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.

Martina Votto,1,2,* Maria De Filippo,1,2,* Amelia Licari,1,2 Alessia Marseglia,2 Mara De Amici,3 Gian Luigi Marseglia1,2 1Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 2Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy; 3Immuno-Allergology Laboratory, Clinical Chemistry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy*These authors contributed equally to this workCorrespondence: Amelia LicariPediatric Clinic, Fondazione IRCCS Policlinico San Matteo, p.le C. Golgi n.19, Pavia, 27100, ItalyTel/Fax +390382502629Email amelia.licari@unipv.itAbstract: Severe uncontrolled asthma is a complex and heterogeneous disease. A multidisciplinary assessment is required to correctly identify and manage children and adolescents with severe asthma because they may require strict monitoring and additional treatment with advanced targeted therapies. Recent research efforts have focused on identifying epidemiologic, clinical, and molecular mechanisms that underlie severe asthma, leading to the recognition of different phenotypes and endotypes and identifying biomarkers able to predict the response to biologic therapies. Additional progress has occurred by introducing biological therapies that have revolutionized the care of chronic allergic diseases in the adult and pediatric population. In this review, we briefly summarized the current literature on biological therapies to treat severe asthma in children and adolescents.Keywords: severe asthma, children, adolescents, biological therapy, endotype, phenotype

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.

Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 were randomized to expanded HD (HDx), performed using a medium cut-off membrane, or standard treatment using a protein-leaking dialyzer (PLD). Circulating levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TLR4 (sTLR4), and interferon-gamma (IFN-γ), were collected at diagnosis, and one and two weeks after. Compared with 14 non-infected HD patients, COVID-19 patients showed lymphopenia and higher ferritin and lactate dehydrogenase levels. Moreover, COVID-19 patients had higher levels of IL-10 (15.2 (12.5) vs. 1.2 (1.4) pg/mL, p = 0.02). Twenty-nine patients were randomized to HDx (n = 15) or PLD (n = 14). After a single treatment, IL-8 showed a significant reduction in both groups, whereas IL-10 decreased only in HDx. All over the study, there were no significant modifications in circulating cytokine levels between the two groups, except for a parallel increase of IL-8 and IL-10 at one week control in the HDx group. No correlations were found between cytokine levels and clinical outcomes. In maintenance HD patients, COVID-19 is not related to a sustained inflammatory response. Therefore, modulation of inflammation seems not to be a suitable therapeutic target in this specific population.

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.

Objectives The purpose of the study was to evaluate the mucosal immune response in women affected by primary human papillomavirus (HPV) infection, in comparison with HPV-negative women with no previous history of HPV. Methods A case-control study comparing the activity of myeloperoxidase (MPO) and lactoferrin (LF) between 19 HPV-positive and 19 HPV-negative women matched for age. Plasmatic and cervicovaginal levels of polymorphonuclear neutrophils (PMN) exhibiting MPO and LF receptors were measured using cytofluorimetric analysis and expressed as mean of percentages. Results Cervicovaginal levels of MPO-/LF- PMN were lower among HPV-negative women, with a mean rate of 18.81% (SD, 21.38), as opposed to a mean rate of 35.56% (SD, 21.02) (P = 0.020) in HPV-positive women. A similar significant difference was not proven in plasma. The mean rates of plasmatic levels of MPO-/LF- PMN were 36.21% (SD, 16.87) and 36.93% (SD, 10.54) (P = 0.875) in cases and controls, respectively. All patients were evaluated 1 year later, and only 6 cases became negative. Conclusions The presence of MPO-/LF- PMN has been considered as a marker of lower rate of apoptosis of HPV-infected cells. This could explain why HPV-positive women are less capable to deal with a primary infection.

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 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.

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.

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.

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.

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.

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.

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

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.

OBJECTIVE: The aim of the present study was to investigate the effect of exogenously administered GH on serum levels of interleukin (IL)-1beta, IL-2, IL-12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and their relation with IGF-I levels in normal short stature children. DESIGN AND METHODS: 23 short prepubertal non GH-deficient children (10 females and 13 males) whose mean+/-s.d. chronological age was 11.95+/-1.85 Years (from 8.80 to 14.89 Years), and mean+/-s.d. bone age was 10.48+/-2.44 Years, were evaluated during a somatomedin generation test (human GH 0.1 IU/kg per day for 4 days) to exclude a partial GH resistance as the cause of short stature; 34 sex- and age-matched healthy subjects were studied as controls. Circulating cytokine values were measured in basal conditions in all children, and 12 h following the 4th GH subcutaneous injection in the 23 short children only. RESULTS: No significant differences were found between short children and controls in basal values of serum IGF-I (192.1+/-18.3 and 198.2+/-28.2 ng/ml respectively). In short subjects there was a significant increase in serum IGF-I levels after the 4th GH injection (from 192.1+/-18.3 ng/ml, i.e. -1.16+/-0.16 standard deviation score (SDS) to 338.2+/-27.1 ng/ml, i.e. 0.14+/-0.17; 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

Introduction: Gut and adipose tissue hormones play an important role in energy balance control, particularly through the regulation at either short- or long-term food intake after bariatric surgery. Case: A 15-year-old obese female (BMI 42.2) who was unresponsive to medical treatment underwent gastroplication. Hunger hormone levels (leptin, ghrelin and insulin), weight loss and eating behavior were monitored at 3, 6 and 12 months after surgery. Results: Weight loss was obtained, progressively achieving a loss of 45.6 kg 1 year after surgery. A strong reduction in insulin concentration and insulin resistance was documented. At 3 months after the operation, a surprising leptin level drop was observed. During the following months a progressive increase in leptin levels and leptin/kg of fat mass were documented. Fasting ghrelin levels increased in the first 3 months, then fell over the next 6 months. Up to 6 months after gastroplication, we observed a less marked drop in plasma ghrelin after meal ingestion, while the values after 1 year showed a substantial fall in the postprandial period despite a further fasting ghrelin increased level. Early achievement of satiety was found. Conclusion: Hunger hormones level changes seem to be involved in weight loss and eating behavior after gastroplication in adolescents.

Objective: Adenoids with obstructive hypertrophy (AH) are considered to be one of the most ancient and common problems in Paediatrics. This study aimed at investigating the expression of CD 64 on monocytes in children who had to undergo to adenoidectomy. Methods: Therefore, 66 children (24 females, 42 males, mean age 4.9 years), affected by AH and requiring adenoidectomy (54%) or adeno-tonsillectomy (46%) were consecutively enrolled into the study. Moreover, 30 healthy children (11 females, 19 males, mean age 11.2 years) were enrolled in this study as controls. CD64 expression on monocytes was measured. Results: Children with severe AH had higher CD64 values than children with AH size 3 and controls. Conclusions: This preliminary study shows that CD64 expression on monocytes may be associated with severe AH, suggesting a more intense immune activation in these subjects.

Purpose. Dupuytren disease is an inherited proliferative and progressive connective disease. Ectopic disease may, however, be located distant from the palmar fascia. Methods. Case report and review of the literature. Results. We describe a case of symmetric bilateral posterior subcapsular cataracts associated with symmetric bilateral Dupuytren disease and symmetric bilateral Ledderhose disease in a 56-year-old Caucasian man. His medical history was negative for glucocorticoids intake, diabetes, and exposure to radiation. Serum transforming growth factor β (TGF-β)1 concentration has been evaluated and was found to be almost double compared to the controls. Conclusions. We speculate that the TGF-β plays an important role for ocular and connective tissue disorders.

