Surface CD3-negative monomorphic epitheliotropic intestinal T-cell lymphoma.

Intestinal T/NK-cell lymphomas include enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), indolent T-cell lymphoproliferative disorders of the GI tract (ITCLPD), extranodal NK/T-cell lymphoma, nasal type (ENKTL), and intestinal T-cell lymphoma NOS (ITCL-NOS). Here we describe a case of surface CD3-negative MEITL. A 63-year-old Japanese female had a tumor located in the conglomerated ileum, which formed multiple mass lesions. The resected tissue showed a diffuse infiltration of monomorphic medium-sized lymphocytes with epitheliotropism. Flowcytometry using a fresh specimen of the tumor revealed positivity for CD7, CD8, CD38, and CD56, but not surface CD3. On immunohistochemistry, the tumor showed positivity for cytoplasmic CD3, CD8, CD56, TIA-1, Granzyme B, and perforin. EBER with in situ hybridization was negative. Moreover, H3K36me3, which is negative in MEITL with SETD2-mutation, was positive. This is an important case of MEITL due to its oncogenesis.

Effects of Exercise Alone or in Combination with High-Protein Diet on Muscle Function, Aerobic Capacity, and Physical Function in Middle-Aged Obese Adults: A Randomized Controlled Trial.

BACKGROUND: Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults. MATERIALS AND METHODS: Sixty-nine middle-aged (50-64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a high-protein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention. RESULTS: After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test). CONCLUSIONS: For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.

Chronic kidney disease-related osteoporosis is associated with incident frailty among patients with diabetic kidney disease: a propensity score-matched cohort study.

Chronic kidney disease (CKD)-related osteoporosis is a major complication in patients with CKD, conferring a higher risk of adverse outcomes. We found that among those with diabetic kidney disease, this complication increased the risk of incident frailty, an important mediator of adverse outcomes. INTRODUCTION: Renal osteodystrophy and chronic kidney disease (CKD)-related osteoporosis increases complications for patients with diabetic kidney disease (DKD). Since musculoskeletal degeneration is central to frailty development, we investigated the relationship between baseline osteoporosis and the subsequent frailty risk in patients with DKD. METHODS: From the Longitudinal Cohort of Diabetes Patients in Taiwan (n = 840,000), we identified 12,027 patients having DKD with osteoporosis and 24,054 propensity score-matched controls having DKD but without osteoporosis. The primary endpoint was incident frailty on the basis of a modified FRAIL scale. Patients were prospectively followed-up until the development of endpoints or the end of this study. The Kaplan-Meier technique and Cox proportional hazard regression were used to analyze the association between osteoporosis at baseline and incident frailty in these patients. RESULTS: The mean age of the DKD patients was 67.2 years, with 55.4% female and a 12.6% prevalence of osteoporosis at baseline. After 3.5 ± 2.2 years of follow up, the incidence rate of frailty in patients having DKD with osteoporosis was higher than that in DKD patients without (6.6 vs. 5.7 per 1000 patient-year, p = 0.04). A Cox proportional hazard regression showed that after accounting for age, gender, obesity, comorbidities, and medications, patients having DKD with osteoporosis had a significantly higher risk of developing frailty (hazard ratio, 1.19; 95% confidence interval, 1.02-1.38) than those without osteoporosis. CONCLUSIONS: CKD-related osteoporosis is associated with a higher risk of incident frailty in patients with DKD.

Sports interest mediating exercise and compulsive internet use among undergraduates.

With the massive growth in Internet technologies, people have become wary of excessive Internet usage, known as compulsive Internet usage or Internet addiction. This study looks into how exercise is related to compulsive Internet usage. Previous research showed varying results regarding the relationship between sports habit and Internet usage; this project clarifies the relationship by investigating mediating variables in terms of interest in different aspects of sports, such as physical education, mastering sport skills, sports participation, and watching sports. Two survey studies were conducted. The participants were 232 male and 107 female Taiwanese undergraduate students in the first survey, totaling 339 students. The second survey had 233 males, 98 female students, and 2 who did not disclose their gender, with a final total of 333. The results reveal that interest in physical education (IPE) mediates sports habit and compulsive Internet usage. As long as the student had a habit of doing sports that increased IPE, this would in turn decrease compulsive Internet use. The importance of igniting students' IPE is discussed.

