Md Sani S.S.,Hospital Kuala Lumpur |
Han W.H.,Hospital Kuala Lumpur |
Bujang M.A.,Biostatistic Unit |
Ding H.J.,Hospital Kuala Lumpur |
And 2 more authors.
BMC Infectious Diseases | Year: 2017
Background: Existing biomarkers such as AST, ALT and hematocrit have been associated with severe dengue but evidence are mixed. Recently, interests in creatine kinase as a dengue biomarker have risen. These biomarkers represent several underlying pathophysiological processes in dengue. Hence, we aimed to assess AST, ALT, CK and hematocrit in identification of severe dengue and to assess the correlational relationship amongst common biomarkers of dengue. Methods: This was a retrospective cohort study of confirmed dengue patients who were warded in Kuala Lumpur Hospital between December 2014 and January 2015. CK, AST, ALT, hematocrit, platelet count, WBC and serum albumin were taken upon ward admission and repeated at timed intervals. Composite indices based on admission AST and ALT were analyzed. Correlation coefficients and coefficients of determination were computed. Results: Among the 365 cases reviewed, twenty-two (6%) patients had severe dengue. AST and ALT were found to be good at identification of severe dengue. The AST2/ALT composite index was the most accurate (AUC 0.83; 95% CI 0.73 - 0.93). Optimal cutoff was 402 with a sensitivity of 59.1% (95% CI: 36.4 - 79.3%) and specificity of 92.4% (95% CI: 89.1 - 95.0%). Modified cutoff of 653 had a sensitivity of 40.9% (95% CI: 20.7 - 63.7%) and specificity of 97.4% (95% CI: 95.1 - 98.8%). Our analyses also suggested that several underlying biological processes represented by biomarkers tested were unrelated despite occurring in the same disease entity. Also, markers of plasma leakage were discordant and AST was likely hepatic in origin. Conclusions: The composite index AST2/ALT may be used as a marker for identification of severe dengue based on admission AST and ALT, with two choices of cutoff values, 402 and 653. AST is most likely of liver origin and CK does not provide additional value. © 2017 The Author(s).
Paroni G.,Gerontology Geriatric Research Laboratory |
Seripa D.,Gerontology Geriatric Research Laboratory |
Fontana A.,Biostatistic Unit |
D'Onofrio G.,Gerontology Geriatric Research Laboratory |
And 9 more authors.
Molecular Neurobiology | Year: 2017
Klotho protein, encoded by the Klotho gene (KL) at locus 13q12, is an antiaging hormone-like protein playing a pivotal role in cell metabolism homeostasis and associated to longevity and age-related diseases. In particular, altered cell metabolism in central nervous system may influence the behavior of serotoninergic neurons. The role of KL in the response to treatment with selective serotonin reuptake inhibitors (SSRIs) in late-life depressive syndromes and late-life major depressive disorder (MDD) is unclear. We genotyped three single-nucleotide polymorphisms (SNPs) of KL in 329 older patients with diagnosis of late-life MDD, treated with SSRIs and evaluated with the Hamilton Rating Scale for Depression 21-items (HRSD-21) at baseline and after 6 months. A reduction ≥50 and <10 % in HDRS-21 score was considered as response or nonresponse to therapy, respectively, and the values of reduction between 10 and 49 % as poor responders. After 6 months of SSRI treatment, 176 patients responded, 54 patients did not respond and 99 patients showed a poor response. Ordinal logistic models showed a significant association between mutation of SNP rs1207568 and responders and, similarly, for each unitary risk allele increase overlapping results were found. Conversely, a significantly higher frequency of the minor genotype of SNP rs9536314 was found in nonresponders. Considering the pre-post differences of HRSD-21 scores as a continue variable, we confirmed a significant improvement of depressive symptoms after treatment in patients carrying at least one minor allele at rs1207568 and a worse response in patients homozygous for the minor allele at rs9536314. Our results were the first that suggested a possible role of KL in the complex pathway of SSRI response in late-life MDD. © 2016, Springer Science+Business Media New York.
Zucali P.A.,Humanitas Clinical and Research Center |
Perrino M.,Humanitas Clinical and Research Center |
Lorenzi E.,Humanitas Clinical and Research Center |
Ceresoli G.L.,Instituto Humanitas Gavazzeni |
And 6 more authors.