Background. Primary myelofibrosis (PMF) is a clonal, neoplastic disorder of the hematopoietic stem cells, characterized by an increased number of circulating CD34+ cells. Available evidence indicates that enhanced activation of JAK-STAT pathway is the main molecular mechanism of myeloproliferation due to somatic mutations in JAK2, CALR or MPL genes. A subset of patients display immune-related abnormalities that suggest an (auto)immune pathogenesis. In addition, it has been reported a significant association between personal history of a broad span of autoimmune diseases and subsequent risk of myeloproliferative neoplasm (Kristinsson SY Haematologica 2010; 95:1216-1220). CD4+ T cells maintain cancer surveillance and immune tolerance. Chronic inflammation has been proposed as a driver of clonal evolution in myeloproliferative neoplasms (MPN) (Hasselbalch HC et al. Leuk Res 2013;37:214-20), suggesting that T cells play an important role in their pathogenesis. A recent paper by Keohane C et al (BJH 2015; doi 10.1111/bjh 13519) shows that peripheral blood (PB) T regulatory cells (Tregs) are reduced in MPN patients compared to healthy subjects (CTRLs) and that this decrease is even more pronounced following JAKi therapy (Massa M et al Leukemia 2014;28:449-51). Unpublished data from our group further indicate a significant (p Study design. To investigate the possible factors favouring a decrease of Tregs, we examined in patients with PMF and Results. 1) The percentages of PB CD4+, CD4+CD25+, or CD4+CD25++CD127low/- cells expressing membrane Annexin V were comparable in patients with PMF and CTRLs (data not shown). 2) The phosphorilation of Stat1, Stat3, Stat5, Stat6, and p38-MAPK (expressed as mean fluorescence intensity: MFI) on CD4+, CD4+CD25-, CD4+CD25+, and CD4+CD25++FOXP3+ cells before and after stimulation with IFNα, IL6, IL4, or PMA was comparable in patients and CTRLs. The Erk1,2 phosphorilation was comparable in patients and CTRLs at baseline condition, while in patients with PMF Erk1,2 phosphorilation following stimulation with PMA was significantly lower in both CD4+CD25+ cells (p=0.039; median MFI 5.4, range 0.3-40) and CD4+CD25++FOXP3+ cells (p=0.01; median MFI 4.3, range 1.4-9.3) than in CTRLs (CD4+CD25+ cells median MFI 8.1, range 4.9-20; CD4+CD25++FOXP3+ cells median MFI 7.3, 3.7-10.8). 3) sIL2rα plasma levels were higher (p=0.01) in patients with PMF (1658 pg/ml, range 476-8968) than in CTRLs (1040 pg/ml, 482-1719); the sIL2rα plasma levels were significantly (R=-0.35, p=0.039) inversely correlated with the percentages of circulating Tregs. No significant correlation was found with the presence (n=13)/absence (n=14) of JAK2V617F mutation. Conclusions. These results indicate that in patients with PMF Tregs present an untuned Erk signaling; moreover, sIL2rα plasma levels are higher in patients than in CTRLs, and significantly inversely correlated with Treg percentages. These findings may partly explain the reduced frequency of Tregs in PMF since Erk signaling is pivotal in T cell differentiation, regulation of T cell homeostasis, and defects in Erk expression have been associated with autoimmunity (Chiung-Fang Chang J Immunol 2012; 189:721-731). Moreover, increased levels of sIL2rα may impact on IL-2-mediated functions and alterate the optimal activation of Erk1/2 that is IL-2 dependent (Lequn Li, Blood. 2005;106:3068-3073), Disclosures No relevant conflicts of interest to declare.

Background. Eosinophilic cationic protein (ECP) has been widely investigated in the clinical practice as a potential biomarker for asthma. However, there are conflicting data concerning its validity in other respiratory disorders. Methods. Serum ECP levels were retrospectively analyzed in 441 patients (227 males and 214 females) suffering from respiratory disease and visited for the first time, and in 33 healthy subjects (17 males and 16 females). Results. The mean of ECP was significantly higher (p = .0001) in patients compared with healthy volunteers. No correlation was found between serum ECP value and peripheral eosinophil absolute number (p = .881; r = .007). The predictive model was significant only for asthma, with a sensitivity of 70% and a specificity of 74% (efficiency 73%). Conclusions. This study demonstrates that serum ECP may be considered a marker for identifying only asthmatic patients with an efficiency of 73% and is not useful for the differentiation of other respiratory disorders.

Background Adipokines may exert pro-inflammatory activities in allergic rhinitis. Resistin is a new adipokine. Only one study reported that resistin may be involved in allergic rhinitis. However, that study was conducted in children. Therefore, the present study aimed at confirming these findings also in adult patients with persistent allergic rhinitis (PER). Methods The study included 85 PER patients subjects 25 (11 males, mean age 35.4 years) with mild symptoms and 60 (27 males, mean age 36.8 years) with moderate–severe ones. All subjects were consecutively evaluated. A skin prick test and blood sampling for assessing serum resistin levels were performed in all subjects. Results Patients with moderate–severe symptoms had higher resistin levels than mild ones ( p = 0.02). Conclusion This study provides the preliminary evidence that resistin serum levels depend on symptom severity also in adults with PER.

Background Several studies have outlined a possible relationship between adipokines and respiratory allergic diseases. However, there are no data about a role for adipsin in allergic rhinitis. Objective The aim of the study was to evaluate the serum adipsin levels in patients with seasonal allergic rhinitis (SAR), subdivided into two sub-groups: treated or not treated with sublingual immunotherapy (SLIT), and in a group of healthy controls. Methods The study included 110 subjects; i) 24 SLIT-treated SAR patients, ii) 62 untreated SAR patients, and iii) 24 normal subjects. All subjects were consecutively evaluated. A skin prick test and blood sampling for assessing serum adipsin levels were performed in all subjects. Results Serum adipsin was increased in SAR patients, even though significant only in males. There was also a significant positive association between adipsin and adiponectin. Conclusion This preliminary study reports that adipsin serum levels may be increased in some SAR patients, but further functional studies should be performed.

