Searching for Effective Methods of Diagnosing Nervous System Lesions in Patients with Alström and Bardet-Biedl Syndromes.

Bardet-Biedl syndrome (BBS) and Alström syndrome (ALMS) are rare multisystem diseases with an autosomal recessive mode of inheritance and genetic heterogeneity, characterized by visual impairment, hearing impairment, cardiomyopathy, childhood obesity, and insulin resistance. The purpose of our study was to evaluate the indicators of nervous system changes occurring in patients with ALMS and BBS using optical coherence tomography (OCT) and magnetic resonance spectroscopy (MRS) methods compared to a group of healthy subjects. The OCT results showed significantly lower macular thickness in the patient group compared to the control group (p = 0.002). The MRS study observed differences in metabolite levels between the study and control groups in brain areas such as the cerebellum, thalamus, and white matter. After summing the concentrations from all areas, statistically significant results were obtained for N-acetylaspartate, total N-acetylaspartate, and total creatine. Concentrations of these metabolites were reduced in ALMS/BBS patients by 38% (p = 0.0004), 35% (p = 0.0008), and 28% (p = 0.0005), respectively. Our results may help to understand the pathophysiology of these rare diseases and identify strategies for new therapies.

Vitamin Status in Children with Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation.

BACKGROUND: The issue of vitamin metabolism in children with cystic fibrosis screen positive, inconclusive diagnosis (CFSPID) is not well known. The aim of this study was to determine the status of vitamins A, D, E, and C in the blood of a group of children with CFSPID. MATERIAL AND METHODS: A total of 89 children were enrolled in the study (Me: 3.6 years, 52.8% boys), as follows: 28 with CFSPID, 31 with CF (cystic fibrosis), and 30 HC (healthy children). Their blood concentrations of vitamins A, D, E, and C, and their dietary intake of these vitamins were analysed in the study groups on the basis of a three-day food diary. RESULTS: The patients with CFSPID had significantly higher serum vitamin D (p = 0.01) and E (p = 0.04) concentrations, compared to the children with CF. None of the children with CFSPID revealed vitamin A or E deficiencies. Patients with CF had been consuming significantly higher vitamin D and E amounts (p = 0.01). The vitamin concentrations did not depend either on the pancreatic/liver function or on anthropometric parameters. In total, 32.14% of patients with CF did not cover the baseline recommended calorie intake, and 53.6% and 36% did not take the recommended vitamin E and vitamin A intake, respectively. CONCLUSION: Children with CF and CFSPID did not fully cover the dietary recommendations for vitamin supply, but vitamin deficiency was found only in CF.

Effect of COVID-19 Lockdowns on Eye Emergency Department, Increasing Prevalence of Uveitis and Optic Neuritis in the COVID-19 Era.

Background: The COVID-19 pandemic led to the reorganization of the health care system. A decline in health- and life-saving procedures has been reported in various medical specialties. However, data on ophthalmic emergencies during lockdowns is limited. Methods: We conducted a retrospective, observational, case-control study of 2351 patients registered at the ophthalmic emergency department of a tertiary hospital in Poland during three national COVID-19 lockdowns (March/April 2020, November 2020, and March/April 2021) and corresponding months in 2019. Results: The total number of visits declined from a mean of 720/month in the non-COVID era to 304/month during COVID-19 lockdowns (p < 0.001). Ocular trauma incidence dropped significantly from 2019 (non-COVID months) to 2020/2021 (COVID group mean 201 vs. 97 patients monthly, respectively, p = 0.03). Of note, the percentage of foreign bodies removal was significantly higher during lockdowns than corresponding time in the non-COVID era. A downward trend for vitreous detachment and macular disorders cases was observed between COVID and non-COVID time. Uveitis and optic neuritis patients were seen more often during lockdowns (p < 0.001 and p = 0.0013, respectively). In contrast, the frequency of conjunctivitis and keratitis, potentially COVID-related problems, decreased significantly in COVID-19 time (mean 138 vs. 23 per month in non-COVID vs. COVID lockdowns, respectively, p < 0.001). Conclusions: The overall number of eye emergency visits declined during COVID-19 lockdowns. Conjunctivitis and keratitis rates dropped during the lockdowns. Interestingly, the frequency of immune-mediated ocular conditions (uveitis, optic neuritis) increased significantly which might be triggered by SARS-CoV2 infection.

