Non-coronary cardiac events,younger age,and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease

Clinical Rheumatology - Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for...     

One week treatment with salmeterol does not prevent early and late asthmatic responses and sputum eosinophilia induced by allergen challenge in asthmatics

Salmeterol is an effective long-acting beta(2)-agonist bronchodilator, able to inhibit, as a single dose, asthmatic responses induced by several stimuli including allergen, and the subsequent increase in sputum eosinophilia. Aim of the present study was to investigate whether these effects of salmeterol persisted after 1 week of continuous treatment, or whether a loss of the bronchoprotective effects of salmeterol can occur over time. We investigated in a cross-over double blind placebo-controlled study, the protective effect of 1 week treatment with salmeterol on allergen-induced early and late responses and the associated airway inflammation in 15 atopic asthmatic subjects. Eosinophil percentage and Eosinophil Cationic Protein (ECP) concentration in peripheral blood and in hypertonic saline induced sputum were measured at baseline and 24 h after allergen inhalation. Salmeterol partially inhibited early asthmatic response, but it did not inhibit late asthmatic response in comparison with placebo. Salmeterol did not inhibit also the increase in sputum eosinophils percentage 24 h after allergen inhalation (E%, median: 22.7 and 15%, after placebo and after salmeterol respectively, p=n.s. between two post-allergen sputum samples). Also, the increase in blood eosinophils and both sputum and serum ECP at 24 h after allergen challenge was not affected by salmeterol pre-treatment. In conclusion, 1 week treatment with salmeterol causes a loss of its protective effect on allergen-induced airway bronchoconstriction, and does not prevent the subsequent increase in sputum and serum eosinophilic markers.     

Growth, growth factors and diabetes

Type 1 diabetes mellitus (T1DM) and other chronic diseases in children are well known to adversely affect linear growth and pubertal development. In the years immediately following the introduction of insulin therapy, short stature was consistently reported in children with T1DM. However, over the past 50 years significant improvement in the prognosis for growth and final height in children with diabetes has been achieved. Although pre-pubertal and post-pubertal growth are important phases in growth, puberty and its related hormonal changes represent a critical phase for growth gain and final height particularly in patients with T1DM. Growth impairment reported in diabetic patients is dependent on abnormalities in physiological bone growth and corresponds to abnormalities of the growth hormone-insulin-like growth-I (GH-IGF-I) axis. These alterations seem to be related to appropriate insulin levels and thereby to glycaemic control as judged by haemoglobin levels. Modern diabetes care, particularly intensified insulin regimens, might improve metabolic control in patients with T1DM, therefore preventing abnormalities of the GH-IGF-I axis and leading to normal growth and final height similar to that of their unaffected peers.     

Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis

BACKGROUND AND AIMS: Cirrhotic patients frequently undergo screening endoscopy for the presence of oesophageal varices (OV). In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aims were (1) to identify clinical, biochemical, and ultrasonographic parameters which might non-invasively predict the presence of OV in patients with liver cirrhosis; (2) to evaluate the reproducibility of the obtained results in a different, although related, further group of patients; and (3) to assess the predictiveness of the identified rules in patients with compensated cirrhosis. METHODS: In the first part of the study we retrospectively evaluated the presence of OV in 145 cirrhotic patients, and in the second part we evaluated the reproducibility of the study results in a subsequent group of 121 patients. Finally, we evaluated these parameters in a subgroup of 145 patients with compensated disease. All 266 patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio was calculated for all patients. RESULTS: The prevalence rates of OV were 61% and 58% in the first and second groups of patients, respectively. In the first part of the study, we found that platelet count, spleen diameter, platelet count/spleen diameter ratio, and Child- Pugh class were significantly different among patients with or without OV, although the platelet count/spleen diameter ratio was the only parameter which was independently associated with the presence of OV in a multivariate analysis. A platelet count/spleen diameter ratio cut off value of 909 had 100% negative predictive value for a diagnosis of OV. This result was reproduced in the second group of patients as well as in patients with compensated disease. In a cost-benefit analysis, screening cirrhotic patients according to the "platelet count/spleen diameter ratio strategy" was far more cost effective compared with the "scope all strategy". CONCLUSIONS: The platelet count/spleen diameter ratio is the only parameter which is independently associated with the presence of OV, and its negative predictive value is reproducible. Its use is of value even in the subgroup of patients with compensated disease, and it is also cost effective.     

