Validation of the Italian Quality of Life in Short Stature Youth (QoLISSY) questionnaire.

PURPOSE: The Quality of Life in Short Stature Youth (QoLISSY) questionnaire is a disease-specific instrument developed to assess health-related quality of life (HrQoL) in children with short stature. While the original instrument was simultaneously developed in five European countries, this study describes the results of the Italian QoLISSY translation, cultural adaptation, and validation. METHODS: Focus group discussions and a cognitive debriefing process with children (N = 12) diagnosed with growth hormone deficiency or idiopathic short stature and one parent each, as well as parents of younger children (N = 20) were conducted to examine the linguistic and content validity of the Italian version. Psychometric testing was performed using data from the subsequent field- and re-test (N = 32). RESULTS: The results of the qualitative testing of the Italian sample revealed comparability of content to data of the original five European countries. The following field- and re-test results were psychometrically satisfactory including good item and scale operating characteristics, sufficient evidence of reliability, and acceptable evidence of construct validity. CONCLUSION: In conclusion, the Italian QoLISSY HrQoL-dimensions are comparable to other European countries. The psychometric quality of the Italian QoLISSY version is satisfactory and the instrument is ready for use in Italian patients and their parents.

Pregnancy in a methylmalonic acidemia patient with kidney transplantation: a case report.

Presently pregnancy is no more exceptional in women with metabolic diseases. However, it still poses significant medical problems both before and after childbirth. The challenge is even greater if the mother has undergone organ transplantation, because of her metabolic disease. We report on a case of pregnancy in a patient 29-year-old with methylmalonic acidemia cblA type (OMIM 251100) who received a renal transplantation at the age of 17 for end-stage renal disease (ESRD) caused by her primary disease. During pregnancy neither metabolic crises nor renal function changes were observed in the mother, with the only exception of a mild increase of her systemic blood pressure. To the fetus pregnancy was uneventful and during the first 30 months after birth the baby's neuropsychomotor development was normal and there were no episodes of metabolic derangement. This is evidence that methylmalonicacidemia cblA, even when treated with renal transplantation for inherent ESRD, is no contraindication to pregnancy. It is even possible that a functioning transplanted kidney contributes to improve metabolic parameters.

Comparison of two advanced hybrid closed loop in a pediatric population with type 1 diabetes: a real-life observational study.

OBJECTIVE: The Advanced Hybrid Closed Loop (AHCL) systems have provided the potential to ameliorate glucose control in children with Type 1 Diabetes. The aim of the present work was to compare metabolic control obtained with 2 AHCL systems (Medtronic 780G system and Tandem Control IQ system) in a pediatric real-life clinical context. RESEARCH DESIGN AND METHODS: It is an observational, real-life, monocentric study; thirty one children and adolescents (M:F = 15:16, age range 7.6-18 years, mean age 13.05 ± 2.4 years, Diabetes duration > 1 year) with T1D, previously treated with Predictive Low Glucose Suspend (PLGS) systems and then upgraded to AHCL have been enrolled. CGM data of the last four weeks of "PLGS system" (PRE period) with the first four weeks of AHCL system (POST period) have been compared. RESULTS: For both AHCL systems, Medtronic 780G and Tandem Control IQ, respectively TIR at 4 weeks significantly increased, from 65.7 to 70.5% (p < 0.01) and from 64.8 to 70.1% (p < 0.01). (p < 0.01). The comparison between CGM metrics of the 2 evaluated systems doesn't show difference at baseline (last four weeks of PLGS system) and after four weeks of AHCL use. CONCLUSIONS: To our knowledge, this study is the first real-life one comparing 2 AHCL systems in a pediatric population with T1D. It shows an improvement in glucose control when upgrading to AHCL. The comparison between the two AHCL systems did not show significant differences in the analyzed CGM metrics, meaning that the algorithms currently available are equally effective in promoting glucose control.

MR in the evaluation of new anterior cruciate ligament and tibial tunnel position: correlation with clinical and functional features.

PURPOSE: This study aimed to evaluate correlations between the position of the tibial tunnel, its alignment with the ligament-screw system, presence of intratunnel fluid, position of the tibial tunnel with respect to the Blumensaat line and clinical knee stability in patients who underwent arthroscopic reconstruction of the anterior cruciate ligament (ACL), by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: Forty-eight patients (40 men, eight women; mean age, 31 years) underwent arthroscopic reconstruction of the ACL using double-strand semitendinosus and gracilis tendons. The new ACL was fixed to the tibial tunnel using Bio-Intrafix (Mitek). All patients underwent MR imaging 12 months after surgery and clinical evaluation at 6 and 12 months using the International Knee Documentation Committee (IKDC) scoring system. MR imaging and clinical features were correlated using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables. RESULTS: Forty-one patients were clinically stable (groups A and B according to the IKDC test) and seven were unstable (group C). Mean values of tibial tunnel position in clinically unstable vs stable patients were, respectively, -3.6 ±3.8 mm vs. -2.8±3.8 mm in relation to the Blumensaat line (p=0.5712) and 77.3°±11.3 vs. 72.5°±5.5 as concerned the angle measured on the coronal view of the new ACL (p=0.3248); fluid was present in the tibial tunnel in 42.9% and 9.8% of cases, respectively (p=0.2104). MR imaging showed misalignment of ligament screw and tibial tunnel in 57.1% of patients in group C and in 12.2% in groups A and B (p=0.017). CONCLUSIONS: Misalignment of the ligament-screw system and the tibial tunnel and the presence of fluid in the tibial tunnel appear to be directly correlated with clinical instability.

Post-traumatic stress disorder (PTSD) in parents of children with type 1 diabetes during Covid-19 pandemic.

INTRODUCTION: The Post-traumatic Stress Disorder (PTSD) is a group of persistent psychological and physiological symptoms due to a traumatic, severe, event. Only few studies focused on the effects of Covid-19 on psychosocial outcomes in children with Type 1 Diabetes (T1D) and their parents. AIM OF THE STUDY: The aim of this study was to evaluate the presence PTSD in parents of children with T1D during COVID-19 pandemic lockdown. PATIENTS AND METHODS: In the period between March and May 2020 we submitted the "Impact of Event Scale - Revised" (IES-R) questionnaire to the parents of 34 children with Type 1 Diabetes, asking them to express their emotions about the ongoing Covid-19 pandemic. RESULTS: A total of thirty mothers (mean age 43.0 ± 4.2 years) and 25 fathers (mean age 45.6 ± 5.9 years) participated in the survey and completed the questionnaires. 29.1% of parents had a score that allows to define a clinically relevant level of PTSD; ten mothers and 6 fathers had a PTSD clinically relevant score, corresponding, respectively, to 28.4 and 24% of total mothers and fathers. Finally, mothers and fathers, both express PTSD symptoms mainly in the form of intrusion and hyperarousal. CONCLUSIONS: The present study confirms a high prevalence symptoms related to PTSD in mothers and fathers of children with Type 1 Diabetes. We believe that psychosocial outcomes of the COVID-19 pandemic should be taken into account in the planning of the next future assistance for children with T1D.

Phenotypic variability, neurological outcome and genetics background of 6-pyruvoyl-tetrahydropterin synthase deficiency.

This study aimed to investigate the clinical variability and factors implied in the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency (PTPSd). Biochemical and clinical phenotype, treatment variables, and 6-pyruvoyl-tetrahydropterin synthase (PTS) genotype, were explored retrospectively in 19 Italian patients (12 males and 7 females, aged 4 months to 33 years). According to the level of biogenic amines in cerebrospinal fluid (CSF) at the diagnosis, the patients were classified as mild (6) (normal level) or severe (13) (abnormal low level) form (MF and SF, respectively). Blood Phe ranged from 151 to 1053 micromol/l in MF (mean +/- SD: 698 +/- 403) and 342-2120 micromol/l in SF (mean +/- SD: 1175 +/- 517) (p = 0.063). Patients with MF showed a normal neurological development (a transient dystonia was detected in one), while all SF patients except one presented with severe neurological impairment and only four had a normal neurological development. The outcome of the SF was influenced by the precocity of the treatment. Serial CSF examinations revealed a decline of 5-hydroxyindolacetic acid in MFs and an incomplete restoration of neurotransmitters in SFs: neither obviously affected the prognosis. PTS gene analysis detected 17 different mutations (seven so far unreported) (only one affected allele was identified in three subjects). A good correlation was found between genotype and clinical and biochemical phenotype. The occurrence of brain neurotransmitter deficiency and its early correction (by the therapy) are the main prognostic factors in PTPSd.

