Search

BACKGROUND Chronic cough is a common symptom, addressed in the clinical setting by empirical treatment together with some laboratory investigations. Purpose of the present study is to investigate the value of testing eosinophilic cationic protein (ECP) serum levels combined with other diagnostic procedures and empirical treatment in the diagnostic workup of chronic cough. METHODS In this study, we evaluated 194 patients with chronic cough. No subject had received any anti-inflammatory treatment before clinical evaluation, and none was an active smoker. ECP was measured with a commercially available fluoroenzyme immunoassay and results were expressed as µg/L. RESULTS The analysis of variance showed that mean ECP level differs among the various diagnosis categories (p < 0.001). Mean ECP level was significantly higher in asthmatic patients, particularly in the active disease. CONCLUSIONS Serum ECP concentration could represent a useful biomarker in the clinical work-up of chronic cough, managing to differentiate asthma from other chronic disorders.

Both obesity and diabetes play a significant role in reproductive disorders in women and insulin resistance (IR) is a confirmedWe recruited 32 female youths: 14 of them presented with T1D (14.6 ± 2.6 years) and 18 with obesity (15.1 ± 2.6 years). The control group included 20 age-matched normal weight females. Each patient underwent physical examination and hormonal assessment. AMH, kisspeptin and adiponectin levels were also measured. IR was calculated as the homeostasis model assessment for insulin resistance (HOMA-IR) and the glucose disposal rate (eGDR) in patients with obesity and with T1D, respectively.adiponectin and kisspeptin levels were significantly different into groups (IR displays a relationship with adiponectin and kisspeptin in young reproductive-aged women with obesity and T1D. Interventions to correct IR in adolescents could be part of an early approach to prevent reproductive disorders and to promote factors associated with longevity in adult women.

The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19.Neutrophils activated with PMA (PMA-Neu), a stimulus known to induce NETs formation, induce both EMT and cell death in the lung epithelial cell line, A549. Notably, NETs isolated from PMA-Neu induce EMT without cell damage. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1β, best-known inducers of NETosis. Lung tissues of COVID-19 deceased patients showed that epithelial cells are characterized by increased mesenchymal markers. These results show for the first time that NETosis plays a major role in triggering lung fibrosis in COVID-19 patients.

BACKGROUND A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD. STUDY In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured. RESULTS Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide. CONCLUSIONS The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients.

Summary Background and aims Non-Celiac Gluten Sensitivity (NCGS) is a recently proposed clinical condition causing both intestinal and extra-intestinal symptoms, without gastrointestinal lesions, which improve on avoiding gluten intake, in the absence of celiac disease and wheat allergy. The prevalence of this condition is still a matter of debate, in part due to the very recent introduction of an accepted diagnostic test, a double-blind, placebo controlled gluten challenge. However, this is a lengthy and cumbersome procedure, theoretically burdened by a significant reduction of patient compliance. ALCAT 5 is an automated in vitro test evaluating the toxic effect of gluten on neutrophils by the exposure of these cells to a gluten-containing extract of gluten-containing cereals. The test is very simple to perform, the results are rapidly obtained, and might represent, if sufficiently accurate, a promising alternative to diagnose gluten intolerance. The aim of this study was the comparison of ALCAT 5 results with those of a double-blind, placebo-controlled, gluten challenge, in a group of patients with clinically-suspected NCGS. Methods Twenty-five patients (M/F 3/22, mean age 32 ± 4 yrs) with severe functional abdominal pain and bloating, who had previously undergone the ALCAT 5 test, were enrolled. All the subjects reported their symptoms on a gluten-containing diet and considered gluten the causal agent. Following the Salerno Experts’ Criteria, they underwent a double-blind, placebo controlled trial with gluten vs placebo. A mean value during gluten ingestion >30% of the value during placebo was considered as indicative of gluten sensitivity. Results After blinded administration of gluten, 13 out of 25 (52%) patients showed an increase in the severity of abdominal pain, and 11 out of 25 (44%) showed an increase in the severity of abdominal bloating. Considering these two symptoms together, in 16 patients out of 25 (64%), blinded gluten administration induced an increase of abdominal pain and/or bloating. The ALCAT 5 test proved to be positive in 20 and negative in 5 patients. In sixteen patients out of 25 the result of ALCAT 5 agreed with the double-blind trial (64%). In particular, both tests were positive in 14 patients and negative in 2. Conclusions In this subgroup of patients, ALCAT 5 could be used to support the clinical suspicion of the presence of NCGS and to address these patients to a blinded gluten challenge.

The purpose of the study was to compare cytokines (CK) and chemokines concentrations in blood and cervico-vaginal samples between human papillomavirus (HPV)-positive and HPV-negative women, who had no previous history of HPV infection. A case-control study compares the activity and the concentration of CK/chemokines between 19 HPV-positive and 22 HPV-negative women matched by age. Plasma and cervico-vaginal levels of CK and chemokines were measured using cytofluorimetric analysis and expressed as mean of percentages. Plasma rates of interleukin (IL)-6 were significantly greater in HPV-negative women (mean value of 5.20±4.79 pg/ml) in comparison with HPV-positive women (mean value of 2.57±3.09 pg/ml) (p = 0.001). On the contrary, plasma levels of Eotaxin and hMCP-1 were significantly higher in HPV-positive women, with a mean value of 13.87±4.54 pg/ml (p = 0.022) and 53.53±19.51 pg/ml (p = 0.005), respectively. Differences in cervico-vaginal CK/chemokines concentrations were statistically not significant. Difference in plasma concentrations of IL-6, Eotaxin, IL-1β and hMCP-1 was statistically significant even by analyzing HPV-16/18 and multiple HPV genotypes infections. Primary HPV infection shows a characteristic pattern of plasma CK/chemokines concentration as opposed to HPV-negative subjects and persistent HPV infection. Keywords: chemokines; cytokines; HPV primary infection; plasma pattern.