Background It has been demonstrated that serum leptin is elevated in females with allergic rhinitis. Recently, it has been reported that one course of sublingual immunotherapy (SLIT) does not affect serum leptin levels. Objective The aim of this study was to evaluate the serum leptin levels in a cohort of patients with pollen-induced allergic rhinitis, before and after two pre-seasonal SLIT courses. Methods Forty-one patients (22 males and 19 females, median age 39 years) with AR, due to pollen allergy, and 34 healthy subjects (16 males and 18 females, median age 43 years) were included in the study. Blood sampling for assessing serum leptin was performed in all subjects before and after the second SLIT course. Results All patients were responders to SLIT. Serum leptin was significantly increased only in males ( p = 0.0056) after the second SLIT course. Conclusion This preliminary study shows that at least two pre-seasonal SLIT courses were required to induce significant modifications in serum leptin levels, but it occurred only in males. Some hypotheses might be outlined, including a leptin protective effect, however further studies must clarify this issue.

Background Several studies have outlined a possible relationship between an increased body mass index and respiratory allergic diseases, such as asthma and rhinitis. Objective The aim of the study was to evaluate the serum adiponectin levels in a cohort of patients with pollen-induced allergic rhinitis, enrolled outside the pollen season, and in a group of healthy controls. Methods The study included 41 patients with moderate-severe persistent allergic rhinitis due to a pollen allergy and 34 normal subjects. All subjects were prospectively and consecutively evaluated. A skin prick test and blood sampling for assessing serum adiponectin levels were performed in all subjects. Results The comparison between allergic patients and normal subjects, globally considered without gender distinction, showed slightly higher values in the allergic population. After analysing genders separately, allergic patients show significantly higher levels than normal males (p = 0.0134), whereas the comparison between allergic and normal females was not significant (p = 0.1419). In addition, in normal males adiponectin serum levels are significantly related with age (p = 0.0123). Conclusion This preliminary study provides the first evidence of significantly higher adiponectin serum levels in male patients with pollen-induced allergic rhinitis as compared to normal male subjects.

We assessed the percentage of endothelial progenitor cells (EPCs) in the peripheral blood of a patient with POEMS with elevated VEGF plasma levels. High VEGF plasma levels were associated with increased EPC concentration and treatment with an anti-VEGF antibody induced a consensual decrease of both parameters. In vitro cultures of the patient BM cells suggested that the stromal compartment could be responsible for VEGF overproduction.

Aims We studied plasma erythropoietin (EPO) levels and their relation with CD34+VEGFR-2+ (mature and progenitor endothelial cells) and CD34+ CD133+VEGFR-2+, or CD34+ CD117+VEGFR-2+ (early/immature endothelial progenitors) cells in patients with acute myocardial infarction (AMI). Methods and results Fifty AMI patients undergoing percutaneous coronary intervention (PCI) within 6 h of symptom onset were enrolled. EPO, measured by ELISA, and cell subsets, by cytofluorimetric analysis, were evaluated before PCI, 24 h and 7 days afterwards. Forty-five healthy subjects (CTRLs) were studied. Plasma EPO levels were higher in AMI patients at admission, 24 h, and 7 days ( P = 0.04, P = 0.0001, P = 0.001, respectively) than in CTRLs. No correlation was evidenced between EPO and haemoglobin (Hb) or haematocrit at admission or 24 h after AMI. Differently, both Hb and haematocrit inversely correlated with EPO at day 7 ( P = 0.0016, P = 0.029, respectively). Plasma EPO levels correlated with CD34+CD133+VEGFR-2+ cells at day 7 ( P = 0.03). Conclusion AMI patients have increased plasma EPO levels until day 7. In the early phase, plasma EPO levels are Hb-independent; at day 7, an Hb-modulated increase of EPO correlates with the percentage of CD34+CD133+VEGFR-2+ cells.

