Effect of DASH vs. mediterranean diet accompanied by a salt restriction on metabolic syndrome and cardiometabolic risk factors in adults with high normal blood pressure or grade 1 hypertension: secondary analyses of a randomized controlled trial.

OBJECTIVE: Lifestyle interventions are recommended as the first-line treatment to control metabolic syndrome components and improve cardiometabolic risk factors. However, studies directly comparing the cardiometabolic effects of the Dietary Approaches to Stop Hypertension (DASH) vs. the Mediterranean diet (MedDiet) accompanied by salt restriction are currently lacking. Thus, with the present secondary analyses of a randomized trial, we aimed to assess the cardiometabolic effects of a 3-month intensive dietary intervention implementing salt restriction alone or on top of the DASH and MedDiet compared to no/minimal intervention in never drug-treated adults with high normal blood pressure (BP) or grade 1 hypertension. METHODS: We randomly assigned individuals to the control group (CG, n = 60), salt restriction group (SRG, n = 60), DASH diet with salt restriction group (DDG, n = 60), or MedDiet with salt restriction group (MDG, n = 60). RESULTS: According to the intention-to-treat analysis, the DDG and the MDG had lower odds ratio (OR) (95% CI) of metabolic syndrome [0.29 (0.12, 0.72), and 0.15 (0.06, 0.41), respectively] compared to the CG. Moreover, the MDG had lower odds of metabolic syndrome compared to the SRG and lower odds of elevated BP levels than the DDG and the SRG. Moreover, total and LDL-cholesterol, fasting glucose, HbA1c, and systolic/diastolic BP were reduced in all three intervention groups compared to the CG. CONCLUSION: On a background of salt restriction, the MedDiet was superior in BP reduction, but the DASH and MedDiet reduced the prevalence of metabolic syndrome to the same extent.

Could it be hereditary angioedema?-Perspectives from different medical specialties.

Hereditary angioedema (HAE) is a rare autosomal dominant disease, with patients often suffering with associated symptoms for many years before receiving a correct diagnosis. The symptoms greatly impact a patient's quality of life (QoL) and include excruciating abdominal pain and angioedema of the skin and submucosa. Angioedema of the larynx represents a significant mortality risk in undiagnosed patients, and a large proportion of patients with HAE receive incorrect diagnoses and undergo unnecessary surgery. HAE-specific treatments can control and prevent acute life-threatening episodes, in addition to improving QoL, emphasizing the value of early diagnosis for patients. Diagnostic delay may be due to a lack of HAE awareness by healthcare professionals and the similarity of HAE symptoms with those of more common conditions, complicating differential diagnosis. The multifaceted nature of the condition may result in visits to one of many different medical settings, for example: the Emergency Room, pediatrics, general practice, otolaryngology, gastroenterology, and dermatology. Therefore, it is crucial that physicians in multiple healthcare specialties are aware of the disease to ensure that patients with HAE receive a timely diagnosis. Using patient cases from various medical specialties, this review highlights the necessity for cross-specialty awareness of HAE and outlines the essential information for the various healthcare professionals that may encounter a patient with HAE symptoms, in order to effectively treat and/or diagnose HAE.

Cardiorenal multimorbidity in hospitalized cardiology patients: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) study.

PURPOSE: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece. METHODS: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample. RESULTS: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%). CONCLUSION: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population.

Chitinase-Induced Airway Hyperreactivity and Inflammation in a Mouse Model of Nonallergic Asthma.

INTRODUCTION: Environmental exposure to mites and fungi has been proposed to critically contribute to the development of IgE-mediated asthma. A common denominator of such organisms is chitin. Human chitinases have been reported to be upregulated by interleukin-13 secreted in the context of Th2-type immune responses and to induce asthma. We assessed whether chitin-containing components induced chitinases in an innate immune-dependent way and whether this results in bronchial hyperresponsiveness. MATERIALS AND METHODS: Monocyte/macrophage cell lines were stimulated with chitin-containing or bacterial components in vitro. Chitinase activity in the supernatant and the expression of the chitotriosidase gene were measured by enzyme assay and quantitative PCR, respectively. Non-sensitized mice were stimulated with chitin-containing components intranasally, and a chitinase inhibitor was administered intraperitoneally. As markers for inflammation leukocytes were counted in the bronchoalveolar lavage (BAL) fluid, and airway hyperresponsiveness was assessed via methacholine challenge. RESULTS: We found both whole chitin-containing dust mites as well as the fungal cell wall component zymosan A but not endotoxin-induced chitinase activity and chitotriosidase gene expression in vitro. The intranasal application of zymosan A into mice led to the induction of chitinase activity in the BAL fluid and to bronchial hyperresponsiveness, which could be reduced by applying the chitinase inhibitor allosamidin. DISCUSSION: We propose that environmental exposure to mites and fungi leads to the induction of chitinase, which in turn favors the development of bronchial hyperreactivity in an IgE-independent manner.