Research Question Infections and/or inflammation processes of male genital tract are highly prevalent and often associated with risk of infertility. These conditions represent a possible cause of leukocytospermia, which is still under debate. Leukocytes are key-factors to reactive oxygen species (ROS) production and the increase of ROS in semen fluid is associated with the worsening of semen parameters. At present, there are not appropriate andrological tests to identify asymptomatic inflammatory conditions when the amount of leukocytes is in the normal range. Design We studied the innate immunity profile of myeloperoxidase and lactoferrin (MPO/LAC) proteins expressed in the semen fluid of 39 men evaluated for couple infertility, in the absence of leukocytospermia. Results The presence of both MPO and LAC proteins was associated with a decrease of sperm concentration and of progressive/total motility, whereas the increase of MPO-/LAC + indicated a worse sperm morphology. It is worth to report the predictive potential of MPO+/LAC + pattern (above 4.36 %) as a biological marker to distinguish normozoospermic from pathological patients. Conclusion Our findings indicate MPO/LAC analysis as a potential diagnostic tool to identify asymptomatic conditions eventually related to male infertility, even when the number of leukocytes in semen fluid is below 1 million/mL.

OBJECTIVE: To assess feasibility and efficacy of subtraction ictal SPECT coregistered to MRI (SISCOM) for epilepsy localization in children who are candidates for resective surgery. METHODS: We retrospectively reviewed all patients ≤16 years with drug-resistant epilepsy screened for epilepsy surgery in the University Hospital of Leuven from January 2009 to January 2018. Fifty-eight hospitalizations for ictal SPECT and 51 SISCOM analyses in 44 patients were included. Mean age was 9.1 years. Hospitalizations for SISCOM were analyzed in terms of multiple variables affecting feasibility and efficacy. The localization of SISCOM was compared with the localization of the presumed epileptogenic zone (PEZ) as determined by video-EEG. RESULTS: SISCOM was feasible in terms of chronic medication management, rescue antiepileptic therapy during hospitalization, and operative timings. Radiotracer injection occurred within 30 seconds from seizure onset in 91.4% of the patients. ictal SPECT imaging was performed within two hours from injection in 100% of the patients (mean: 40 minutes). SISCOM was able to localize the PEZ in 51.0% (26/51) and to additionally lateralize the PEZ in 17.6% (9/51), achieving better localizations than ictal SPECT, FDG-PET, and MRI (P

The only curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). PEA requires cardiopulmonary bypass (CPB) which is associated with a high acute kidney injury (AKI) risk. Circulating endothelin-1 (ET-1) levels are elevated in CTEPH, and ET-1 plays a pivotal role in AKI. Because AKI is burdened by high morbidity and mortality, we aimed to evaluate the association between preoperative ET-1 and the risk to develop AKI in CTEPH individuals who undergo PEA. We also evaluated the association of AKI and ET-1 with kidney function and mortality at 1 year after PEA. In 385 consecutive patients diagnosed with CTEPH who underwent PEA at the Foundation IRCC Policlinico San Matteo (Pavia, Italy) from January 2009 to April 2015, we assessed preoperative circulating ET-1 by ELISA and identified presence of AKI based on 2012 KDIGO criteria. AKI occurred in 26.5% of the 347 patients included in the analysis, and was independently associated with preoperative ET-1 (p = 0.008), body mass index (BMI) (p = 0.022), male gender (p = 0.005) and duration of CPB (p = 0.002). At 1-year post PEA, estimated glomerular filtration rate (eGFR) significantly improved in patients who did not develop AKI [ΔeGFR 5.6 ml/min/1.73 m2 (95% CI 3.6–7.6), p

Aim: Elevated calprotectin levels have been reported in obese adults but have not been evaluated in pediatric population. We investigated the characteristics of serum calprotectin in overweight and obese children and its association with metabolic comorbidities. Methods: We enrolled 131 children (11.7 ± 4.1 years). According to body mass index (BMI), the subjects were divided into 3 groups: obese > 95th percentile; overweight BMI 75th–95th percentile, and normal weight BMI < 75th percentile. Patients were classified as having Metabolic Syndrome if they met 3 or more of the following criteria for age and sex: BMI > 97th percentile, triglycerides > 95th percentile, high-density lipoprotein cholesterol < 5th percentile, systolic and/or diastolic blood pressure > 95th percentile, and impaired glucose tolerance. In all patients, calprotectin serum levels were also detected. Results: Calprotectin was higher in obese and overweight children than normal weight subjects (p < 0.001), with calprotectin in females being significantly higher than in males (p = 0.04). Increased calprotectin was related to pathological fasting blood glucose (p < 0.001) and insulin resistance (p = 0.03), while BMI (p = 0.001), and diastolic pressure (p = 0.001) are independent factors for increased calprotectin. Conclusions: Our findings confirm the association between increased calprotectin and obesity also in children and suggest the potential utility of this biomarker in the monitoring of its metabolic complications.

Background: Allergic rhinitis (AR) is a common disorder. The diagnosis is based on the concordance between allergy sensitization and history. Serum allergen specific immunoglobulin E (sIgE) assessment allows characterization of the relevant sensitizing allergens. Presently, Allergic Rhinitis and its Impact on Asthma (ARIA) classification subdivides AR based on symptoms severity and duration. However, the relationship between sIgE levels and symptom severity is still a matter of debate. Objective: Therefore, this study aimed at relating sIgE levels with symptom severity assessed by ARIA classification in a group of patients with AR. Methods: We enrolled 217 patients with AR (123 women; median age, 39.5 years). The sIgE levels (expressed in kUA/L) to house-dust mite were detected by the fluorescence enzyme immunoassay in peripheral blood samples. The IgE calibrators were traceable to the second international reference preparation 75/502 of human serum IgE from the World Health Organization. Symptom severity was assessed by ARIA classification. Results: We found a significant difference in sIgE levels in patients with mild intermittent versus mild persistent symptoms (p < 0.05), mild intermittent versus moderate-to-severe persistent symptoms (p < 0.001), moderate-to-severe intermittent versus moderate-to-severe persistent symptoms (p < 0.01), and mild persistent versus moderate-to-severe persistent symptoms (p < 0.05). Conclusion: Analysis of these findings indicated that the sIgE level to house-dust mite might be a reliable biomarker for symptom severity in patients with AR. This outcome might be clinically relevant, particularly in candidates for immunotherapy.

