Parainfluenza viruses: A trigger for type 1 diabetes new onset?

Type 1 diabetes (T1DM) ethiopathogenesis is still being studied, since the role of environmental factors , especially viruses, is not yet clear. This study was conducted on 31 paediatric patients with T1DM at onset. We analysed: Coxsackieviruses A (CoxA), Coxsackieviruses B (CoxB), Echoviruses (Echo); Influenzavirus A and B (IV-A and IV-B); Adenovirus (AdV); Parainfluenza viruses 1-2 and 3 (PiV 1-2-3); Cytomegalovirus (CMV) and Respiratory Syncytial Virus (RSV). Enteroviruses, especially CoxB and Echo, are most represented. Unexpectedly, Parainfluenza viruses were detected in seasonal subgroups, with peaks in autumn and spring, and spread homogeneously in different age groups.

Diffuse brain damage in normal tension glaucoma.

Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP <21 mm Hg despite the typical glaucomatous findings, represents the most suitable model of glaucoma to test the validity of this hypothesis. We acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing. Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging-derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532-541, 2018. © 2017 Wiley Periodicals, Inc.

Are they functional hypogonadal men? Testosterone serum levels unravel male idiopathic infertility subgroups.

PURPOSE: To evaluate total testosterone distribution in male idiopathic infertility. METHODS: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with alterations in semen parameters and normal gonadotropin levels, and after excluding all known causes of male infertility. Controls were male subjects who underwent semen analysis for screening purposes, without any abnormality detected. The total testosterone distribution was evaluated in cases and controls. Further analyses were performed subgrouping cases according to total testosterone reference threshold suggested by scientific societies (i.e., 3.5 ng/mL). RESULTS: Cases included 214 idiopathic infertile men (mean age 38.2 ± 6.2 years) and controls 224 subjects with normozoospermia (mean age 33.7 ± 7.5 years). Total testosterone was not-normally distributed in both cases and controls, with positive asymmetric distribution slightly shifted on the left in cases. The rate of subjects with testosterone lower than 3.5 ng/mL was higher in cases (23.8%) than controls (4.5%) (p < 0.001). In cases with testosterone lower than 3.5 ng/mL, a significant direct correlation between testosterone and the percentage of normal morphology sperms was highlighted, also applying multivariate stepwise linear regression analysis (R = 0.430, standard error = 0.3, p = 0.020). CONCLUSION: Although idiopathic infertile men show by definition altered semen analysis and gonadotropins within reference ranges, testosterone serum levels are widely variable in this population. Approximately a quarter of these patients present some sort of functional hypogonadism. Our data support the need to better classify idiopathic male infertility and total testosterone serum levels could be a supportive parameter in tracing the patient's therapeutic profile.

How does diabetes type 1 affects immune response to hepatitis B virus vaccine in pediatric population? Evaluation of a booster dose in unresponsive subjects with type 1 diabetes.

BACKGROUND: Hepatitis B virus (HBV) vaccine reduced the incidence of Hepatitis B worldwide. Genetic variability, by the presence of specific haplotypes of HLA system (HLA-DR3, HLA-DR4), influences the response to the vaccination. Subjects affected by type 1 diabetes (T1D), contrary to non-diabetics, have a high prevalence of Hepatitis B. METHODS: The objective of the study was to evaluate anti-HBs antigen (anti-HBsAg) antibody (Ab) in a group of 201 children (age range: 2-18 years), regularly vaccinated against HBV according to the national vaccination schedule. Patients with anti-HBs Ab≥10 mIU/mL have been defined "responders" and those with anti-HBs Ab<10mIU/mL have been defined "non-responders." The possible association between the T1D and a low immune response to the vaccine has been subsequently valued. Besides the presence of T1D, other possible influential variables have been studied: sex, age, presence of celiac disease and Hashimoto's thyroiditis, intervening years from the diagnosis of diabetes and presence/absence of diabetic ketoacidosis at time of diagnosis. RESULTS: Among the 201 subjects with T1D, 90 (44.8%) were responders, while 111 (55.2%) were non-responders; among the 145 subjects without T1D, 86 (59.3%) were responders and 59 (40.7%) non-responders. We invited "Subjects with T1D non-responders" to undergo a booster dose of the same vaccine. Of these, 21 refused the booster, reducing the sample to 90 patients. After 4 weeks from the booster dose 81 patients showed seroconversion ("false non-responders"), and 9 did not ("true non-responders"). CONCLUSIONS: After the booster dose, immune response in our cross-section has been similar to general population. Given the high frequency of "false non-responders" anti-HBsAg Ab should be tested in T1D patients and a booster dose should be administrated in non-responders.

Microbiota Composition and Probiotics Supplementations on Sleep Quality-A Systematic Review and Meta-Analysis.

The gut microbiota (GM) plays a crucial role in human health. The bidirectional interaction between GM and the central nervous system may occur via the microbiota-gut-brain axis, possibly regulating the sleep/wake cycle. Recent reports highlight associations between intestinal dysbiosis and sleep disorders, suggesting that probiotics could ameliorate this condition. However, data are poor and inconsistent. The aim of this quantitative metanalytic study is to assess the GM composition in sleep disturbances and evaluate probiotics' effectiveness for managing sleep disorders. A systematic review was carried out until July 2022 in online databases, limiting the literature research to human studies and English language articles. No significant GM diversity between patients with sleep disturbances versus healthy controls was found, revealed by α-diversity, while ß-diversity is missing due to lack of proper reporting. However, probiotics supplementation significantly reduced the self-assessed parameter of sleep quality and disturbances Pittsburgh Sleep Quality Index (PSQI) score compared with the placebo. No difference in the Epworth Sleepiness Scale (ESS) score was found. While available data suggest that GM diversity is not related to sleep disturbances, probiotics administration strongly improves sleep quality as a subjective perception. However, heterogeneity of data reporting in the scientific literature should be considered as a limitation.

No effects of COVID-19 on the development of type 1 diabetes autoimmunity and no evidence of an increased frequency of SARS-CoV-2 antibodies in newly diagnosed type 1 diabetes patients relative to healthy subjects.

AIMS: To evaluate the relationship between SARS-CoV-2 infection and autoimmunity in type 1 diabetes (T1D) and SARS-CoV-2 antibodies frequency at diagnosis of T1D during pandemic. METHODS: The presence of T1D-specific autoimmunity was evaluated in a cohort of 99 children and adolescents without diabetes that contracted SARS-CoV-2 infection. Moreover, the frequency of IgM- and IgG-SARS-CoV-2 antibodies was evaluated in 41 newly diagnosed T1D patients not yet vaccinated against SARS-CoV-2 disease, collected during the pandemic, compared to healthy subjects (CTRL). RESULTS: None of the 99 patients that contracted SARS-CoV-2 infection during the pandemic period was found positive for T1D autoantibodies. The frequency of SARS-CoV-2 antibodies was not significantly different in patients newly diagnosed with T1D (12.2%), compared with CTRL (8.4%). Among SARS-CoV-2 antibody positive T1D patients, 80% were target of diabetes autoantibodies and 60% had another concomitant autoimmune disease. Among the CTRL subjects positive for SARS-CoV-2Abs (n = 10), none was found positive for T1D autoantibodies. CONCLUSIONS: The results of the present study do not confirm, at least in the short term, a role of COVID-19 as a potential trigger of T1D autoimmunity and do not provide evidence of an increased frequency of SARS-CoV-2 antibodies in newly diagnosed T1D patients in comparison with healthy population.

Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia.

Kabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and inflammatory disorders, and an underlying immunological phenotype characterized by immunodeficiency and immune dysregulation. Up to 17% of KS patients present with immune thrombocytopenia characterized by a severe, chronic or relapsing course, and often associated to other hematological autoimmune diseases including autoimmune hemolytic anemia, eventually resulting in Evans syndrome (ES). A 23-year-old woman, clinically diagnosed with KS and presenting from the age of 3 years with ES was referred to the Rare Diseases Centre of our Pediatric Department for corticosteroid-induced hyperglycemia. Several ES relapses and recurrent respiratory infections in the previous years were reported. Severe hypogammaglobulinemia, splenomegaly and signs of chronic lung inflammation were diagnosed only at the time of our observation. Supportive treatment with amoxicillin-clavulanate prophylaxis and recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin replacement were immediately started. In KS patients, the failure of B-cell development and the lack of autoreactive immune cells suppression can lead to immunodeficiency and autoimmunity that may be undiagnosed for a long time. Our patient's case is paradigmatic since she presented with preventable morbidity and severe lung disease years after disease onset. This case emphasizes the importance of suspecting immune dysregulation in KS. Pathogenesis and immunological complications of KS are discussed. Moreover, the need to perform immunologic evaluations is highlighted both at the time of KS diagnosis and during disease follow-up, in order to allow proper treatment while intercepting avoidable morbidity in these patients.

Prolactin and spermatogenesis: new lights on the interplay between prolactin and sperm parameters.

PURPOSE: To clarify the relationship between one the most gender-specific hormone, i.e. prolactin (PRL), and semen parameters in men. METHODS: A retrospective, observational, cohort, real-world study was carried out, enrolling all men performing a semen analysis and PRL examination from 2010 to 2022. For each patient, the first semen analys was extracted, associated to PRL, total testosterone (TT), follicle stimulating hormone (FSH) and luteinizing hormone (LH). Hyperprolactinaemia (>35 ng/mL) was excluded. RESULTS: 1211 subjects were included. PRL serum levels were lower in normozoospermia compared to azoospermia (p = 0.002) and altered semen parameters (p = 0.048) groups. TT serum levels were not different among groups (p = 0.122). Excluding azoospermic men, PRL serum levels were lower in normozoospermic patients, when compared to other groups of semen alterations. An inverse correlation was detected between PRL and sperm concentration. Considering normozospermic subjects, PRL was directly related to both non-progressive sperm motility (p = 0.014) and normal sperm morphology (p = 0.040). Subdiving the cohort in quartiles according to PRL distribution, the highest motilities were observed in the second PRL quartile (8.30-11.10 ng/mL) and asthenozoospermia was significantly predicted by FSH (p < 0.001) and second PRL quartile (p = 0.045). CONCLUSION: The PRL-spermatogenesis connection seems to be mild, although low-normal PRL levels are associated with the best spermatogenetic profile. PRL serum levels could mirror the immunoregulatory status within the testis, suggesting that there is a sort of 'PRL optimal window' reflecting an efficent spermatogenesis. Alternatively, men with good semen parameters might have a higher central dopaminergic tone resulting in low PRL levels.

Two Cases of Wolfram Syndrome Who Were Initially Diagnosed With Type 1 Diabetes.

Objective: Early diagnosis of syndromic monogenic diabetes allows for proper management and can lead to improved quality of life in the long term. This report aimed to describe 2 genetically confirmed cases of Wolfram syndrome, a rare endoplasmic reticulum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Case Report: A 16-year-old Caucasian male patient and a 25-year-old Caucasian female patient with a history of diabetes mellitus and optic nerve atrophy presented at our medical center. Both patients were initially diagnosed with type 1 diabetes but negative for islet autoantibodies. Their body mass indexes were under 25 at the diagnosis. Their history and presentation were highly suspicious for Wolfram syndrome. Discussion: The genetic tests revealed a known Wolfram syndrome 1 (WFS1) pathogenic variant (homozygous) in the 16-year-old male patient and 2 known WFS1 pathogenic variants (compound heterozygous) in the 25-year-old female patient with diabetes mellitus and optic nerve atrophy, confirming the diagnosis of Wolfram syndrome. The first patient had a moderate form, and the second patient had a milder form of Wolfram syndrome. Conclusion: Providers should consider monogenic diabetes genetic testing, including WFS1 gene, for patients with early-onset diabetes who are negative for islet autoantibodies and lean. Two patients described in this article could have been diagnosed with Wolfram syndrome before they developed optic nerve atrophy. Genetic testing is a valuable tool for the early detection of Wolfram syndrome, which leads to proper management and improved quality of life in patients with this rare medical condition.

Subthreshold Micropulse Laser for Long-Lasting Submacular Fluid after Rhegmatogeous Retinal Detachment Surgery.

Purpose: To assess the safety and efficacy of subthreshold micropulse laser (SML) photo-stimulation in the management of persistent subfoveal fluid (PSF) after surgery for rhegmatogenous retinal detachment (RRD). Methods: In this pilot study, 11 eyes of 11 patients (8 men, 3 women) with long-lasting (12-18 months) PSF after surgery for RRD were evaluated before and after photostimulation with subthreshold micropulse yellow laser. Ophthalmic examination included best-corrected visual acuity (BCVA), Amsler grid test, ophthalmoscopy, autofluorescence (AF), and optical coherence tomography (OCT) with measurement of central point foveal thickness (CPFT). Primary outcome was subfoveal fluid resolution and secondary outcome was BCVA improvement. Results: The mean CPFT and BCVA were, respectively, 436.8 ± 28.8 µm and 0.25 ± 0.1 µm decimal equivalent (DE) before photostimulation and 278 ± 54.4 µm and 0.57 ± 0.2 µm DE after photostimulation, a statistically significant difference (P < 0.001). Nine (81.8%) eyes showed improved BCVA, disappearance of macular detachment on ophthalmoscopy, reduced retinal pigment epithelium distress on AF, and restored macular profile with no neuroretinal alterations on OCT scans. Conclusion: Although PSF after RRD surgery is often a self-limiting disease, our results suggest that SML photostimulation may be effective and safe in patients with clinically significant long-lasting PSF. Larger case-control studies are necessary to confirm these results.

