The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes

Aims/hypothesis

We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion.

Methods

Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627). A monophasic curve was defined as an increase in OGTT glucose between 30 and 90 min followed by a decline of ≥ 0.25 mmol/l between 90 and 120 min. A biphasic response curve was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 0.25 mmol/l. Associations of type 1 diabetes risk with glucose curve shapes were examined using cumulative incidence curve comparisons and proportional hazards regression. C-peptide responses were compared with and without adjustments for potential confounders.

Results

The majority of participants had a monophasic curve at baseline (n = 1732 [66%] vs n = 895 [34%]). The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). Compared with the biphasic group, the monophasic group had a lower early C-peptide (30–0 min) response, a lower C-peptide index (30–0 min C-peptide/30–0 min glucose), as well as a greater 2 h C-peptide level (p < 0.001 for all).

Conclusions/interpretation

Those with biphasic glucose curves have a lower risk of progression to type 1 diabetes than those with monophasic curves, and the risk among the monophasic group is increased when the glucose peak occurs at 90 min than at 30 min. Differences in glucose curve shapes between the monophasic and biphasic groups appear to be related to C-peptide responses.

     

Influence of <Emphasis Type="Italic">TGFB1</Emphasis>+<Emphasis Type="Italic">869T</Emphasis>>C functional polymorphism in non-small cell lung cancer (NSCLC) risk

Purpose

Lung cancer is the third most common type of cancer in Europe and is the first cause of death by cancer worldwide. Non-small cell lung cancer accounts for 75–85% of all histological types of LC. The transforming growth factor beta 1 is a multifunctional regulatory polypeptide that controls many aspects of cellular function (cellular proliferation, differentiation, migration, apoptosis, immune surveillance). TGFB1+869T>C is a functional polymorphism described in TGFB1 gene and this transition has been associated with higher circulating levels of TGFß1 that may modulate cellular microenvironment and consequently LC development and prognosis.

Methods

We studied TGFB + 869T > C functional polymorphism by allelic discrimination using 7300 real-time polymerase chain reaction system in 305 patients with NSCLC and 380 healthy individuals.

Results

We found an increased risk for C carriers to develop NSCLC, both epidermoid NSCLC and non-epidermoid NSCLC (odds ratio (OR) = 2.03, P < 0.0001, OR = 2.37, P < 0.001 and OR = 1.83, P = 0.001, respectively). TGFB1+869T>C functional polymorphism may influence NSCLC susceptibility with impact in cellular microenvironment.

Conclusions

Our results suggest that individual differences influence the susceptibility to LC and tumoral behavior. This genetic profiling may help define higher risk groups for an individualized chemoprevention strategy and therapy.

     

Disseminated nocardiosis caused by <Emphasis Type="Italic">Nocardia elegans</Emphasis>: a case report and review of the literature

Background

Disseminated nocardiosis is a rare disease mostly occurring in immunocompromised patients.

Methods

We report a case of disseminated nocardiosis in a diabetic patient with both pulmonary and cutaneous involvement. Nocardia elegans was isolated and identified using the 16s ribosomal RNA gene sequence data.

Results

Clinical improvement was observed within 3 months after initiation of antimicrobial treatment with oral doxycycline, trimethoprim-sulfamethoxazole and intravenous penicillin, but the patient died 5 months later after arbitrary discontinuation of the treatment.

Conclusions

This is the first case report of disseminated nocardiosis caused by Nocardia elegans in China.

     

HbA<Subscript>1c</Subscript>, diabetes and cognitive decline: the English Longitudinal Study of Ageing

Aims/hypothesis

The aim of the study was to evaluate longitudinal associations between HbA_1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period.

Methods

Data from wave 2 (2004–2005) to wave 7 (2014–2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3–7. Linear mixed models were used to evaluate longitudinal associations.

Results

The study comprised 5189 participants (55.1% women, mean age 65.6?±?9.4 years) with baseline HbA_1c levels ranging from 15.9 to 126.3 mmol/mol (3.6–13.7%). The mean follow-up duration was 8.1?±?2.8 years and the mean number of cognitive assessments was 4.9?±?1.5. A 1 mmol/mol increment in HbA_1c was significantly associated with an increased rate of decline in global cognitive z scores (?0.0009 SD/year, 95% CI ?0.0014, ?0.0003), memory z scores (?0.0005 SD/year, 95% CI ?0.0009, ?0.0001) and executive function z scores (?0.0008 SD/year, 95% CI ?0.0013, ?0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by ?0.012 SD/year (95% CI ?0.022, ?0.002) and ?0.031 SD/year (95% CI ?0.046, ?0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes.