Background Pollen allergy may be frequently associated with fruit-vegetables: the so-called pollen food syndrome. Pru p 3 is the most relevant peach allergen. Previously, it has been reported that serum specific IgE level to Pru p 3 depends on age in a limited geographic area. Objective This study aimed to to test the hypothesis about the differences of Pru p 3 sensitization across Italy, mainly concerning the impact of age. Methods The current study was retrospective and multicentre, involving 2 labs in Northern Italy (709 subjects), 1 in Genoa (1,040 subjects), and 1 in Southern Italy (2,188 subjects). All of them referred to labs for IgE testing because of suspected food allergy. Serum IgE to Pru p 3 was assessed in all subjects. Results Sixteen point seven percent (16.7%) of subjects were sensitized to Pru p 3. Sensitization percentage sigificantly decreased over time. The serum IgE levels increased up to young adulthood and then decreased until aging. Conclusion Our experience demonstrates that Pru p 3 sensitization and production are closely age-dependent phenomena.

Complete interferon-γ receptor 1 deficiency is a monogenic primary immunodeficiency caused by IFNGR1 germline defects, with autosomal dominant or recessive inheritance, which results in invasive mycobacterial diseases with varying degrees of severity. Most of the autosomal recessive IFNGR1 mutations are homozygous loss-of-function single-nucleotide variants, whereas large genomic deletions and compound heterozygosity have been very rarely reported. Herein we describe the clinical presentation, diagnosis, and successful treatment with hematopoietic stem cell transplantation of a child with disseminated Mycobacterium avium infection due to compound heterozygosity for a subpolymorphic copy number variation and a novel splice-site variant.

Introduction: Allostatic load (AL) refers to the physiological response associated with the burden of chronic stress. Excessive weight is an important source of physiological stress that promotes a detrimental chronic low-inflammation state. In order to define a correlation between cumulative biological dysregulation and excess weight, we measured AL scores in a pediatric population.Patients and Methods: We enrolled 164 children and adolescents (11.89 ± 3.89). According to their body mass index (BMI) threshold, subjects were classified as normal in the BMI < 75th percentile, overweight in the BMI 75–95th percentile or obese in the BMI >95th percentile. Data based on 16 biomarkers were used to create the AL score. A dichotomous outcome for high AL was defined in those who had more than four dysregulated components.Results: High AL was noted in 88/164 subjects (53.65%), without significant differences between genders (p = 0.07) or pubertal status (p = 0.10). Subjects with a high AL, in addition to a higher BMI (p < 0.001), showed higher WC and WC/HtR (p < 0.001), triglycerides (p = 0.002), fasting blood glucose (p = 0.03), insulin resistance (p < 0.001), systolic (p < 0.001) and diastolic blood pressure (p = 0.001), GGT (p = 0.01), PCR (p = 0.01), and calprotectin (p < 0.01) as well as lower HDL cholesterol (p = 0.002) than subjects with a low AL. The rate of the cumulative biological dysregulation increased progressively with increases in BMI (p < 0.001).Conclusions: A high AL was associated with excess weight. AL may be considered a significant factor correlated with increased morbidity in children who are overweight/obese.

Primary eosinophilic gastrointestinal disorders (EGIDs) are emerging chronic/remittent inflammatory diseases of unknown etiology, which may involve any part of the gastrointestinal (GI) tract, in the absence of secondary causes of GI eosinophilia. Eosinophilic esophagitis is the prototype of eosinophilic gastrointestinal disorders and is clinically characterized by symptoms related to esophageal inflammation and dysfunction. A few studies have assessed the nutritional status of patients with eosinophilic gastrointestinal disorders, showing conflicting results. This review summarizes the current evidence on the nutritional status of patients with EGIDs, focusing on the pediatric point of view and also speculating potential etiological mechanisms.

Weight loss surgery (WLS) is efficacious for long-term weight reduction and decreases overall mortality in severely obese patients. The mechanisms implicated in long-term weight loss are not fully understood. Proposed mechanisms include changes in gut hormones and brain regulation of appetite and satiety. We aimed to investigate the long-term ghrelin and leptin profiles and changes in food preference and eating behavior after WLS in adolescent patients. Two obese females aged 15 years and 14 4/12 years, who did not respond to lifestyle changes, including dietary intervention and physical exercise in combination with medical therapy, underwent robotic-assisted gastroplication. Anthropometric measurements, food habits and eating behavior, as well as metabolic and hormonal changes during long-term post-surgical follow-up were monitored. Long-term weight reduction was obtained in both patients, with a significant decrease in waist circumference. Resting energy expenditure showed a decrease over time, with a respiratory quotient that increased showing a shift from oxidation of a high-fat diet before surgery to oxidation of a mixed diet two and three years later. Both subjects improved their eating habits and lifestyle. Co-morbidity resolution was also noted. Increased pre-prandial ghrelin levels as well as higher post-prandial ghrelin and a leptin drop compared with pre-surgery values were observed in both patients. Persistent weight loss after gastroplication is associated with a favorable change in gut hormones and food preferences. The role of hormonal and sensory components in long-term results seems crucial. Particularly in adolescent patients, a multidisciplinary approach and continuous nutritional care is mandatory for weight maintenance and consolidation of changes.

Background/Aims: Patients with type 1 diabetes mellitus (T1DM), autoimmune thyroiditis (ATD), and celiac disease (CD) are at increased risk for developing other autoimmune diseases. We evaluated zinc transporter 8 (ZnT8) prevalence in patients with ATD and/or CD in order to define the usefulness of ZnT8 autoantibodies for prediabetes screening. Methods: Eighty-one young patients with ATD and/or CD were included in the study; 32 subjects with clinical onset of T1DM were enrolled as a control group. GAD65, IA-2, and ZnT8 antibodies were measured. An intravenous glucose tolerance test, C-peptide, glycosylated hemoglobin levels, and genomic analysis of HLA-DQA1* and -DQB1* were also considered in patients positive for autoantibodies. Results: The ZnT8 prevalence was higher in T1DM patients than in patients with other autoimmune diseases (p < 0.001); positive ZnT8 detection was found in 2 ATD (p = 0.004) and 3 ATD + CD (p = 0.04) patients. Positive ZnT8 was associated with GAD65 (p = 0.01) but not with IA-2 positivity. No correlation between ZnT8 detection and the number of T1DM-susceptible HLA-DQ heterodimers was found. Pathological C-peptide levels and insulin response were found in subjects with islet autoimmunity and genetic susceptibility. Conclusion: ZnT8 autoantibodies detection in ATD and/or CD patients is low, and routine ZnT8 screening is not justified. ZnT8 evaluation may be recommended in subjects with autoimmune diseases as a marker for predicting compromised insulin secretion.

