A volumetric prediction model for postoperative cyst shrinkage

Clinical Oral Investigations - With only limited information available on dimensional changes after jaw cyst surgery, postoperative cyst shrinkage remains largely unpredictable. We aimed to propose...     

Sleep disturbances in patients with mild-stage Alzheimer's disease

We examined the ability of sleep/wake measures to discriminate 45 control subjects from 44 mild Alzheimer's disease (AD) patients. Sleep fragmentation was observed as indicated by significant increases in time awake (37-52%) and number of awakenings (31-36%) during the night as compared to controls. Further, slow wave sleep (SWS) was significantly reduced (22%) in AD patients relative to controls. These findings are consistent with our earlier observations of increased wakefulness and decreased SWS in mild-moderate, moderate-severe, and severe stage AD patients. However, when we used these sleep/wake stage measures in discriminant analyses to classify the current AD subjects vs control subjects, the analyses failed to confirm our earlier high classification rate (90%). The present groups were discriminated at overall classification rates of only 63-67%. We conclude that while sleep/wake patterns are significantly disturbed in AD, this phenomenon is not diagnostically useful for discrimination of mild stage AD.     

The prevalence of hypertension,obesity and dyslipidemia in individuals of over 30 years of age belonging to minorities from the pasture area of Xinjiang

Background

Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity.

Methods/Design

The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure.

Discussion

Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.

Trial Registration

Chinese clinical trial registry (Primary registry in the WHO registry network) Identifier: ChiCTR-TRC-00000402     

Pre-emptive treatment of CMV DNAemia in paediatric stem cell transplantation: the impact of recipient and donor CMV serostatus on the incidence of CMV disease and CMV-related mortality

Cytomegalovirus (CMV) DNAemia was detected by PCR in 30/125 (24%) consecutive paediatric patients undergoing allogeneic stem cell transplantation. All patients with CMV DNAemia received pre-emptive ganciclovir until two consecutive negative results were obtained. CMV-IgG-positive patients (R+) had a significantly increased risk of DNAemia as compared to CMV-IgG-negative (R-) patients (62% vs 8%) P<0.0001. The incidence of DNAemia was 71% (10/14) in R+ transplanted from seronegative donors (D-) compared to 54% (13/32) in those transplanted from seropositive donors (D+). Of 30 (40%) children with DNAemia, 12 developed CMV disease despite pre-emptive treatment. The overall incidence of disease was 0% (0/59) for R-/D-, 9% (3/23) for R+/D+, 7% (2/29) for R-/D+ and 57% (8/14) for R+/D-. In patients with DNAemia, 4/20 (20%) patients with D+ and 8/10 (80%) with D- became symptomatic. In the multivariate analysis of both groups, patients at risk (R+ and/or D+) and patients with DNAemia, a negative donor serostatus was the only factor associated with a significantly increased incidence of disease. Seven of 9 patients with lethal CMV disease had received CMV-IgG-negative grafts. The data suggest that in CMV seropositive recipients donor CMV seropositivity is associated with a reduced incidence of CMV disease and a favourable outcome following pre-emptive treatment.     

Motility-related protein-1/CD9 expression in head and neck squamous cell carcinoma

INTRODUCTION: Motility-related protein (MRP)-1/CD9 is implicated in cell adhesion and motility and was shown to be clearly involved in tumor prognosis and angiogenesis. Elevated MRP-1/CD9 expression on tumor cells has been linked to a favorable prognosis in breast cancer, colon cancer, lung cancer, and HNSCC. Because MRP-1/CD9 is associated with angiogenesis, it might play a role in tumor angiogenesis as well. METHODS: We analyzed MRP-1/CD9 expression in HNSCC specimens and cell lines by real-time RT-PCR and in HNSCC biopsy specimens and stromal vessels by immunohistochemistry. Kruskal Wallis and Chi2 test, univariate and multivariate Cox regression, and Kaplan-Meier methods were used for statistical analysis. RESULTS: Real-time and PCR RT showed elevated expression of MRP-1/CD9 in one (SCC25) of four HNSCC cell lines and two of six HNSCC patients, whereas two cell lines (SCC9 and JPPA) and one HNSCC patient had lower MRP-1/CD9 levels compared with other specimens. Immunohistochemistry demonstrated strong MRP-1/CD9 IR expression on tumor cells in 13 patients (39%), whereas 21 patients (61%) had less to medium MRP-1/CD9 IR expression. Increased MRP-1/CD9 expression on tumor cells was correlated with prolonged patient survival (p =.02) and a longer disease-free interval (p =.004), a diminished recurrence rate (p =.02), and lower stages of neck lymph nodes (p =.04). MRP-1/CD9 IR was also found in a subpopulation of vessels that seem to be less in tumor specimens than in normal mucosa (p <.0001). MRP-1/CD9+ vessels are podoplanin+ and are therefore regarded as lymphatic vessels. CONCLUSIONS: Our results revealed that elevated MRP-1/CD9 expression on HNSCC is linked to a favorable clinical outcome and confirmed reports of MRP-1/CD9 expression in other carcinomas. MRP-1/CD9+ vessels were found to be lymphatic in nature. The number and staining intensity of these vessels is decreased in tumor tissue, which suggests a stabilizing role for this protein in lymphangiogenesis.     