Superselective endovascular tissue access using trans-vessel wall technique: feasibility study for treatment applications in heart, pancreas and kidney in swine.

OBJECTIVES: With the emergence of targeted cell transplantation and gene therapy, there is a need for minimally invasive tissue access to facilitate delivery of therapeutic substrate. The objective of this study was to demonstrate the suitability of an endovascular device which is able to directly access tissue and deliver therapeutic agent to the heart, kidney and pancreas without need to seal the penetration site. METHODS: In vivo experiments were performed in 30 swine, including subgroups with follow-up to evaluate complications. The previously described trans-vessel wall (VW) device was modified to be sharper and not require tip detachment to seal the VW. Injections into targets in the heart (n = 13, 24-h follow-up n = 5, 72-h follow-up n = 3), kidney (n = 8, 14-day follow-up n = 3) and pancreas (n = 5) were performed. Some animals were used for multiple organ injections. Follow-up consisted of clinical monitoring, angiography and necropsy. Transvenous (in heart) and transarterial approaches (in heart, kidney and pancreas) were used. Injections were targeted towards the subepicardium, endomyocardium, pancreas head and tail, and kidney subcapsular space and cortex. RESULTS: Injections were successful in target organs, visualized by intraparenchymal contrast on fluoroscopy and by necropsy. No serious complications (defined as heart failure or persistent arrhythmia, haemorrhage requiring treatment or acute kidney injury) were encountered over a total of 157 injections. CONCLUSIONS: The trans-VW device can achieve superselective injections to the heart, pancreas and kidney for delivery of therapeutic substances without tip detachment. All parts of these organs including the subepicardium, pancreas tail and renal subcapsular space can be efficiently reached.

Risk of Myocardial Infarction and Ischemic Stroke after Dental Treatments.

The association between invasive dental treatments (IDTs) and a short-term risk of myocardial infarction (MI) and ischemic stroke (IS) remains controversial. Bacterial dissemination from the oral cavity and systemic inflammation linked to IDT can induce a state of acute vascular dysfunction. The aim of study is to investigate the relation of IDTs to MI and IS by using case-only study designs to analyze data from a large Taiwanese cohort. A nationwide population-based study was undertaken by using the case-crossover and self-controlled case series design to analyze the Taiwanese National Health Care Claim database. Conditional logistic regression model and conditional Poisson regression model were used to estimate the risks of MI/IS. In addition, we used burn patients as negative controls to explore the potential effect of residual confounding. In total, 123,819 MI patients and 327,179 IS patients in the case-crossover design and 117,655 MI patients and 298,757 IS patients were included in the self-controlled case series design. Results from both study designs showed that the risk of MI within the first 24 wk after IDT was not significantly different from or close to unity except for a modest risk during the first week for patients without other comorbidities (odds ratios [95% confidence intervals] of 1.31 [1.08-1.58] and 1.15 [1.01-1.31] for 3 d and 7 d, respectively). We also observed no association between IDTs and IS, or the risk ratio was close to unity. IDTs did not appear to be associated with a transient risk of MI and IS in the Taiwanese population, with consistent findings from both case-only study designs. However, we cannot exclude that dental infections and diseases may yield a long-term risk of MI and IS.

Abdominal tuberculosis: a descriptive case series of the experience in a Canadian tuberculosis clinic.

