Defining renal remission in an international cohort of 248 children and adolescents with lupus nephritis.

OBJECTIVE: We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. METHODS: Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.

Psoriasis and Cardiovascular Risk in Children: The Usefulness of Carotid Intima-Media Thickness.

Psoriasis is a skin disorder which mostly affects adults, beginning in childhood in almost one-third of patients. In adults it is associated with increased risk for cardiovascular diseases (CVD), while this association is still debated at younger age. Our aim was to evaluate the association between psoriasis and metabolic markers and cardiovascular findings in this age group. Twenty consecutive patients previously diagnosed with psoriasis (group A) were enrolled and compared with healthy non- psoriatic age- and sex-matched subjects (group B). The severity of the disease, CV risk factors, including anthropometric data with adiposity and its distribution, blood pressure (BP), laboratory metabolic tests, echocardiography and vascular ultrasound (transcranial echo-Doppler and carotid artery echo-Doppler with carotid intima-media thickness, cIMT) were performed for each subject. Personal history for CV risk, BP, anthropometric data were similar between the two groups, while familiar history for psoriasis was more frequent in group A (p < 0.02). C-IMT was significantly higher in group A compared to B (right, p = 0.001; left, p = 0.002). In addition, c-IMT was positively correlated with disease duration, triglycerides and triglycerides/glucose. Cerebral flow velocities, cardiac measurements, systo-diastolic function, ventricle geometry and mass were normal and comparable between the two groups, and did not correlate with CV risk factors. In childhood psoriasis c-IMT could represent a marker of pre-clinical cardiovascular involvement and contribute to start a personalized management, while cardiac findings seem to be normal in the early stage of disease. Longitudinal studies can clarify the progression of CV involvement in paediatric-onset psoriasis.

Further delineation and long-term evolution of electroclinical phenotype in Mowat Wilson Syndrome. A longitudinal study in 40 individuals.

BACKGROUND: Epilepsy is a main feature of Mowat Wilson Syndrome (MWS), a congenital malformation syndrome caused by ZEB2 variants. The aim of this study was to investigate the long-term evolution of the electroclinical phenotype of MWS in a large population. METHODS: Forty-individuals with a genetically confirmed diagnosis were enrolled. Three age groups were identified (t1 = 0-4; t2 = 5-12; t3 = >13 years); clinical data and EEG records were collected, analyzed, and compared for age group. Video-EEG recorded seizures were reviewed. RESULTS: Thirty-six of 40 individuals had epilepsy, of whom 35/35 aged >5 years. Almost all (35/36) presented focal seizures at onset (mean age at onset 3.4 ±â€¯2.3 SD) that persisted, reduced in frequency, in 7/22 individuals after the age of 13. Absences occurred in 22/36 (mean age at onset 7.2 ±â€¯0.9 SD); no one had absences before 6 and over 16 years old. Paroxysmal interictal abnormalities in sleep also followed an age-dependent evolution with a significant increase in frequency at school age (p = 0.002) and a reduction during adolescence (p = 0.008). Electrical Status Epilepticus during Sleep occurred in 14/36 (13/14 aged 5-13 years old at onset). Seven focal seizure ictal video-EEGs were collected: all were long-lasting and more visible clinical signs were often preceded by prolonged electrical and/or subtle (erratic head and eye orientation) seizures. Valproic acid was confirmed as the most widely used and effective drug, followed by levetiracetam. CONCLUSIONS: Epilepsy is a major sign of MWS with a characteristic, age-dependent, electroclinical pattern. Improvement with adolescence/adulthood is usually observed. Our data strengthen the hypothesis of a GABAergic transmission imbalance underlying ZEB2-related epilepsy.

Lung ultrasound for the diagnosis of pneumonia in children with acute bronchiolitis.

