Coated-platelet levels in patients with Type 1 and with Type 2 diabetes mellitus

Coated-platelet levels were quantified in 58 people with Type 1 diabetes, 90 with Type 2 diabetes, and 54 non-diabetic controls. In diabetes high coated-platelet levels were related to smoking and glucose control drugs, but not to glycaemia or other drugs. Prospective studies should evaluate coated-platelets and complications and drug effects.

Predicting the need for insulin therapy in late onset (40-69 years) diabetes mellitus

A six-year prospective study of 144 newly diagnosed, symptomatic diabetic patients aged 40-69 years showed that 21 (15%) required insulin therapy, commencing 1-61 months after diagnosis. The plasma insulin response to oral glucose was assessed at the time of diagnosis. All 12 patients with very low peak insulin response (less than or equal to 6 mU/l) required insulin therapy. Thirty-six patients had an intermediate insulin response (greater than 6 less than or equal to 18 mU/l); of these, 7 with a mean weight 88% (range 73-96%) of average body weight required insulin, while 29 with a mean weight 117% (range 98-158%) of average body weight, did not. Ninety-six patients had a peak insulin response (greater than 18 mU/l); 2 patients whose weights were 96% and 100% of average body weight, required insulin, while the remainder did not. Consideration of initial body weight and peak insulin response provides a useful prediction of the eventual need for insulin.

Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction--a randomised placebo-controlled trial (KARE):study protocol

Acute lung injury is a common, devastating clinical syndrome associated with substantial mortality and morbidity with currently no proven therapeutic interventional strategy to improve patient outcomes. The objectives of this study are to test the potential therapeutic effects of keratinocyte growth factor for patients with acute lung injury on oxygenation and biological indicators of acute inflammation, lung epithelial and endothelial function, protease:antiprotease balance, and lung extracellular matrix degradation and turnover.

The relationship between breastfeeding and postpartum weight change-a systematic review and critical evaluation

Pregnancy and the postpartum period is a time of increased vulnerability for retention of excess body fat in women. Breastfeeding (BF) has been shown to have many health benefits for both mother and baby; however, its role in postpartum weight management is unclear. Our aim was to systematically review and critically appraise the literature published to date in relation to the impact of BF on postpartum weight change, weight retention and maternal body composition. Electronic literature searches were carried out using MEDLINE, EMBASE, PubMed, Web of Science, BIOSIS, CINAHL and British Nursing Index. The search covered publications up to 12 June 2012 and included observational studies (prospective and retrospective) carried out in BF mothers (either exclusively or as a subgroup), who were 2 years postpartum and with a body mass index (BMI) >18.5 kg m(-2), with an outcome measure of change in weight (including weight retention) and/or body composition. Thirty-seven prospective studies and eight retrospective studies were identified that met the selection criteria; studies were stratified according to study design and outcome measure. Overall, studies were heterogeneous, particularly in relation to sample size, measurement time points and in the classification of BF and postpartum weight change. The majority of studies reported little or no association between BF and weight change (n=27, 63%) or change in body composition (n=16, 89%), although this seemed to depend on the measurement time points and BF intensity. However, of the five studies that were considered to be of high methodological quality, four studies demonstrated a positive association between BF and weight change. This systematic review highlights the difficulties of examining the association between BF and weight management in observational research. Although the available evidence challenges the widely held belief that BF promotes weight loss, more robust studies are needed to reliably assess the impact of BF on postpartum weight management.International Journal of Obesity advance online publication, 20 August 2013; doi:10.1038/ijo.2013.132.

PET-CT as a predictor of outcome in resectable colorectal liver metastases

Introduction
PET-computed tomography (PET-CT) is a useful staging imaging modality in colorectal liver metastases (CRLM). This study aimed to determine whether PET-CT parameters, standardized uptake value (SUV) and reconstructed tumour volume (RTV), are predictors of prognosis and survival.

