Haemodynamics and flow modification stents for peripheral arterial disease:a review

Endovascular stents are widely used for the treatment of peripheral arterial disease (PAD). However, the development of in-stent restenosis and downstream PAD progression remain a challenge. Stent revascularisation of PAD causes arterial trauma and introduces abnormal haemodynamics, which initiate complicated biological processes detrimental to the arterial wall. The interaction between stent struts and arterial cells in contact, and the blood flow field created in a stented region, are highly affected by stent design. Spiral flow is known as a normal physiologic characteristic of arterial circulation and is believed to prevent the development of flow disturbances. This secondary flow motion is lost in atheromatous disease and its re-introduction after endovascular treatment of PAD has been suggested as a method to induce stabilised and coherent haemodynamics. Stent designs able to generate spiral flow may support endothelial function and therefore increase patency rates. This review is focused on secondary flow phenomena in arteries and the development of flow modification stent technologies for the treatment of PAD

Initial experience with a synthetic sealant PleuraSeal™ after pulmonary resections: a prospective study with retrospective case matched controls

The objective of this study was to evaluate postoperative outcome and efficacy of a hydrogel tissue sealant for prevention of alveolar leakage after open lung resections

Maternal iron deficiency perturbs embryonic cardiovascular development in mice.

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women

Calculating total health service utilisation and costs from routinely collected electronic health records using the example of patients with irritable bowel syndrome before and after their first gastroenterology appointment

INTRODUCTION: Health economic models are increasingly important in funding decisions but most are based on data, which may therefore not represent the general population. We sought to establish the potential of real-world data available within the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) to determine comprehensive healthcare utilisation and costs as input variables for economic modelling. METHODS: A cohort of patients with irritable bowel syndrome (IBS) who first saw a gastroenterologist in 2008 or 2009, and with 3 years of data before and after their appointment, was created in the CPRD. Primary care, outpatient, inpatient, prescription and colonoscopy data were extracted from the linked CPRD and HES. The appropriate cost to the NHS was attached to each event. Total and stratified annual healthcare utilisation rates and costs were calculated before and after the gastroenterology appointment with distribution parameters. Absolute differences were calculated with 95 % confidence intervals. RESULTS: Total annual healthcare costs over 3 years increase by £935 (95 % CI £928–941) following a gastroenterology appointment for IBS. We derived utilisation and cost data with parameter distributions stratified by demographics and time. Women, older patients, smokers and patients with greater comorbidity utilised more healthcare resources, which generated higher costs. CONCLUSIONS: These linked datasets provide comprehensive primary and secondary care data for large numbers of patients, which allows stratification of outcomes. It is possible to derive input parameters appropriate for economic models and their distributions directly from the population of interest

The effect of on-line position correction on the dose distribution in focal radiotherapy for bladder cancer

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to determine the dosimetric effect of on-line position correction for bladder tumor irradiation and to find methods to predict and handle this effect.</p> <p>Methods</p> <p>For 25 patients with unifocal bladder cancer intensity modulated radiotherapy (IMRT) with 5 beams was planned. The requirement for each plan was that 99% of the target volume received 95% of the prescribed dose. Tumor displacements from -2.0 cm to 2.0 cm in each dimension were simulated, using 0.5 cm increments, resulting in 729 simulations per patient. We assumed that on-line correction for the tumor was applied perfectly. We determined the correlation between the change in D_99%and the change in path length, which is defined here as the distance from the skin to the isocenter for each beam. In addition the margin needed to avoid underdosage was determined and the probability that an underdosage occurs in a real treatment was calculated.</p> <p>Results</p> <p>Adjustments for tumor displacement with perfect on-line position correction resulted in an altered dose distribution. The altered fraction dose to the target varied from 91.9% to 100.4% of the prescribed dose. The mean D_99%(± SD) was 95.8% ± 1.0%. There was a modest linear correlation between the difference in D_99%and the change in path length of the beams after correction (R²= 0.590). The median probability that a systematic underdosage occurs in a real treatment was 0.23% (range: 0 - 24.5%). A margin of 2 mm reduced that probability to < 0.001% in all patients.</p> <p>Conclusion</p> <p>On-line position correction does result in an altered target coverage, due to changes in average path length after position correction. An extra margin can be added to prevent underdosage.</p