BACKGROUND: Guidelines currently do not recommend the routine use of chest x-ray (CXR) in bronchiolitis. However, CXR is still performed in a high percentage of cases, mainly to diagnose or rule out pneumonia. The inappropriate use of CXR results in children exposure to ionizing radiations and increased medical costs. Lung Ultrasound (LUS) has become an emerging diagnostic tool for diagnosing pneumonia in the last decades. The purpose of this study was to assess the diagnostic accuracy and reliability of LUS for the detection of pneumonia in hospitalized children with bronchiolitis and to evaluate the agreement between LUS and CXR in diagnosing pneumonia in these patients. METHODS: We enrolled children admitted to our hospital in 2016-2017 with a diagnosis of bronchiolitis and undergone CXR because of clinical suspicion of concomitant pneumonia. LUS was performed in each child by a pediatrician blinded to the patient's clinical, laboratory and CXR findings. An exploratory analysis was done in the first 30 patients to evaluate the inter-observer agreement between a pediatrician and a radiologist who independently performed LUS. The diagnosis of pneumonia was established by an expert clinician based on the recommendations of the British Thoracic Society guidelines. RESULTS: Eighty seven children with bronchiolitis were investigated. A final diagnosis of concomitant pneumonia was made in 25 patients. Sensitivity and specificity of LUS for the diagnosis of pneumonia were 100% and 83.9% respectively, with an area under-the-curve of 0.92, while CXR showed a sensitivity of 96% and specificity of 87.1%. When only consolidation > 1 cm was considered consistent with pneumonia, the specificity of LUS increased to 98.4% and the sensitivity decreased to 80.0%, with an area under-the-curve of 0.89. Cohen's kappa between pediatrician and radiologist sonologists in the first 30 patients showed an almost perfect agreement in diagnosing pneumonia by LUS (K 0.93). CONCLUSIONS: This study shows the good accuracy of LUS in diagnosing pneumonia in children with clinical bronchiolitis. When including only consolidation size > 1 cm, specificity of LUS was higher than CXR, avoiding the need to perform CXR in these patients. Added benefit of LUS included high inter-observer agreement. TRIAL REGISTRATION: Identifier: NCT03280732 . Registered 12 September 2017 (retrospectively registered).

Management of a Multicomorbid Patient with Heart Failure.

The optimal use of sacubitril/valsartan in clinical practice needs further investigation, in particular for patients with multiple comorbidities, as such patients are usually poorly represented in clinical trials. To this end, well-documented case reports may add further evidence to the bulk of "field practice" experience on sacubitril/valsartan. We report here the case of a patient with heart failure with reduced ejection refraction with multiple comorbidities treated with sacubitril/valsartan. Overall, sacubitril/valsartan led to a prompt (within a few months) improvement in LVEF (+15%, from 38 to 53%), without any noticeable adverse events. This therapy also allowed the patient to discontinue furosemide.

Effect of monochloramine treatment on colonization of a hospital water distribution system by Legionella spp.: a 1 year experience study.

Contamination of hot water distribution systems by Legionella represents a great challenge due to difficulties associated with inactivating microorganisms, preserving the water characteristics. The aim of this study was to examine over the course of 1 year in 11 fixed sites, the impact of monochloramine disinfection on Legionella, heterotrophic bacteria (36 °C), Pseudomonas aeruginosa contamination, and chemical parameters of a plumbing system in an Italian hospital. Three days after installation (T0), in the presence of monochloramine concentration between 1.5 and 2 mg/L, 10/11 sites (91%) were contaminated by L. pneumophila serogroups 3 and 10. After these results, the disinfectant dosage was increased to between 6 and 10 mg/L, reducing the level of Legionella by three logarithmic unit by 2 months postinstallation (T2) until 6 months later (T3). One year later (T4), there was a significant reduction (p = 0.0002) at 8/11 (73%) sites. Our data showed also a significant reduction of heterotrophic bacteria (36 °C) in 6/11 (55%) sites at T4 (p = 0.0004), by contrast the contamination of P. aeruginosa found at T0 in two sites persisted up until T4. The results of the present study show that monochloramine is a promising disinfectant that can prevent Legionella contamination of hospital water supplies.

Factors associated with nurses' opinions and practices regarding information and consent.

