Tomas Ahern

The IL-6 G-174C polymorphism may be associated with ischaemic stroke in patients without a history of hypertension

BACKGROUND Recent data suggest that inflammatory reactions are involved in the pathogenesis of cerebral ischaemia. AIM To investigate whether certain inflammatory genetic polymorphisms are associated with the occurrence of ischaemic stroke. METHODS We investigated the prevalence of six polymorphisms in cytokine genes (IL-6, TNF-alpha, TNF-beta, IL-1beta, IL-10, and IL-1Ralpha) in a group of ischaemic stroke patients (n = 105) and in a control population (n = 389). We analysed the prevalence of these polymorphisms in different stroke subtypes and in relation to outcome six months post-stroke. RESULTS There was no significant variation in cytokine gene polymorphism frequencies between control and stroke populations or for different stroke subtypes. Subgroup analysis demonstrated that the prevalence of the IL-6 -174 CC genotype was significantly lower in stroke patients without a history of hypertension compared to controls. CONCLUSION The IL6 -174 CC genotype may be protective against stroke in those patients who have no history of hypertension. Further studies are required to verify these findings.

Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study.

Background  Diabetes and obesity are more prevalent amongst psoriasis patients as is disturbance of the innate immune system. GLP‐1 analogue therapy considerably improves weight and glycaemic control in people with type 2 diabetes and its receptor is present on innate immune cells.

Sitagliptin for severe psoriasis.

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Obesity-related chronic lymphoedema-like swelling and physical function

BACKGROUND People with severe obesity (body mass index [BMI] > 40 kg/m(2)) have an 85% higher mortality than people with a healthy BMI. Poor physical function may contribute to this excess mortality. Lymphoedema-like swelling can affect the legs of severely obese people with normal lymphoscintigraphy. AIM We sought to determine the relationship between the presence of lymphoedema-like swelling and physical function in the severely obese. DESIGN AND METHODS In people with severe obesity, we ascertained whether lower leg lymphoedema-like swelling was present and determined the circumference of the lower leg, time taken to ascend and descend a 17-cm step 50 times and time taken to walk 500 m. RESULTS The 330 participants, 33% of whom were male, were aged 43.4 ± 12.7 years (mean ± standard deviation) and had a BMI of 51.7 ± 8.4 kg/m(2). Lymphoedema-like swelling was present in approximately one-third (n = 108) in whom a prior history of cellulitis and venous thromboembolism was more common (relative risks 6.16 and 3.86, respectively) than in those without lymphoedema-like swelling. Participants with lymphoedema-like swelling, compared with non-affected counterparts, had a higher lower leg circumference (35.0 ± 7.1 vs. 32.4 ± 4.8 cm), a slower step speed (0.40 ± 0.12 vs. 0.43 ± 0.10 steps/s) and a slower walking speed (0.97 ± 0.37 vs. 1.08 ± 0.30 m/s, P < 0.05 for all comparisons). CONCLUSIONS In this cross-sectional study, 33% of our severely obese participants had lymphoedema-like swelling. Participants with lymphoedema-like swelling had worse physical function than those without. This association was independent of BMI. The presence of obesity-related chronic lymphoedema-like swelling should lead to interventions that improve physical function.

Association Between Vitamin D Status and Physical Function in the Severely Obese

CONTEXT Mortality is 85% higher in severely obese subjects (body mass index [BMI] > 40 kg/m(2)) than in subjects with a healthy BMI; poor physical function may be contributory. Hypovitaminosis D is common in obese subjects and is associated with physical dysfunction in the elderly. OBJECTIVE We determined the relationship between vitamin D status and physical function in severely obese subjects. DESIGN, SETTING, AND PATIENTS We conducted a clinic-based, cross-sectional study of severely obese subjects. Participants were stratified into three groups according to the Institute of Medicine (IOM) vitamin D status categorization. MAIN OUTCOME MEASURES We compared levels of self-reported activity and times taken to walk 500 m and to ascend and descend a 17-cm step 50 times. RESULTS We recruited 252 subjects (age, 43.7 ± 11.2 y; BMI, 50.7 ± 9.7 kg/m(2)); 25-hydroxyvitamin D (25OHD) concentrations were less than 30 nmol/L in 109 participants. Participants with a 25OHD > 50 nmol/L, compared to those with a 25OHD < 30 nmol/L, had the highest activity levels (3.1 ± 3.4 h/wk versus 1.5 ± 2.5 h/wk; P = .015) and the shortest 500-m walk times (6.2 ± 1.1 min versus 7.4 ± 1.5 min; P = .003). Serum 25OHD concentrations had a weakly positive association with activity level (r = 0.19; P = .008) and a moderately negative association with 500-m walk time (r = -0.343; P < .001). CONCLUSIONS Vitamin D status had a significant relationship with physical activity and physical function in this cohort of severely obese subjects. Low activity levels are likely to perpetuate the problem of hypovitaminosis D due to less time spent outdoors. Studies exploring the effects of vitamin D supplementation in this population are warranted.