The basophil activation is emerging as a reliable and robust in vitro biomarker of in vivo allergy reactions. Basophil Activation Test (BAT), intended as in vitro stimulation of patient blood basophil with allergens, followed by flow cytometric detection and quantification of such activation, is nowadays a well-established assay in a growing number of routine diagnostic labs. The advancements in the standardization of BAT testing and first convincing clinical evidence are behind this spreading of the assay in clinical lab. BAT is essentially an assay with superior specificity compared to any other allergy testing and, if appropriately used, it can have a valuable clinical utility in different field of allergy diagnosis. In drug allergy, very few testing opportunities are available for the numbers of drugs actually in the market. Antibiotics and analgesics are just two of the categories of drugs were BAT testing can have an added value for the limited specificity of IgE testing or limited availability of other lab testing. In food allergy, BAT is emerging as the more accurate assay to predict an in vivo reaction to food, helping in the discrimination of patients that are only sensitized versus the patient really allergic to an allergen. Furthermore, BAT testing determining the basophil sensitivity can be useful for monitoring the natural resolution of allergies and clinical responses to immunomodulatory treatment for food allergies. For this characteristic, BAT has the potential to reduce the need of OFC. In the hymenoptera venom allergy, BAT is an effective tool in identifying primary sensitizing antigen and in the follow up of patient in venom immunotherapy. With this review, we want to present current state of BAT testing focusing on the clinical laboratory parameters and issue of this assay. A highlight on the standardization needs of BAT is provided, together with considerations on further developments and clinical evidences still to be achieved.

Background The purpose of this study was to determine headache characteristics, impact on daily activities and medication attitudes among a large sample of adolescents in Italy. Methods Secondary school classes were randomly selected from a national stratified multistage sampling. Data regarding socio-familial factors, headache characteristics, impact on daily activities and medication use were recorded with an anonymous multiple-choice questionnaire. Results The survey involved 2064 adolescents. 1950 questionnaires were considered for analysis. Study population included 944 males (48.4%) and 1006 females (51.6%), aged between 11 and 16 years (mean 13.5 ± 1.87). Headache prevalence was 65.9%. Mean age at headache onset was 8.33 years. 9.8% suffered from headache > 1/week, 14.3% > 1/month, 24.2% monthly and 17.7% less than monthly. The mean duration of a headache episode was less than 30 min in 32.9%, 1 hour in 28.1%, 2 hours in 19.3% and several hours in 19.5%. Pain intensity was moderate in 52.2% and severe in 9.5%. School represented the main trigger factor (67%). Impact on daily activities was noted in 57.5%. 69.2% of adolescents reported the use of pain relievers. Up to 5.7% declared self-medication, while only 20.6% followed a physician’s prescription. Female adolescents experienced headache more frequently (70.2% vs 60%) and more intensely than male peers. Girls had a higher family history of headache, could more frequently identify a trigger factor, and were more affected into their daily activities than boys. Conclusions Population-based studies of headache disorders are important, as they inform needs assessment and underpin service policy for a disease that is a public-health priority. Headache has a high prevalence among adolescents and carries a significant burden in terms of impact on daily activities and use of medication. Furthermore, underdiagnose is common, while trigger factors are often detectable. Special consideration should be given to female adolescents and self-medication attitudes.

Introduction.The correct diagnosis of neonatal sepsis is a relevant problem because sepsis is one of the most important causes of neonatal morbidity, mortality, and prolonged hospital stay. Calprotectin is an antimicrobial, calcium and zinc binding heterocomplex protein that could be used as a nonspecific marker for activation of granulocytes and mononuclear phagocytes. Calprotectin has been proposed for the diagnosis of inflammatory conditions. Our aim is to study serum calprotectin as a biomarker for neonatal sepsis diagnosis.Methods.41 (20 females, 21 males) infants who underwent blood culture due to suspected sepsis were enrolled in the study. Serum calprotectin was measured by a commercial ELISA assay (Calprest, Eurospital, Trieste, Italy). Statistical analysis was performed using the statistical software package Stata 13.1 (Stata Corporation, College Station, Texas, USA).Results.8 neonates (19.51%) showed sepsis with positive culture and 33 (80.49%) showed suspected sepsis. The optimal cut-off for calprotectin is 2.2 μg/mL with a sensitivity of 62.5% and a specificity of 69.7%.Conclusions.Calprotectin may be considered a promising early, sensitive, specific marker of sepsis thanks to the importance of calprotectin in defense mechanisms and physiological functions of the immune system.

Background: Cardiovascular risk is reported in disabled children and epicardial fat (EF) is considered an independent predictor of cardiovascular disease (CVD). No data on the EF thickness (EFT) evaluation in disabled children have been published. Objective: We investigated EFT in neurologically impaired (NI) children; its relationship with their metabolic profile was also considered. Methods: Clinical data, body composition estimation, biochemical profile, and ultrasound-measured EFT were performed in 32 disabled patients (12.4 ± 6.3 years). Pathological parameters were defined using the following criteria: waist circumference >95th percentile, waist to height ratio (WHtR) >0.5, total cholesterol and triglycerides (TG) values >95th percentile, high density lipoprotein cholesterol 100 mg/dL, homeostasis model assessment for insulin resistance (HOMA) >97.5th percentile, and EFT >3.6 mm. Results: EFT values in NI children were higher compared with control group values (p = 0.02). EFT correlated with gender (p < 0.001), age (p = 0.02), pubertal stage (p = 0.04), as well as WHtR (p = 0.03). A correlation between EFT and leptin was also noted (p = 0.04). EFT levels significantly correlated with pathological TG (p = 0.01) and HOMA-IR (p = 0.04). Conclusions: Higher EFT was observed in NI children compared with controls. EFT values correlated with clinical, metabolic, and endocrinological parameters. Ultrasound-measured EFT could be used to promptly detect subclinical CVD and to prevent adverse outcomes in disabled children.