This cross-sectional survey aimed to investigate nurses' opinions and practices regarding information and consent in the context of a large Italian teaching hospital and to explore potential influences of gender, age, university education, length of professional experience, and care setting. A questionnaire was administered to 282 nurses from six different care settings (Emergency Room, Emergency Medicine, Surgery, Hematology-Oncology, Geriatrics, and Internal Medicine). Overall, 84% (n = 237) of nurses returned the questionnaire (men: 24%; mean age: 36.2 ± 8 years; university degree: 35%; mean length of professional experience: 12 ± 8.2 years). Most respondents regularly informed patients about medications and nursing procedures and asked for consent prior to invasive procedures, but some provided information to relatives instead of patients. Lack of time or opportunity was the main difficulty in informing patients. The work setting was the foremost factor significantly associated with participants' opinions and practices. Further investigations are needed to confirm these findings in similar and other care settings.

Marfan and Loeys-Dietz aortic phenotype: A potential tool for diagnosis and management.

Objective: In heritable aortic diseases, different vascular involvement may occur with potential variable implications in aortic dilation/dissection risk. This study aimed to analyze the aortic anatomy of individuals with Marfan syndrome and Loeys-Dietz syndrome to identify possible morphological differences. Methods: Computed tomography and magnetic resonance imaging of the thoracoabdominal aorta from the proximal supra-aortic vessels to the femoral bifurcation level of 114 patients with Marfan and Loeys-Dietz syndromes and 20 matched control subjects were examined. Aortic diameters, areas, length, and tortuosity were measured in different aortic segments using specific vessel analysis software. Results: Patients with Marfan syndrome showed a higher prevalence of ascending aorta and aortic root dilation (P = .011), larger and longer aortic roots (P = .013) with pear-shaped phenotype, larger isthmus/descending aorta diameter ratio (P = .015), and larger suprarenal aorta and iliac arteries. Patients with Loeys-Dietz syndrome showed longer indexed segments and a significantly longer arch (P = .006) with type 2/3 arch prevalence (P = .097). Measurement ratios analysis provided cut-off values (aortic root to ascending aorta length/aortic root diameter, aortic root/sinotubular junction, aortic root/ascending aorta diameter) differentiating patients with Marfan syndrome from patients with Loeys-Dietz syndrome, even in the early stage of the disease. Conclusions: Both syndromes show peculiar anatomic patterns at different aortic levels irrespective of aortic dilation and disease severity. These features may represent the expression of different genetic mutations on aortic development, with a potential impact on prognosis and possibly contributing to better management of the diseases. The systematic adoption of whole body imaging with magnetic resonance or computed tomography should always be considered, because they allow a complete vascular assessment with practical indicators of differential diagnosis.

Effect of vitamin D receptor activator therapy on vitamin D receptor and osteocalcin expression in circulating endothelial progenitor cells of hemodialysis patients.

BACKGROUND: The effects of vitamin D receptor (VDR) and osteocalcin (OC) expression as well as VDR agonist (VDRA) therapy on circulating endothelial progenitor cells (EPCs) has not been elucidated yet. METHODS: We therefore analyzed EPCs in 30 healthy controls and 82 patients undergoing dialysis (no VDRA therapy: 28; oral calcitriol: 30, and intravenous paricalcitol, PCTA: 24). The percentage of EPCs (CD34+/CD133-/KDR+/CD45-) expressing VDR or OC, and VDR and OC expression defined by mean fluorescence intensity (MFI) were analyzed using flow cytometry. The in vitro effect of VDRAs was evaluated in EPCs isolated from each patient group. RESULTS: The percentage of VDR+ EPCs correlated positively with VDRA therapy and 25(OH)D, and negatively with diabetes, C-reactive protein, hemoglobin and osteopontin. VDR-MFI correlated positively with VDRA therapy, parathyroid hormone (PTH) and 25(OH)D, and negatively with diabetes and osteopontin. The percentage of OC+ EPCs correlated positively with the calcium score, PTH and phosphate, and negatively with 25(OH)D. OC-MFI correlated positively with calcium score, PTH, phosphate and hemoglobin, and negatively with albumin, 25(OH)D and osteopontin. Cell cultures from patients without VDRA therapy had the highest levels of calcium deposition and OC expression, which both significantly decreased following in vitro VDRA administration: in particular extracellular calcium deposition was only reduced by adding PCTA. CONCLUSIONS: Our data suggest that 25(OH)D serum levels and VDRA therapy influence VDR and OC expression on circulating EPCs. Since OC expression may contribute to vascular calcification, we hypothesize a putative protective role of VDRA therapy.