Hereditary angioedema in children and adolescents - A consensus update on therapeutic strategies for German-speaking countries.

BACKGROUND/METHODS: At a consensus meeting in August 2018, pediatricians and dermatologists from German-speaking countries discussed the therapeutic strategy for the treatment of pediatric patients with type I and II hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) for Germany, Austria, and Switzerland, taking into account the current marketing approval status. HAE-C1-INH is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible and an optimal management of the disease are important to avoid ineffective therapies and to properly treat swelling attacks. This article provides recommendations for developing appropriate treatment strategies in the management of HAE-C1-INH in pediatric patients in German-speaking countries. An overview of available drugs in this age-group is provided, together with their approval status, and study results obtained in adults and pediatric patients. RESULTS/CONCLUSION: Currently, plasma-derived C1 inhibitor concentrates have the broadest approval status and are considered the best available option for on-demand treatment of HAE-C1-INH attacks and for short- and long-term prophylaxis across all pediatric age-groups in German-speaking countries. For on-demand treatment of children aged 2 years and older, recombinant C1-INH and bradykinin-receptor antagonist icatibant are alternatives. For long-term prophylaxis in adolescents, the parenteral kallikrein inhibitor lanadelumab has recently been approved and can be recommended due to proven efficacy and safety.

Dietary Approaches to Stop Hypertension (DASH) Diet and Blood Pressure Reduction in Adults with and without Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The Dietary Approaches to Stop Hypertension (DASH) diet is recognized as an effective dietary intervention to reduce blood pressure (BP). However, among randomized controlled trials (RCTs) investigating the DASH diet-mediated BP reduction, there are significant methodological and clinical differences. The purpose of this study was to comprehensively assess the DASH diet effect on BP in adults with and without hypertension, accounting for underlying methodological and clinical confounders. We systematically searched Medline and the Cochrane Collaboration Library databases and identified 30 RCTs (n = 5545 participants) that investigated the BP effects of the DASH diet compared with a control diet in hypertensive and nonhypertensive adults. Both random-effects and fixed-effect models were used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted. Compared with a control diet, the DASH diet reduced both SBP and DBP (difference in means: -3.2 mm Hg; 95% CI: -4.2, -2.3 mm Hg; P < 0.001, and -2.5 mm Hg; 95% CI: -3.5, -1.5 mm Hg; P < 0.001, respectively). Hypertension status did not modify the effect on BP reduction. The DASH diet compared with a control diet reduced SBP levels to a higher extent in trials with sodium intake >2400 mg/d than in trials with sodium intake ≤2400 mg/d, whereas both SBP and DBP were reduced more in trials with mean age <50 y than in trials of older participants. The quality of evidence was rated as moderate for both outcomes according to the Grading of Recommendations, Assessment, Development, and Evaluation approach. The adoption of the DASH diet was accompanied by significant BP reduction in adults with and without hypertension, although higher daily sodium intake and younger age enhanced the BP-lowering effect of the intervention. This meta-analysis was registered at www.crd.york.ac.uk/prospero as CRD42019128120.

Predictors of switching from nonsteroidal anti-inflammatory drugs to corticosteroids in patients with acute pericarditis and impact on clinical outcome.

BACKGROUND: Aspirin and nonsteroidal anti-inflammatory drugs (A/NSAIDs) are the mainstay treatments for acute pericarditis. We sought to identify factors predicting failure of A/NSAIDs and switch to corticosteroid treatment (STCT) as well as the impact of STCT on pericarditis recurrence. METHODS: We enrolled 148 patients with acute pericarditis receiving A/NSAIDs (n=110) or corticosteroids (n=38) as first-line treatment according to clinical indications. In case of poor response to A/NSAIDs (n=37), STCT was performed and factors contributing to such failure were explored. All patients were followed-up prospectively for 18 months for pericarditis recurrence. RESULTS: In multivariate analysis, female sex (odds ratio [OR] =3.57, 95% confidence interval [CI]: 1.00-12.5), age (per decade, OR=0.75, 95% CI: 0.57-0.99), PR-segment depression (OR=4.43, 95% CI: 1.02-19.34), and a secondary cause of pericarditis (OR=13.52, 95% CI: 1.51-117.8) were independent predictors of poor response to A/NSAIDs and STCT. In cox regression analysis, the risk of recurrence was higher in patients requiring STCT (hazards ratio [HR] =3.22, 95% CI: 1.70-6.13) and in those initially treated with corticosteroids (H=2.06, 95% CI: 1.01-4.21) than in patients receiving A/NSAIDs only. CONCLUSIONS: Treatment failure with A/NSAIDs in acute pericarditis can be anticipated by certain patient characteristics. STCT identifies patients who are at the highest risk for recurrences, a risk that is approximately threefold higher than that of A/NSAIDs and 1.5-fold higher than that of corticosteroids as first-line treatment.