[Fetal and neonatal outcomes in infants of mothers with TSH receptor antibody positivity in pregnancy]. / Esiti feto-neonatali nei figli di madri con positivita' degli anticorpi anti-recettore del tsh in gravidanza.

OBJECTIVES: To know the mother's frequency with TRAb (TSH receptor antibodies) positivity during pregnancy in the population afferent to Agostino Gemelli Hospital in the five years 2002-2007 and the itself antibodies's role determining fetal and neonatal symptoms. MATERIALS AND METHODS: We performed a prospective analysis with maternal and neonatal variables detection in 16 couples mother-newborn with TRAb positivity during the pregnancy. The method to dose neonatal TRAb is ELISA (enzyme linked immunosorbant assay). RESULTS: The prevalence of newborns of mothers with TRAb positivity during pregancy results 0.1 per thousand (16/16783). The prevalence of neonatal hyperthyroidism, clinical and biochemical, in the studied population results especially elevated equal to about 30% (5/16). The 5 newborns are born to mothers with Basedow disease with TRAb serum levels greater than TRAb levels of newborn without hyperthyroidism: 2 are showed the symptoms of clinical hyperthyroidism and 3 a transient biochemical hyperthirodism. 3 newborns with hyperthyroidism among 5 are born to mother undergo thyroidectomy with L-tiroxina teraphy during the pregnancy. Then the newborns of thyroidectomized mothers also many years before the pregnancy must be considered high risk of developing neonatal hyperthyroidism because of long-lasting persistence of mother's TRAb. The neonatal hyperthyroidism, clinical and biochemical, appears later in newborns of mothers using antithyroid drugs. The pharmacological treatment of neonatal hyperthyroidism was difficult to standardize and highly individualized. CONCLUSIONS: Although the neonatal hyperthyroidism is a very rare disease it is essential to apply specific protocol assistance, both during pregnancy and the neonatal period, in the presence of maternal TRAb positive for the risk of serious cardiovascular complications.

PNKP deficiency mimicking a benign hereditary chorea: The misleading presentation of a neurodegenerative disorder.

PNKP gene encodes for a kinase/phosphatase involved in DNA damage response, controlled and stabilized by ATM phosphorylation. PNKP deficiency, thus far described in 40 subjects, has been associated with a complex neurological phenotype encompassing microcephaly, seizures, developmental delay, ataxia, oculomotor apraxia and polyneuropathy. We report a new case expanding the clinical phenotype of this rare disorder. This 25 years old girl presented with chorea at the age of 2 years and remained stable up to the adult age when the emergence of fatigability and asthenia of lower limbs prompted a new examination disclosing a sensory-motor axonal demyelinating neuropathy. Clinical exome sequencing revealed two previously described variants in PNKP gene. This case highlights the phenotypic variability of PNKP associated disorders, showing that an early onset apparently non progressive chorea can be the presenting symptoms of this rare condition.

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study.

OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

Treatment monitoring of brain creatine deficiency syndromes: a 1H- and 31P-MR spectroscopy study.