Recognition of elder abuse by Italian nurses and nursing students: evaluation by the Caregiving Scenario Questionnaire.

Elder abuse appears to be widely underestimated by health professionals. We aimed to evaluate the recognition of elder abuse among Italian nurses and nursing students related to their professional, personal experiences and socio-demographic characteristics. 193 nursing students and 76 nurses attending a post-graduate nursing management master's degree at the University of Bologna (Italy) completed the Caregiving Scenario Questionnaire measuring the ability to recognize elder abuse. Data on age, gender, previous professional and personal experiences as well as nursing school teaching were collected. Regarding abusive items, preventing elder's movements by putting a table over the elder's lap was identified by almost all participants, while locking someone at home was identified by half of them. Neglect was recognized by 25 % of nurses and 20 % of students, respectively. The majority of nurses and students correctly identified non-abusive strategies. Reporting being taught on elder abuse was inversely associated with a good performance in detecting neglect. Italian nurses' and nursing students' uncertainty in identifying abusive strategies, especially neglect, was consistent with results of previous studies in other countries. Standardized education in healthcare core curriculum, reference guidance and training are strongly needed to improve elder abuse recognition in Italy.

Evaluation of persistence and adherence to teriparatide treatment in patients affected by severe osteoporosis (PATT): a multicenter observational real life study.

INTRODUCTION: Osteoporosis is a chronic condition leading to an increased risk of developing fractures, with high morbidity and mortality in aging population. Efficacy of anti-osteoporotic treatment is based on drug potency but also on compliance and persistence to treatment regimen, which is very low, as already described for other diseases. Teriparatide (TPTD) is the first anabolic agent developed for the treatment of osteoporosis. Since it appears that persistence to Teriparatide declines over time, aim of this pilot multicenter observational study was to evaluate persistence and adherence to TPTD (20 µg daily injection regimen for 18 months) treatment (PATT) in patients affected by severe osteoporosis in an every day clinical practice. METHODS: Patients affected by severe osteoporosis were selected among those who referred to 5 different specialized centers for osteoporosis in North, Center and South of Italy. A sample of 475 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the Italian osteoporosis guidelines was included. At the beginning of TPTD treatment patients were instructed on the use of the device by the referring specialist of the center, a resident fellow or a nurse. Bone biochemical markers were evaluated the same morning and after 1, 3, 6, 12 and 18 months. Patients were visited at time 0 and after 6, 12 and 18 months for clinical follow up. RESULTS: The results included observations of 441/475 patients (98% women) who completed the 18 months treatment; mean age for women was 73±8 and for men 65±9. After 6 months of TPTD treatment persistence was of 89,79%, 87,75% after 12 months and 86,85% after 18 months. Adherence was of 100% at 6,12 and 18 months. Total dropouts were 13,15% (71/441), which was usually higher within the first 6 months of TPTD treatment. Most common adverse events (arthralgies 2,7%, dizziness 1,8%, migraine 1,8%, depression 1,6%, hypertension 1,1%) were reported in 62/441 patients (14%) of patients, but were not reason for stopping treatment. CONCLUSIONS: The persistence and adherence to TPTD treatment obtained in this multicenter observational real life study was very high as compared to studies performed by others. These encouraging results suggest that different key factors such quality of information, frequency of visits, motivations given to patients, opportunity to call the doctor might play a pivotal role in the high persistence and adherence to TPTD treatment obtained in our study and need to be carefully considered before prescribing chronic anti-osteoporotic therapy.

Exposure to outdoor air pollution and risk of hospitalization for bronchiolitis in an urban environment: A 9-year observational study.