Background: Allostatic load (AL) is the cumulative physiological wear and tear that results from repeated efforts to adapt to stressors over time. The life stress response is modified by nutritional status. Aim: We estimated AL scores among neurologically impaired (NI) children; the association with malnutrition was also evaluated. Methods: Forty-one patients with severe disabilities were included. Data based on 15 biomarkers were used to create the AL score. A dichotomous outcome of high AL was defined for those who had ≥6 dysregulated components. Body mass index (BMI)-standard deviation score (SDS) Results: High AL was noted in 17/41 of the whole sample (41.47%). Malnutrition occurred in 36.6% of the subjects. A significant correlation between high AL and malnutrition was observed (p = 0.01; ar ea under the receiver operating characteristic curve, 0.7457). High AL subjects had a significantly higher BMI (p = 0.009) and lower BMI-SDS (p = 0.003) than low AL subjects. AL score correlated with fat mass (p ≤ 0.01) and negatively correlated with fat-free mass (p ≤ 0.02). Conclusion: In NI children, high AL was associated with malnutrition. Body composition is a better indicator than BMI of allostatic adjustments. AL estimation should be considered a measure of health risk and be used to promote quality of life in at-risk disabled populations.

Background: Plasma soluble interleukin-2 receptor alpha (sIL-2Rα), that is released from the cell surface of activated T and B lymphocytes, is one of the best markers of immune activation. High levels of sIL-2Rα have been correlated with poor prognosis in different types of cancers. In patients with primary myelofibrosis (PMF) elevated plasma levels of the receptor are associated with risk of blast transformation and death. In this study we aimed to analyze how increased levels of sIL-2Rα mark the disease progression to improve our knowledge on the immune regulation of the disease. Methods: sIL-2Rα plasma concentration values were obtained by a commercial immunoassay (R&D Systems), according to the Manufacturer's Instructions, and expressed in pg/ml. Health care data of persons with PMF were obtained from the data-base of the Center for the Study of Myelofibrosis at the IRCCS Policlinico S. Matteo Foundation in Pavia. We excluded persons treated with disease-modifying drugs at any time before or on the date of base-cohort entry, and persons with acute inflammatory diseases, autoimmune diseases, other neoplasms, and severe liver or renal dysfunction. The final study cohort consisted of 300 subjects. Thirty-four healthy normal subjects matched for age and sex represented the control group. The study was approved by the local Ethic Committee, and was conducted complying with the principles of the Declaration of Helsinki. Results: In patients with PMF, plasma sIL-2Rα values ranged from 275 to 13,860 pg/ml, with a mean value of 1693 ± 1529 pg/mL standard deviation (SD). sIL2Rα metrics in healthy controls were: mean, 740 ± 346 pg/mL (SD), range, 207 to 1718 pg/mL. Difference in plasma sIL2Rα levels between subjects with PMF and normals was significant (P 10 cm from the left costal margin), 26 (24.1%) leukocytosis (WBC >12 x109/L), and 22 (20.4%) an alarming number of HSP-CD34+ cells in PB (>100 x 106/L). Moreover, 10 (9.2%) received an allogeneic hematopoietic stem cell transplantation (HSCT), 15 (13.8%) incurred in blast transformation (BT), and 8 (7.4%) died. In patients with JAK2V617F mutation, having elevated level of sIL-2Rα gave a higher risk of incurring in severe anemia (hazard ratio (HR), 3.70, 95% CI, 1.31-10; P=0.009), large splenomegaly (HR, 8.33; 95% CI, 2.12-33.3; P=0.002) and alarming HSP-CD34+ cells (HR, 4.14; 95% CI, 1.02-20; P=0.050). Moreover, JAK2V617F mutants with elevated levels of sIL-2Rα had higher risk of death than those with non-elevated sIL-2Rα (HR, 9.09; 95% CI, 1.75-50; P=0.008). On the contrary, in CALR mutants no interaction with the levels of sIL-2Rα and risk of disease progression was evidenced. By using a composite endpoint that considered death for any cause, BT or HSCT, PMF patients with JAK2V617F mutation carrying an elevated sIL-2Rα presented a shorter time to event as compared to those with non-elevated sIL-2Rα (P=0.011), while in CALR mutants this difference disappeared (P=0.80) (Figure). Conclusion: The results of this study give a strong proof of concept that the immune landscape of PMF is associated with the presence/absence of JAK2V617F or CALR mutation. Acquiring direct evidence that elevated levels of sIL-2Rα represents an immune- mediated modality of disease progression in JAK2V617F but not in CALR mutated patients opens new areas of investigation towards an individualized therapeutic approach of PMF. Figure Disclosures No relevant conflicts of interest to declare.

Aging is accompanied by a progressive decline in almost all functions of the immune system. To investigate a possible impact of age on IgE production, this study evaluated total and allergen-specific serum IgE levels in a large cohort of allergic patients. This study included 6,370 allergic patients (2,961 females, 3,409 males; mean age, 21.7 years; age range, 0-96 years). Total and allergen-specific serum IgE levels were measured by immunoenzymatic assay. The analysis of variance showed a significant difference (P

Background:Malnutrition is reported in pediatric neuromotor disability and impacts the child’s health. We described the nutritional and metabolic status in neurologically impaired (NI) children undergoing surgery.Methods:Anthropometry, body composition, hormonal and nutritional evaluations were performed in 44 NI subjects (13.7±8.0 years). Energy needs were calculated by Krick’s formula. Metabolic syndrome (MS) was defined applying the following criteria (≥3 defined MS): fasting blood glucose >100 mg/dL and/or homeostasis model assessment for insulin resistance (HOMA-IR) >97.5th percentile, trygliceride level >95th percentile, high-density lipoprotein (HDL)-cholesterol level 95th percentile; whilebody mass index – standard deviation score (BMI-SDS) Results:Energy intake was not adequate in 73.8% of the patients; no correlation between energy intake and BMI was noted. Undernutrition was noted in 34.1% of patients and MS in 11.36% of subjects. Fifty percent of the patients presented with insulin resistance, which was not related to BMI, body composition or other MS components.Conclusions:Nutritional and metabolic monitoring of disabled children and young adults is recommended to prevent adverse outcomes associated with malnutrition.