OBJECTIVE: To describe the experience with abdominal tuberculosis (TB), including potential risk factors, presentation, diagnosis, treatment and clinical course, at one Canadian clinic. DESIGN: This was a retrospective case series of all patients with abdominal TB (excluding the genito-urinary system and abdominal muscle) who received care at the Saint Michael's Hospital TB Clinic (Toronto, ON, Canada) from April 2003 to July 2016. RESULTS: Of 590 active TB cases encountered between April 2003 and July 2016, 24 (4.1%) had abdominal TB. All cases were foreign-born, and over 50% occurred among individuals who were not recent immigrants. Background abdominal illnesses and immunocompromised health status were rarely seen. Lymphadenitis (58.3%) and the peritoneum (41.7%) were the most common forms of abdominal TB, bowel involvement was infrequent and most had concomitant extra-abdominal disease (62.5%). All cases were cured, largely using ⩾9 months of pharmacotherapy. Gastrointestinal intolerance and liver dysfunction were rarely observed side effects of therapy. CONCLUSIONS: Several traditional TB risk factors occurred infrequently among our cases, which highlights the importance of having a low threshold for considering abdominal TB in the appropriate clinical setting. Although abdominal TB often occurred in the context of disseminated disease, cure was achievable, but ⩾9 months of treatment may generally be needed.

Preadmission statin use improves the outcome of less severe sepsis patients - a population-based propensity score matched cohort study.

BACKGROUND: Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied. METHODS: We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications. RESULTS: We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78-0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78-0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission. CONCLUSIONS: In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.

Functional links between Disabled-2 Ser723 phosphorylation and thrombin signaling in human platelets.

Essentials Disabled-2 (Dab2) phosphorylation status in thrombin signaling of human platelet was investigated. Ser723 was the major Dab2 phosphorylation site in human platelets stimulated by thrombin. Dab2 S723 phosphorylation (pS723) caused the dissociation of Dab2-CIN85 protein complex. Dab2-pS723 regulated ADP release and integrin αIIbß3 activation in thrombin-treated platelets. SUMMARY: Background Disabled-2 (Dab2) is a platelet protein that is functionally involved in thrombin signaling in mice. It is unknown whether or not Dab2 undergoes phosphorylation during human platelet activation. Objectives To investigate the phosphorylation status of Dab2 and its functional consequences in thrombin-stimulated human platelets. Methods Dab2 was immunoprecipitated from resting and thrombin-stimulated platelet lysates for differential isotopic labeling. After enrichment of the phosphopeptides, the phosphorylation sites were analyzed by mass spectrometry. The corresponding phospho-specific antibody was generated. The protein kinases responsible for and the functional significance of Dab2 phosphorylation were defined by the use of signaling pathway inhibitors/activators, protein kinase assays, and various molecular approaches. Results Dab2 was phosphorylated at Ser227, Ser394, Ser401 and Ser723 in thrombin-stimulated platelets, with Ser723 phosphorylation being the most significantly increased by thrombin. Dab2 was phosphorylated by protein kinase C at Ser723 in a Gαq -dependent manner. ADP released from the stimulated platelets further activated the Gßγ -dependent pathway to sustain Ser723 phosphorylation. The Cbl-interacting protein of 85 kDa (CIN85) bound to Dab2 at a motif adjacent to Ser723 in resting platelets. The consequence of Ser723 phosphorylation was the dissociation of CIN85 from the Dab2-CIN85 complex. These molecular events led to increases in fibrinogen binding and platelet aggregation in thrombin-stimulated platelets by regulating αIIb ß3 activation and ADP release. Conclusions Dab2 Ser723 phosphorylation is a key molecular event in thrombin-stimulated inside-out signaling and platelet activation, contributing to a new function of Dab2 in thrombin signaling.

Effect of Liquid Feed-Stock Composition on the Morphology of Titanium Dioxide Films Deposited by Thermal Plasma Spray.