Conclusions/interpretation

Significant longitudinal associations between HbA_1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.

     

<Emphasis Type="Italic">SLC30A8</Emphasis> polymorphism and BMI complement <Emphasis Type="Italic">HLA-A*24</Emphasis> as risk factors for poor graft function in islet allograft recipients

Aims/hypothesis

HLA-A*24 carriership hampers achievement of insulin independence in islet allograft recipients. However, less than half of those who fail to achieve insulin independence carry the allele. We investigated whether genetic polymorphism at the recipients’ zinc transporter 8-encoding SLC30A8 gene (rs13266634) could complement their HLA-A*24 status in predicting functional graft outcome.

Methods

We retrospectively analysed data of a hospital-based patient cohort followed for 18 months post transplantation. Forty C-peptide-negative type 1 diabetic individuals who received >2 million beta cells (>4000 islet equivalents) per kg body weight in one or two intraportal implantations under similar immunosuppression were genotyped for SLC30A8. Outcome measurements included achievement and maintenance of graft function. Metabolic benefit was defined as <25% CV of fasting glycaemia in the presence of >331 pmol/l C-peptide, in addition to achievement of insulin independence and maintenance of C-peptide positivity.

Results

In multivariate analysis, HLA-A*24 positivity, presence of SLC30A8 CT or TT genotypes and BMI more than or equal to the group median (23.9 kg/m²) were independently associated with failure to achieve insulin independence (p?=?0.015–0.046). The risk increased with the number of factors present (p?<?0.001). High BMI interacted with SLC30A8 T allele carriership to independently predict difficulty in achieving graft function with metabolic benefit (p?=?0.015). Maintenance of C-peptide positivity was mainly associated with older age at the time of implantation. Only HLA-A*24 carriership independently predicted failure to maintain acceptable graft function once achieved (p?=?0.012).

Conclusions/interpretation

HLA-A*24, the SLC30A8 T allele and high BMI are associated with poor graft outcome and should be considered in the interpretation of future transplantation trials.

Trial registration

ClinicalTrials.gov NCT00798785 and NCT00623610

     

Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus

Aims/hypothesis

We aimed to identify circulating microRNA (miRNA) that predicts clinical progression in a cohort of 123 children with new-onset type 1 diabetes mellitus.

Methods

Plasma samples were prospectively obtained at 1, 3, 6, 12 and 60 months after diagnosis from a subset of 40 children from the Danish Remission Phase Cohort, and profiled for miRNAs. At the same time points, meal-stimulated C-peptide and HbA_1c levels were measured and insulin-dose adjusted HbA_1c (IDAA_1c) calculated. miRNAs that at 3 months after diagnosis predicted residual beta cell function and glycaemic control in this subgroup were further validated in the remaining cohort (n?=?83). Statistical analysis of miRNA prediction for disease progression was performed by multiple linear regression analysis adjusted for age and sex.

Results

In the discovery analysis, six miRNAs (hsa-miR-24-3p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-197-3p, hsa-miR-301a-3p and hsa-miR-375) at 3 months correlated with residual beta cell function 6–12 months after diagnosis. Stimulated C-peptide at 12 months was predicted by hsa-miR-197-3p at 3 months (p?=?0.034). A doubling of this miRNA level corresponded to a sixfold higher stimulated C-peptide level. In addition, a doubling of hsa-miR-24-3p and hsa-miR-146a-5p levels at 3 months corresponded to a 4.2% (p?<?0.014) and 3.5% (p?<?0.022) lower IDAA_1c value at 12 months. Analysis of the remaining cohort confirmed the initial finding for hsa-miR-197-3p (p?=?0.018). The target genes for the six miRNAs revealed significant enrichment for pathways related to gonadotropin-releasing hormone receptor and angiogenesis pathways.

Conclusions/interpretation

The miRNA hsa-miR-197-3p at 3 months was the strongest predictor of residual beta cell function 1 year after diagnosis in children with type 1 diabetes mellitus.

     

HbA<Subscript>1c</Subscript> is associated with altered expression in blood of cell cycle- and immune response-related genes

Aims/hypothesis

Individuals with type 2 diabetes are heterogeneous in their glycaemic control as tracked by blood HbA_1c levels. Here, we investigated the extent to which gene expression levels in blood reflect current and future HbA_1c levels.