To the editor: Although primary myelofibrosis (PMF) is generally regarded as arising from a mutated stem or progenitor hematopoietic cell, immune dysregulation is common. For example, there are increased plasma levels of inflammatory cytokines and clinical and laboratory manifestations of

Little is known about soluble HLA-G (sHLA-G) concentrations in obese pregnant women with uncomplicated pregnancies.To investigate the role of sHLA-G in obese pregnancies.Case-control study, from 2013 to 2015.A tertiary care centre.168 healthy normal weight women and 59 overweight/obese women; to avoid the effect of preeclampsia on sHLA-G concentrations, cases were further divided in two groups: 42 with normotensive pregnancy and 17 who developed preeclampsia.all the women enrolled received standard antenatal care and plasma sample collections were performed.sHLA-G concentrations during pregnancy, before delivery and in cord blood.Maternal sHLA-G concentrations in overweight/obese with normotensive pregnancies increased by 14.7% (IQR=-26.4 to +89.6) in the 2nd trimester and by 19.6% (IQR=-33 to +104) before delivery and were significantly higher than in controls (p=0.024). Median cord blood sHLA-G concentrations were 53.5ng/ml (IQR=36-62.7) in the overweight/obese women with uncomplicated pregnancies (p0.001 compared to controls) and 19.7ng/ml (IQR=7.5-36.3) in controls. Maternal concentrations of sHLA-G in the two trimesters and before delivery were significantly lower among subjects who developed preeclampsia than in controls (p0.001) or in obese subjects with normotensive pregnancies (p0.001).sHLA-G concentratons are higher in normotensive overweight/obese women and their babies while lower in preeclamptic overweight/obese women and their cords. Obesity influences maternal and fetal sHLA-G concentrations during pregnancy, to optimize the reproductive success, while preeclampsia impairs the mother-offspring antinflammatory response.

Objectives: This study included a cohort of advanced renal cell carcinoma patients treated with sunitinib. Since resistance to sunitinib may be mediated through angiogenic cytokines other than VEGF, we measured the circulating levels of three pro-angiogenic cytokines: basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin (IL)-6. Methods: Cytokines were measured at baseline and on the first day of each treatment cycle until progression in 85 advanced kidney cancer patients treated with sunitinib using a quantitative sandwich enzyme immunoassay (ELISA) technique. Results: Even though no statistically significant differences in the titers of the three cytokines were observed between baseline and the time of progression in the whole patient cohort, in 45.3, 46.6, and 37.3% of the patients a more than 50% increase between baseline and the time of progression was shown in circulating IL-6, bFGF, and HGF, respectively. Furthermore, this increase was more than 100% in 37.3, 44, and 30.6% of the patients, respectively. We also demonstrated that, in these patients, cytokines tended to increase and to remain high immediately before progression. Conclusions: In a large percentage of kidney cancer patients, progression is preceded by a significant increase in pro-angiogenic cytokines other than VEGF.

Atopic dermatitis (AD) is an inflammatory disorder of the skin characterized by impaired immune response. Th9 cells are a sub-population of T cells that release interleukin (IL)-9. No study has investigated the role of IL-9 in AD. This study compared 64 children with AD with 45 healthy children. Serum IL-9 levels were measured and clinical symptoms were assessed. Children with AD had higher serum IL-9 levels than controls (p = 0.01). Clinical severity was significantly related to IL-9 level, indicating that IL-9 might exert a pathogenic role in symptom occurrence in individuals with AD. Children with AD may have higher serum IL-9 levels than healthy children, and IL-9 levels are significantly related to symptom severity.

Background: Dendritic cells (DC) play a key role in cell-mediated immunity. We aimed to analyse the number and function of peripheral blood (PB) myeloid and plasmacytoid DC (mDC/pDC) in patients with severe sepsis. Methods: Twenty-six septic patients, 20 surgical patients (abdominal aortic aneurysm) and 20 healthy controls were enrolled in this prospective study. Results: At day 1 (enrollment in the study), septic patients showed in comparison with healthy controls, decreased mDC (P < 0.001) and increased pDC (P = 0.03), resulting in a reduction of the mDC/pDC ratio (P < 0.001). Surgery induced a decrease in both mDCs and pDCs level, without modification of mDC/pDC ratio. Septic patients included 15 survivors and 11 nonsurvivors. At day 1 no significant difference was found in mDC between the two groups, while pDCs were significantly higher in nonsurvivors (P = 0.03). At the outcome, mDC were selectively increased with respect to day 1 in survivors (P = 0.001), while no significant differences were observed as far as pDC count is concerned in both groups. Sorted DC from septic patients showed in comparison with healthy controls, reduced levels of HLA DR (P < 0.001), CD11c (P < 0.001), CD83 (P = 0.006) and of costimulatory molecule CD86 (P = 0.003); an up-regulation of chemokine receptor CXCR4 (P = 0.031) and increased apoptosis (P < 0.001). Conclusions: Sepsis has a profound effect on PB DC compartment. These alterations appear to be sepsis-specific. Increased apoptosis and alteration of migration and trafficking mechanism may be involved in DC compartment modification. DC alterations could contribute to sepsis-mediated immunoparalysis. © 2010 International Clinical Cytometry Society

Background A few studies have outlined a possible relationship between an increased body mass index and allergic rhinitis. A single study reported that males with seasonal allergic rhinitis (SAR), evaluated outside the pollen season, had increased serum adiponectin levels. Objective The aim of this preliminary study was to evaluate the serum adiponectin levels in a cohort of SAR normo-weight patients evaluated during the pollen season, comparing them with SAR patients evaluated out of pollen season and a group of healthy controls. Methods The study included 137 subjects; 62 SAR patients evaluated in their pollen season, while symptomatic, 41 SAR patients studied out their pollen season, while they were without symptoms, and 34 normal subjects. All subjects were consecutively evaluated. All of them were normo-weight. A skin prick test and blood sampling for assessing serum adiponectin levels were performed in all subjects. Results After analysing genders separately, symptomatic male patients had significantly higher levels than both symptomless and normal males ( p = 0.0041 and 0.0001 respectively), symptomatic female patients showed significantly higher levels than both symptomless and normal females ( p = 0.0001 and 0.0071 respectively). Conclusion This study provides the preliminary evidence that adiponectin serum levels might depend on allergen exposure in SAR normo-weight patients.