BACKGROUND: Outdoor air pollution is supposed to influence the course of bronchiolitis, but the evidence is limited. The present study aimed at evaluating the role of outdoor air pollutants on hospitalization for bronchiolitis. METHODS: Infants aged ≤12 months referred for bronchiolitis to our Pediatric Emergency Department in Bologna, Italy, from 1 October 2011 to 16 March 2020 (nine epidemic seasons) were retrospectively included. Daily concentrations of benzene (C6 H6 ), nitrogen dioxide (NO2 ), particulate matter ≤2.5 µm (PM2.5 ), and ≤10 µm (PM10 ), and the mean values of individual patient exposure in the week and the 4 weeks before hospital access were calculated. The association between air pollutants exposure and hospitalization was evaluated through logistic regression analysis. RESULTS: A total of 2902 patients were enrolled (59.9% males; 38.7% hospitalized). Exposure to PM2.5 in the 4 weeks preceding bronchiolitis was identified as the main parameter significantly driving the risk of hospitalization (odds ratio [95% confidence interval]: 1.055 [1.010-1.102]). After stratifying by season, higher values of other outdoor air pollutants were found to significantly affect hospitalization: 4-week exposure to C6 H6 (Season 2011-2012, 4.090 [1.184-14.130]) and PM2.5 (Season 2017-2018, 1.282 [1.032-1.593]), and 1-week exposure to C6 H6 (Season 2012-2013, 6.193 [1.552-24.710]), NO2 (Season 2013-2014, 1.064 [1.009-1.122]), PM2.5 (Season 2013-2014, 1.080 [1.023-1.141]), and PM10 (Season 2018-2019, 1.102 [0.991-1.225]). CONCLUSION: High levels of PM2.5 , C6 H6 , NO2 , and PM10 may increase the risk of hospitalization in children affected by bronchiolitis. Open-air exposure of infants during rush hours and in the most polluted areas should be avoided.

Which is the best MRI marker of malignancy for atypical cirrhotic nodules: hypointensity in hepatobiliary phase alone or combined with other features? Classification after Gd-EOB-DTPA administration.

PURPOSE: To investigate whether the malignancy of atypical nodules in cirrhosis can be identified at gadoxetic-acid-disodium(Gd-EOB-DTPA)-MRI by their hypointensity in the hepatobiliary(HB)-phase alone or combined with any other MR imaging features. MATERIALS AND METHODS: One hundred eleven atypical nodules detected in 77 consecutive Gd-EOB-DTPA-MRIs were divided, based on arterial-phase behavior, into: Class I, isovascular (n = 82), and Class II, hypervascular without portal/delayed washout (n = 29). The two classes were further grouped based on HB-phase intensity (A/B/C hypo/iso/hyperintensity). Portal/venous/equilibrium-phase behavior and T2w features were also collected. Histology was the gold standard. Per-nodule sensitivity, specificity, negative and positive predictive values (NPV/PPV), and diagnostic accuracy were calculated for HB-phase hypointensity alone, and combined with vascular patterns and T2w hyperintensity. RESULTS: Histology detected 60 benign and 51 malignant/premalignant nodules [10 overt hepatocellular carcinomas (HCCs) and 41 high-grade dysplastic nodules (HGDN)/early HCC]. Class IA contained 31 (94%) malignancies, IB one (3%), and IC only benign lesions. Class IIA had 100% malignancies, IIB three (37.5%) and IIC only two (28.5%). HB-phase hypointensity alone (Classes I-IIA) had 88% sensitivity, 91% NPV, and 93% diagnostic accuracy, superior (P < 0.05, P < 0.006, and P < 0.05, respectively) to any other MR imaging feature alone or combined. CONCLUSION: In atypical cirrhotic nodules, HB-phase hypointensity by itself is the strongest marker of malignancy.

Understanding the environmental factors related to the decrease in Pediatric Emergency Department referrals for acute asthma during the SARS-CoV-2 pandemic.

BACKGROUND: Lockdown measures during the SARS-CoV-2 pandemic determined radical changes to behavioral and social habits, that were reflected by a reduction in the transmission of respiratory pathogens and in anthropogenic atmospheric emissions. OBJECTIVE: This ecological study aims to provide a descriptive evaluation on how restrictive measures during the SARS-CoV-2 pandemic impacted Pediatric Emergency Department (PED) referrals for asthma exacerbations, and their potentially associated environmental triggers in Bologna, a densely populated urban area in Northern Italy. METHODS: Files of children evaluated for acute asthma during 2015 to 2020 at the PED of Sant'Orsola University Hospital of Bologna were retrospectively reviewed. Historical daily concentration records of particulate (PM2.5 , PM10 ) and gaseous (NO2 , C6 H6 ) air pollutants, and pollen were concurrently evaluated, including specific PM chemical tracers for traffic-related air pollution (TRAP). RESULTS: In 2020, asthma-related PED referrals decreased compared to referral rates of the previous 5 years (p < 0.01). This effect was particularly marked during the first lockdown period (March to May), when the drastic drop in PED referrals was associated with a reduction of high-priority cases up to 85% and by 54%, on average. A concomitant reduction in the concentrations of traffic-related air pollutants was observed in the range of 40%-60% (p < 0.01). CONCLUSIONS: The lower rate of asthma exacerbations in childhood was in this study paralleled with reduced TRAP levels during the pandemic. Synergic interactions of the multiple consequences of lockdowns likely contributed to the reduced exacerbations, including decreased exposure to ambient pollutants and fewer respiratory infections, identified as the most important factor in the literature.

Tinnitus in elderly patients and prognosis of mild-to-moderate congestive heart failure: a cross-sectional study with a long-term extension of the clinical follow-up.

BACKGROUND: The complex mechanism responsible for tinnitus, a symptom highly prevalent in elderly patients, could involve an impaired control of the microcirculation of the inner ear, particularly in patients with poor blood pressure control and impaired left ventricular (LV) function. METHODS: In order to define the relationship between the presence of tinnitus and the severity and clinical prognosis of mild-to-moderate chronic heart failure (CHF) in a large population of elderly patients (N = 958), a cross-sectional study was conducted with a long-term extension of the clinical follow-up. Blood pressure, echocardiographic parameters, brain natriuretic peptide (BNP), hospitalization, and mortality for CHF were measured. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure. RESULTS: The presence of tinnitus was ascertained in 233 patients (24.3%; mean age 74.9 ± 6 years) and was associated with reduced systolic and diastolic blood pressure (123.1 ± 16/67.8 ± 9 vs 125.9 ± 15/69.7 ± 9; P = .027/P = .006), reduced LV ejection fraction (LVEF%; 43.6 ± 15 vs 47.9 ± 14%, P = .001), and increased BNP plasma levels (413.1 ± 480 vs 286.2 ± 357, P = .013) in comparison to patients without symptoms. The distribution of CHF functional class was shifted toward a greater severity of the disease in patients with tinnitus. Combined one-year mortality and hospitalization for CHF (events/year) was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with an adjusted hazard ratio (HR) of 0.61 (95% confidence interval (CI): 0.37 to 0.93, P <.002). CONCLUSIONS: Our preliminary data indirectly support the hypothesis that tinnitus is associated with a worse CHF control in elderly patients and can have some important clinical implications for the early identification of patients who deserve a more aggressive management of CHF.

Effects of unfractioned heparin and low-molecular-weight heparin on osteoprotegerin and RANKL plasma levels in haemodialysis patients.

BACKGROUND: This randomized crossover study investigated the effects of unfractioned heparin (UFH) and low-molecular-weight heparin (LMWH) on intra- and post-dialytic blood levels of osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL) and inflammatory cytokines. METHODS: Forty patients on haemodialysis for at least 12 months were selected. UFH or LMWH was randomly assigned and maintained for 1 month, and then, in the following month, each patient was switched to the other form of heparin. In the mid-week session, we determined the changes in anti-Xa activity, OPG, RANKL, IL-1ß, IL-6 and TNF-α values before heparin administration and after 15 min, 4, 8 and 24 h (T0, T1, T2, T3 and T4 respectively). Since these parameters at the various experimental times showed a non-normal distribution, log transformation was applied in order to run parametric ANOVA, with Bonferroni correction for multiple comparisons. RESULTS: The changes in anti-Xa activity over time were similar but not the same for the UFH and LMWH. A highly significant (P<0.001) increase in anti-Xa activity was detected at T1, regardless of the type of heparin, as confirmed in the comparison of T0 vs T1 using one-way ANOVA. Moreover, with both heparins, significant differences were found in the comparisons of anti-Xa activity at T1 vs T2 (both P<0.001) and at T2 vs T3 (P=0.0003 with UFH; P<0.001 with LMWH). Conversely, the difference in anti-Xa activity at T3 vs T4 was still significant with UFH (P=0.0186) but not significant with LMWH (P=0.728). When comparing anti-Xa activity at T4 vs T0, no significant differences were found either with UFH (P=0.1996) or with LMWH (P=0.7470), thus indicating that 24 h after heparin infusion, anti-Xa activity returned back to the pre-infusion values. When we analysed the changes in OPG levels over time, we found that the administration of heparin, regardless of the type, determined an increase in circulating OPG with a zenith at 15 min (T1), with a return back to the baseline levels within the 24th hour post-infusion. One-way ANOVA revealed significant differences in OPG blood levels at T0 vs T1 with both UFH (P=0.0112) and LMWH (P=0.0288), whereas no significant difference was observed in the comparisons of OPG levels at T1 vs T2, T2 vs T3, T3 vs T4 and T4 vs T0, either with UFH or with LMWH. The circulating levels of RANKL, IL-1ß, IL-6 and TNF-α at the different intra- and post-dialytic times did not show significant variations following heparin administration, either with UFH or with LMWH. One-way ANOVA performed on the log-transformed values of RANKL, IL-1ß, IL-6 and TNF-α at the various experimental times (T0 vs T1, T1 vs T2, T2 vs T2, T3 vs T4 and T4 vs T0) revealed no significant intra- and post-dialytic changes in their blood levels, thus confirming that heparin infusion did not affect their blood levels. CONCLUSIONS: These results suggest that heparin-regulated cyclic increases of OPG might play a role in the vascular pathology of haemodialysis patients.

VDR expression on circulating endothelial progenitor cells in dialysis patients is modulated by 25(OH)D serum levels and calcitriol therapy.

BACKGROUND/AIMS: Vitamin D deficiency is associated with endothelial dysfunction in uremic patients, possibly by the impairment in the number and function of endothelial progenitor cells (EPCs). In 89 hemodialysis patients, we investigated the factors associated with the number of circulating EPCs (CD34+/CD133+/KDR+ and CD34+/CD133-/KDR+ cells), the presence of VDR and the determinants of VDR expression on EPCs, in particular in calcitriol therapy. METHODS: EPC counts, percentages of VDR-positive EPCs and VDR expression were assessed by flow cytometry. Cells isolated from a subgroup of patients were cultured to analyze colony-forming units, specific markers expression and a capillary-like structure formation. RESULTS/CONCLUSIONS: Our study demonstrates the presence of VDR on EPCs. In our dialysis patients, the parameters studied on both CD34+/CD133+/KDR+ and CD34+/CD133-/KDR+ cells, in particular VDR expression, seem to be influenced by uremia-related factors, including anemia, inflammation, diabetes, 25(OH)D serum levels and calcitriol therapy.

Pigmented purpuric dermatoses: analysis of epidemiological, clinical and histopathological aspects in relation to the prognosis of 70 patients, including infants and adults.