Reversal of childhood idiopathic scoliosis in an adult, without surgery: a case report and literature review

<p>Abstract</p> <p>Background</p> <p>Some patients with mild or moderate thoracic scoliosis (Cobb angle <50-60 degrees) suffer disproportionate impairment of pulmonary function associated with deformities in the sagittal plane and reduced flexibility of the spine and chest cage. Long-term improvement in the clinical signs and symptoms of childhood onset scoliosis in an adult, without surgical intervention, has not been documented previously.</p> <p>Case presentation</p> <p>A diagnosis of thoracic scoliosis (Cobb angle 45 degrees) with pectus excavatum and thoracic hypokyphosis in a female patient (DOB 9/17/52) was made in June 1964. Immediate spinal fusion was strongly recommended, but the patient elected a daily home exercise program taught during a 6-week period of training by a physical therapist. This regime was carried out through 1992, with daily aerobic exercise added in 1974. The Cobb angle of the primary thoracic curvature remained unchanged. Ongoing clinical symptoms included dyspnea at rest and recurrent respiratory infections. A period of multimodal treatment with clinical monitoring and treatment by an osteopathic physician was initiated when the patient was 40 years old. This included deep tissue massage (1992-1996); outpatient psychological therapy (1992-1993); a daily home exercise program focused on mobilization of the chest wall (1992-2005); and manipulative medicine (1994-1995, 1999-2000). Progressive improvement in chest wall excursion, increased thoracic kyphosis, and resolution of long-standing respiratory symptoms occurred concomitant with a >10 degree decrease in Cobb angle magnitude of the primary thoracic curvature.</p> <p>Conclusion</p> <p>This report documents improved chest wall function and resolution of respiratory symptoms in response to nonsurgical approaches in an adult female, diagnosed at age eleven years with idiopathic scoliosis.</p

Statistical analyses and quality of individual participant data network meta-analyses were suboptimal: a cross-sectional study

Background Network meta-analyses using individual participant data (IPD-NMAs) have been increasingly used to compare the effects of multiple interventions. Although there have been many studies on statistical methods for IPD-NMAs, it is unclear whether there are statistical defects in published IPD-NMAs and whether the reporting of statistical analyses has improved. This study aimed to investigate statistical methods used and assess the reporting and methodological quality of IPD-NMAs. Methods We searched four bibliographic databases to identify published IPD-NMAs. The methodological quality was assessed using AMSTAR-2 and reporting quality assessed based on PRISMA-IPD and PRISMA-NMA. We performed stratified analyses and correlation analyses to explore the factors that might affect quality. Results We identified 21 IPD-NMAs. Only 23.8% of the included IPD-NMAs reported statistical techniques used for missing participant data, 42.9% assessed the consistency, and none assessed the transitivity. None of the included IPD-NMAs reported sources of funding for trials included, only 9.5% stated pre-registration of protocols, and 28.6% assessed the risk of bias in individual studies. For reporting quality, compliance rates were lower than 50.0% for more than half of the items. Less than 15.0% of the IPD-NMAs reported data integrity, presented the network geometry, or clarified risk of bias across studies. IPD-NMAs with statistical or epidemiological authors often better assessed the inconsistency (P = 0.017). IPD-NMAs with a priori protocol were associated with higher reporting quality in terms of search (P = 0.046), data collection process (P = 0.031), and syntheses of results (P = 0.006). Conclusions The reporting of statistical methods and compliance rates of methodological and reporting items of IPD-NMAs were suboptimal. Authors of future IPD-NMAs should address the identified flaws and strictly adhere to methodological and reporting guidelines

A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway

Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-XL overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria