Metabolic syndrome is an independent predictor of cardiovascular events in high-risk patients with occlusive and aneurysmatic peripheral arterial disease

Objective

Metabolic syndrome (MetSyn) is a well-known risk factor for cardiovascular (CV) disease in the general population; however, the additional predictive value for CV events in high-risk patients with peripheral arterial disease (PAD) is unknown. The aims of the current study were to assess and compare: (1) prevalence of MetSyn, and (2) predictive value of MetSyn for CV events, in patients with either occlusive or aneurysmatic PAD.

Methods

We screened 2069 patients scheduled for lower occlusive arterial revascularization (n = 1031) or abdominal aortic aneurysm repair (n = 1038) for the presence of MetSyn. Adult Treatment Panel III report (ATP III) was used for defining MetSyn. Central obesity was defined as body-mass-index >30 kg/m². Main outcomes were the occurrence of CV events and CV mortality during a median follow-up of 6 years (IQR 2–9 years).

Results

Metabolic syndrome was diagnosed in 421 (41%) and 432 (42%) patients with occlusive and aneurysmatic PAD, respectively (p = 0.72). Patients with occlusive or aneurysmatic PAD and MetSyn had an increased risk for the development of CV events, when compared to patients without MetSyn (27% vs. 18% and 27% vs. 19%, p < 0.001, respectively). In occlusive and aneurysmatic PAD, MetSyn was independently associated with an increased risk of CV events (HR = 1.6; 95%CI 1.2–2.1 and HR = 1.4; 95%CI 1.1–1.8). No significant association between the presence of MetSyn and CV mortality was observed.

Conclusions

Metabolic syndrome is highly prevalent in high-risk PAD patients. In occlusive and aneurysmatic PAD patients, MetSyn is an independent predictor of long-term CV events.     

The accuracy of multivariate models predicting ovarian reserve and pregnancy after in vitro fertilization: a meta-analysis

BACKGROUND: To review the accuracy of multivariate models for the predictionof ovarian reserve and pregnancy in women undergoing IVF comparedwith the antral follicle count (AFC) as single test. METHODS: We performed a computerized MEDLINE and EMBASE search to identifyarticles published on multivariate models for ovarian reservetesting in patients undergoing IVF. In order to be selected,articles had to contain data on the outcome of IVF in termsof either pregnancy and/or poor response and on the predictionof these events based on a multivariate model. For the selectedstudies, sensitivity and specificity of the test in the predictionof poor ovarian response and non-pregnancy were calculated.Overall performance was assessed by estimating a summary receiveroperating characteristic (ROC) curve, which was compared withthe ROC curve for the AFC as the current best single test. RESULTS: We identified 11 studies reporting on the predictive capacityof multivariate models in ovarian reserve testing. All studiesreported on the prediction of poor ovarian response, whereasnone reported on the occurrence of pregnancy. The sensitivityfor prediction of poor ovarian response varied between 39% and97% and the specificity between 50% and 96%. Logistic regressionanalysis indicated that cohort studies provided a significantlybetter discriminative performance than case–control studies.As cohort studies are superior to case–control studies,further analysis was limited to the cohort studies. For thecohort studies, a summary ROC curve could be estimated, whichhad a shape similar to that previously made for the AFC. CONCLUSIONS: The accuracy of multivariate models for the prediction of ovarianresponse in women undergoing IVF is similar to the accuracyof AFC. No data are available on the capacity of these modelsto predict pregnancy, let alone live birth. On the basis ofthese findings, the use of more than one single test for theassessment of ovarian reserve cannot currently be supported.     