Lung Cancer | Year: 2014
Background: Pemetrexed-platinum chemotherapy is the standard first-line treatment of unresectable malignant pleural mesothelioma (MPM). At progression, patients are generally selected to experimental trials, when available, or, in every-day clinical practice, they are offered second-line chemotherapy. The optimal treatment has not yet been defined. The aim of this retrospective, single-center study was to evaluate the activity and toxicity of vinorelbine administered to a consecutive series of pemetrexed-pretreated MPM patients. Methods: Vinorelbine 25mg/m2 was administered intravenously as a single agent on days 1, 8 every three weeks, either as second-line (2L) or further-line (>2L) therapy. Treatment was repeated for a maximum of 6 cycles, until progression, or unacceptable toxicity. Results: Fifty-nine patients were included in this analysis. Vinorelbine was given to 34 patients as 2L, and to 25 as >2L treatment. The median age was 69 years (range 45-80). Forty-two patients (71.2%) had a good EORTC prognostic score. Partial response was observed in 9 (15.2%) cases, stable disease in 20 (33.9%). The overall disease control rate (DCR) was 49.1%. Median progression-free survival (PFS) and overall survival (OS) were 2.3 and 6.2 months, respectively. ECOG performance status (PS) (HR0 vs. 1-2 0.50; 95%CI: 0.3-0.8; p=0.014) and PFS≥6 months following first-line (FL) chemotherapy (HRFL-PFS>6ms vs. <6ms 0.50; 95%CI: 0.3-0.9; p=0.031) were significantly associated to OS in multivariate analysis. No difference was observed in terms of DCR, PFS, and OS in relation to age, histology, sex, line of vinorelbine therapy, or response to FL treatment. Hematological toxicity was acceptable, with grade 3/4 neutropenia occurring in 5 (8.4%) patients, and there were no cases of febrile neutropenia. The main non-hematological toxicities were grade 2 fatigue in 17 (28.8%) and constipation in 7 (11.8%) patients. Conclusions: Vinorelbine was moderately active in pemetrexed-pretreated MPM patients, with an acceptable toxicity profile, particularly in patients with ECOG-PS0 and FL-PFS ≥6 months. © 2013 Elsevier Ireland Ltd.
Sissing L.,PROMEC Unit |
Marnewick J.,Cape Peninsula University of Technology |
De Kock M.,University of the Western Cape |
Swanevelder S.,Biostatistic Unit |
And 4 more authors.
Nutrition and Cancer | Year: 2011
Widespread consumption of herbal teas has stimulated interest in their role as cancer preventive agents. The present investigation monitored the modulation of methylbenzylnitrosamine (MBN)-induced esophageal squamous cell carcinogenesis by rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) herbal and Camellia sinensis teas in male F344 rats. The tumor multiplicity was significantly (P < 0.05) inhibited by unfermented honeybush (45.5%), green (50%), and black (36%) teas, while the other teas exhibited weaker effects (<30% inhibition). The mean total papilloma size was reduced by unfermented rooibos (87%), unfermented honeybush (94%), and fermented honeybush (74%) due to the absence of large papillomas (>10 mm3). Reduction of the mean total papilloma number correlated with the total polyphenol (TPP) (r = 0.79; P < 0.02) and flavanol/proanthocyanidin (FLAVA) (r = 0.89; P < 0.008) intake (mg/100 g body weight) of the teas and the FLAVA (r = 0.89; P < 0.04) and flavonol/flavones/xanthones (r = 0.99; P < 0.002) intake when considering only the herbal teas. A daily TPP intake threshold of 7 mg/100 g body weight existed below where no inhibition of papilloma development was observed. Fermentation of herbal teas reduced the inhibitory effects on papilloma development associated with a reduction in the polyphenolic constituents. The inhibitory effect of herbal teas on papilloma development is associated with different flavonoid subgroups and/or combination thereof. Copyright © 2011, Taylor & Francis Group, LLC.
Rouscoff Y.,University of Nice Sophia Antipolis |
Falk A.T.,Sophia University |
Durand M.,University of Nice Sophia Antipolis |
Gal J.,Biostatistic Unit |
And 6 more authors.
Radiation Oncology | Year: 2014
Purpose: To assess clinical outcomes of high-dose rate interstitial brachytherapy (HIB) in localized penile carcinoma.Material and methods: From 03/2006 to 08/2013, patients with biopsy-proven T1-T2 (<4 cm) non-metastatic localized penile squamous cell carcinoma underwent HIB. Under general anaesthesia, after Foley catheter placement, needles were placed in the target volume using a dedicated template. Planification was carried out with a post-implant CT-scan to deliver a total dose of 36 Gy in 9 fractions over 5 days (in adjuvant setting) or 39 Gy in 9 fractions over 5 days (as monotherapy). Dose-volume adaptation was manually achieved using graphical optimization. Dosimetric data and clinical outcomes were retrospectively analyzed. Toxicities were graded using the CTC v4.0.Results: With a median follow-up of 27 months [5.1-83], 12 patients including 8 T1a, 3 T1b and 1 T2 N0 underwent HIB (sole therapy: 11 pts; adjuvant: 1 pt). The actuarial 5-year relapse-free, cause-specific and overall survival rates were 83%, 100% and 78% respectively. Comparing pre and post treatment evaluation, no IPSS or IIEF-5 changes were reported. Dermatitis was reported systematically 1 month after HIB including 6 G1, 5 G2 and 1 G3. Only 1 experienced long-term G3 successfully treated with hyperbaric oxygen therapy. One urethral meatus stenosis G3 required meatotomy.Conclusion: In selected patients with T1-T2 localized penile cancer, HIB may be considered as an optional conservative therapy. Longer follow-up is needed to confirm these encouraging preliminary results. © 2014 Rouscoff et al.; licensee BioMed Central Ltd.