The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction

STUDY OBJECTIVE: To determine the protective effect of salbutamol, 100 microg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine. DESIGN: Randomized, double-blind, cross-over, placebo-controlled study. PATIENTS: Eighteen subjects with stable, moderate asthma, asymptomatic, receiving regular treatment with salmeterol, 50 microg bid, and inhaled beclomethasone dipropionate, 250 microg bid, in the last 6 months, with high hyperreactivity to methacholine (baseline provocative dose of methacholine causing a 20% fall in FEV(1) [PD(20)] geometric mean [GM], 0.071 mg). Subjects were classified into two groups: subjects with incorrect (n = 5) pMDI inhalation technique, and subjects with correct (n = 13) inhalation technique. METHODS AND MEASUREMENTS: After cessation of therapy for 3 days, all subjects underwent four methacholine challenge tests, each test 1 week apart, each time 15 min after inhalation of salbutamol, 100 microg (via pMDI, pMDI + spacer, or Autohaler), or placebo. The protective effect on methacholine challenge test was evaluated as the change in the PD(20), and expressed in terms of doubling doses of methacholine in comparison with placebo treatment. RESULTS: The PD(20) was significantly higher after salbutamol inhalation than after placebo inhalation, but no significant difference was observed among the three different inhalation techniques. Only when salbutamol was inhaled via pMDI + spacer, PD(20) was slightly but not significantly higher (pMDI GM, 0.454 mg; pMDI + spacer GM, 0.559 mg; and Autohaler GM, 0.372 mg; not significant [NS]) than other inhalation techniques. Similar results (mean +/-SEM) were obtained with doubling doses of methacholine (pMDI, 2 +/- 0.47; pMDI + spacer, 3 +/- 0.35; and Autohaler, 2.4 +/- 0.40; NS). No significant difference was found among techniques when subjects with correct or incorrect inhalation technique were separately considered. CONCLUSIONS: Our data show that the protective effect of salbutamol, 100 microg, on methacholine-induced bronchoconstriction is not affected by the different inhalation techniques, although inhalation via pMDI + spacer tends to improve the bronchoprotective ability of salbutamol. These data confirm the clinical efficacy of salbutamol, whatever the device, and the patient's inhalation technique.     

Self-rated health among older adults: a cross-national comparison

Self-rated health (SRH) may have different implications in various social and cultural settings. However, few studies are available concerning SRH among older persons across countries. The aim of this study was to analyse whether there are cross-national differences in the association between status characteristics, several diseases common among older persons, activities of daily living (ADL), and SRH. The study base was the Comparison of Longitudinal European Studies on Aging (CLESA), which includes data from six population-based studies on aging conducted in Finland, Israel, Italy, The Netherlands, Spain and Sweden. The study population comprised 5,629 persons, with participants from all countries except Italy. Logistic regression analyses were used to assess the relationship between status characteristics, health conditions, ADL and SRH. To examine whether the association among status characteristics, health conditions, ADL and outcome differed across the CLESA countries, interaction terms defined as variable*country were considered separately for each variable. Regression analyses revealed that sex, education, lifetime occupation, heart disease and respiratory disease were differently distributed across countries. Among homogeneous factors, marital status (OR=1.21), hypertension (OR=1.41), stroke (OR=1.67), diabetes (OR=2.15), cancer (OR=1.47), musculoskeletal diseases (OR=2.44), and ADL (OR=2.72) turned out to be significantly associated with fair or poor SRH. The results indicate that there are differences in self-ratings of health across countries. These differences cannot be explained entirely by status characteristics, self-reported diseases or functional ability. However, an important finding was that in all countries most of the indicators of medical and functional health were homogeneously associated with SRH.     

Role of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS)

The aim of this study was to evaluate the role of markers of bone remodelling, and osteoclast activation/function in patients with monoclonal gammopathy of undetermined significance (MGUS). We have measured serum levels of soluble RANKL (sRANKL), osteoprotegerin (OPG), macrophage inflammatory protein-1alpha (MIP-1alpha), markers of bone resorption [N-telopeptide of collagen type-I (NTX), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)] and bone formation [bone-alkaline phosphatase (bALP)] in 40 MGUS patients. These parameters were compared with those of 42 newly diagnosed myeloma patients, and 45 healthy, gender- and age-matched controls. MGUS patients had elevated levels of NTX, sRANKL, and sRANKL/OPG ratio compared with controls (P < 0.0001). Furthermore, TRACP-5b, MIP-1alpha and NTX were decreased in patients with MGUS compared with myeloma patients (P < 0.001), while OPG and bALP were increased (P < 0.001). Serum levels of MIP-1alpha, as well as TRACP-5b, and sRANKL/OPG ratio were reduced, while bALP was increased in MGUS patients, even when compared with myeloma patients who had stage I/II disease. These results demonstrate that increased osteoclastogenesis leading to increased bone resorption is present in MGUS but seems to be compensated for by normal bone formation, which is absent in MM. Furthermore MIP-1alpha, bALP, and sRANKL/OPG may be useful tools for distinguishing between cases of MGUS and early myeloma.     

Predictors and Clinical Impact of Prosthesis-Patient Mismatch After Self-Expandable TAVR in Small Annuli

ObjectivesThe aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli.BackgroundTAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet.MethodsPredictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled.ResultsIntra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6).ConclusionsAmong patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality.