MedLink through a randomized controlled trial to evaluate the efficacy of improving processes of care, patient adherence and symptoms of depression.
Smoking, longer disease duration and absence of rhinosinusitis are related to fixed airway obstruction in Koreans with severe asthma: findings from the COREA study
Authors: Lee Taehoon , Lee Yoon Su , Bae Yun-Jeong , Kim Tae-Bum , Kim Seon Ok , Cho Sang-Heon , Moon Hee-Bom ,   COhort for Reality and Evolution of adult Asthma in Korea study group (COREA study group), Cho You Sook 
Published: August 2016

Abstract

Background
The clinical manifestations of severe asthma are heterogeneous. Some individuals with severe asthma develop irreversible fixed airway obstruction, which is associated with poor outcomes. We therefore investigated the factors associated with fixed airway obstruction in Korean patients with severe asthma.

Methods
Severe asthma patients from a Korean adult asthma cohort were divided into two groups according to the results of serial pulmonary function tests. One group had fixed airway obstruction (FAO) [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7, n = 119] and the other had reversible airway obstruction (RAO) [FEV1/FVC ratio ≥ 0.7, n = 116]. Clinical and demographic parameters were compared between the two groups.

Results
Multivariate analysis showed that longer duration of disease, greater amount of cigarette smoking and absence of rhinosinusitis were significantly related to the development of FAO in severe asthmatics. Other parameters, including atopic status, pattern of airway inflammatory cells in induced sputum, and frequency of asthma exacerbations did not differ between the FAO and RAO groups.

Conclusion
Severe asthma patients with longer disease duration and the absence of rhinosinusitis are more likely to develop FAO. This study also demonstrates the importance of quitting smoking in order to prevent irreversible airway obstruction. Further investigation is required to determine the mechanism by which these factors can modify the disease course in Korean patients with severe asthma.