The risk of hypertension and cardiovascular disease in women with uterine fibroids

Women with fibroids have a notably high hypertension risk. However, adjusted data regarding other cardiovascular disease (CVD) risk factors are scarce. In this cross‐sectional study, CVD risk factors, hemodynamic parameters, and asymptomatic organ damage were analyzed between women with uterine fibroids and controls in a multi‐ethnic population. In total, 104 women with self‐reported fibroids and 624 controls were included. Women with fibroids had significantly higher odds to have hypertension (OR 3.4; 95% CI 2.2‐5.2), diabetes (1.7; 1.0‐2.9), and hypercholesterolemia (1.8; 1.1‐3.2). After adjustment for confounders, only the odds ratio for hypertension was significant (1.8; 1.1‐3.1). Asymptomatic organ damage occurred significantly more often in women with fibroids (66.7%; 95% CI 55.8%‐77.6% vs 42.9%; 38.0‐47.8 in controls), especially in the younger age group (respectively 48.5%; 31.1%‐65.9% vs 22.1%; 17.0‐27.2). In this study, women with fibroids had a remarkably high hypertension risk compared to controls, with more asymptomatic organ damage, in particular young women.     

Systematic review: antihypertensive drug therapy in patients of African and South Asian ethnicity

Despite the large differences in the epidemiology of hypertension across Europe, treatment strategies are similar for national populations of white European descent. However, hypertensive patients of African or South Asian ethnicity may require ethnic-specific approaches, as these population subgroups tend to have higher blood pressure at an earlier age that is more difficult to control, a higher occurrence of diabetes, and more target organ damage with earlier cardiovascular mortality. Therefore, we systematically reviewed the evidence on antihypertensive drug treatment in South Asian and African ethnicity patients. We used the Cochrane systematic review methodology to retrieve trials in electronic databases including CENTRAL, PubMed, and Embase from their inception through November 2015; and with handsearch. We retrieved 4596 reports that yielded 35 trials with 7 classes of antihypertensive drugs in 25,540 African ethnicity patients. Aside from the well-known blood pressure efficacy of calcium channel blockers and diuretics, with lesser effect of ACE inhibitors and beta-blockers, nebivolol was not more effective than placebo in reducing systolic blood pressure levels. Trials with morbidity and mortality outcomes indicated that lisinopril and losartan-based therapy were associated with a greater incidence of stroke and sudden death. Furthermore, 1581 reports yielded 16 randomized controlled trials with blood pressure outcomes in 1719 South Asian hypertensive patients. In contrast with the studies in African ethnicity patients, there were no significant differences in blood pressure lowering efficacy between drugs, and no trials available with mortality outcomes. In conclusion, in patients of African ethnicity, treatment initiated with ACE inhibitor or angiotensin II receptor blocker monotherapy was associated with adverse cardiovascular outcomes. We found no evidence of different efficacy of antihypertensive drugs in South Asians, but there is a need for trials with morbidity and mortality outcomes. Screening for cardiovascular risk at a younger age, treating hypertension at lower thresholds, and new delivery models to find, treat and follow hypertensives in the community may help reduce the excess cardiovascular mortality in these high-risk groups.     

Pressor effect of a soccer match (1988 European championship), registered via the Portapress

With the Portapres, continuous ambulatory non-invasive measurement of finger arterial blood pressure is possible. By means of this system blood pressure measurements were made in five healthy male subjects watching a match of the Dutch National team at home, during the 1988 European Championship. In two of them an evident pressor response was found.     

Microalbuminuria in adults after prenatal exposure to the Dutch famine

Maternal undernutrition during gestation is associated with an increase in cardiovascular risk factors in the offspring in adult life. The effect of famine exposure during different stages of gestation on adult microalbuminuria (MA) was studied. MA was measured in 724 people, aged 48 to 53, who were born as term singletons in a university hospital in Amsterdam, the Netherlands, around the time of the Dutch famine 1944 to 1945. Twelve percent of people who were exposed to famine in mid gestation had MA (defined as albumin/creatinine ratio >/=2.5) compared with 7% of those who were not prenatally exposed to famine (odds ratio 2.1; 95% confidence interval 1.0 to 4.3). Correcting for BP, diabetes, and other influences that affect MA did not attenuate this association (adjusted odds ratio 3.2; 95% confidence interval 1.4 to 7.7). The effect of famine was independent of size at birth. Midgestation is a period of rapid increase in nephron number, which is critical in determining nephron endowment at birth. Fetal undernutrition may lead to lower nephron endowment with consequent MA in adult life.     