Circulating myeloid colony-forming cells predict survival in myelodysplastic syndromes

The growth characteristics and the prognostic value of cytokine-stimulated myeloid colony formation from peripheral blood mononuclear cells (PBMC) of patients with myelodysplastic syndromes (MDS) are largely unknown. In this study we have determined the number of myeloid colony-forming units (mCFUs) in semisolid medium from 112 MDS patients and correlated them with French-American-British (FAB) type, the international prognostic scoring system (IPSS), karyotype, peripheral blood (PB) and bone marrow (BM) blast cells, cytopenias, lactate dehydrogenase (LDH), and survival data. Concerning the FAB classification, lower median mCFUs were found in patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) compared to refractory anemia with excess of blast cells (RAEB) and refractory anemia with excess of blasts cells in transformation (RAEB-T). In vitro growth in MDS clearly correlated with the cytogenetic risk groups defined by the IPSS (30.5/10(5) PBMCs with favorable karyotypes, 191 in the intermediate prognostic group, 677 with unfavorable cytogenetics, p=0.015 favorable vs unfavorable). BM blast cells >5% (60.5 vs 255 colonies, p=0.032) as well as LDH levels above the normal limit (64.5 vs 425 colonies, p=0.045) were also associated with higher colony formation. Patients were stratified according to the number of circulating mCFUs into a low growth, intermediate growth and high growth group. Median survival was 343 days in the high growth, 1119 days in the low growth, and 2341 days in the intermediate growth group ( p=0.0002). Multivariate analyses revealed colony growth ( p=0.0056), PB blast cells ( p=0.0069), cytogenetic risk group ( p=0.024), and platelet count ( p=0.018) to predict survival in our patients. After inclusion of the IPSS risk categories, mCFU levels remained a highly predictive parameter for survival ( p=0.0056) and acute myeloblastic leukemia (AML) transformation ( p=0.0003).     

Intraoperative extracorporeal membrane oxygenation and the possibility of postoperative prolongation improve survival in bilateral lung transplantation

Objectives

The value of intraoperative extracorporeal membrane oxygenation (ECMO) in lung transplantation remains controversial. In our department, ECMO has been used routinely for intraoperatively unstable patients for more than 15 years. Recently, we have extended its indication to a preemptive application in almost all cases. In addition, we prolong ECMO into the early postoperative period whenever graft function does not meet certain quality criteria or in patients with primary pulmonary hypertension. The objective of this study was to review the results of this strategy.

Challenging a dogma – Surgery yields superior long-term results for T1a squamous cell carcinoma of the glottic larynx compared to radiotherapy

Aims

The aim of this study was to compare laser surgery, conventional endoscopic surgery and radiotherapy in the treatment of early T1a glottic cancer.

Methods

We conducted a retrospective analysis of patients with early vocal cord cancer (who underwent either conventional surgery via endoscopy or laryngofissur, or primary radiotherapy) at the Medical University of Vienna. By univariate and multivariate Cox regression models the influence of treatment and other parameters on survival and locoregional control were analysed.

Results

337 Patients were analyzed with a mean follow-up period of 133.8 months. Overall survival rates where similar in all three treatment groups. Five-year, 10-year and 15-year estimates of disease specific survival for laser-treated patients were 100%, for conventional surgery were 100%, 98% and 98%, and for radiotherapy were 96%, 92% and 91%, respectively. Locoregional recurrences were observed after laser surgery in 10%, after conventional surgery in 13% and after radiotherapy in 30% of the patients treated. According to the log-rank test, time to relapse was significantly shorter for irradiated patients compared to patients who underwent surgery (p < 0.0001). Mortality caused by the laryngeal tumour was significantly higher in the radiotherapy group (p = 0.003).

Conclusion

Patients undergoing laser or conventional surgery have a significantly lower incidence of locoregional recurrences and longer disease-free intervals when compared to patients treated by radiotherapy.     

Fallback tests for co‐primary endpoints

When efficacy of a treatment is measured by co‐primary endpoints, efficacy is claimed only if for each endpoint an individual statistical test is significant at level α. While such a strategy controls the family‐wise type I error rate (FWER), it is often strictly conservative and allows for no inference if not all null hypotheses can be rejected. In this paper, we investigate fallback tests, which are defined as uniform improvements of the classical test for co‐primary endpoints. They reject whenever the classical test rejects but allow for inference also in settings where only a subset of endpoints show a significant effect. Similarly to the fallback tests for hierarchical testing procedures, these fallback tests for co‐primary endpoints allow one to continue testing even if the primary objective of the trial was not met. We propose examples of fallback tests for two and three co‐primary endpoints that control the FWER in the strong sense under the assumption of multivariate normal test statistics with arbitrary correlation matrix and investigate their power in a simulation study. The fallback procedures for co‐primary endpoints are illustrated with a clinical trial in a rare disease and a diagnostic trial. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.     

Joint genotype‐ and ancestry‐based genome‐wide association studies in admixed populations

In genome‐wide association studies (GWAS) genetic loci that influence complex traits are localized by inspecting associations between genotypes of genetic markers and the values of the trait of interest. On the other hand, admixture mapping, which is performed in case of populations consisting of a recent mix of two ancestral groups, relies on the ancestry information at each locus (locus‐specific ancestry). Recently it has been proposed to jointly model genotype and locus‐specific ancestry within the framework of single marker tests. Here, we extend this approach for population‐based GWAS in the direction of multimarker models. A modified version of the Bayesian information criterion is developed for building a multilocus model that accounts for the differential correlation structure due to linkage disequilibrium (LD) and admixture LD. Simulation studies and a real data example illustrate the advantages of this new approach compared to single‐marker analysis or modern model selection strategies based on separately analyzing genotype and ancestry data, as well as to single‐marker analysis combining genotypic and ancestry information. Depending on the signal strength, our procedure automatically chooses whether genotypic or locus‐specific ancestry markers are added to the model. This results in a good compromise between the power to detect causal mutations and the precision of their localization. The proposed method has been implemented in R and is available at http://www.math.uni.wroc.pl/~mbogdan/admixtures/ .