Food as a trigger for abdominal angioedema attacks in patients with hereditary angioedema.

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited disease. In most HAE-affected subjects, defined trigger factors precede angioedema attacks. Mechanisms of how trigger factors stimulate the contact activation pathway with bradykinin generation are not well elucidated. In recent studies, hypersensitivity reactions and food were stated as relevant triggers. We investigated HAE affected people for possible hypersensitivity reactions or intolerances and their relation in triggering angioedema attacks. METHODS: A questionnaire was filled in, recording date of birth, gender, and self-reported angioedema attacks associated with the ingestion of foodstuffs, administration of drugs, hymenoptera stings and hypersensitivity reactions against inhalation allergens. All participants performed a skin prick test against inhalation allergens and food. In patients who stated an association of possible hypersensitivity with angioedema, a serological ImmunoCAP test was also performed. RESULTS: From the 27 women and 15 men analyzed, 79% stated trigger factors. From those food was mentioned in 36%. The suspected food included tomato, green salad, fish, citrus fruits, apple, onion, garlic, cheese, chili, kiwi, milk, tree nuts, strawberry, pineapple, shrimps, bread, banana, leek, chicken and alcohol, and were associated with abdominal angioedema. Neither the skin prick test nor the ImmunoCAP-test turned out positive for the tested food allergens. CONCLUSION: Food seems to be a relevant trigger factor, causing angioedema in HAE affected patients. The reason, however, is not IgE-mediated hypersensitivity, but most probably an intolerance reaction to food products.

Childhood fish oil supplementation modifies associations between traffic related air pollution and allergic sensitisation.

BACKGROUND: Studies of potential adverse effects of traffic related air pollution (TRAP) on allergic disease have had mixed findings. Nutritional studies to examine whether fish oil supplementation may protect against development of allergic disease through their anti-inflammatory actions have also had mixed findings. Extremely few studies to date have considered whether air pollution and dietary factors such as fish oil intake may interact, which was the rationale for this study. METHODS: We conducted a secondary analysis of the Childhood Asthma Prevention Study (CAPS) birth cohort, where children were randomised to fish oil supplementation or placebo from early life to age 5 years. We examined interactions between supplementation and TRAP (using weighted road density at place of residence as our measure of traffic related air pollution exposure) with allergic disease and lung function outcomes at age 5 and 8 years. RESULTS: Outcome information was available on approximately 400 children (~ 70% of the original birth cohort). Statistically significant interactions between fish oil supplementation and TRAP were seen for house dust mite (HDM), inhalant and all-allergen skin prick tests (SPTs) and for HDM-specific interleukin-5 response at age 5. Adjusting for relevant confounders, relative risks (RRs) for positive HDM SPT were RR 1.74 (95% CI 1.22-2.48) per 100 m local road or 33.3 m of motorway within 50 m of the home for those randomised to the control group and 1.03 (0.76-1.41) for those randomised to receive the fish oil supplement. The risk differential was highest in an analysis restricted to those who did not change address between ages 5 and 8 years. In this sub-group, supplementation also protected against the effect of traffic exposure on pre-bronchodilator FEV1/FVC ratio. CONCLUSIONS: Results suggest that fish oil supplementation may protect against pro-allergic sensitisation effects of TRAP exposure. Strengths of this analysis are that supplementation was randomised and independent of TRAP exposure, however, findings need to be confirmed in a larger experimental study with the interaction investigated as a primary hypothesis, potentially also exploring epigenetic mechanisms. More generally, studies of adverse health effects of air pollution may benefit from considering potential effect modification by diet and other factors. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry. www.anzctr.org.au Registration: ACTRN12605000042640 , Date: 26th July 2005. Retrospectively registered, trial commenced prior to registry availability.

Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the Dots.