BACKGROUND AND PURPOSE: Brain creatine (Cr) deficiencies (BCr-d) are rare disorders of creatine biosynthesis and transport. We performed consecutive measures of total Cr (tCr) and of its phosphorylated fraction, phosphocreatine (PCr), in the brains of children affected by Cr synthesis defects during a long period of therapy. The aim was to identify the optimal treatment strategy for these disorders. MATERIALS AND METHODS: Two patients with guanidinoacetate methyltransferase defect (GAMT-d) were treated with different amounts of Cr and with diet restrictions aimed at reducing endogenous guanidinoacetate (GAA) synthesis. Three patients with arginine:glycine amidinotransferase defect (AGAT-d) were treated with different Cr intakes. The patients' treatments were monitored by means of (1)H- and (31)P-MR spectroscopy. RESULTS: Cr and PCr replenishment was lower in GAMT-d than in AGAT-d even when GAMT-d therapy was carried out with a very high Cr intake. Cr and especially PCr replenishment became more efficient only when GAA blood values were reduced. Adenosine triphosphate (ATP) was increased in the baseline phosphorous spectrum of GAMT-d, and it returned to a normal value with treatment. Brain pH and brain P(i) showed no significant change in the AGAT-d syndrome and at any Cr intake. However, 1 of the 2 GAMT-d patients manifested a lower brain pH level while consuming the GAA-lowering diet. CONCLUSIONS: AGAT-d treatment needs lower Cr intake than GAMT-d. Cr supplementation in GAMT-d treatment should include diet restrictions aimed at reducing GAA concentration in body fluids. (1)H- and especially (31)P-MR spectroscopy are the ideal tools for monitoring the therapy response to these disorders.

A link between lead and cadmium kinetic speciation in seawater and accumulation by the green alga Ulva lactuca.

In this work, studies on the bioaccumulation of Cd and Pb by Ulva lactuca at different sites of Gulf San Jorge (Patagonia, Argentina) are presented. Higher values of bioaccumulated Cd were found in Punta Maqueda - a site believed to serve as a control - in comparison to those in Punta Borja, a place highly exposed to urban and industrial activities. Consequently; the labile fractions of Cd and Pb in seawater were determined with a flow injection-preconcentration manifold interfaced to a graphite furnace-atomic absorption spectrometer (FI-GFAAS). The results obtained by kinetic speciation showed that the variable that correctly explains heavy metals accumulation in the alga, is the labile metal fraction in seawater. We propose to use an enhancement ratio - on the basis of the kinetically labile metal fraction - for calculation of the metal accumulated by the alga relative to its environment.

Impact of long-term use of eHealth systems in adolescents with type 1 diabetes treated with sensor-augmented pump therapy.

Telemedicine in diabetes includes telemonitoring and transmission of important data (self monitoring of blood glucose data, insulin therapy, pump setting, etc.) from the patient s home to the diabetic unit, with a real-time health feedback. Moreover, an eHealth approach is thought to facilitate diabetes management and to improve compliance to CSII/SAP treatment in adolescents, but to date, limited literature related to this topic is available and long-term studies are still lacking. The main aim of this study was to compare the long-term effect on glycometabolic control of eHealth intervention and traditional care in T1DM SAP-treated adolescents. In our study we demonstrated a favorable impact of monthly teleassistance on treatment compliance. Adolescents receiving frequent feedback provided by the medicalmultidisciplinary team, due to the telemonitoring, resulted more compliant in self-management of diabetes. In particular, the medical team feedback resulted in interventions on behavioral errors and insulin therapy adjustments, leading to an improved glycometabolic control.

Brain creatine depletion: guanidinoacetate methyltransferase deficiency (improving with creatine supplementation).

The authors describe an Italian child with guanidinoacetate methyltransferase deficiency, neurologic regression, movement disorders, and epilepsy during the first year of life. Brain MRI showed pallidal and periaqueductal alterations. In vivo 1H-MRS showed brain creatine depletion. The assessment of guanidinoacetic acid concentration in biologic fluids confirmed the diagnosis. Clinical, biochemical, and neuroradiologic improvement followed creatine supplementation.

DNA elution and amplification by polymerase chain reaction from dried blood spots.

A quick, sensitive and easily automatizable method for PCR amplification of genomic DNA eluted from dried blood spots is described. DNA is eluted from a 3-mm spot routinely used for neonatal screening of inherited diseases either by boiling or by sonication. A preliminary and brief spot-autoclaving step is mandatory to ensure optimal and reproducible PCR amplifications. Only 1% of the eluted DNA is required for PCR analysis allowing the execution of multiple genetic tests on the same blood spot. The method has been successfully applied to the detection of a known phenylketonuria-causing mutation and will facilitate the analysis of the genetic repository provided by Guthrie's cards stored in neonatal screening laboratories.

