Summary
We conducted a large, retrospective cohort study using data from Taiwan’s National Health Insurance Research Database to evaluate whether the risk of developing osteoporosis is associated ...with sepsis. Our study found that adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis.
Introduction
There have been limited studies regarding the osteoporosis risk associated with sepsis. Our purpose is to evaluate whether the risk of developing osteoporosis is associated with sepsis.
Methods
We conducted a large, retrospective cohort study using data from Taiwan’s National Health Insurance Research Database. From the insurance claims data, a total of 13,178 patients diagnosed with sepsis from 2000 to 2012 were included in the sepsis cohort, and a propensity score-matched cohort included 13,178 individuals without sepsis. To calculate the incidence of osteoporosis, both groups were followed until 2013. Cox regression analysis was performed to obtain the hazard ratios (HRs) to assess the risk of developing osteoporosis. The Kaplan–Meier method was used to estimate the cumulative incidence of osteoporosis.
Results
The overall incidences of osteoporosis (per 1,000 person-years) in the sepsis and non-sepsis groups were 10.2 and 10.7, respectively. The risk of osteoporosis significantly increased in the presence of sepsis (adjusted HR = 1.17, 95% confidence interval (CI) = 1.04–1.31). The risk of osteoporosis in the sepsis group was significantly higher than that in the non-sepsis group for young patients aged 20–49 years and patients aged 50–64 years (adjusted HR = 1.93, 95% CI = 1.08–3.44; adjusted HR = 2.01, 95% CI = 1.52–2.65, respectively). The Kaplan–Meier curves of cumulative probability also showed a significantly increased risk of osteoporosis in patients aged 20–49 years and aged 50–64 years with sepsis compared with non-sepsis (
P
= 0.025;
P
< 0.001, respectively).
Conclusion
Adults younger than 65 years with sepsis had a significantly increased risk of developing osteoporosis.
Summary
There is conflicting evidence whether allogeneic blood transfusion influences survival or cancer recurrence after resection of hepatocellular cancer. We followed up 1469 patients who had ...undergone hepatocellular resection for a median (IQR range) of 45 (21–78 0–162) months, of whom 626 (43%) had had blood transfusion within 7 days of surgery. Both disease‐free survival and patient survival were measured using a proportional hazards regression model and inverse probability of treatment weighting. We used restricted cubic splines for the association of the number of packed red blood cell units transfused with cancer recurrence and survival. We found that peri‐operative blood transfusion was independently associated with survival and cancer recurrence after resection of hepatocellular carcinoma. Adjusted hazard ratios (95%CI) for the association of blood transfusion with cancer recurrence and all‐cause mortality were 1.3 (1.1–1.4) and 1.9 (1.6–2.3), p < 0.001 for both. With more units transfused cancer recurrence was more likely and survival was shorter. The association of the number of transfused units was non‐linear for cancer recurrence and linear response for all‐cause mortality.
Blood loss during liver surgery is found to be correlated with central venous pressure (CVP). The aim of the current retrospective study is to find out the cutoff value of CVP and stroke volume ...variation (SVV), which may increase the risk of having intraoperative blood loss of more than 100 mL during living liver donor hepatectomies.
Twenty-seven adult living liver donors were divided into 2 groups according to whether they had intraoperative blood loss of less (G1) or more than 100 mL (G2). The mean values of the patients' CVP and SVV at the beginning of the transaction of the liver parenchyma was used as the cutoff point. Its correlation to intraoperative blood loss was evaluated using the χ2 test; P < .001 was regarded as significant.
The cutoff points of CVP and SVV were 8 mm Hg and 13% respectively. The odds ratio of having blood loss exceeding 100 mL was 91.25 (P < .001) and 0.36 (P < .001) for CVP and SVV, respectively.
CVP less than 5 mm Hg, as suggested by most authors, is not always clinical achievable. Our results show that a value of less than 8 mm Hg or SVV 13% is able to achieve a minimal blood loss of 100 mL during parenchyma transaction during a living donor hepatectomy. Measurements used to lower the CVP or increased SVV in our serial were intravenous fluids restriction and the use of a diuretic.