Hannoun-Levi J.-M.,Sophia University |
Resch A.,University of Vienna |
Gal J.,Biostatistic Unit |
Kauer-Dorner D.,University of Vienna |
And 5 more authors.
Radiotherapy and Oncology | Year: 2013
Purpose To analyse the clinical outcome after salvage lumpectomy and multi-catheter brachytherapy (MCB) for ipsilateral breast tumour recurrence (IBTR). Material and methods Between 09/00 and 09/10, 217 patients presenting an IBTR underwent lumpectomy and MCB (low, pulsed, or high-dose rate). Survival rates without second local recurrence (2nd LR), distant metastasis (DM), and overall survival (OS) were analysed as well as late effects and cosmetic results. Univariate and multivariate analyses (MVA) based on IBTR data were performed to find prognostic factors for 2nd LR, DM, and OS. Results Median follow-up after the IBTR was 3.9 years [range: 1.1-10.3]. Five and 10-year actuarial 2nd LR rates were 5.6% [range: 1.5-9.5] and 7.2% [range: 2.1-12.1], respectively. Five and 10-year actuarial DM rates were 9.6% [range: 5.7-15.2] and 19.1% [range: 7.8-28.3], respectively. Five and 10-year actuarial OS rates were 88.7% [range: 83.1-94.8] and 76.4% [range: 66.9-87.3], respectively. In MVA, histological grade was prognostic factor for 2nd LR (p = 0.008) and OS (p = 0.02); while tumour size was prognostic factor for DM (p = 0.03). G3-4 complication rate was 11%. Excellent/good cosmetic result was achieved in 85%. Conclusion This study suggests that in case of IBTR, lumpectomy plus MCB is feasible and effective in preventing 2nd LR with an OS rate at least equivalent to those achieved with salvage mastectomy. © 2013 Elsevier Ireland Ltd. All rights reserved.
Koppe L.,Hospital E Herriot |
Klich A.,Biostatistic Unit |
Dubourg L.,Hospital E Herriot |
Ecochard R.,Biostatistic Unit |
Hadj-Aissa A.,Hospital E Herriot
Journal of Nephrology | Year: 2013
Background: The current equations for estimating glomerular filtration rate (GFR) have limited precision in older people. The Berlin Initiative Study (BIS-1) equation has recently been developed to improve the precision and accuracy of GFR estimation in older people, over the previous simplified Modification of Diet in Renal Disease (MDRD) Study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Methods: The study included 224 white patients aged >70 years who had simultaneous measurements of plasma creatinine and renal clearance of inulin. Creatinine assays used an enzymatic method with calibrators defined by isotope dilution mass spectrometry. The performance of BIS-1, MDRD and CKD-EPI equations in estimating GFR were compared. Results: BIS-1 was the most accurate: the percentage of GFR estimates that fell within the range of measured GFR ± 30% (P30) was 75.56% vs. 70.67% with MDRD and 72% with CKD-EPI. BIS-1 had the lowest median bias: (interquartile range) (4.1 (11.4) vs 5.8 (12.7) and 5.4 (12.8) respectively) the highest precision (the SD of the estimated GFR minus measured GFR differences was 9.21 vs 12.78 and 10.83 mL/min/1.73 m2 respectively) and the highest concordance correlation coefficient (CCC) (0.82 vs. 0.74 and 0.79 respectively, p<0.05). However, in chronic kidney disease (CKD) stages 4 and 5, the CKD-EPI equation had the highest P30, the lowest median bias and the highest CCC: it was more accurate than the BIS-1 equation. Conclusion: Among the 3 creatinine-based equations compared, BIS-1 was the most reliable for assessing renal function in older white patients, especially in those with CKD stages 1 to 3. © 2013 Società Italiana di Nefrologia.
PubMed | Liver Unit, Biostatistic Unit, Aarhus University Hospital, Monash University and 2 more.