BACKGROUND: Pigmented purpuric dermatoses (PPDs) are a group of chronic-relapsing, inflammatory purpuras without vasculitis that typically involve the lower limbs. Five major types could be distinguished, according to the clinical and histopathologic analysis. The etiopathogenesis is still unknown and multiple factors have been considered. Prognosis seems not to be influenced by the different clinical forms of PPDs; nevertheless, no previous studies have investigated whether it could be influenced by the anatomical distribution of the disease. METHODS: We enrolled 70 consecutive patients, including both adults and children with a clinical and histopathological diagnosis of PPD, to investigate possible correlations between the different types of PPDs, their anatomical distribution and prognosis. RESULTS: We observed that patients, both adults and children, with an uncommon localization of the dermatoses, in particular with a diffuse localization (more than one body area affected), presented more frequently a persistent form of PPDs. CONCLUSIONS: This is the first study that attempts to relate the anatomical extension of PPDs and their evolution over time. According to our analysis, it seems to be a statistical significance for the prognosis only for patients with Schamberg disease and involvement of lower limbs. However, studies on a larger population are needed.

Evaluation of twelve formulas for LDL-C estimation in a large, blinded, random Italian population.

BACKGROUND AND AIMS: Low-density lipoprotein-cholesterol (LDL-C) is the major determinant of cardiovascular disease (CVD) burden. Being the direct assays time consuming, expensive, not fully standardized and not worldwide available, indirect formulas represent the most used laboratory estimation of LDL-C. In this study we analyzed the accuracy of twelve formulas for LDL-C estimation in an Italian population of 114,774 individuals. METHODS: All lipid samples were analyzed using direct homogeneous assay. The population was divided into various subgroups based on triglycerides and directly dosed LDL-C (D-LDL) levels. Twelve formulas (Friedewald, DeLong, Hata, Hattori, Puavillai, Anandaraja, Ahmadi, Chen, Vujovic, de Cordova, Martin, and Sampson) were compared in terms of their mean absolute deviations and the correlation and concordance of their estimated LDL-C with the respective D-LDL values. RESULTS: LCL-C measured by Friedewald formula and direct assay differed by more than 9 mg/dL. For D-LDL>115 mg/dl, we observed a concordance rate of only 55% between Friedewald and the respective D-LDL values. For TG<250 mg/dl, the proportion of reclassification between the different formulas and D-LDL was 14.1% with Vujovic, 14.4% Sampson, 15.9% DeLong, 16.5% Puavilai, 19.9% Martin, 21.9% Friedewald, 23.5% Chen, 29% Anandaraja, 31.1% Ahmadi, 31.5% Hata, 33.2% Hattori, and 44.4% with De Cordova formula. CONCLUSIONS: Our study compared for the first time 12 different LDL-C formulas on a Southern European population of more than 100,000 people. 'Several formulas showed better accuracy compared to Friedewald. Sampson, Martin and Vujovic resulted the most accurate formulas.

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

OBJECTIVES: Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. METHODS: Multicenter retrospective and prospective study including 372 consecutive children (58% boys; mean age 34.3 ± 30.3 months, Caucasian 85%) was diagnosed with KD. We divided the cohort into 2 groups according to the presence of coronary anomalies (CAA) and aneurysms. We compared the groups and studied the risk factors for CAA and for aneurysms, the most severe lesions. RESULTS: Children with CAA were 91/372 (24.46%, aneurysms 20/372, 5.37%). Children with CAA were more likely to have a longer duration of fever (p < 0.001), later day of treatment (p < 0.001), to be IVIG non-responders and late treated (p < 0.001), while age, clinical presentation, and seasonality were not different. They also had significantly higher WBC and neutrophils, lower lymphocytes, Hb and Na during the acute stage, and slower resolution of inflammation. Age, IVIG unresponsiveness, and presence of non-coronary cardiac findings were independent risk factors for CAA and for aneurysms, while neutrophils just for CAA. Age under 6 months was a risk factor for the aneurysm. Aneurysms occurred more frequently in the first quartile of the age of KD onset (under 14 months). CONCLUSION: Very young children with non-coronary cardiac findings are at increased risk for a more severe form of KD with aneurysms. These children could benefit from adjunctive therapy beside IVIG, especially if they have higher markers of inflammation, particularly neutrophils. Key points • Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. • Risk factors for coronary involvement have been extensively studied in the Asian population, and others have been validated in cohorts with mixed ethnicities. • In our predominantly Caucasian population, non-coronary cardiac findings, age younger than 6 months, and IVIG unresponsiveness are independent risk factors for a more severe form of KD with aneurysms.