Methods

HbA_1c levels at baseline and 1 and 2 year follow-up were compared with gene expression levels in 391 individuals with type 2 diabetes from the Hoorn Diabetes Care System Cohort (15,564 genes, RNA sequencing). The functions of associated baseline genes were investigated further using pathway enrichment analysis. Using publicly available data, we investigated whether the genes identified are also associated with HbA_1c in the target tissues, muscle and pancreas.

Results

At baseline, 220 genes (1.4%) were associated with baseline HbA_1c. Identified genes were enriched for cell cycle and complement system activation pathways. The association of 15 genes extended to the target tissues, muscle (n = 113) and pancreatic islets (n = 115). At follow-up, expression of 25 genes (0.16%) associated with 1 year HbA_1c and nine genes (0.06%) with 2 year HbA_1c. Five genes overlapped across all time points, and 18 additional genes between baseline and 1 year follow-up. After adjustment for baseline HbA_1c, the number of significant genes at 1 and 2 years markedly decreased, suggesting that gene expression levels in whole blood reflect the current glycaemic state and but not necessarily the future glycaemic state.

Conclusions/interpretation

HbA_1c levels in individuals with type 2 diabetes are associated with expression levels of genes that link to the cell cycle and complement system activation.

     

Manual Intrapleural Saline Flushing Plus Urokinase: A Potentially Useful Therapy for Complicated Parapneumonic Effusions and Empyemas

Purpose

We sought to evaluate the safety profile and effectiveness of manual pleural saline flushing, in addition to urokinase, for managing complicated parapneumonic effusions and empyemas.

Methods

Retrospective comparative review of 23 consecutive patients with complicated parapneumonic effusions or empyemas who received saline flushing plus urokinase through small-bore chest catheters, and 39 who were only treated with fibrinolytics. Both groups had similar baseline characteristics and treatments were mostly protocol-driven.

Results

As compared with patients only receiving urokinase, those additionally treated with saline flushing needed less fibrinolytic doses (a single dose being sufficient in 15 vs 44%, p = 0.019), chest tube duration (5 vs 2 days, p < 0.01), and length of hospital stay (8 vs 6 days, p = 0.011). There were no adverse events attributed to saline therapy.

Conclusions

Manual pleural saline flushing via chest tube, in addition to urokinase, is a safe and potentially beneficial therapy in patients with pleural infection.

     

Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback

Objective

To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes.

Design

Before–after study.

Setting

National university hospital with 934 beds.

Intervention

Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration.

Methods

The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia.

Results

The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend).

Conclusion

The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.

     

GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis

Aims/hypothesis

GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD?+?alum vaccine in human participants have so far given conflicting results.

Methods

In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine).

Results

We estimate that there is a 98% probability that 20 μg GAD with alum administered twice yields a positive biological effect. The effect is probably a 15–20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between ?0.250 and ?0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of ?0.294 pmol/ml at 1 year for untreated newly diagnosed patients.

Conclusions/interpretation

The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

     

Random non-fasting C-peptide testing can identify patients with insulin-treated type 2 diabetes at high risk of hypoglycaemia

Aims/hypothesis

The aim of this study was to determine whether random non-fasting C-peptide (rCP) measurement can be used to assess hypoglycaemia risk in insulin-treated type 2 diabetes.

Methods

We compared continuous glucose monitoring-assessed SD of blood glucose and hypoglycaemia duration in 17 patients with insulin-treated type 2 diabetes and severe insulin deficiency (rCP < 200 pmol/l) and 17 matched insulin-treated control patients with type 2 diabetes but who had preserved endogenous insulin (rCP > 600 pmol/l). We then assessed the relationship between rCP and questionnaire-based measures of hypoglycaemia in 256 patients with insulin-treated type 2 diabetes and a comparison group of 209 individuals with type 1 diabetes.

Results

Continuous glucose monitoring (CGM)-assessed glucose variability and hypoglycaemia was greater in individuals with rCP < 200 pmol/l despite similar mean glucose. In those with low vs high C-peptide, SD of glucose was 4.2 (95% CI 3.7, 4.6) vs 3.0 (2.6, 3.4) mmol/l (p < 0.001). In the low-C-peptide vs high-C-peptide group, the proportion of individuals experiencing sustained hypoglycaemia ≤ 4 mmol/l was 94% vs 41% (p < 0.001), the mean rate of hypoglycaemia was 5.5 (4.4, 6.7) vs 2.1 (1.4, 2.9) episodes per person per week (p = 0.004) and the mean duration was 630 (619, 643) vs 223 (216, 230) min per person per week (p = 0.01). Hypoglycaemia ≤ 3 mmol/l was infrequent in individuals with preserved C-peptide (1.8 [1.2, 2.6] episodes per person per week vs 0.4 [0.1, 0.8] episodes per person per week for low vs high C-peptide, p = 0.04) and only occurred at night. In a population-based cohort with insulin-treated type 2 diabetes, self-reported hypoglycaemia was twice as frequent in those with rCP < 200 pmol/l (OR 2.0, p < 0.001) and the rate of episodes resulting in loss of consciousness or seizure was five times higher (OR 5.0, p = 0.001). The relationship between self-reported hypoglycaemia and C-peptide was similar in individuals with type 1 and type 2 diabetes.