The dermatological consequences of obesity

Obesity is emerging as a global epidemic with at least 300 million people thought to be obese worldwide. This has implications for health professionals including dermatologists. Recent interest has focused on the role of obesity in psoriasis, but obesity is implicated in many dermatoses. Perhaps most worrying is emerging data which suggest that obesity may constitute a risk factor for the development of skin cancer. Its rising incidence ensures that obesity‐related skin disease will represent an increasing proportion of dermatologists’ work load. In this article, we review dermatoses associated with obesity and review the epidemiology and treatment for obesity.

Liraglutide in combination with acitretin for severe recalcitrant psoriasis

oxalate to urinary oxalate excretion. Kidney Int 2001; 59:270–6. 14 Holmes RP, Ambrosius WT, Assimos DG. Dietary oxalate loads and renal oxalate handling. J Urol 2005; 174:943–7; discussion 947. 15 Liebman M, Costa G. Effects of calcium and magnesium on urinary oxalate excretion after oxalate loads. J Urol 2000; 163:1565–9. 16 Clark J, Vandorpe D, Chernova M. Species differences in Cl affinity and in electrogenicity of SLC26A6-mediated oxalate/Cl exchange correlate with the distinct human and mouse susceptibilities to nephrolithiasis. J Physiol 2008; 586:1291–306. 17 Worcester EM, Nakagawa Y, Bushinsky DA, Coe FL. Evidence that serum calcium oxalate supersaturation is a consequence of oxalate retention in patients with chronic renal failure. J Clin Invest 1986; 77:1888–96. 18 Balcke P, Schmidt P, Zazgornik J et al. Secondary oxalosis in chronic renal insufficiency. N Engl J Med 1980; 303:944. 19 Salyer WR, Keren D. Oxalosis as a complication of chronic renal failure. Kidney Int 1973; 4:61–6.

Nonandrogenic anabolic hormones predict risk of frailty : European male ageing study prospective data

Context Objective Design/setting Participants Intervention Main outcome measures Analysis ResultsContext: Low levels of nonandrogenic anabolic hormones have been linked with frailty, but evidence is conflicting and prospective data are largely lacking. Objective: To determine associations between nonandrogenic anabolic hormones and prospective changes in frailty status. Design/Setting: A 4.3-year prospective observational study of community-dwelling men participating in the European Male Ageing Study. Participants: Men (n = 3369) aged 40 to 79 years from eight European centers. Main Outcome Measures: Frailty status was determined using frailty phenotype (FP; n = 2114) and frailty index (FI; n = 2444). Analysis: Regression models assessed relationships between baseline levels of insulinlike growth factor 1 (IGF-1), its binding protein 3 (IGFBP-3), dehydroepiandrosterone sulfate (DHEA-S), 25-hydroxyvitamin D (25OHD), and parathyroid hormone (PTH), with changes in frailty status (worsening or improving frailty). Results: The risk of worsening FP and FI decreased with 1 standard deviation higher IGF-1, IGFBP-3, and 25OHD in models adjusted for age, body mass index, center, and baseline frailty [IGF-1: odds ratio (OR) for worsening FP, 0.82 (0.73, 0.93), percentage change in FI, −3.7% (−6.0, −1.5); IGFBP-3: 0.84 (0.75, 0.95), −4.2% (−6.4, −2.0); 25OHD: 0.84 (0.75, 0.95); −4.4%, (−6.7, −2.0)]. Relationships between IGF-1 and FI were attenuated after adjusting for IGFBP-3. Higher DHEA-S was associated with a lower risk of worsening FP only in men >70 years old [OR, 0.57 (0.35, 0.92)]. PTH was unrelated to change in frailty status. Conclusions: These longitudinal data confirm the associations between nonandrogenic anabolic hormones and the changes in frailty status. Interventional studies are needed to establish causality and determine therapeutic implications.

Adipokines, psoriasis, systemic inflammation, and endothelial dysfunction

Adipokines are secreted by white adipose tissue, an active endocrine organ, and play a role in the regulation of metabolic functions such as lipid metabolism, inflammation, and vascular homeostasis. Adipokines are secreted in excess in obesity and contribute to the development of associated comorbidities such as metabolic syndrome and atherosclerosis. Psoriasis, a chronic immune‐mediated skin disease, is associated with obesity and increased cardiovascular risk. Understanding the role of adipokines in psoriasis may in part explain the association between psoriasis and cardiovascular disease. This review summarizes the data regarding key adipokines in patients with psoriasis and the change in adipokine profiles with psoriasis therapy. Adipokines may be mediators of cutaneous inflammation suggesting a role in the pathophysiology of psoriasis and the development of comorbidities.

Elevated luteinizing hormone despite normal testosterone levels in older men—natural history, risk factors and clinical features

Elevated luteinizing hormone (LH) with normal testosterone (T) suggests compensated dysregulation of the gonadal axis. We describe the natural history, risk factors and clinical parameters associated with the development of high LH (HLH, LH >9.4 U/L) in ageing men with normal T (T ≥ 10.5 nmol/L).