Identification of bone metabolism disorders in patients with Alström and Bardet-Biedl syndromes based on markers of bone turnover and mandibular atrophy.

Objectives: Causative variants in genes responsible for Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) cause damage to primary cilia associated with correct functioning of cell signaling pathways in many tissues. Despite differences in genetic background, both syndromes affect multiple organs and numerous clinical manifestations are common including obesity, retinal degeneration, insulin resistance, type 2 diabetes and many others. The aim of the study was to evaluate bone metabolism abnormalities and their relation to metabolic disorders based on bone turnover markers and presence of mandibular atrophy in patients with ALMS and BBS syndromes. Material and methods: In 18 patients (11 with ALMS and 7 with BBS aged 5-29) and in 42 age-matched (p < 0.05) healthy subjects, the following markers of bone turnover were assessed: serum osteocalcin (OC), osteoprotegerin (OPG), s-RANKL and urinary deoxypyridinoline - DPD. In addition, a severity of alveolar atrophy using dental panoramic radiograms was evaluated. Results: Lower serum OC (p = 0.0004) and urinary DPD levels (p = 0.0056) were observed in the study group compared to controls. In ALMS and BBS patients, serum OC and urinary DPD values negatively correlated with the HOMA-IR index, while a positive correlation between the OC and 25-OHD levels and a negative correlation between s-RANKL and fasting glucose concentrations were found. A significant difference in the incidence of low-grade mandibular atrophy between patients with ALMS and BBS and controls (p < 0.0001) was observed. Conclusions: The identification of bone metabolism disorders in patients with ALMS and BBS syndromes indicates the necessity to provide them with appropriate diagnosis and treatment of these abnormalities.

Bacterial strains colonizing the sensor electrodes of a continuous glucose monitoring system in children with diabetes.

INTRODUCTION: The higher frequency of infections in diabetic patients is caused by a hyperglycemic environment, which promotes immune dysfunction. People with diabetes are more prone to skin infections. A continuous glucose monitoring (CGM) system provides information on changes in blood glucose (BG) levels throughout the day. Its use facilitates optimal therapeutic decisions for a diabetic patient. One of the factors limiting the use of CGM is inflammation at the insertion site. AIM OF THE STUDY: The aim of the study was the microbiological identification of the bacterial strains which are found on CGM sensor electrodes. MATERIAL AND METHODS: We performed microbiological tests on patients' CGM Enlite Medtronic electrodes, which were removed after 6 days of usage according to the manufacturer's instructions. 31 sensors were examined from 31 children (14 girls) aged from 0.5 to 14.6 years. The microbiological analysis was routinely performed at the Department of Children's Diabetology Medical University of Silesia in Katowice, Poland. RESULTS: 12 (39%) of the electrodes were colonized. In 11 (92%) cases the electrodes were colonized by one bacteria strain. 7 times methicillin-sensitive coagulase negative staphylococcus (MSCNS) was detected. We also found one case of Klebsiella pneumoniae, Ochrobactrum tritici, Bacillus sonorensis and methicillin-resistant coagulase-negative Staphylococci (MRCNS) colonization. One electrode was colonized by the mixed flora Enterococcus faecalis, methicillin-susceptible coagulase-negative Staphylococci (MSCNS), Pseudomonas stutzeri, methicillin-susceptible Staphylococcus aureus (MSSA). The median HbA1c in the group with colonization of electrodes was 6, 85% (6, 3-7, 6%) versus 6, 3% (5, 8-7, 5%) in the group without colonization. The median BMI in the group with colonization of the electrodes was 17.10 kg/m2 (16.28-18.62 kg/m2) versus 15.98 kg/m2 (15.14-17.96 kg/m2) in the group without colonization. Statistically, significantly more frequently electrodes are colonized in older children (median age in the group with colonization of electrodes 11.43 years (6.52-12.27 years), without colonization 8.42 years. (3.098-9.375 years); (p = 0.033). CONCLUSIONS: It seems that older children are more likely to have their sensor electrode colonized by bacterial strains.