Blood pressure in adults after prenatal exposure to famine

BACKGROUND: Many studies have shown that low birth weight is associated with high blood pressure. The composition of the diet of pregnant women has also been found to affect blood pressure in their children. We assessed the effect of prenatal exposure to the Dutch famine of 1944-1945, during which the caloric intake from protein, fat and carbohydrate was proportionally reduced, on blood pressures in adults now aged about 50 years. METHODS AND RESULTS: We measured blood pressures at home and in the clinic among people born at term in one hospital in Amsterdam, The Netherlands, between November 1 1943 and February 28 1947, for whom we had detailed birth records. Blood pressures of people exposed to famine during late (n = 120), mid-(n = 109) or early gestation (n = 68) were compared with those of people born in the year before or conceived in the year after the famine (unexposed subjects, n = 442). No effect of prenatal exposure on systolic and diastolic blood pressure was observed. The mean systolic blood pressure taken in the clinic in those exposed in late gestation, and adjusted for sex and age, was 1.3 mmHg higher than in the unexposed group (95% confidence interval -1.9 to 4.4). The mean systolic blood pressure differed by -0.6 mmHg (95% confidence interval -3.9 to 2.7) for those exposed in mid-gestation and -1.7 mmHg (95% confidence interval -5.6 to 2.2) for those exposed in early gestation. People who were small at birth had higher blood pressures. A 1 kg increase in birth weight was associated with a decrease of 2.7 mmHg (95% confidence interval 0.3 to 5.1) in systolic blood pressure. Analyses of blood pressures measured at home gave similar results. CONCLUSION: High blood pressure was not linked to prenatal exposure to a balanced reduction of macronutrients in the maternal diet. However, it was linked to reduced fetal growth. We postulate that it might be the composition rather than the quantity of a pregnant woman's diet that affects her child's blood pressure in later life.     

Dysfunctional BLK in common variable immunodeficiency perturbs B-cell proliferation and ability to elicit antigen-specific CD4+ T-cell help

Common Variable Immunodeficiency (CVID) is the most prevalent primary antibody deficiency, and characterized by defective generation of high-affinity antibodies. Patients have therefore increased risk to recurrent infections of the respiratory and intestinal tract. Development of high-affinity antigen-specific antibodies involves two key actions of B-cell receptors (BCR): transmembrane signaling through BCR-complexes to induce B-cell differentiation and proliferation, and BCR-mediated antigen internalization for class-II MHC-mediated presentation to acquire antigen-specific CD4⁺ T-cell help.We identified a variant (L3P) in the B-lymphoid tyrosine kinase (BLK) gene of 2 related CVID-patients, which was absent in healthy relatives. BLK belongs to the Src-kinases family and involved in BCR-signaling. Here, we sought to clarify BLK function in healthy human B-cells and its association to CVID.BLK expression was comparable in patient and healthy B-cells. Functional analysis of L3P-BLK showed reduced BCR crosslinking-induced Syk phosphorylation and proliferation, in both primary B-cells and B-LCLs. B-cells expressing L3P-BLK showed accelerated destruction of BCR-internalized antigen and reduced ability to elicit CD40L-expression on antigen-specific CD4⁺ T-cells.In conclusion, we found a novel BLK gene variant in CVID-patients that causes suppressed B-cell proliferation and reduced ability of B-cells to elicit antigen-specific CD4⁺ T-cell responses. Both these mechanisms may contribute to hypogammaglobulinemia in CVID-patients.     

Autologous skin substitute for hard‐to‐heal ulcers: Retrospective analysis on safety,applicability, and efficacy in an outpatient and hospitalized setting

Chronic ulcers ((arterio)venous, decubitus, or postoperative) have no tendency to heal within a period of at least 3 months despite optimal therapy according to internationally accepted guidelines. This retrospective study evaluates the safety and efficacy of an autologous, dermal‐epidermal skin substitute (SS) for treating ulcers of various origins. Ulcers were treated within 7 Dutch centers over 5 years. Sixty‐six ulcers (size: 0.75–150 cm²; duration: 0.25–32 years) with a follow‐up time of 24 weeks after a single‐skin substitute application were assessed. Wound‐bed preparation consisted of vacuum‐assisted‐closure‐therapy (5 days, hospitalized) or application of acellular dermis (5–7 days, outpatient). Time to heal, adverse events, and recurrence 1 year after complete healing were recorded. Complete ulcer healing occurred in 36 of 66 ulcers (55%) at 24 weeks. At that time point, a further 29% of ulcers showed decrease in ulcer size between 50 and 99%. No difference was observed between the hospitalized vs. outpatient treatment with complete healing. There were 32 of 36 healed ulcers that were available for follow‐up 1 year after complete closure, of which 27 (84%) were still closed. Only two minor/moderate possibly related adverse events were recorded. This retrospective analysis shows that SS provides a safe and successful treatment for particularly chronic ulcers of various origins.     

Airway and interstitial lung disease are distinct entities in paediatric common variable immunodeficiency

Common variable immunodeficiency (CVID) is a common primary immune deficiency, caused by undefined defects in lymphocyte function, and is treated routinely by immunoglobulin substitution. CVID complications include airway disease (AD) and interstitial lung disease (ILD). It was not known if AD and ILD in CVID have a common immunological aetiology and should be considered separate features of the same disease, or as distinct syndromes that require specialized monitoring and treatment. We used high-resolution computed tomography (CT) to diagnose AD or ILD in paediatric CVID patients. Spirometry and body plethysmography did not differentiate between ILD and AD. Patients with AD (n = 11, 20%) developed more pneumonias while children with ILD (n = 8, 15%) showed immune dysregulation characterized by autoimmune complications, more severe memory B cell reduction and expansion of non-naive cytotoxic T cells. In conclusion, ILD and AD in CVID have dissimilar clinical and immunological characteristics, suggesting distinct aetiology requiring tailored monitoring and treatment of these patient subgroups.