Titanium dioxide coatings were deposited on the surface of titanium foils by Thermal Plasma Spray (TPS) process. Three different TiO2 coatings were prepared using the commercial TiO2-P25 nanopowder and titanium isopropoxide precursor solution as feed-stocks. Structure and morphology of the TiO2-P25 powder and the plasma sprayed coatings were analyzed by X-ray diffraction (XRD), Raman spectroscopy, N2 adsorption-desorption isotherms, UV-visible spectroscopy and Scanning Electron Microscopy (SEM). XRD and Raman results indicate that the TiO2 coatings were composed of an anatase/rutile mixture that is conditioned by the suspension composition used to be sprayed. Coatings prepared from TiO2-P25 nanoparticles in water suspension (NW-P25) and titanium isopropoxide solution suspension (NSP-P25) are incorporated into the coatings without phase transformation and their anatase/rutile ratio percentage remains very similar to the starting TiO2-P25 powder. On the contrary, when titanium isopropoxide solution is used for spraying (SP), the amount of rutile increases in the final TiO2 coating. SEM analysis also reveals different microstructure morphology, coating thickness, density and porosity of the three TiO2 films that depend significantly on the type of feed-stock employed. Interestingly, we have observed the role of titanium isopropoxide in the formation of more porous and cohesive layers of TiO2. The NSP-P25 coating, prepared with a mix of titanium isopropoxide solution based on TiO2 nanoparticles, presents higher deposition efficiencies and higher coating thickness than the film prepared with nanoparticles suspended in water (NW-P25) or with titanium isopropoxide solutions (SP). This is due to the precursor solution is acting as the cement between TiO2 nanoparticles, improving the cohesive strength of the coating. In sum, NSP-P25 and NW-P25 coatings display a good photocatalytic potential, based on their light absorption properties and mechanical stability. Band gap of the nanoparticulated coatings displays a light absorption at wavelengths below 379 and 399 nm for NW-P25 and NSP-P25 respectively. On the contrary, the SP coating, despite to present lower band-gap value, has bad cohesive properties with surface crackings that makes it mechanically unstable. Therefore, mixtures of P25 nanoparticles with titanium isopropoxide as feed-stock materials can produce promising photocatalytic coatings.

Fentanyl-induced cough is a risk factor for postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) and fentanyl-induced cough (FIC) are two common anaesthesia-related events, which seem to have common risk factors. In this prospective cohort study, we investigate whether patients who have FIC during induction of anaesthesia have an increased incidence of PONV. METHODS: We studied adult non-smoking gynaecological surgical patients enrolled between July 1, 2011 and July 30, 2012. The presence of FIC during induction and the occurrence of PONV were recorded. Fentanyl-induced cough and other perioperative variables were subjected to multivariate analysis to determine the association between FIC and PONV. RESULTS: All 502 patients enrolled in this study had at least two risk factors for PONV, and 154 (31%) developed FIC. The incidence of PONV in the FIC group was higher than in the non-FIC group (56.5 vs 38.2%; P<0.0001). Multivariate logistic regression analysis found FIC to be a predictive risk factor for the development of PONV (adjusted odds ratio 2.08, 95% confidence interval 1.41-3.07). CONCLUSIONS: Non-smoking women undergoing gynaecological surgery who develop FIC during induction of anaesthesia have a higher incidence of PONV.

Responses of blood pressure and lactate levels to various aquatic exercise movements in postmenopausal women.

AIM: Middle-aged and elderly women represent the main attending group in head-out aquatic exercise (HOAE). Blood pressure (BP) significantly increases both during water immersion and aquatic walking. Based on risk concerns, it is important to evaluate BP responses in postmenopausal women doing HOAE. The aim of this study was to determine BP, lactate levels, and rating of perceived exertion (RPE) changes associated with performing 3 different movements at 3 levels of exercise intensity in water. METHODS: Twelve postmenopausal women (59.9±0.6 years old) participated in 3 aquatic trials involving running (RU), rocking (RO), and scissor kicks (SK) on separate days. Systolic BP, mean arterial pressure (MAP), lactate levels, RPE, and motion cadence were measured at rest; upon reaching 50%, 65%, and 80% of heart rate reserve for 6 minutes; and 10 and 30 minutes after exercise. RESULTS: Under similar RPE responses at 3 levels of intensity, SK resulted in higher systolic BP, MAP, and lactate levels than RO at 10 minutes after exercise (P<0.05) and the lowest motion cadence (P<0.05). RO resulted in the lowest MAP and diastolic BP responses during exercise (P<0.05). RU resulted in lower responses of lactate levels at high exercise intensity (P<0.05). CONCLUSION: RO resulted in lower diastolic BP and MAP responses compared with RU and SK during exercise. These findings suggest that RO movement in aquatic exercises is more suitable for people at high risk for cardiovascular disease.