Conclusions/interpretation

Low rCP is associated with increased glucose variability and hypoglycaemia in patients with insulin-treated type 2 diabetes and represents a practical, stable and inexpensive biomarker for assessment of hypoglycaemia risk.

     

Improved glycaemia in high-fat-fed neprilysin-deficient mice is associated with reduced DPP-4 activity and increased active GLP-1 levels

Aim/hypothesis

Neprilysin, a widely expressed peptidase, is upregulated in metabolically altered states such as obesity and type 2 diabetes. Like dipeptidyl peptidase-4 (DPP-4), neprilysin can degrade and inactivate the insulinotropic peptide glucagon-like peptide-1 (GLP-1). Thus, we investigated whether neprilysin deficiency enhances active GLP-1 levels and improves glycaemia in a mouse model of high fat feeding.

Methods

Nep ^+/+ and Nep ^?/? mice were fed a 60% fat diet for 16 weeks, after which active GLP-1 and DPP-4 activity levels were measured, as were glucose, insulin and C-peptide levels during an OGTT. Insulin sensitivity was assessed using an insulin tolerance test.

Results

High-fat-fed Nep ^?/? mice exhibited elevated active GLP-1 levels (5.8?±?1.1 vs 3.5?±?0.8 pmol/l, p?<?0.05) in association with improved glucose tolerance, insulin sensitivity and beta cell function compared with high-fat-fed Nep ^+/+ mice. In addition, plasma DPP-4 activity was lower in high-fat-fed Nep ^?/? mice (7.4?±?1.0 vs 10.7?±?1.3 nmol ml^?1 min^?1, p?<?0.05). No difference in insulin:C-peptide ratio was observed between Nep ^?/? and Nep ^+/+ mice, suggesting that improved glycaemia does not result from changes in insulin clearance.

Conclusions/interpretation

Under conditions of increased dietary fat, an improved glycaemic status in neprilysin-deficient mice is associated with elevated active GLP-1 levels, reduced plasma DPP-4 activity and improved beta cell function. Thus, neprilysin inhibition may be a novel treatment strategy for type 2 diabetes.

     

Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes

Aims/hypothesis

The aim of this study was to identify genetic variants associated with beta cell function in type 1 diabetes, as measured by serum C-peptide levels, through meta-genome-wide association studies (meta-GWAS).

Methods

We performed a meta-GWAS to combine the results from five studies in type 1 diabetes with cross-sectionally measured stimulated, fasting or random C-peptide levels, including 3479 European participants. The p values across studies were combined, taking into account sample size and direction of effect. We also performed separate meta-GWAS for stimulated (n?=?1303), fasting (n?=?2019) and random (n?=?1497) C-peptide levels.

Results

In the meta-GWAS for stimulated/fasting/random C-peptide levels, a SNP on chromosome 1, rs559047 (Chr1:238753916, T>A, minor allele frequency [MAF] 0.24–0.26), was associated with C-peptide (p?=?4.13?×?10^?8), meeting the genome-wide significance threshold (p?<?5?×?10^?8). In the same meta-GWAS, a locus in the MHC region (rs9260151) was close to the genome-wide significance threshold (Chr6:29911030, C>T, MAF 0.07–0.10, p?=?8.43?×?10^?8). In the stimulated C-peptide meta-GWAS, rs61211515 (Chr6:30100975, T/–, MAF 0.17–0.19) in the MHC region was associated with stimulated C-peptide (β [SE]?=???0.39 [0.07], p?=?9.72?×?10^?8). rs61211515 was also associated with the rate of stimulated C-peptide decline over time in a subset of individuals (n?=?258) with annual repeated measures for up to 6 years (p?=?0.02). In the meta-GWAS of random C-peptide, another MHC region, SNP rs3135002 (Chr6:32668439, C>A, MAF 0.02–0.06), was associated with C-peptide (p?=?3.49?×?10^?8). Conditional analyses suggested that the three identified variants in the MHC region were independent of each other. rs9260151 and rs3135002 have been associated with type 1 diabetes, whereas rs559047 and rs61211515 have not been associated with a risk of developing type 1 diabetes.

