Effectiveness of a standardized scenario in teaching the management of pediatric diabetic ketoacidosis (DKA) to residents: a simulation cross-sectional study.

BACKGROUND: Diabetic ketoacidosis (DKA) is a frequent manifestation at the onset of type 1 diabetes mellitus in children, possibly associated with a wide range of complications, often as a consequence of wrong or delayed treatment. Due to its complex and risky management, direct exposure to real situations alone is not sufficient to achieve adequate skills in pediatric DKA for residents. Simulation could be a valuable aid, allowing to practice a standardized scenario of a complex real-world situation. We aimed to test the effectiveness of a standardized scenario of pediatric DKA in teaching its recognition and treatment. METHODS: We develop a standardized scenario able to guide step-by-step the learners through the flowchart of DKA management and considering alternative evolutions in the case of possible deviations from guidelines. It was a real-life simulation with the use of a high-fidelity pediatric simulator. It was played by 78 pediatrics 20 and emergency medicine residents. At the end of the simulation, a validated questionnaire was administered to collect feedback from participants regarding the impact of the simulation on learning. All materials to reproduce the DKA scenario are provided. RESULTS: Overall, the scenario was rated as realistic (mean score 4.37 ± 0.68, from 1 to 5) and relevant to professional training (4.72 ± 0.47), useful in increasing confidence in interpreting laboratory tests (3.97 ± 0.65), group organization and communication strategies (3.49 ± 0.94), and managing the treatment of DKA (3.46 ± 0.92). CONCLUSIONS: The use of a standardized scenario of pediatric DKA may be a valid tool to reinforce theoretical knowledge in residents, both in pediatrics and in emergency medicine, and to directly and safely practice pediatric DKA management.

Nutritional and Anthropometric Indices in Children Receiving Haemodiafiltration vs Conventional Haemodialysis - The HDF, Heart and Height (3H) Study.

BACKGROUND: The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. METHODS: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. RESULTS: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. CONCLUSIONS: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

Multiple, random spot urine sampling for estimating urinary sodium excretion.

The measurement of sodium intake may be important for the management of hypertension. Dietary surveys and 24-h urinary collection are often unreliable and/or impractical. We hypothesized that urinary sodium excretion can be accurately estimated through multiple spot urine samples from different days. All enrolled subjects were children of the coauthors of the study. Fifty-two 24-h urinary collections (4 per subject) for measuring sodium excretion and the 297 related urinary samples (1 per voiding) were collected for calculating the urinary sodium/urinary creatinine ratio in 13 children. The mean of 4 measured sodium excretions served as the individual "gold standard". Twenty-four urinary collections were used to generate the equation predicting the mean measured sodium excretion from the mean of 4 urinary sodium/urinary creatinine [= 0.016 × urinary sodium (mmol/L) / urinary creatinine (mmol/L) ratio + 3.3)]; the remaining 28 urinary collections and 153 urinary samples were used for the external validation. All subjects underwent an additional validation procedure involving 12 urinary samples randomly collected on different days 6 months apart. The performance of sodium excretion calculated from a total of over 22,000 possible means of 4 out of all the available urinary samples, randomly taken on different days, was analyzed as to precision (by means of the coefficient of variation) and as to accuracy (by means of the P30). The coefficients of variations of measured vs. calculated sodium excretion were 25.3% vs. 25.8%, and the P30 of calculated sodium excretion was 100%. The excellent performance of calculated sodium excretion was confirmed both by external validation and by samples collected 6 months apart with mean P30s, all between 86 and 100%.Conclusion: In the described experimental conditions, urinary sodium excretion was estimated with equal precision and more accurately (and practically) by the mean of 4 urinary sodium/urinary creatinine ratios from random samples from different days than by a single urinary collection. In real life, with several errors systematically affecting urinary collection, the superiority of calculated sodium excretion is likely to be even greater. What is Known: • The measurement of sodium intake with the current standards of care (dietary survey or 24-h urinary collection) is laborious and can be inaccurate. What is New: • The study provides evidence that sodium intake can be estimated equally precisely, more accurately and more practically with the urinary sodium-to-urinary creatinine ratio from 4 urine samples taken on different days than with a single urinary collection.

The perception of Italian pregnant women and new mothers about their psychological wellbeing, lifestyle, delivery, and neonatal management experience during the COVID-19 pandemic lockdown: a web-based survey.