INTRODUCTION: Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF. Most importantly, we focused on treatment options targeting HT as a preventive strategy for delaying the progression of diastolic dysfunction or decreasing the odds for developing HFpEF. CONCLUSION: Along this line, we summarized the evidence and efficacy associated with different classes of antihypertensive medications in HFpEF patients. Finally, non-pharmacological approaches, including renal denervation and lifestyle modifications, to achieve optimal blood pressure (BP) control in HFpEF patients are reported. Unfortunately, no specific antihypertensive treatment has established a major survival benefit in this high risk subjects. Until the results of the efficacy of the novel drug LCZ696 (valsartan/ sacubitril) are available, the continuous monitoring and lowering of the BP by pharmacological and non-pharmacological means should be considered the major preventive and treatment strategy in HFpEF patients.

Hereditary angioedema due to C1 - inhibitor deficiency in Switzerland: clinical characteristics and therapeutic modalities within a cohort study.

BACKGROUND: Registration of trigger factors, prodromal symptoms, swelling localization, therapeutic behavior and gender-specific differences of the largest cohort of patients with hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) in Switzerland. METHODS: Questionnaire survey within a cohort study: Consenting eligible patients with diagnosed HAE according to clinical history, physical examination and laboratory results, including plasma values for C1-INH and C4 were selected. To each participant we sent a questionnaire assessing patients' birthday, sex, date of first symptoms and diagnosis, trigger factors, prodromal symptoms, frequency and localization of angioedema, medication use and co-morbidities. Clinical information was collected in each center and then transmitted to the cohort database. Frequencies and distributions were summarized. Associations between gender and trigger factors or prodromal symptoms or localization of angioedema were assessed in multivariate analyses correcting for patients' age. RESULTS: Of 135 patients, data from 104 patients (77%) were available for analysis. Fifty- four percent were female, mean age at diagnosis was 19.5 years (SD 14.1), Mean age when completing the questionnaire was 44.0 (SD 19.8). More women than men were symptomatic (44/57 vs. 36/47; p = 0.005). This association remained when correcting for age at diagnosis (16.10. 95%CI (5.17 to 26.70); p = 0.004). Swelling episodes ranged between 1 and 136 episodes/year. Swelling was more common among female than among male (-13.15 (95% CI; -23.10 to -3.22), p = 0.010). Age at diagnosis was inversely associated with the total number of attacks 0.50 (-0.88 to -.011); p = 0.012). One third of patients were on danazol prophylaxis. CONCLUSION: We found large differences of HAE in male and female both in terms of symptom number and swelling episodes. Women are more affected by intensity and frequency of angioedema episodes than men. Danazol treatment remains widely used as effective prophylaxis despite its side effects. New therapies which selectively influence the hormonal estrogen balance could open new therapeutic options mainly for women and maybe also for men.

Expert consensus on the rational clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, have recently been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. These fully human monoclonal antibodies selectively block PCSK9, thus permitting the low-density lipoprotein (LDL) receptor to effectively recycle to the surface of liver cells. The administration of these antibodies leads to robust LDL cholesterol (LDL-C) lowering by 50-60% on top of maximum hypolipidemic treatment. At least 4 randomized, placebo-controlled studies are under way and will address the question of whether the administration of these PCSK9 inhibitors is associated with a significant reduction of cardiovascular events. Because of the high cost associated with the use of these medications it is very important to consider which patients may gain the most benefit, at least until the results of outcome studies are available. In this Consensus paper, 34 clinicians/scientists define 3 groups of patients that should be currently considered as candidates for the use of these novel drugs. These include: 1a. Adults with established cardiovascular disease and LDL-C≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 1b. Adults with diabetes and established cardiovascular disease or chronic kidney disease or target organ damage and LDL-C ≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 2. Adults with familial hypercholesterolemia (FH) without established cardiovascular disease and LDL-C ≥130 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe (evolocumab is also indicated in children above 12 years with homozygous FH), and 3. Adults at high or very high cardiovascular risk who are statin intolerant and have an LDL-C ≥100 and ≥130 mg/dL, respectively, while on any tolerated hypolipidemic treatment.

Allergen-specific IL-5 responses in early childhood predict asthma at age eight.

BACKGROUND: The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life. METHODS: Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640), had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), 5 years (n = 370) and 8 years (n = 275). We measured interleukin (IL-) 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ), at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression. RESULTS: HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years. CONCLUSION: HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.

Left ventricle enlargement and increased systolic velocity in the mitral valve are indirect markers of the hepatopulmonary syndrome.