Type: | Journal: Scientific reports | Year: 2016
Primary biliary cholangitis (PBC) has been regarded as female-predominant without evidence of gender difference in survival. We aimed to compare the overall survival, incidence and prevalence of PBC in two well defined population-based studies over a recent decade, considering also sex ratios and mortality. We have taken advantage of population-wide records, during 2000-2009, in Lombardia, Northern Italy, and Denmark. We focused on the incident cases of PBC, including gender and outcome, among 9.7 million inhabitants of Lombardia and 5.5 million of Denmark. In Lombardia there were 2,970 PBC cases with a female:male ratio of 2.3:1. The age/sex-adjusted annual incidence of PBC was 16.7 per million. Point prevalence was 160 per million on January 1(st) 2009. In Denmark there were 722 cases of incident PBC, female:male ratio was 4.2:1, and the annual incidence was 11.4 per million, a point prevalence of 115 per million in 2009. Cox regression multivariate analysis identified male sex as an independent predictor of all-cause mortality in both Italian (HR 2.36) and Danish population (HR 3.04). Our data indicate for PBC a sex ratio significantly lower than previously cited, a reversal of the usual latitudinal difference in prevalence and a surprisingly higher overall mortality for male patients.
PubMed | Gerontology Geriatric Research Laboratory, Galliera Hospital NR HS, Biostatistic Unit and University of Bari
Type: | Journal: Molecular neurobiology | Year: 2016
Klotho protein, encoded by the Klotho gene (KL) at locus 13q12, is an antiaging hormone-like protein playing a pivotal role in cell metabolism homeostasis and associated to longevity and age-related diseases. In particular, altered cell metabolism in central nervous system may influence the behavior of serotoninergic neurons. The role of KL in the response to treatment with selective serotonin reuptake inhibitors (SSRIs) in late-life depressive syndromes and late-life major depressive disorder (MDD) is unclear. We genotyped three single-nucleotide polymorphisms (SNPs) of KL in 329 older patients with diagnosis of late-life MDD, treated with SSRIs and evaluated with the Hamilton Rating Scale for Depression 21-items (HRSD-21) at baseline and after 6months. A reduction 50 and <10% in HDRS-21 score was considered as response or nonresponse to therapy, respectively, and the values of reduction between 10 and 49% as poor responders. After 6months of SSRI treatment, 176 patients responded, 54 patients did not respond and 99 patients showed a poor response. Ordinal logistic models showed a significant association between mutation of SNP rs1207568 and responders and, similarly, for each unitary risk allele increase overlapping results were found. Conversely, a significantly higher frequency of the minor genotype of SNP rs9536314 was found in nonresponders. Considering the pre-post differences of HRSD-21 scores as a continue variable, we confirmed a significant improvement of depressive symptoms after treatment in patients carrying at least one minor allele at rs1207568 and a worse response in patients homozygous for the minor allele at rs9536314. Our results were the first that suggested a possible role of KL in the complex pathway of SSRI response in late-life MDD.
PubMed | Azienda Ospedaliera Pugliese Ciaccio, Biostatistic Unit and Azienda Ospedaliera di Cosenza
Type: Clinical Trial | Journal: European journal of haematology | Year: 2016
A comprehensive prognostic index that includes clinical (i.e., age, sex, ECOG performance status), serum (i.e., 2-microglobulin, thymidine kinase [TK]), and molecular (i.e., IGVH mutational status, del 17p, del 11q) markers developed by the German CLL Study Group (GCLLSG) was externally validated in a prospective, community-based cohort consisting of 338 patients with early chronic lymphocytic leukemia (CLL) using as endpoint the time to first treatment (TTFT). Because serum TK was not available, a slightly modified version of the model based on seven instead of eight prognostic variables was used. By German index, 62.9% of patients were scored as having low-risk CLL (score 0-2), whereas 37.1% had intermediate-risk CLL (score 3-5). This stratification translated into a significant difference in the TTFT [HR = 4.21; 95% C.I. (2.71-6.53); P < 0.0001]. Also the 2007 MD Anderson Cancer Center (MDACC) score, barely based on traditional clinical parameters, showed comparable reliability [HR = 2.73; 95% C.I. (1.79-4.17); P < 0.0001]. A comparative performance assessment between the two models revealed that prediction of the TTFT was more accurate with German score. The c-statistic of the MDACC model was 0.65 (range, 0.53-0.78) a level below that of the German index [0.71 (range, 0.60-0.82)] and below the accepted 0.7 threshold necessary to have value at the individual patient level. Results of this external comparative validation analysis strongly support the German score as the benchmark for comparison of any novel prognostic scheme aimed at evaluating the TTFT in patients with early CLL even when a modified version which does not include TK is utilized.