Conclusions/interpretation

We identified a locus on chromosome 1 and multiple variants in the MHC region, at least some of which were distinct from type 1 diabetes risk loci, that were associated with C-peptide, suggesting partly non-overlapping mechanisms for the development and progression of type 1 diabetes. These associations need to be validated in independent populations. Further investigations could provide insights into mechanisms of beta cell loss and opportunities to preserve beta cell function.

     

The association between <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity and risk of new-onset diabetes: a prospective cohort study

Aims/hypothesis

Previous studies have suggested a possible connection between Helicobacter pylori (H. pylori) infection and diabetes risk. However, prospective studies examining direct associations between these two factors are relatively lacking. In this prospective cohort study, we aimed to evaluate the association between H. pylori infection and risk of developing diabetes.

Methods

We performed a population-based prospective study, recruiting participants aged 45–74 years and without diabetes from the Chinese Multi-provincial Cohort Study in 2002, with a 10 year follow-up to investigate development of diabetes. H. pylori serostatus was determined by measuring serum H. pylori antibodies. H. pylori seropositivity was defined as the antibody concentration ≥ 10 U/ml. To examine the association between H. pylori seropositivity and diabetes risk, modified Poisson regression was performed.

Results

Of 2085 participants without diabetes, 1208 (57.9%) were H. pylori seropositive in 2002. After multivariate adjustment of possible diabetes risk factors, H. pylori seropositivity was associated with lower risk of diabetes (RR 0.78 [95% CI 0.63, 0.97], p = 0.022). Of the 1275 participants with H. pylori antibody measurements in both 2002 and 2007, 677 (53.1%) were persistently seropositive. A lower risk of diabetes was also observed in participants with persistent H. pylori seropositivity (RR 0.61 [95% CI 0.41, 0.93], p = 0.020), compared with those persistently seronegative.

Conclusions/interpretation

H. pylori seropositivity was associated with lower risk of diabetes in this prospective cohort study. Extrapolation of these results and the mechanism underlying the observed association require further investigation.

     

Acne inversa complicated by <Emphasis Type="Italic">Actinomyces neuii</Emphasis>

Introduction

Acne inversa (AI) is a chronic and recurrent inflammatory skin disease. It occurs in intertriginous areas of the skin and causes pain, drainage, malodor and scar formation. While supposedly caused by an autoimmune reaction, bacterial superinfection is a secondary event in the disease process.

Methods

A unique case of a 43-year-old male patient suffering from a recurring AI lesion in the left axilla was retrospectively analysed.

Results

A swab revealed Actinomyces neuii as the only agent growing in the lesion. The patient was then treated with Amoxicillin/Clavulanic Acid 3 × 1 g until he was cleared for surgical excision. The intraoperative swab was negative for A. neuii. Antibiotics were prescribed for another 4 weeks and the patient has remained relapse free for more than 12 months now.

Conclusion

Primary cutaneous Actinomycosis is a rare entity and the combination of AI and Actinomycosis has never been reported before. Failure to detect superinfections of AI lesions with slow-growing pathogens like Actinomyces spp. might contribute to high recurrence rates after immunosuppressive therapy of AI. The present case underlines the potentially multifactorial pathogenesis of the disease and the importance of considering and treating potential infections before initiating immunosuppressive regimens for AI patients.

     

Teaching Medical Students to Help Patients Quit Smoking: Outcomes of a 10-School Randomized Controlled Trial

Background

Early in medical education, physicians must develop competencies needed for tobacco dependence treatment.

Objective

To assess the effect of a multi-modal tobacco dependence treatment curriculum on medical students’ counseling skills.

Design

A group-randomized controlled trial (2010–2014) included ten U.S. medical schools that were randomized to receive either multi-modal tobacco treatment education (MME) or traditional tobacco treatment education (TE).

Setting/Participants

Students from the classes of 2012 and 2014 at ten medical schools participated. Students from the class of 2012 (N?=?1345) completed objective structured clinical examinations (OSCEs), and 50 % (N?=?660) were randomly selected for pre-intervention evaluation. A total of 72.9 % of eligible students (N?=?1096) from the class of 2014 completed an OSCE and 69.7 % (N?=?1047) completed pre and post surveys.