A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

Anal HPV 16 and 18 viral load: A comparison between HIV‐negative and ‐positive MSM and association with persistence

Does anal HPV viral load explain the difference in anal HPV persistence between HIV‐negative and ‐positive men who have sex with men (MSM)? MSM ≥18 years were recruited in Amsterdam, the Netherlands, in 2010‐2011. Anal self‐swabs were collected every 6 months and genotyped (SPF₁₀‐PCR‐DEIA‐LIPA₂₅‐system). HPV16 and HPV18 load was determined with a type specific quantitative (q)PCR, and compared between HIV‐negative and ‐positive men using ranksum test. Persistence was defined as ≥3 positive samples for the same HPV‐type. Determinants of persistent HPV16/18 infection and its association with HPV16/18 load were assessed with logistic regression. Of 777 recruited MSM, 54 and 22 HIV negative men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV‐positive MSM. The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1‐38.0) and of HPV18 8.6 (95%CI 2.7‐27.5) DNA copies/human cell. HPV16 and HPV18 load did not differ significantly between HIV‐negative and ‐positive MSM (P = 0.7; P = 0.8, respectively). In multivariable analyses HPV16 load was an independent determinant of HPV16 persistence (OR 1.8, 95%CI 1.3‐2.4). No difference in anal HPV viral load was found between HIV‐positive and HIV‐negative MSM. HPV 16/18 viral load is an independent determinant of type‐specific persistence.     

Noninvasive fetal genotyping of human platelet antigen-1a

We describe a reliable noninvasive fetal human platelet antigen (HPA)-1a genotyping assay on a real-time polymerase chain reaction (PCR) platform using cell-free fetal DNA isolated from maternal blood. Nonspecific amplification of maternal cell-free DNA is overcome by pre-PCR digestion of the cell-free DNA with the Msp1 restriction enzyme. Noninvasive fetal HPA-1a genotyping offers a safe method for alloimmunised pregnant women to determine whether their fetus is at risk of fetal or neonatal alloimmune thrombocytopenia (FNAIT) and whether interventions to prevent intracranial haemorrhage are required. The availability of this test is relevant to the ongoing debate on screening pregnancies for HPA-1a-mediated FNAIT.     

Systemic inflammatory immune signatures in a patient with CRB1 linked retinal dystrophy

Background: In this report we describe, for the first time, the activation of the peripheral immune compartment in a patient with a CRB1 linked retinal degenerative disease, masquerading as intermediate uveitis.

Methods: To monitor the immune system during systemic immunosuppressive treatment, given for the initial diagnosis of intermediate uveitis, blood samples were taken before and during therapy, for analysis of peripheral blood mononuclear cell-subsets and circulating immune mediators.

Results: The levels of various pro-inflammatory immune mediators (including MIF, TSLP, CCL2/MCP-1, CXCL9, CXCL10, IFN-β, IL-6, IL-17, IL-21, IL-22, and IL-23) were elevated in serum at the first time point, and decreased under immunosuppressive treatment. In parallel, the frequency of activated (CD86+) CD1c+ myeloid dendritic cells in blood was proportional to the central foveal thickness measured by optical coherence tomography.

Conclusions: These observations challenge the current view on the distinct pathophysiology of retinal degenerative and retinal inflammatory conditions in this patient.     

Health state preferences associated with weight status in children and adolescents

Background  

Childhood obesity is a substantial public health problem. The extent to which health state preferences (utilities) are related to a child's weight status has not been reported. The aims of this study were (1) to use a generic health state classification system to measure health related quality of life and calculate health utilities in a convenience sample of children and adolescents and (2) to determine the extent to which these measures are associated with weight status and body mass index (BMI).     

Genital asymmetry in men

This study examined genital asymmetry in a large sample of men. The probands were 6544 non-delinquent men who were interviewed by the Kinsey Institute for Research in Sex, Gender and Reproduction from 1938 to 1963. The measures were four indicators of penile and scrotal asymmetry, along with self-reported handedness, from Kinsey's interview protocol. Most men reported some degree of lateral asymmetry in their flaccid penis and in their testicles; less asymmetry was reported for their erect penis. The asymmetry typically occurred in the left direction, and this pattern occurred in both right- and nonright- handers. However, this 'leftward' pattern was significantly less pronounced in nonright-handers. The results are discussed in relation to previous findings of genital asymmetry in men, the possible relationship of genital asymmetry to functional cerebral asymmetry, and recent data suggesting genital asymmetry may predict patterns of cognitive performance and genital/sexual organ cancers.