•Blood loss in liver surgery is found to be correlated with central venous pressure (CVP).•A CVP less than 5 mm Hg is suggested in the literature.•A CVP less than 5 mm Hg as suggested by most authors is not always clinically achievable. Our results show that a CVP of less than 8 mm Hg or an SVV of 13% can achieve minimal blood loss of 100 mL during parenchyma transactions in living donor hepatectomy.
MicroRNAs (miRNAs) are small non-coding RNA molecules that can negatively regulate gene expression and thus control numerous cellular mechanisms. This work develops a resource, miRNAMap 2.0, for ...collecting experimentally verified microRNAs and experimentally verified miRNA target genes in human, mouse, rat and other metazoan genomes. Three computational tools, miRanda, RNAhybrid and TargetScan, were employed to identify miRNA targets in 3′-UTR of genes as well as the known miRNA targets. Various criteria for filtering the putative miRNA targets are applied to reduce the false positive prediction rate of miRNA target sites. Additionally, miRNA expression profiles can provide valuable clues on the characteristics of miRNAs, including tissue specificity and differential expression in cancer/normal cell. Therefore, quantitative polymerase chain reaction experiments were performed to monitor the expression profiles of 224 human miRNAs in 18 major normal tissues in human. The negative correlation between the miRNA expression profile and the expression profiles of its target genes typically helps to elucidate the regulatory functions of the miRNA. The interface is also redesigned and enhanced. The miRNAMap 2.0 is now available at http://miRNAMap.mbc.nctu.edu.tw/.
Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase ...(FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung epithelial cells had elevated ligand-induced epidermal growth factor receptor (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell migration, and VHR deficiency resulted in a higher cell migratory ability. VHR-knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting trailing ends and slower turnover of focal adhesions. These collective data indicate that VHR is a FAK phosphatase and participates in regulating the formation and disassembly of focal adhesions.
The recent revision of the Declaration of Helsinki and the existence of many new therapies that affect survival or serious morbidity, and that therefore cannot be denied patients, have generated ...increased interest in active‐control trials, particularly those intended to show equivalence or non‐inferiority to the active‐control. A non‐inferiority hypothesis has historically been formulated in terms of a fixed margin. This margin was historically designed to exclude a ‘clinically meaningful difference’, but has become recognized that the margin must also be no larger than the assured effect of the control in the new study. Depending on how this ‘assured effect’ is determined or estimated, the selected margin may be very small, leading to very large sample sizes, especially when there is an added requirement that a loss of some specified fraction of the assured effect must be ruled out. In cases where it is appropriate, this paper proposes non‐inferiority analyses that do not involve a fixed margin, but can be described as a two confidence interval procedure that compares the 95 per cent two‐sided CI for the difference between the treatment and the control to a confidence interval for the control effect (based on a meta‐analysis of historical data comparing the control to placebo) that is chosen to preserve a study‐wide type I error rate of about 0.025 (similar to the usual standard for a superiority trial) for testing for retention of a prespecified fraction of the control effect. The approach assumes that the estimate of the historical active‐control effect size is applicable in the current study. If there is reason to believe that this effect size is diminished (for example, improved concomitant therapies) the estimate of this historical effect could be reduced appropriately. The statistical methodology for testing this non‐inferiority hypothesis is developed for a hazard ratio (rather than an absolute difference between treatments, because a hazard ratio seems likely to be less population dependent than the absolute difference). In the case of oncology, the hazard ratio is the usual way of comparing treatments with respect to time to event (time to progression or survival) endpoints. The proportional hazards assumption is regarded as reasonable (approximately holding). The testing procedures proposed are conditionally equivalent to two confidence interval procedures that relax the conservatism of two 95 per cent confidence interval testing procedures and preserve the type I error rate at a one‐sided 0.025 level. An application of this methodology to Xeloda, a recently approved drug for the treatment of metastatic colorectal cancers, is illustrated. Other methodologies are also described and assessed – including a point estimate procedure, a Bayesian procedure and two delta‐method confidence interval procedures. Published in 2003 by John Wiley & Sons, Ltd.
Developing effective exercise programmes for the paediatric population is a strategy for decreasing obesity and is expected to help in eventually limiting obesity-associated long-term health and ...societal impact. In this study, the effects of a 12-week twice weekly additional exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises, in additional to typical physical education sessions, on aerobic fitness, body composition and serum C-reactive protein (CRP) and lipids were analysed in 13- to 14-year-old obese boys contrasted with a control group.