Anaphylactic responses to histamine in mice utilize both histamine receptors 1 and 2.

BACKGROUND: Anaphylaxis is a severe, potentially life-threatening reaction that can occur in response to common triggers, including food allergens (e.g., peanut), insect stings, and several medications. Activation of mast cells and basophils to release preformed mediators, such as histamine, is thought to be an important process that underlies reactions. Histamine can exert effects through four different receptors, termed H1R-H4R. Despite clinical use of both H1R and H2R blockers in the therapy for acute allergic reactions, there is little mechanistic evidence to support the necessity for blocking H2R, a receptor best characterized for its role in stomach acid production. METHODS: Here, we sought to define the necessity for histamine receptors in the pathology of anaphylaxis using H1R and H2R knockout (KO) mice, as well as a H1R/H2R double KO strain. RESULTS: In response to IgE-mediated systemic anaphylaxis, the symptoms and decreases in core body temperature observed in wild-type mice were reduced but not ablated in either H1R or H2R KO. In contrast, H1R/H2R KO were significantly protected and were indistinguishable from histamine-deficient mice. Intravenous injection of histamine was sufficient to elicit these responses, and similar to IgE-mediated anaphylaxis, loss of both H1R and H2R was necessary for complete protection. CONCLUSION: Our data demonstrate definitively that both H1R and H2R participate in the immediate systemic responses during histamine-associated pathophysiology and mechanistically support the utility of H2R-blocking therapeutics in alleviating symptoms of anaphylaxis.

Correlation between microRNA-34a levels and lens opacity severity in age-related cataracts.

PURPOSE: MicroRNA 34a (miR-34a) is involved in regulating tissue senescence. However, the role of miR-34a in age-related cataracts is unclear. In this study, we evaluated the correlations among the severity of lens opacity, patient age, and miR-34a expression level in the lens epithelium of age-related cataracts for clarifying the role of miR-34a in the lens senescence. METHODS: This study was carried as a case control study in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan. We recorded age of each patient at the time of their cataract surgery and information regarding lens opacity according to a modified version of the Lens Opacities Classification System III. Correlations among age, lens opacity, and miR-34a expression levels were evaluated. RESULTS: This study evaluated 110 patients with a mean age of 73.19 years (SD±10.2). Older patients had higher nuclear cataract (NC), cortical (C), and posterior subcapsular cataract (P) scores (one-way analysis of variance (ANOVA), P<0.05). miR-34a expression levels were significantly different between each age group (ANOVA post hoc Bonferroni's test, P<0.001), and there were moderate correlations between high NC, C, and P cataract scores and high miR-34a levels (Pearson correlation coefficient; R=0.606, 0.575, and 0.515, respectively). CONCLUSIONS: The current study demonstrated positive correlations between high miR-34a levels and high lens opacity severity in NC, C, or P cataracts. These results suggest that miR-34a expression has a role in lens senescence.

Photofrin binds to procaspase-3 and mediates photodynamic treatment-triggered methionine oxidation and inactivation of procaspase-3.