Background:Allergic rhinitis (AR) is characterized by inflammation sustained by dysregulated immune response. T-regulatory cells are involved in AR pathogenesis, mainly producing IL-10 and transforming growth factor (TGF)-β. Indeed, there is a functional and allergen-specific defect of T-regulatory cells in AR. However, there are no data about the influence of allergen exposure on TGF-β serum levels. Therefore, the aim of this preliminary study was to evaluate TGF-β serum levels in patients with seasonal AR. Patients were evaluated either outside the pollen season and after 1 preseasonal sublingual immunotherapy (SLIT) course (38 subjects) or during the pollen season (57 subjects). Methods:All patients were allergic to Parietaria and/or grasses alone. TGF-β was measured by a commercially available kit. Symptoms, drug use and eosinophils were evaluated.Serum allergen-specific IgG and IgA levels were also measured by the ELISA method. Results:TGF-β serum levels were significantly lower in patients evaluated outside the pollen season in comparison with the other 2 situations. SLIT induced the significantly highest TGF-β serum levels. There was a significant negative relationship between TGF-β and eosinophils in patients after SLIT. IgG and IgA levels were higher in SLIT-treated patients. Conclusion: This preliminary study provides evidence that TGF-β serum levels are significantly dependent on allergen exposure.

Several studies have outlined a possible relationship between an increased body mass index (BMI) and respiratory allergic diseases, such as asthma and rhinitis. Very recently, it has been demonstrated that serum adipokines, such as leptin and adiponectin, may be increased in patients with allergic rhinitis. The aim of the study was to evaluate the serum leptin and adiponectin levels in a cohort of patients with pollen-induced allergic rhinitis, before and after a single preseasonal course of sublingual immunotherapy (SLIT). A total of 41 patients (22 male and 19 female, median age 39 years) with AR due to pollen allergy, along with 34 normal subjects, were included in the study. Blood sampling for assessing serum adipokines, immunoglobulin E (IgE) levels, and eosinophils were performed in all subjects before and after the SLIT course. An increasing trend of both adipokines was observed after SLIT, albeit without statistical significance and with gender difference. Leptin was significantly related to some clinical parameters and peripheral eosinophil counts. Conversely, adinopectin showed an inverse significant correlation with peripheral eosinophils counts but only for men. In conclusion, the results of this preliminary study show that a single preseasonal SLIT course does not induce significant modifications in serum adipokines levels but induces only a slight increase.

Asthma allergic rhinitis and atopic dermatitis are multifactorial disorders influenced by various familial and environmental factors. The correlation between maternal and fetal immunoglobulin E (IgE) seems to be caused by genetic factors rather than placental transfer. The purpose of this study was to evaluate and quantify the relationship of IgE levels between mothers and their offspring during the 1st year of life. Total serum IgE levels were assessed in 104 healthy pregnant women just before delivery, as well as in 104 newborns in the 1st days of life and then again at 3, 5, 6, 11 and 12 months of age. A serum IgE increase in infants during the 1st year of life is related to maternal serum IgE levels (and may be divided into three classes, according to IgE concentrations of100,100, and260 kU/L), as shown by significant correlation coefficients and regression slopes. Our findings show that IgE levels in infants of mothers who presented serum IgE levels of100 kU/L exceeded the norm during the 1st year of life, in the absence of overt atopic disease. It seems useful to consider different categories of infants, as a function of their mothers' IgE, to plan a particular follow-up for children in higher risk classes.

Dear Editor, B-cell chronic lymphocytic leukemia (B-CLL) patients with unmutated IgV genes frequently show trisomy 12 and a poor clinical outcome, while those with mutated IgV genes often show 13q14 deletions (13q−) and a favorable prognosis [1]. A small B-CLL proportion may present with a serum monoclonal component and lympho-plasmacytoid elements, distinguishable from those CD5− and CD23− cells of lympho-plasmacytoid lymphoma [2]. Fludarabine is a very effective drug for the treatment of B-CLL [3] and indolent lymphomas [4]. However, it is associated with decreased immuno-surveillance determining a high incidence of opportunistic infections and secondary cancers [5]. Moreover, the occurrence of a large B-cell lymphoma, referred to as Richter’s syndrome (RS), is one possible natural evolution even in untreated B-CLL patients [6]. Herein, we report on a 58-year-old woman in apparent good health who came to our clinic for evaluation because of the incidental discovery of hyperleucocytosis. Her clinical parameters and biological findings at diagnosis and during the follow-up are summarized in Table 1. She never showed any monoclonal component in either serum or urine samples; however, 1 month after the fourth course of fludarabine dual monoclonal components (12.0 g/dl), both typified as IgG kappa were detected in the serum (Fig. 1c and d). On admission to our ward, a lymphnode biopsy demonstrated the complete disruption of the normal architecture by a lymphomatous B-cell population, which presented a parafollicular and nodular pattern of infiltration. This cell population was formed by small mature B-cells, lympho-plasmacytoid elements and plasma cells, prolymphocytes and paraimmunoblasts. These last cells were grouped in nodular aggregates, that constituted 24% of the entire cell population. In conclusion, the lymphnode histology pointed to a B-CLL in RS evolution. On clinical diagnosis and during the follow-up, flourescent in situ hybridization (FISH) was always performed with the CLL probe panel, including the following five multicolor probes: LSI p53/LSI ATM/LSI D13S319/LSI 13q34/CEP 12 (Vysis, Downers Grove, IL, USA). At diagnosis, loss of one D13S319 locus was revealed in 48% of marrow cells (Fig. 1e), whereas upon progression, the same locus was Ann Hematol (2007) 86:619–622 DOI 10.1007/s00277-007-0281-y

Background Protocols of controlled ovarian hyper-stimulation (COH) require, as a crucial step, the identification of reliable predictors of ovarian reserve. Anti-Mullerian hormone (AMH) is one of the most reliable predictors of ovarian reserve but other factors including autoimmune thyroid diseases (ATD) have been associated with reduced fertility and poor COH outcome. Aim of the present study was to evaluate the relationship between ATD and AMH, and their role on the outcome of COH. Methods The study group included 288 sub-fertile euthyroid women aged less than 40 years attending a single center for Reproductive Medicine. Among them, 55 were ATD-positive and 233 ATD-negative. The serum levels of AMH, FSH, LH, estradiol (E2), and TSH were measured before COH. The ratio between serum E2 concentration on the day of oocytes pick-up and the total dose of administered recombinant FSH (r-FSH) (E2/r-FSH ratio) was calculated. Results The serum levels of AMH were significantly related to E2/r-FSH ratio, total dose of r-FSH and number of M II oocytes, both in ATD-positive and ATD-negative women. Within the low stratum of AMH levels, the presence of ATD did not further affect the outcome of COH. When the serum levels of AMH were in the high stratum, the presence of ATD significantly affected the E2/rFSH ratio, the total dose of r-FSH and the number of M II oocytes. Conclusions The probability of a poor response to COH is high, and independent from ATD, in women with low AMH serum levels. In women with a good ovarian reserve, as assessed by high AMH serum levels, the presence of ATD impairs the outcome of COH.