BACKGROUND: In response to the COVID-19 pandemic, drastic measures for social distancing have been introduced also in Italy, likely with a substantial impact in delicate conditions like pregnancy and puerperium. The study aimed to investigate the changes in lifestyle, access to health services, and mental wellbeing during the first Italian lockdown in a sample of Italian pregnant women and new mothers. METHODS: We carried out a web-based survey to evaluate how pregnant women and new mothers were coping with the lockdown. We collected data about healthy habits (physical exercise and dietary habits), access to health services (care access, delivery and obstetric care, neonatal care, and breastfeeding), and mental wellbeing (psychological well-being and emotive support). Descriptive analysis was performed for both groups of participants, whereas a Poisson analysis was used to measure the association between some structural variables (age, education, socio-economic data, partner support, contact, free time, previous children, and pregnancy trimester) and anxiety or depression, difficulties in healthy eating and reduction in physical activity after lockdown started. Chi2 and Adjusted Prevalence Ratios were estimated only for pregnant women. RESULTS: We included 739 respondents (response rate 85.8 %), 600 were pregnant (81.2 %), and 139 (18.8 %) had delivered during lockdown (new mothers). We found a high score for anxiety and depression in 62.8 % of pregnant women and 61.9 % of new mothers. During the lockdown, 61.8 % of pregnant women reduced their physical exercise, and 44.3 % reported eating in a healthier way. 94.0 % of new mothers reported to have breastfed their babies during the hospital stay. Regarding the perceived impact of restrictive measures on breastfeeding, no impact was reported by 56.1 % of new mothers, whereas a negative one by 36.7 %. CONCLUSIONS: The high prevalence of anxiety and depressive symptoms in pregnant women and new mothers should be a public health issue. Clinicians might also recommend and encourage "home" physical exercise. On the other hand, about half of the sample improved their approach towards healthy eating and a very high breastfeeding rate was reported soon after birth: these data are an interesting starting point to develop new strategies for public health.

Management and Nutrition of Neonates during the COVID-19 Pandemic: A Review of the Existing Guidelines and Recommendations.

OBJECTIVE: We aimed at reviewing the currently available guidelines and scientific recommendations regarding the neonatal in-hospital management and feeding in the light of the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: We systematically searched the guideline databases, Medline, Embase, and nationale/international neonatal societies websites as of June 19, 2020, for guidelines on neonatal management and feeding during the COVID-19 pandemic, at the same time assessing the methodological quality using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: Eleven guidelines were included. The Chinese and American recommendations suggest separation of the mother and her neonate, whereas in French, Italian, UK, Canadian, and World Health Organization consensus documents the rooming-in is suggested, with Centers for Disease Control and Prevention guidelines suggesting to decide on a case-by-case basis. All the guidelines recommend breastfeeding or feeding with expressed maternal milk; the only exception is the Chinese recommendations, these last suggesting to avoid breastfeeding. CONCLUSION: This review may provide a useful tool for clinicians and organizers, highlighting differences and similarities of the existing guidelines on the management and feeding strategies in the light of the COVID-19 pandemic. KEY POINTS: · This study compares guidelines on management and nutrition of a newborn born to a mother with SARS-CoV-2 infection.. · Existing guidelines on neonatal management and nutrition during the SARS-CoV-2 pandemic show many differences.. · The majority of recommendations are mainly based on experts' opinion and are not evidence-based..

Small-for-gestational-age birth is linked to cardiovascular dysfunction in early childhood.

BACKGROUND: The aim of this study was to assess clinical and echographic markers of cardiovascular dysfunction in infants born small for gestational age (SGA) compared to a control group of subjects born adequate for gestational age (AGA). METHODS: This was a single-center cross-sectional case-control study. We recruited 20 SGA and 20 gestational age-matched AGA subjects at 24 months of age. The study population underwent anthropometric and Doppler 2-dimensional echocardiographic assessments, and carotid artery intima-media thickness (cIMT) and endothelium-dependent vasodilation evaluation (FMD). The pressure-volume curve during diastole was calculated using the algorithm for the elastance calculation on 1 single beat. RESULTS: SGA children showed lower stroke volume, lower left ventricle (LV) dimensions and volume, and greater LV thickness. Diastolic function was impaired in SGA with lower capacitance and higher elastance. Birth weight standard deviation score was positively associated with capacitance and negatively associated with E/E' ratio and elastance, and in SGA infants, the end-diastolic pressure-related volume curve was shifted to the left compared to AGA. cIMT and systemic vascular resistance were significantly higher, while FMD was lower, in SGA compared to AGA; birth weight standard deviation score was directly correlated with FMD and inversely correlated with cIMT. Finally, a longer breastfeeding duration was associated to a lower cIMT even after correction for confounding factors. CONCLUSIONS: This study shows that infants born SGA present an early and subtle cardiovascular dysfunction compared to AGA controls. These alterations are strongly related to weight at birth. Finally, breastfeeding exerts an important protective and beneficial cardiovascular effect.

Simulation-based medical training for paediatric residents in Italy: a nationwide survey.

BACKGROUND: A prompt start to an appropriate neonatal and paediatric resuscitation is critical to reduce mortality and morbidity. However, residents are rarely exposed to real emergency situations. Simulation-based medical training (SBMT) offers the opportunity to improve medical and non-technical skills in a controlled setting. This survey describes the availability and current use of SBMT by paediatric residents in Italy with the purpose of understanding residents' expectations regarding neonatal and paediatric emergency training, and identifying gaps and potential areas for future implementation. METHODS: A survey was developed and distributed to Italian residents. SBMT was defined as any kind of training with a mannequin in a contextualised clinically realistic scenario. RESULTS: The response rate was 14.4%, covering the 71% of Italian paediatric residency programmes. Among them, 88% stated that Out of the 274 residents, 88% stated that they received less than 5 h of SBMT during the past training year, with 66% not participating in any kind of simulation activity. In 62% of the programmes no simulation training facility was available to residents. Among those who received SBMT, 46% used it for procedures and skills, 30% for clinical scenarios, but only 24% of them reported a regular use for debriefing. Of the overall respondents, 93% were interested in receiving SBMT to improve decision-making abilities in complex medical situations, to improve technical/procedural skills, and to improve overall competency in neonatal and paediatric emergencies, including non-technical skills. The main barriers to the implementation of SBMT programmes in Italian paediatric residencies were: the lack of experts (57%), the lack of support from the school director (56%), the lack of organisation in planning simulation centre courses (42%) and the lack of teaching materials (42%). CONCLUSIONS: This survey shows the scarce use of SBMT during paediatric training programmes in Italy and points out the main limitations to its diffusion. This is a call to action to develop organised SBMT during paediatric residency programs, to train qualified personnel, and to improve the quality of education and care in this field.

Improving clinical diagnosis in SHOX deficiency: the importance of growth velocity.

BackgroundThe aim of this study was to estimate the prevalence of haploinsufficiency of short stature homeobox containing gene (SHOX) deficiency (SHOXD) in a population of short-statured children, and to analyze their phenotype and the performance of clinical scores.MethodsScreening for SHOXD was performed in 281 children with short stature by direct sequencing and multiplex ligation probe-dependent amplification. Subjects with SHOXD were compared with 117 matched short patients without SHOXD. We calculated the cutoff of growth velocity associated with the highest sensitivity and specificity as a screening test for SHOXD by receiver operating characteristic curves.ResultsThe prevalence of SHOXD was 6.8%. Subjects with SHOXD showed a lower growth velocity (P<0.05) and a higher prevalence of dysmorphic signs. The best cutoff for growth velocity was -1.5 standard deviation score (SDS) both in the whole population and in subjects with a Rappold score <7 and <4 points. Growth velocity was ≤-1.5 SDS or Rappold score was >7/>4 points in 17/17 of 19 children with SHOXD and in 49/65 of 117 subjects without SHOX mutations.ConclusionsGrowth rate ≤-1.5 SDS, even with negative Rappold score, may be useful to detect precociously children with SHOXD. Selecting children deserving the genetic test by using growth velocity or the Rappold score significantly increases the sensitivity in detecting mutations and decreases the specificity.

Unacylated ghrelin and obestatin: promising biomarkers of protein energy wasting in children with chronic kidney disease.

BACKGROUND: Impairment in orexigenic/anorexigenic hormone balance may be key in the pathogenesis of protein energy wasting in children with chronic kidney disease (CKD). Measurement of ghrelin and obestatin concentrations in children with CKD would help assess the potential contribution of these hormones to uremic protein energy wasting. METHODS: This was a cross-sectional case-control study. Acylated and unacylated ghrelin and obestatin were measured in 42 children on conservative treatment (CT), 20 children on hemodialysis, 48 pediatric renal transplant (RTx) recipients and 43 controls (CTR) (mean age 11.9, range 5-20 years). Weight, height and bicipital, tricipital, subscapular and suprailiac folds were measured, and the body mass index-standard deviation score (BMI-SDS), percentage of fat mass and fat-free mass were calculated. Urea and creatinine were measured and the glomerular filtration rate (GFR) calculated. RESULTS: Unacylated ghrelin level was higher in patients than controls (p = 0.0001), with the highest levels found in hemodialysis patients (p = 0.001 vs. CKD-CT, p = 0.0001 vs. RTx, p < 0.0001 vs. CTR). Obestatin level was significantly higher in patients on hemodialysis than those on conservative treatment, RTx recipients and controls (p < 0.0001 in each case). Unacylated ghrelin negatively correlated with weight-SDS (p < 0.0001), BMI-SDS (p = 0.0005) and percentage fat mass (p = 0.004) and positively correlated with percentage fat-free mass (p = 0.004). Obestatin concentration negatively correlated with weight-SDS (p = 0.007). Unacylated ghrelin and obestatin concentrations positively correlated with creatinine and urea and inversely with eGFR, even after adjustments for gender, age, puberty and BMI-SDS (p < 0.0001 for each model). CONCLUSIONS: Unacylated ghrelin and obestatin, negatively related to renal function, seem to be promising inverse indicators of nutritional status in children with CKD. Potential therapeutic implications in terms of optimization of their removal in patients on hemodialysis could be hypothesized.

Comparison of neurally-adjusted ventilator assist in infants before and after extubation.

BACKGROUND: To compare invasive (iNAVA) and non-invasive (nivNAVA) neurally adjusted ventilatory assist in infants, respect to gas exchange, breathing pattern, respiratory drive, infant-ventilator interaction and synchrony, vital parameters and required sedation. METHODS: Ten consecutive intubated term infants admitted for respiratory failure of different etiology underwent to 2-hour not-randomized trials of iNAVA and, after extubation, nivNAVA, the latter with unchanged ventilator settings and with air-leaks compensating software. Arterialized capillary blood was sampled at the end of each trial. We computed: 1) the minimum (EAdimin) and peak (EAdipeak) values of the diaphragm electrical activity; 2) ventilator (RRmec) and own patients' (RRneu) respiratory rates; 3) inspiratory (delayTR-insp) and expiratory trigger delays (delayTR-exp) and the time of synchrony between patient's effort and ventilator assistance (Timesynch/Tineu); 4) the asynchrony index. Vital parameters and required sedation were also recorded. RESULTS: iNAVA and nivNAVA did not differ between in terms of gas exchange (pH (7.35 [7.31-7.41] vs. 7.36 [7.30-7.40], P=0.745), PcCO2 (38.4 [34.8-42.6] vs. 36.9 [33.9-41.6] mmHg, P=0.469) and PcO2/FiO2 (211 [168-323] vs. 214 [189-282], P=0.195), respectively). EAdimin, EAdipeak, RRmec and RRneu were similar before and after extubation. Both modes confirmed an optimal infant-ventilator interaction (i.e. delayTR-insp, delayTR-exp and Timesynch/Tineu), irrespective of the interface, and no patients showed clinical relevant asynchronies. A low requirement of sedation with fentanyl was recorded during both trials, without differences between. CONCLUSIONS: We found iNAVA and nivNAVA to be characterized by similar gas exchange, breathing pattern, respiratory drive, infant-ventilator interaction and synchrony, vital parameters and required sedation.

Nonrandomised interventional study showed that early aggressive nutrition was effective in reducing postnatal growth restriction in preterm infants.

AIM: This study evaluated whether an early aggressive nutrition (EAN) strategy could limit extrauterine growth restriction (EUGR) in a cohort of preterm infants. METHODS: This prospective nonrandomised interventional study was carried out in the neonatal intensive care unit of an Italian hospital from January 2013 to December 2015. The prevalence of EUGR was assessed in 100 infants with a gestational age of ≤34 weeks, 50 after the introduction of an EAN regimen in October 2014 and 50 before. RESULTS: The prevalence of EUGR at discharge was significantly lower after the introduction of EAN than before for weight (34% vs. 66%), head circumference (22% vs. 42%) and length at discharge (20% vs. 48%). The Z-scores for all measurements were significantly higher after the introduction of EAN. In the EAN group, weight velocity was significantly higher and maximum weight loss and negative changes in the Z-scores from birth to discharge for weight were lower than in the pre-intervention controls. In extremely low birthweight subjects, the weight Z-score and weight velocity were significantly higher in the EAN group than the control group. CONCLUSION: The use of EAN at a very early age reduced EUGR and improved auxological outcomes in preterm infants.