Interventions

The MME included a Web-based course, a role-play classroom demonstration, and a clerkship booster session. Clerkship preceptors in MME schools participated in an academic detailing module and were encouraged to be role models for third-year students.

Measurements

The primary outcome was student tobacco treatment skills using the 5As measured by an objective structured clinical examination (OSCE) scored on a 33-item behavior checklist. Secondary outcomes were student self-reported skills for performing 5As and pharmacotherapy counseling.

Results

Although the difference was not statistically significant, MME students completed more tobacco counseling behaviors on the OSCE checklist (mean 8.7 [SE 0.6] vs. mean?8.0 [SE 0.6], p?=?0.52) than TE students. Several of the individual Assist and Arrange items were significantly more likely to have been completed by MME students, including suggesting behavioral strategies (11.8 % vs. 4.5 %, p?<?0.001) and providing information regarding quitline (21.0 % vs. 3.8 %, p?<?0.001). MME students reported higher self-efficacy for Assist, Arrange, and Pharmacotherapy counseling items (ps?≤0.05).

Limitations

Inclusion of only ten schools limits generalizability.

Conclusions

Subsequent interventions should incorporate lessons learned from this first randomized controlled trial of a multi-modal longitudinal tobacco treatment curriculum in multiple U.S. medical schools.NIH Trial Registry Number: NCT01905618

     

Associations of <Emphasis Type="Italic">TIM</Emphasis>-<Emphasis Type="Italic">1</Emphasis> Genetic Polymorphisms with Asthma: A Meta-analysis

Purpose

Recently, the roles of TIM-1 genetic polymorphisms in asthma have been extensively studied, with conflicting results. Therefore, we performed the present meta-analysis to better assess potential associations of TIM-1 genetic polymorphisms with asthma.

Methods

Eligible articles were searched in PubMed, Medline, EMBASE, Google Scholar, and CNKI up to December 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between TIM-1 genetic polymorphisms and asthma.

Results

A total of 12 articles including 3120 asthma patients and 2825 control subjects were analyzed. The overall and subgroup analyses revealed that TIM-1-416G>C single nucleotide polymorphism was significantly associated with asthma for the Asian population in the codominant (G/G vs. G/C, p = 0.0003, OR 1.86, 95% CI 1.33–2.60) and dominant (G/G vs. G/C + C/C, p < 0.0001, OR 1.94, 95% CI 1.40–2.69) genetic models. Nevertheless, we failed to detect any significant associations between TIM-1-416G>C single nucleotide polymorphism and asthma in Caucasians. Additionally, according to our analyses, TIM-1 5383_5397 insertion/deletion polymorphism was not correlated with asthma in both Asians and Caucasians.

Conclusions

In conclusion, our findings suggest that TIM-1-416G>C single nucleotide polymorphism is associated with asthma susceptibility for the Asian ethnicity in certain genetic models. However, TIM-1 5383_5397 insertion/deletion polymorphism may not be correlated with the risk of asthma.

     

Overexpression of <Emphasis Type="Italic">LAPTM4B</Emphasis>: an independent prognostic marker in breast cancer

Purpose

Lysosome-associated protein transmembrane 4 beta (LAPTM4B), a novel oncoprotein, has been shown to be overexpressed in several human malignancies. Our purpose was to evaluate the expression of LAPTM4B in breast carcinoma and its significance, which was not previously studied by others.

Methods

Through immunohistochemistry, LAPTM4B expression was evaluated in 35 benign breast tumor specimens and 194 breast cancer specimens. The correlation of LAPTM4B expression with clinicopathological parameters was assessed using χ ² analysis. The survival status of patients was analyzed using the Kaplan–Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors.

Results

The immunohistochemistry results showed that the expression level of LAPTM4B in breast cancer cases was significantly higher than that in benign breast tumor tissues (P < 0.001). Moreover, statistical analysis also showed that high LAPTM4B expression was positively related to TNM stage, lymph node metastasis, and recurrence. Furthermore, it was also shown that patients with high LAPTM4B expression had significantly poorer overall survival and disease-free survival compared with patients with low expression of LAPTM4B (P = 0.019 and P = 0.005, respectively). Multivariate Cox regression analysis revealed that high LAPTM4B expression level was an independent prognostic factor for both overall survival and disease-free survival of patients with breast cancer (P = 0.041 and P = 0.023, respectively).

Conclusions

Overexpression of LAPTM4B may contribute to the tumor progression and poor prognosis of breast cancer, thus testing the expression of LAPTM4B will be helpful for predicting prognosis in breast cancer.