Adenoid hypertrophy (AH) is very common in children and can cause airway obstruction. The aim of this retrospective study was to investigate the relationship between AH and other factors, including age, possible related symptoms, and allergies.Seven hundred and ninety-five patients (460 males, 335 females; mean age=5.9 years; range age: 1-14 years) were seen in an ENT clinic for nasal symptoms. Nasal endoscopy was performed with a pediatric flexible endoscope. One hundred and sixty-nine patients had documented allergy sensitization. Patients were divided into two groups according to their age: group 1 included children aged 1-7 years, and group 2 included subjects aged 8-14 years.Adenoid size was related to age (p0.0001). A logistic regression model - performed to evaluate adenoid grade considering, as dependent variables, age, sex, and the presence or absence of symptoms - was statistically significant (p0.001). Moreover, AH was more common (p=0.0104) in patients with allergy sensitization, in particular in patients aged 8-14 years (p=0.0043). Nasal obstruction (OR=3.27) significantly predicted AH, whereas major age was not associated with pathological AH (OR=0.81).The present retrospective study described the relationship between AH and other demographic and clinical factors. In conclusion, our findings demonstrated a significant association among pathological AH, age, and nasal obstruction.

We report a case of a patient with myelofibrosis with myeloid metaplasia (MMM) who presented with progressive dyspnea of unexplained origin. Splenomegaly, blood smear, and bone marrow findings allowed diagnosis of MMM. High-resolution CT chest scan revealed diffuse septal thickening, while echocardiography and electrocardiogram showed no indirect evidence of pulmonary hypertension. Finally, lung biopsy revealed irregularly distributed interstitial fibrosis with islands of erythroblasts, immature granulocytic elements, and dysplastic megakaryocytes, allowing diagnosis of pulmonary extramedullary hematopoiesis (EMH). The patient received hydroxyurea as cytoreductive agent, obtaining a good hematologic response and an improvement of dyspnea. Note that, in this patient, dyspnea was the first clinical symptom of MMM; the dyspnea was not associated with pulmonary hypertension and improved following cytoreductive treatment. This case points to the importance of suspecting pulmonary EMH when unexplained progressive dyspnea occurs in a patient with MMM. Early recognition of pulmonary EMH may prevent PH and favor a better response to therapy.

We treated with thalidomide seven patients with primary MDS and observed reduction of the transfusion requirement in three cases and reduction of bone marrow blasts in one case. The apoptotic rate of bone marrow cells diminished significantly from a mean of 43.8% to a mean of 17.5%, whereas the proliferative activity did not change. Plasma TNF-α, bFGF, IL-1β levels decreased variably, whereas VEGF levels tended to increase. Matrix metalloproteinases 2 and 9 expression decreased in bone marrow cells of responders. A reduction of CD4 cells and an increase of NK cells was observed in the peripheral blood. Thus, thalidomide may produce a fairly good hematological improvement in erythroid series in MDS, with complex biological mechanisms.

RAGE is a transmembrane receptor expressed on immune and endothelial cells, whose binding with its ligands, the S100 calgranulins, leads to chronic inflammation. Conversely, its soluble form (sRAGE) plays a protective role by acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and S100A12 serum levels in patients with Crohn’s disease (CD) and ulcerative colitis (UC) and searched for a correlation with clinical and biological markers of activity. We enrolled 60 CD, 67 UC patients, and 66 controls (all adults). Disease activity was scored through the clinical, endoscopic, and histologic indexes of severity, whilst disease location and behaviour were assessed according to the Montreal classification. In all cases, the levels of serum sRAGE, S100A12, C-reactive protein, and faecal calprotectin were measured. sRAGE levels were significantly lower in UC, both active and inactive, than in controls and CD (817.35, range 437.3–1449; 1211, range 843.7–1618; 1207.5, range 743.15–1875.75; P

Background:Pro-inflammatory cytokines contribute to the pathophysiology of heart failure (HF) and are up-regulated in affected patients. We investigated whether pro-inflammatory cytokines might predict the response to cardiac resynchronization therapy (CRT).Methods and Results:Plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 were assessed in 91 patients before CRT. Response to CRT was defined as a decrease ≥15% in left ventricular end-systolic volume (LVESV) at 6 months. Baseline TNF-α did correlate with LVESV reduction (P=0.001) after CRT. The subject group was divided according to tertiles of TNF-α. From the lower to the upper tertile LVESV (–31±28%, –17±17%, –9±22%) and LV end-diastolic volume (–23±25%, –14±16%, –4±18%) were progressively less reduced after CRT (P

Allergic rhinitis (AR) is characterized by an inflammatory reaction sustained by Th2 polarization, whereas systemic lupus erythematosus (SLE) is a typical autoimmune disorder. Vascular endothelial growth factor (VEGF) is a critical mediator of inflammation. The aim of this study was to compare serum VEGF levels in three groups of subjects: 40 normal subjects, 40 allergic patients, evaluated before and after specific immunotherapy, and 40 patients with inactive SLE. Patients who were allergic before immunotherapy had the lowest VEGF serum levels, which significantly increased after treatment; SLE patients had the highest VEGF serum levels. This comparative study provides evidence that serum VEGF levels depend on the type of immune response: they are high in autoimmune disease and low in Th2-polarized allergic reaction. The relevance of this phenomenon is further apparent, as it is also observed in patients with inactive disease.