Background: Peroxisome Proliferator-Activated Receptor ! (PPAR! ) is a nuclear receptor that regulates the transcription of genes associated with lipid and glucose metabolism. Recently, it has been shown that PPAR! modulates the activity of T cells, resulting in inhibition of T cell proliferation and IL-2 release. In this study we investigated whether the PPAR! ligand rosiglitazone (R) enhances in vitro the immunosuppressive effects of cyclosporine A (CsA). Methods: CD4 + T cells isolated from peripheral blood mononuclear cells of healthy donors were activated either with mitogens or by one-way mixed lymphocyte reaction. The activated T cells were treated with (1) CsA at low and high concentration (50, 150 ng/ml); (2) R (20 " M); (3) R (20 " M) in combination with CsA at low concentration (50 ng/ml). We studied the effects of the various treatments on cell proliferation (incorporation of [ 3 H] thymidine), the cell-cycle phases (FACS analysis), IL-2 release (ELISA), and IL-2 receptor (CD25) expression (FACS analysis). Results: R used alone reduced T cell proliferation and CD25 expression. Low-dose CsA combined with R was significantly more powerful than either high-dose CsA alone or R alone in suppressing IL-2 release, arresting the T cell cycle, and blocking the growth of activated T cells. Conclusion: PPAR! ligand R potentiates in vitro the inhibitory action of CsA on activated T helper cells. The combined use of PPAR! ligands and low-dose CsA represents a rationale therapeutic approach aimed to prevent CsA nephrotoxicity while maintaining adequate immunosuppression. © 2007 Elsevier B.V. All rights reserved.

Summary Objectives Autoimmune targeting of hypothalamic-neurohypophyseal structures in children and young adults with posterior pituitary and anterior pituitary dysfunction, as well as pituitary stalk involvement, are not yet completely understood. Design We aimed to (1) evaluate the presence of circulating vasopressin-cell autoantibodies (AVPc-Abs) in young patients with central diabetes insipidus (CDI), (2) detect organ-specific autoantibodies as markers of autoimmunity, and (3) define the relationship between immune markers and neuroimaging findings. Patients Tw enty patients were evaluated at a median age of 16·3 years. Tw elve patients had idiopathic CDI, six had Langerhans cell histiocytosis (LCH) and two had germinoma. AVPc-Abs were evaluated in 40 healthy children. Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region was performed longitudinally in all subjects. Measurements Circulating arginine vasopressin (AVP), protein tyrosine phosphatase (IA2), glutamic acid decarboxylase (GAD), 21-hydroxylase (21-OH), endomysium antibodies (EMA), parietal cell (PCA), thyroid peroxidase (TPO), thyroglobulin (TG) and TSHreceptor (TSHr) autoantibodies were evaluated. Results Circulating AVPc-Abs were found in 15 patients (75%), nine with idiopathic CDI, four with LCH and two with germinoma; the pituitary stalk was involved in most of them. Five patients with idiopathic CDI showed a persistence of AVPc-Abs during follow-up and one became positive subsequently. Serum IA2 autoantibodies were demonstrated in 14 patients (70%) and 21-OH autoantibodies in three of them. Conclusion In idiopathic CDI, circulating AVPc-Abs suggest an autoimmune involvement of the neurohypophyseal system. The identification of AVPc-Abs in subjects who could have either idiopathic CDI or LCH or germinoma, however, indicates that AVPc-Abs cannot be considered a completely reliable marker of autoimmune CDI. Thus, close clinical and MRI follow-up are needed because AVPc-Abs may mask germinoma or LCH.

Using a commercial ELISA assay, we evaluated circulating VEGF and bFGF levels in 203 consecutive patients with solid tumors, and sought a correlation between them and with the grade of anemia. Serum VEGF values were within the normal range in 128 patients (63.05%), with a mean value of 675.04 pg/ml (median, 571.00; range, 0-2796.54). The analysis of VEGF values per tumor group did not provide any statistically significant difference. Regarding bFGF, 143 patients (70.44%) had measurable, and thus abnormal, bFGF values. Overall, mean bFGF serum value was 57.14 pg/ml (median, 8.30; range, 0-4334.71), with the highest bFGF levels found in breast carcinoma patients. As expected, a large number of our patients was fairly anemic, mean hemoglobin level being 11.47 g/dl (median, 11.30; range, 7.1-19.20), the lowest titers being observed in prostate carcinoma patients. No statistically significant correlation was found between serum VEGF and hemoglobin values (r=0.004) but a significant negative correlation was seen between serum bFGF and hemoglobin (r=-0.22, p

Hepatocellular carcinoma (HCC) is a major global health problem, accounting for more than 626,000 new cases worldwide each year...