Both the exercise group (EG, n = 12) and control group (CG, n = 12) participated in the typical 2 sessions of 40-minute physical education (PE) per week in schools, but only EG participated in additional 2 sessions per week of 45 to 60 minutes per session of exercise training, which comprised a combination of circuit-based resistance training and aerobic exercises maintained at 65% to 85% maximum heart rate (HRmax = 220 - age). Body composition was measured using dual energy X-ray absorptiometry (DEXA). Fasting serum CRP and blood lipids were analysed pre- and postexercise programme. Aerobic fitness was measured by an objective laboratory submaximal exercise test, PWC170 (Predicted Work Capacity at HR 170 bpm).
Exercise training significantly improved lean muscle mass, body mass index, fitness, resting HR, systolic blood pressure and triglycerides in EG. Serum CRP concentrations were elevated at baseline in both groups, but training did not result in a change in CRP levels. In the CG, body weight increased significantly at the end of the 12-week period.
This study supports the value of an additional exercise training programme, beyond the typical twice weekly physical education classes, to produce physiological benefits in the management of obesity in adolescents, including prevention of weight gain.
MK‐7246, an antagonist of the chemoattractant receptor on T helper type 2 (Th2) cells, is being developed for the treatment of respiratory diseases. In a first‐in‐human study, we investigated whether ...genetic polymorphisms contributed to the marked intersubject variability in the pharmacokinetics of MK‐7246 and its glucuronide metabolite M3. Results from in vitro enzyme kinetic studies suggested that UGT2B17 is probably the major enzyme responsible for MK‐7246 metabolism in both the liver and the intestine. As compared with those with the UGT2B17*1/*1 wild‐type genotype, UGT2B17*2/*2 carriers, who possess no UGT2B17 protein, had 25‐ and 82‐fold greater mean dose‐normalized values of area under the plasma concentration–time curve (AUC) and peak concentration of MK‐7246, respectively, and a 24‐fold lower M3‐to‐MK‐7246 AUC ratio. The apparent half‐life of MK‐7246 was not as variable between these two genotypes. Therefore, the highly variable pharmacokinetics of MK‐7246 is attributable primarily to the impact of UGT2B17 genetic polymorphisms and extensive first‐pass metabolism of MK‐7246.
Clinical Pharmacology & Therapeutics (2012); 92 1, 96–102. doi:10.1038/clpt.2012.20
A monolithic passively
-switched Nd:YAG laser under periodic pulse pumping is originally exploited to emulate the response of a single neuron cell stimulated by periodic pulse inputs. Experimental ...results reveal that the output characteristics of the monolithic passively
-switched laser can analogously manifest not only the firing patterns but also the frequency-locked plateaus of the single neuron cell. Moreover, the sine circle map is innovatively used to generate the output pulse sequences that can exactly correspond to experimental firing patterns. The present exploration indicates that a monolithic passively
-switched solid-state laser is highly feasible to be developed as a compact artificial neuron cell.
Whether opioid use in cancer surgery would promote tumor dissemination in humans is inconclusive. We investigated the effect of intraoperative fentanyl dose on colorectal cancer (CRC) prognosis ...following resection in this retrospective study. A total of 1679 patients with stage I-III CRC undergoing tumor resection between January 2011 and December 2014 were evaluated through August 2016. Postoperative recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox regression models. Multivariable Cox regression analysis demonstrated no dose-response association between the amount of fentanyl dose and RFS (adjusted hazard ratio: 1.03, 95% CI: 0.89-1.19) or OS (adjusted hazard ratio: 0.84, 95% CI: 0.64-1.09). Patients were further classified into the high- and low-dose groups by the median of fentanyl dose (3.0 μg·kg
), and there was no significant difference in RFS or OS between groups, either (adjusted hazard ratio: 0.93, 95% CI: 0.74-1.17 for RFS; 0.79, 95% CI: 0.52-1.19 for OS). We concluded that intraoperative fentanyl consumption has no impact on recurrence-free or overall survival in patients after curative CRC resection.
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