Chilblain-like lesions onset during SARS-CoV-2 infection in a COVID-19-vaccinated adolescent: case report and review of literature.

BACKGROUND: COVID toes or chilblain-like skin lesions have been widely reported during COVID-19 pandemic. Most cases were described in patients with negative microbiological tests for SARS-CoV-2, therefore the possible relationship with SARS-CoV-2 infection, as well as with the nowadays broadly available mRNA-based vaccination, has not been fully elucidated.  CASE PRESENTATION: We here describe the case of a 14-year-old male who developed chilblain-like skin eruptions during SARS-CoV-2 infection despite two mRNA-based vaccine doses and review the clinical and epidemiological characteristics of chilblain-like lesions as a cutaneous presentation of COVID-19 in children. CONCLUSIONS: Most children and adolescent with COVID toes have a mild or asymptomatic SARS-CoV-2 infection. Our report aims to highlight the possible onset of these skin lesions in vaccinated children, if infection has occurred, and the potential use of systemic corticosteroids as a first line treatment. Additional evidence is required to better understand SARS-CoV-2 infection and cutaneous manifestations in children and determine the relationship between chilblain-like lesions and COVID-19 vaccination.

Skeletal status in children and adolescents with new-onset type 1 diabetes: a preliminary study based on bone densitometry and quantitative ultrasound.

INTRODUCTION: Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality. MATERIAL AND METHODS: We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual ß-cell function. RESULTS: 17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of ß-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values. CONCLUSIONS: Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual ß-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.

Blue eyes as a risk factor for type 1 diabetes.

BACKGROUND: A high frequency of blue eyes and fair skin are reported in northern European Caucasians with type 1 diabetes (T1D). Also there is an inverse relationship between latitude and T1D incidence. We determined whether iris colour and skin pigmentation are risk factors in a Caucasian population living in two Mediterranean regions located at the same latitude with higher ultraviolet B irradiance, but with different T1D incidence. METHODS: We studied iris colour in 281 consecutive subjects with T1D and 298 controls. Skin type was evaluated by melanin quantification. RESULTS: In Lazio, blue eyes and fair skin type are significantly more common in T1D subjects than in controls (21 versus 9%, p = 0.002; 50 versus 35%, p < 0.001, respectively). In Sardinia, the frequency of blue eyes in T1D subjects is twice that in controls (5.8 versus 2.6% and significantly higher when compared to the expected calculated frequency in the entire population). By logistic regression analysis, only blue eyes are independent and significant predictors of T1D [odds ratio for blue eyes = 2.2; 95% confidence interval (1.1-4.4), p = 0.019]. CONCLUSIONS: As previously shown in a Caucasian population from northern Europe, blue eyes and a trend for fair skin increase the risk for T1D also in a Caucasian population born and residing in a Mediterranean region (Continental Italy). This finding may be relevant for explaining different T1D incidence as prevalence of blue eyes differ substantially between northern and southern European Caucasians.

Microdeletion 3q syndrome.

The authors present the clinical case of a 5-month-old boy, affected by multimalformative syndrome with features of microdeletion 3q syndrome. In the literature so far, the real incidence is unknown because of its rarity. The goal of this study was to describe the salient findings of this rare malformative syndrome, which needs a multidisciplinary approach. The patient had 3q interstitial chromosome deletion (q22.1-q25.2). He showed the following clinical features: microcephaly, microphthalmia, epicantus inversus, blepharophimosis, palpebral ptosis, short neck with pterygium, brachycephaly, round face, hypotelorism, broad nasal bridge, beaked nose, large and low-set ears, soft cleft palate, retromicrognathia with large mouth, arthrogryposis of the superior limbs and knees in association with clinodactyly, overlapping of second and third digits of both hands and feet, and gastroesophageal reflux. The patient developed physical and motor development delay. He was affected by Dandy-walker malformation, characterized by cerebellum vermis hypoplasia. The placement of the patient in contiguous gene syndrome (Dandy walker syndrome, Pierre-Robin sequence, and Seckel syndrome) was carried out by a multidisciplinary team to have a holistic evaluation of clinical findings. Thanks to this approach, it was possible to establish a complete diagnostic and therapeutic course. The genetic analysis enables to arrange an assistive program. Surgeons' attention was focused on the malformations, which represented an obstacle for normal development and social life.

Surveying work-as-done in post-operative delirium risk factors collection and diagnosis monitoring.