Diverse death phenotypes of cancer cells can be induced by Photofrin-mediated photodynamic therapy (PDT), which has a decisive role in eliciting a tumor-specific immunity for long-term tumor control. However, the mechanism(s) underlying this diversity remain elusive. Caspase-3 is a critical factor in determining cell death phenotypes in many physiological settings. Here, we report that Photofrin-PDT can modify and inactivate procaspase-3 in cancer cells. In cells exposed to an external apoptotic trigger, high-dose Photofrin-PDT pretreatment blocked the proteolytic activation of procaspase-3 by its upstream caspase. We generated and purified recombinant procaspase-3-D(3)A (a mutant without autolysis/autoactivation activity) to explore the underlying mechanism(s). Photofrin could bind directly to procaspase-3-D(3)A, and Photofrin-PDT-triggered inactivation and modification of procaspase-3-D(3)A was seen in vitro. Mass spectrometry-based quantitative analysis for post-translational modifications using both (16)O/(18)O- and (14)N/(15)N-labeling strategies revealed that Photofrin-PDT triggered a significant oxidation of procaspase-3-D(3)A (mainly on Met-27, -39 and -44) in a Photofrin dose-dependent manner, whereas the active site Cys-163 remained largely unmodified. Site-directed mutagenesis experiments further showed that Met-44 has an important role in procaspase-3 activation. Collectively, our results reveal that Met oxidation is a novel mechanism for the Photofrin-PDT-mediated inactivation of procaspase-3, potentially explaining at least some of the complicated cell death phenotypes triggered by PDT.

(G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD.

(G2019S) mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Twelve- to sixteen-month-old (G2019S) LRRK2 transgenic mice prepared by us displayed progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurons and parkinsonism phenotypes of motor dysfunction. LRRK2 is a member of mixed lineage kinase subfamily of mitogen-activated protein kinase kinase kinases (MAPKKKs). We hypothesized that (G2019S) mutation augmented LRRK2 kinase activity, leading to overphosphorylation of downstream MAPK kinase (MKK) and resulting in activation of neuronal death signal pathway. Consistent with our hypothesis, (G2019S) LRRK2 expressed in HEK 293 cells exhibited an augmented kinase activity of phosphorylating MAPK kinase 4 (MKK4) at Ser(257), and protein expression of active phospho-MKK4(Ser257) was upregulated in the SN of (G2019S) LRRK2 transgenic mice. Protein level of active phospho-JNK(Thr183/Tyr185) and phospho-c-Jun(Ser63), downstream targets of phospho-MKK4(Ser257), was increased in the SN of (G2019S) LRRK2 mice. Upregulated mRNA expression of pro-apoptotic Bim and FasL, target genes of phospho-c-Jun(Ser63), and formation of active caspase-9, caspase-8 and caspase-3 were also observed in the SN of (G2019S) LRRK2 transgenic mice. Our results suggest that mutant (G2019S) LRRK2 activates MKK4-JNK-c-Jun pathway in the SN and causes the resulting degeneration of SNpc dopaminergic neurons in PD transgenic mice.

Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis.

AIM: Most guidelines recommend metformin as first-line therapy in patients with type 2 diabetes. However, the choice of a second-line drug lacks consistent consensus. We aimed to assess available information of antidiabetic drugs added to metformin on the change in glycated haemoglobin A1c (A1C), risk of hypoglycaemia and change in body weight. METHODS: PubMed and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) written in English through December 2011. We analysed direct and indirect comparisons of different treatments using Bayesian network meta-analysis. RESULTS: Thirty-nine RCTs involving 17 860 individuals were included. Glucagon-like peptide-1 (GLP-1) analogues resulted in greater decrease in A1C compared with sulfonylureas, glinides, thiazolidinediones, α-glucosidase inhibitors and DPP-4 inhibitors [-0.20% (95% CI -0.34 to -0.04%), -0.31% (95% CI -0.61 to -0.02%), -0.20% (95% CI -0.38 to -0.00), -0.36% (95% CI -0.64 to -0.07%), -0.32% (95% CI -0.47 to -0.17%), respectively] and was comparable with basal insulin and biphasic insulin. A1C decrease was greater for sulfonylureas compared with DPP-4 inhibitors [-0.12% (-0.23 to -0.03%)], and for biphasic insulin compared with glinides (-0.36%; 95% CI -0.82 to -0.11%). Compared with placebo, the risk of hypoglycaemia was increased in the sulfonylureas, glinides, basal insulin and biphasic insulin. Weight increase was seen with sulfonylureas, glinides, thiazolidinediones, basal insulin and biphasic insulin, and weight loss was seen with α-glucosidase inhibitors and GLP-1 analogues. CONCLUSIONS: Biphasic insulin, GLP-1 analogues and basal insulin were ranked the top three drugs in terms of A1C reduction. GLP-1 analogues did not increase the risk of hypoglycaemia and resulted in a significant decrease in body weight. Most oral antidiabetic drugs had similar effects on A1C, but some agents had a lower risk of hypoglycaemia and body weight gain.