Influence of Ultraviolet Radiation on the Association between 25-Hydroxy Vitamin D Levels and Cardiovascular Risk Factors in Obesity.

OBJECTIVE: To establish if the correction with estimates of ultraviolet (UV) exposure influences the association between 25-OH-vitamin D (25OHD) levels and metabolic variables. STUDY DESIGN: A cross-sectional study was performed in 575 obese children and adolescents (>6 years of age) in a tertiary referral center. Cardiovascular risk factors were measured. The estimate of UV exposure was evaluated by 3 methods: (1) season; (2) mean of UV radiation (UVR); and (3) mean of UV index (UVI). UVR and UVI were considered at 1 (UVR 1 month prior to testing [UVR1], UVI 1 month prior to testing [UVI1]) or 3 (UVR 3 months prior to testing [UVR3], UVI 3 months prior to testing [UVI3]) months prior to testing. All analyses were corrected for confounders (sex, age, puberty, body mass index, waist circumference, the inclusion and exclusion of estimates of UV exposure). RESULTS: The 25OHD levels were associated with seasons, UVR1, UVR3, UVI1, and UVI3, and best associations with UVR3 and UVI3. In all models, total cholesterol, low-density lipoprotein cholesterol and triglycerides were negatively associated with 25OHD levels. The strength of the association increased with no correction, correction for seasons, UVR, and UVI. UVR3 and UVI3 performed better than UVR1 and UVI3. CONCLUSIONS: Higher lipid concentrations were associated with low 25OHD levels in obese children and adolescents with the power of the association dependent on the estimates of UVR. As the mean values 3 months prior to testing for both UVR and UVI determined the best associations, the interval of the steady state time of 25OHD levels could be preferentially used in the metabolic studies. Controlling for an estimate of UVR is important to decrease the heterogeneity of studies.

Hemolytic uremic syndrome in children.

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption. Moreover, new studies have shown that the complement system is an important factor also in the typical HUS, in which the infection could highlight an underlying dysregulation of complement factors. Clinical signs and symptoms may overlap among the different forms of HUS. Shiga toxin-producing Escherichia Coli (STEC) infection cause a spectrum of clinical sings ranging from asymptomatic carriage to non-bloody diarrhea, hemorrhagic colitis, HUS and death. The average interval between ingestion of STEC and illness manifestation is approximately 3 days, although this can vary between 2 and 12 days. Patients with pneumococcal HUS usually have a severe clinical picture with microangiopathic hemolytic anemia, respiratory distress, neurological involvement. The atypical HUS, in contrast to STEC-HUS which tends to occur as a single event, is a chronic condition and involves a poorer prognosis. Early diagnosis and identification of underlying pathogenic mechanism allow instating specific support measures and therapies. Typical management of STEC-HUS patients relies on supportive care of electrolyte and water imbalance, anemia, hypertension and renal failure. For the aHUS the initial management is supportive and similar to the approach for STEC-HUS; currently we have moved from the historic plasma therapy to new therapeutic approaches, first of all eculizumab, a monoclonal antibody that blocks the C5 cascade. This drug has shown an improvement in platelet count, cessation of hemolysis, improvement of renal function within a few days after the treatment. In patients with end-stage renal disease (ESRD) renal transplantation from a non-related donor and prophylactic administration of eculizumab to prevent recurrent disease in the allograft could be considered.

Metabolic syndrome is strictly associated with parental obesity beginning from childhood.