Post-operative delirium (POD) is a health hazard condition for the patients and it is associated with increased costs for the healthcare system. Following a system-theoretic approach, firstly a model, then a questionnaire, have been designed to probe the collective awareness about POD throughout the entire patient's perioperative pathway. The 58 reported answers pointed out that most of the information, specifically associated with POD, are routinely recorded but not used to stratify the patients' individual risk to develop POD. The results suggest the need for design a new socio-technical role within modern health care systems: the POD analyst. A Systems-Theoretic Accident Model and Processes (STAMP) model is proposed both to propel the awareness about POD and as a template for future POD risk factors collections.

Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy.

OBJECTIVE: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. DESIGN: Retrospective analysis of the Italian data set of patients with TNDM. METHODS: Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. RESULTS: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. CONCLUSIONS: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.

Altered Large-Scale Brain Functional Connectivity in Ocular Hypertension.

We hypothesized that assessment of brain connectivity may shed light on the underpinnings of ocular hypertension (OHT), characterized by raised intraocular pressure (IOP) and no typical glaucomatous findings. OHT carries a risk for future glaucoma development, thus representing a model of presymptomatic condition. In previous studies on glaucoma, we showed altered brain connectivity since the early stage and in case of normal IOP. In this pilot study, we used a multimodal MRI approach by modeling voxelwise measures of gray matter volume, anatomical connectivity along white matter(WM) tracts, and large-scale functional connectivity in OHT subjects (n = 18, age: 58.3 ± 9.8 years) and demographically matched normal controls (n = 29). While OHT brain had no structural alterations, it showed significantly decreased functional connectivity in key cognitive networks [default mode network, frontoparietal working memory network (WMN), ventral attention network (VAN), and salience network (SN)] and altered long-range functional connectivity, which was decreased between default mode and SNs and increased between primary and secondary visual networks (VN). Overall, such findings seem to delineate a complex neuroplasticity in the OHT brain, where decreased functional connectivity in non-visual networks may reflect a type of temporarily downregulated functional reserve while increased functional connectivity between VN may be viewed as a very early attempt of adaptive functional reorganization of the visual system.

Long-term posaconazole treatment and follow-up of rhino-orbital-cerebral mucormycosis in a diabetic girl.

To demonstrate that the 2-yr clinical follow-up of our patient strongly suggests that long-term therapy with posaconazole (POS) is safe and beneficial in treatment and prevention of relapses of, otherwise fatal, central nervous system mucormycosis. Mucormycosis is a very rare opportunistic mycotic infection of diabetic children. We present the 30-month follow-up of a 12-yr-old girl affected by diabetic ketoacidotic coma, complicated by rhinocerebral mucormycosis and successfully treated with POS at the initial daily dose of 5 mg/kg t.i.d. with fatty food for 3 wk, followed by a daily dose of 10 mg/kg in four doses for 2 months and then 20 mg/kg/d in four doses for 16 months and in two doses for further 5 months. The previous amphotericin B, granulocyte colony-stimulating factor, hyperbaric oxygen and nasal and left maxillary sinus surgical debridement therapy was ineffective in stopping the progression of the infection to the brain. The patient improved within 10 d with reduced ocular swelling and pain, and 6 months after therapy stop, she is in good health and cultures are sterile. This article demonstrates that POS may be a useful drug in mucormycosis in children. We also strongly draw the attention to the main preventive procedure against invasive fungal infection that is the correct management of antidiabetic therapy that prevents the predisposing temporary neutrophils activity deficit, contributing to a better survival rate of diabetic children.

Epilepsy in children with type 1 diabetes mellitus: Pathophysiological basis and clinical hallmarks.

We provide an overview on the current knowledge about the association between epilepsy and type 1 diabetes mellitus (T1DM). People with T1DM have a 2-6-fold higher risk of epilepsy than the general population. The onset of T1DM anticipates the onset of epilepsy by a mean period between 1,5 and 2,8 years. These two disorders share four potential distinct pathogenic factors: a) genetic predisposition; b) factors involved in autoimmune responses (i.e. anti-glutamic acid decarboxylase antibodies-GADAbs); c) effects of hypo/hyperglycaemia; d) cerebrovascular damages resulting in ischaemic processes. Seizures semiology prominently includes focal (up to patterns of epilepsia partialis continua) or secondarily generalized seizures but also reflex seizures and various forms of generalized seizures. EEG abnormalities are more common in people with an inappropriate metabolic control with a prominent involvement of fronto-temporal regions. Epilepsy management does not differ between patients with and without diabetes and insulin, nutritional recommendations and physical activity may also produce significant benefits on seizures control. Possible therapeutic alternatives in selected cases include immunosuppressive drugs (in patients with GADAbs) and ketogenic diet.