Automated high-performance liquid chromatographic method for the determination of homocysteine in plasma samples.

Plasma homocysteine determination is essential for the diagnosis of inborn errors of metabolism of sulfur amino acids and is achieving considerable importance as a possible risk marker in vascular occlusive pathology. The aim of this study was therefore to develop a fast and sensitive method to assay total and free homocysteine and total and free cysteine in plasma samples, using an automated precolumn sample pretreatment including reduction with 2-mercaptoethanol, carboxymethylation of free thiols and derivation with o-phthalaldehyde. The chromatographic separation was accomplished in 7 min, the within-run and between-run R.S.D.s were all less than 4.3%, the response was linear in the range 0.4-150 microM for homocysteine and 4-1000 microM for cysteine and the mean recoveries were higher than 96%. Moreover, with minimal modification, the method allowed the evaluation of methionine, another important marker of transsulfuration and remethylation defects. The method was applied to the diagnosis of inborn errors involving sulfur amino acids metabolism and to detect mild hyperhomocysteinemia.

Automated method for the measurement of amino acids in urine by high-performance liquid chromatography.

An automatic and sensitive HPLC method for the determination of primary and secondary amino acids included cystine and homocystine in urine samples is described. After a simple ultrafiltration, urine samples were subjected to reduction of disulfides, carboxymethylation of free thiols and double precolumn derivatization with o-phthalaldehyde-3-mercaptopropionic acid and 9-fluroenylmethyl chloroformate. All reactions were fully automated by means of an injector programme and were accomplished in 10 min. Since urine samples contain a large number of amino compounds, a good resolution was required. By optimization of the conditions, separation of 40 amino acids in 92 min was achieved. The recovery of amino acids ranged from 83% for TRP to 105% for CIT. The within-run and between-run R.S.D.s of urinary amino acid concentrations were below 10% for most amino acids except for HYL, LYS and ORN. The method was applied to the diagnosis of genetic disorders of amino acid metabolism.

Application of extraction disks in dissolution tests of clenbuterol and levothyroxine tablets by capillary electrophoresis.

Sample preparation procedures using octadecyl (C18) extraction disks were developed to obtain accurate and reproducible results for determinations of clenbuterol(20 micrograms per dose) and levothyroxine (100 micrograms per dose) in dissolution media of solid oral dosage forms. Preconcentration of samples allowed final concentrations of 1.1 micrograms/ml of clenbuterol and 4.0 micrograms/ml of levothyroxine to be reached prior to CE analysis. The results obtained by CE were in good agreement with those of HPLC. The precision of the migration time, peak area, peak height and accuracy were determined in both intra-day (n = 6) and inter-day (n = 18) assays. Linearity was demonstrated over the ranges 0.5-80.0 micrograms/ml of clenbuterol and 1.0-30.0 micrograms/ml of levothyroxine. The mean recoveries were higher than 94.0%, ranging from 50 to 125% levels with respect to dose potencies. The proposed methodology may be generally applied to determine drugs at ng/ml concentrations.

Analysis of cis-trans isomers and enantiomers of sertraline by cyclodextrin-modified micellar electrokinetic chromatography.

In this work development, optimization and validation of a cyclodextrin-modified micellar electrokinetic chromatography (CD-modified MEKC) method is proposed to resolve separation of the sertraline hydrochloride and synthesis-related substances. Sertraline hydrochloride, the cis-(1S,4S) enantiomer form, is used as an antidepressant therapeutic agent. A buffer concentration composed of 20 mM sodium borate, pH 9.0 with 50 mM sodium cholate, 15 mM sulfated beta-cyclodextrin and 5 mM hydroxypropyl-beta-cyclodextrin was found to be the most suitable background electrolyte. Quantitation of the impurities at levels of 0.1% in different samples of the bulk drug was determined. A comparison of the results with those obtained by HPLC methodology was also accomplished. The method proved appropriate for testing the purity of sertraline hydrochloride in bulk drug.