OBJECTIVE: We aimed to identify potential correlates or risk factors for metabolic syndrome (MetS) in a cohort of schoolchildren. We quantified the prevalence of MetS, analysed the clustering of MetS components and described the distribution of metabolic parameters not included in MetS definition. DESIGN: Population-based, cross-sectional study. PATIENTS AND MEASUREMENTS: A total of 489 children (6·7-13 years) representing the 92·6% of the whole school population between the 1st year of primary school and the 2nd year of junior high school living in a centre of southern Italy. Weight, height, waist circumference, blood pressure (BP), laboratory parameters (indexes of glucose metabolism, lipid profile and uric acid), anamnestic and parental information, lifestyle and dietary habits were collected. Dietary habits data were available only for 353 children. RESULTS: MetS prevalence was 9·8%. Of 48 children with MetS, 38 (79·2%) were simultaneously positive for abdominal obesity and elevated BP. In children with MetS, the prevalence of insulin resistance, high insulin, high non-HDL(high-density lipoprotein) cholesterol and high uric acid was higher than in children without MetS. In 6·7-10-year-old children, only the presence of parental history of obesity [odds ratio (OR) = 4·3, 95% CI = 1·8-10·2] was higher in those with MetS than in those without. In 10·1-13-year-old children, the presence of parental history of obesity, the habits of no walking/cycling to school, long screen time and no breakfast consumption were higher in children with MetS than in those without, but only parental history of obesity (adjusted OR = 3·8, 95% CI = 1·7-8·4) remained significantly related to MetS in multivariate logistic regression. CONCLUSIONS: Parental obesity was strictly associated with MetS in all children and should be considered in clinical practice. In older children, wrong lifestyle and dietary habits were related to parental obesity.

Chronic renal failure of unknown origin is caused by HNF1B mutations in 9% of adult patients: a single centre cohort analysis.

BACKGROUND: HNF1B gene mutations might be an underdiagnosed cause of nephropathy in adult patients mainly because of their pleomorphic clinical presentations. As most studies are based on paediatric populations, it is difficult to assess the likelihood of finding HNF1B mutations in adult patients and consequently define clinical settings in which genetic analysis is indicated. The aim of this study was the search for mutations in the HNF1B gene in a cohort of unrelated adult patients with nephropathy of unknown aetiology. METHODS: Patients were tested for the HNF1B gene if they had chronic kidney disease of unknown origin and renal structure abnormalities (RSA) or a positive family history of nephropathy. The HNF1B coding sequence and intron-exon boundaries were analysed by direct sequencing. The search for gene deletions was performed by Multiple Ligation Probe Analysis (MLPA). RESULTS: Heterozygous mutations were identified in 6 out of 67 screened patients (9.0%) and included two whole gene deletions, one nonsense (p.Gln136Stop), two missense (p.Gly76Cys and p.Ala314Thr) mutations and a frameshift microdeletion (c.384_390 delCATGCAG), the latter two (c.384_390 del and p.Ala314Thr) not ever being reported to date. Mean age of the mutated patients at screening was 48.5 years with a M/F ratio of 2/4. The clinical manifestations of affected patients were extremely pleomorphic, including several urological and extra-renal manifestations. CONCLUSIONS: Mutations of HNF1B could explain chronic kidney disease in up to 9% of adult patients with a nephropathy of unknown aetiology and RSA: therefore an HNF1B mutation analysis should be considered in this group of patients.

Eosinophilic esophagitis improved by the discontinuation of sublingual immunotherapy for aeroallergens: a case report.

Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammation of the esophagus, characterized by symptoms related to esophageal dysfunction, resulting from severe eosinophilic infiltration of the esophageal mucosa. It is common in atopic subjects and food antigens have been identified as the most common triggers. However, a seasonal variation in EoE prevalence, correlated with air pollen levels, is reported, suggesting that also aeroallergens may play a role. Little is known about the interplay between EoE and concomitant atopy treatment for aeroallergens. Case presentation: We describe the case of an 11-year-old boy who presented dysphagia, vomiting, drooling, and chest pain while eating meat, developed 15 months after receiving sublingual immunotherapy (SLIT) for Alternaria (SUBLIVAC®). He underwent esophagogastroduodenoscopy (EGD) revealing severe eosinophilic predominant inflammation (100 eos/HPF), consistent with the diagnosis of EoE, not improving at the EGDs performed after both omeprazole and topical corticosteroids treatment, despite symptom improvement. Afterward, immunotherapy was switched from sublingual to injective form. At the EGD performed 1 month later, macroscopic examination of the esophageal mucosa was normal and eosinophilic infiltration was significantly decreased (5-10 eos/HPF). Conclusions: SLIT may induce EoE by chronic antigenic exposure of oral mucosa in patients with a robust allergic susceptibility: while attenuating the IgE-mediated immune reactions, the progressive contact with the causative allergen might induce a chronic stimulation of the immune system with the consequent activation of tissue eosinophils. Our data suggest monitoring patients receiving SLIT for EoE symptoms and to discontinue SLIT on their earlier appearance, possibly as a first-line treatment.