Methods
A study of all resectable CRLM patients in the regional HPB unit from 2007–2009 was performed. Preoperative PET-CT scans were retrospectively reviewed; SUV, diameter and RTV for each lesion was recorded. Correlation analysis was performed with other pathological and biochemical parameters, by Pearson’s correlation analysis. Survival analysis was performed using Cox regression hazard model. A P value of less than 0.05 was considered statistically significant.

Results
A total of 79 patients were included. SUV moderately correlated with tumour diameter, both PET-CT (r=0.4927; P<0.0001) and histology (r=0.4513; P=0.0003); RTV (r=0.4489; P<0.001), preoperative carcinoembryonic antigen (CEA) (r=0.4977; P=0.0001), and postoperative CEA (r=0.3727; P=0.004). Multivariate analysis found that an independent predictor of SUVmax was preoperative CEA (P=0.03). RTV strongly correlated with preoperative CEA (r=0.9389; P<0.0001). SUV and RTV had a negative effect on survival.

Conclusion
PET-CT, in the setting of CRLM, may have a prognostic role in assessing survival. Although no definite conclusions can be drawn regarding the prognostic role of SUV and RTV, it acts to reinforce the need for further prospective studies to validate these findings.

Multiple Biomarkers for the prediction of ischemic stroke: the PRIME study

Objective: To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke, including biomarkers of hemostasis, inflammation, and endothelial activation as well as chemokines and adipocytokines.
Methods and Results: The Prospective Epidemiological Study on Myocardial Infarction (PRIME) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years. In a nested case–control study, 95 ischemic stroke cases were matched with 190 controls. After multivariable adjustment for traditional risk factors, fibrinogen (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03–2.28), E-selectin (OR, 1.76; 95% CI, 1.06–2.93), interferon-γ-inducible-protein-10 (OR, 1.72; 95% CI, 1.06–2.78), resistin (OR, 2.86; 95% CI, 1.30–6.27), and total adiponectin (OR, 1.82; 95% CI, 1.04–3.19) were significantly associated with ischemic stroke. Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 (95% CI, 0.612–0.745) to 0.785 and 0.788, respectively, and yielded a categorical net reclassification improvement of 29.9% (P=0.001) and 28.4% (P=0.002), respectively. Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 (95% CI, 0.770–0.877) and resulted in an net reclassification improvement of 41.4% (P<0.001). Results were confirmed when using continuous net reclassification improvement.
Conclusion: Among multiple biomarkers from distinct biological pathways, E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke.

Periodontal systemic associations: review of the evidence

Aim: To critically appraise recent research into associations between periodontal disease and systemic diseases and conditions specifically respiratory disease, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer.

Methods: A MEDLINE literature search of papers published between 2002 and April 2012 was conducted. Studies that included periodontitis as an exposure were identified. Cross-sectional epidemiological investigations on large samples, prospective studies and systematic reviews formed the basis of the narrative review. A threshold set for the identification of periodontitis was used to identify those studies that contributed to the conclusions of the review.

Results: Many of the investigations were cross-sectional secondary analyses of existing data sets in particular the NHANES studies. There were a small number of systematic reviews and prospective studies. There was substantial variability in the definitions of exposure to periodontitis. A small number of studies met the threshold set for periodontitis and supported associations; however, in some of the chronic diseases there were no such studies. There was strong evidence from randomized controlled trials that interventions, which improve oral hygiene have positive effects on the prevention of nosocomial pneumonias.

Conclusions: There was substantial heterogeneity in the definitions used to identify periodontitis and very few studies met a stringent threshold for periodontitis. Published evidence supports modest associations between periodontitis and some, although not all, of the diseases and conditions reviewed. There is a need to reach a consensus on what constitutes periodontitis for future studies of putative associations with systemic diseases.

Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection

Background: Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection. Methods: Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the “gold standard” for the diagnosis of infection. Results: The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75). Conclusions: The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment

Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor alpha (TNF-alpha) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.

Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-gamma-secreting Th1 cells and IFN-alpha-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.

Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL23 antibody therapy is a highly effective therapy for these lesions.