BACKGROUND AND AIMS: Hepatopulmonary syndrome (HPS) has been associated with left atrial enlargement, but the presence of other markers of left and right diastolic and/or systolic cardiac dysfunction has not been clarified. We prospectively evaluated the possible associations between echocardiographical-Doppler findings and HPS. METHODS: Seventy-nine cirrhotic patients without endogenous heart or pulmonary disease were included. HPS was diagnosed by the presence of increased arterial-alveolar-difference and intrapulmonary right-to-left shunt at contrast-enhanced transthoracic echocardiography. Echocardiographical systolic and diastolic indices, tissue Doppler imaging (TDI) of mitral and tricuspid annular motion and M-mode echocardiography measurements were recorded. RESULTS: Hepatopulmonary syndrome was diagnosed in 12 (15.2%) patients. Patients with compared with those without HPS had significantly younger age, albumin levels and saturation of oxygen (SaO(2)) in an erect position, but higher left ventricular end diastolic diameter (LVEDD), ejection fraction, E-wave peak velocity of tricuspid valve, left atrial volume, TDI E wave (early diastolic period) at the right free wall/tricuspid annulus (cm/s) and TDI S wave (systolic) at the left lateral wall/mitral annulus (TDI Smv). In multivariate analysis, the presence of HPS was found to be independently associated with younger age (P=0.027), lower SaO(2) in an erect position (P=0.023), higher LVEDD (P=0.019) and higher TDI Smv (P=0.026). LVEDD and TDI Smv offered good diagnostic accuracy for HPS diagnosis (AUROC/c-statistic: 0.724 and 0.736 respectively). CONCLUSIONS: We confirmed that in patients with cirrhosis, the development of HPS is associated with higher cardiac output and hyperdynamic circulation. Left ventricle enlargement and higher systolic velocity in the mitral valve represent satisfactory indirect markers of HPS.

IL-5 T-cell responses to house dust mite are associated with the development of allergen-specific IgE responses and asthma in the first 5 years of life.

BACKGROUND: Allergen-specific T(H)2-like cytokine responses are considered to be important in sensitization and allergic diseases. OBJECTIVE: To examine the profile of house dust mite (HDM) stimulated T-cell cytokines and their relationship to allergic disease in children over the period of the first 5 years of life. METHODS: Subjects with a family history of asthma who were enrolled antenatally in the Childhood Asthma Prevention Study and had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of lymphocyte cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), and 5 years (n = 370). IL-13 at 3 and 5 years and IL-5, IL-10, and IFN- gamma at 18 months, 3 years, and 5 years were measured by ELISA. RESULTS: House dust mite-specific cytokine responses increased with age for all cytokines except IFN-gamma. HDM-specific IL-5 responses at 3 years and 5 years were significantly positively related to skin prick test positivity at 5 years. IL-5 responses at 5 years were also significantly related to asthma at 5 years. Other HDM-specific cytokine responses were not related to asthma or eczema at 5 years. Responses were not altered by a HDM avoidance intervention. CONCLUSION: IL-5 responses to HDM, the dominant local inhalant allergen, are related to the expression of clinical illness at age 5 years. CLINICAL IMPLICATIONS: The T-cell response to HDM, as reflected in IL-5 production, is acquired over the first years of life and may play a role in the expression of allergic airways disease.

Pelvic osteomyelitis: a diagnostic challenge in children.

BACKGROUND: Acute hematogenous osteomyelitis (AHOM) in children usually occurs in tubular bones. Acute hematogenous osteomyelitis of the pelvis is rare and is often not recognized primarily. METHODS: To review the experience with pelvic AHOM at our institution, we analyzed records from children diagnosed with pelvic AHOM (1984-2003) and compared with those reported in the literature. RESULTS: Among 220 children with AHOM (median age, 6.4 years), those 19 (9%) with pelvic AHOM were significantly older (median age, 9.0 years; range, 0.04-15.6). All children presented with limping or refused to walk. Twelve of 19 patients were febrile, 16 of 18 had elevated C-reactive protein (>20 mg/L), and 6 of 19 had leukocytes greater than 12 G/L. Staphylococcus aureus was isolated from blood or bone aspirates in 9 of 17 patients, and Streptococcus pneumoniae was isolated in 1. Scintigraphy was diagnostic in 15 of 15 children, and magnetic resonance imaging in 7 of 7 children. The mean time between initial symptoms and diagnosis was 3 days (range, 1-8 days). Infection resolved completely in all children after antibiotic therapy. CONCLUSION: Pelvic AHOM should be considered in children with limping and pain referred to the hip, thigh, or abdomen. Diagnosis by scintigraphy or magnetic resonance imaging followed by local puncture and microbiological workup allows for specific antibiotic treatment and results in an excellent outcome of pelvic AHOM.

Genetic polymorphism on endothelial nitric oxide synthase affects endothelial activation and inflammatory response during the acute phase of myocardial infarction.

OBJECTIVES: This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event. BACKGROUND: Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown. METHODS: The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS: The risk for MI in 894TT was 1.992 (95% confidence interval [CI], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% CI, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vWF was higher in GT+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS: G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event.