Relationship of initial glucose level and all-cause death in patients with ischaemic stroke: the roles of diabetes mellitus and glycated hemoglobin level.

BACKGROUND AND PURPOSE: Previous studies demonstrated that post-stroke hyperglycemia was associated with poor outcome in non-diabetic patients. However, evidence was inconclusive amongst patients with diabetes. The aim of this study was to evaluate the relationship between initial glucose levels and mortality amongst patients with acute ischaemic stroke, and further, to assess whether the association varied by diabetes mellitus and glycated hemoglobin (HbA(1c) ) levels. METHODS: Data were collected from the medical records of 1277 first-ever stroke patients admitted to the emergency room between January 1, 2008 and June 30, 2009. Cox regression analysis was performed to assess the relationship between initial glucose level and mortality. RESULTS: Compared with the lowest quartile of initial glucose level, a significant association with all-cause death [hazard ratio (HR), 2.18; 95% CI, 1.36-3.48] and cardiovascular death (HR, 1.91; 95% CI, 1.01-3.61) was seen in the highest quartile. In non-diabetic subgroup, those patients within the highest quartile of initial glucose level had a 3.29-fold relative risks (RR) [95% confidence interval (CI), 1.62-6.68] for all-cause and a 2.54-fold RR (95% CI, 1.43-8.77) for cardiovascular death compared with those within the lowest quartile. However, the association between initial glucose levels and the risk of death was not significant amongst those with diabetes (P for interaction = 0.01). In addition, the risk amongst patients with diabetes varied by the HbA(1c) levels. CONCLUSIONS: A significant association was confirmed between initial glucose level and mortality in non-diabetic ischaemic stroke patients. The possible relationship between initial glucose level, HbA(1c) level, and mortality amongst ischaemic stroke patients with diabetes warrants further research.

[CT imaging of chronic interstitial lung diseases: from diagnosis to automated quantification]. / Imagerie des pneumopathies infiltratives diffuses chroniques en tomodensitométrie : du diagnostic à la quantification automatisée.

Computed tomography is important for the diagnosis and follow-up of chronic diffuse interstitial lung diseases. Image quality has improved from each generation of scanner to the next and this continues to allow a better characterization of extent of pathology, or even the nature of the pathological process (potentially reversible inflammatory lesions compared to fibrotic lesions). The diagnostic imaging approach has evolved at the same time as technological developments. We initially thought in terms of the predominant lesions (nodular, alveolar consolidation, ground-glass opacity), and then moved to reasoning based on patterns, which are a combination of several elementary lesions (typically for the diagnosis of idiopathic pulmonary fibrosis). Nowadays, studies are focused on building models characterizing a specific disease and which combine several distinct patterns (typically for ground-glass opacity analysis). CT also allows a quantification of the extent of lung disease, which is linked to the prognosis of the disease and helps to monitor its progression. This quantification is usually based on visual criteria, the principles of which are summarized here. The development of automated quantification software could in the near future, be a support for the radiologist.