Family-based associations in measures of psychological distress and quality of life in a cardiac screening clinic for inheritable cardiac diseases: a cross-sectional study

BACKGROUND: Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic.

METHODS: Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data.

RESULTS: There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance.

CONCLUSIONS: High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

Genomovar diversity amongst Burkholderia cepacia complex isolates from an Australian adult cystic fibrosis unit

In this study, a combination of recA-based PCR assays and 16S rDNA restriction fragment length polymorphism (RFLP) analysis was used to determine the genomovar diversity of clinical Burkholderia cepacia complex isolates. Twenty-eight isolates were prospectively collected from patients attending a large Australian adult cystic fibrosis (CF) unit, 22 isolates were referred from other Australian CF units and a further eight isolates originated from patients without CF. The 28 prospectively collected isolates were distributed amongst the following genomovars: Burkholderia cepacia genomovar I (28.6%), Burkholderia multivorans (21.4%), Burkholderia cepacia genomovar III (39.3%), Burkholderia vietnamiensis(3.6%) and Burkholderia ambifaria (7.1%). The results of this study highlight the usefulness of 16S rDNA RFLP typing for the identification of other Burkholderia spp. and non-fermenting gram-negative bacteria.

A study of patient attitudes towards fasting prior to intravenous sedation for dental treatment in a dental hospital department

INTRODUCTION: Intravenous sedation is the most commonly used method of sedation for the provision of adult dental care. However, disparity exists in pre-operative fasting times in use for patients throughout the United Kingdom.

AIMS: The aims of the study were to obtain information on the effects of existing extended pre-operative fasting regimens, to canvas patient opinions on the fasting process, and to record their positive and negative experiences associated with it.

METHODS: A prospective cross-sectional descriptive study using survey methodology was conducted of adult patients attending a dental hospital for operative treatment under intravenous sedation. Sixty-four questionnaires were distributed over a four-month period, beginning 2nd October 2007.

RESULTS: The surveyed patient pool consisted of 38 females and 14 males with a mean age of 32.4 years. The response rate achieved was 81.2%. Seventy-one per cent of patients indicated that normally they consumed something for breakfast, the most common items being tea and toast. Fifty-one per cent of patients indicated that they would wish to eat the same as normal prior to their appointment and 59% wished to drink as normal. Only 19% of respondents reported that they did not wish to eat anything, with 8% preferring not to drink anything at all. Seventy-nine per cent of the patients reported that they had experienced at least one adverse symptom after fasting and 42% had experienced two or more such symptoms. In general, those patients with more experience of sedation found fasting less unpleasant than those attending for the first time (P<0.05). In addition, one-quarter of all patients indicated that the fasting process had made them feel more nervous about their sedation appointment.

CONCLUSIONS: The extended fasting regimen prior to intravenous sedation appeared to affect patients' wellbeing, as the majority reported adverse symptoms.

β-Blocker usage and colorectal cancer mortality:a nested case-control study in the UK Clinical Practice Research Datalink cohort

BACKGROUND: Epidemiological and laboratory studies suggest that β-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic β-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort.

PATIENTS AND METHODS: A nested case-control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to β-blocker usage (data from GP-prescribing records).

RESULTS: Post-diagnostic β-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78-1.02). Similar associations were found when analysing drug frequency, β-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in β-blocker users (adjusted OR = 0.88; 95% CI 0.77-1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40-0.97; P = 0.04).

CONCLUSIONS: In this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic β-blocker use and colorectal cancer-specific mortality.

CLINICAL TRIALS NUMBER: NCT00888797.

Predictive Factors for Local Control in Primary and Metastatic Lung Tumours after Four to Five Fraction Stereotactic Ablative Body Radiotherapy: A Single Institution's Comprehensive Experience

AIMS: We report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control.

MATERIALS AND METHODS: In total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60 Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses.

RESULTS: Of the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control.

CONCLUSIONS: Lung SABR of 48-60 Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.

Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches

In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.