Fetuin-A and Interleukine-8 in Children with the Clinical Remission of Type 1 Diabetes.

BACKGROUND: Clinical partial remission (CPR) in most patients with type 1 diabetes (T1D) is observed shortly after clinical diagnosis. Increasing body weight and impaired insulin sensitivity may play a role in the pathogenesis of CPR. Several cytokines can also participate in the development of insulin resistance. OBJECTIVE: To evaluate the relationship between birth weight, body mass index, and the concentrations of IL-8 and Fetuin-A, and the presence of clinical partial remission in children at the T1D onset. METHODS: The study group consisted of 134 children with a newly diagnosed T1D in whom the presence of CPR was evaluated in a further 2-year course of diabetes. The control group included 47 children without glucose tolerance disorders. The concentrations of IL-8 and Fetuin-A were determined by the ELISA method. RESULTS: CPR occurred in 75.34% of T1D patients. At T1D onset, higher values of BMI SDS in the remitters as compared to the patients without remission were observed. At the T1D onset, the concentrations of Fetuin-A (p=0.031) and IL-8 (p=0.042) were significantly higher in patients compared to those without CPR. CONCLUSION: Evaluation of Fetuin-A and IL-8 levels in patients with a newly diagnosed T1D can differentiate between patients with or without CPR.

The Usefulness of Genotyping of Celiac Disease-Specific HLA among Children with Type 1 Diabetes in Various Clinical Situations.

Aim: The aim of the study was to determine the usefulness of HLA DQ2/DQ8 genotyping in children with T1D in various clinical situations: as a screening test at the diabetes onset, as a verification of the diagnosis in doubtful situations, and as a test estimating the risk of CD in the future. Materials and methods. Three groups of patients with T1D were included: newly diagnosed (n = 92), with CD and villous atrophy (n = 92), with CD and villous atrophy (n = 92), with CD and villous atrophy (n = 30), and with potential CD (n = 23). Genetic tests were performed (commercial test, PCR, and REX), and clinical data were collected. Results: The results of genetic tests confirmed the presence of DQ2/DQ8 in 94% of children with diabetes (group I) and in 100% of children with diabetes and CD (groups II and III, respectively). Comparative analysis of the HLA DQ2/DQ8 distribution did not show any differences. Allele DRB1∗04 (linked with HLA DQ8) was significantly less common in children with diabetes and CD (group I versus groups II and III, 56.5% vs. 24.5%; p = 0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529; p = 0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529; p = 0.001). The probability of developing CD in DRB1∗04-positive patients was 4 times lower (OR 0.25; 95% CI 0.118-0.529. Conclusions: Genotyping HLA DQ2/DQ8 as a negative screening has limited use in assessing the risk of CD at the diabetes onset and does not allow to verify the diagnosis of CD in doubtful situations. The presence of the DRB1∗04 allele modulates the risk of CD and significantly reduces it and can predict a potential form.

Central Corneal Thickness can be Related to Diabetic Peripheral Neuropathy in Children with Type 1 Diabetes.

AIMS: Diabetic eye disease with its various manifestations as well as diabetic neuropathy may occur in patients with type 1 diabetes (T1D) after several years of diabetes duration. Pachymetry is a promising method evaluating central corneal thickness (CCT) in diabetic patients. The aim of the study was to evaluate the CCT values in children with T1D and its relationship to neurophysiological markers of diabetic neuropathy. METHODS: The study groups included 119 T1D children with average 5.3 years of diabetes duration and 38 age-matched controls. CCT index was measured with pachymeter in all subjects and in 19/119 of T1D patients the CCT values were referred to the ENG-EMG-SSR study results. RESULTS: In T1D patients the higher CCT values were observed as compared to healthy controls (p=0.037). Correlations between CCT values and both distal latency of the motor fibers of the median nerve (R=0.51; p=0.044) and conduction velocity of this nerve (R=-0.55; p=0.027) were noted. A conduction velocity of the sensory fibers of sural nerve correlated negatively with CCT index (R=-0.50; p=0.045) in the T1D patients. CONCLUSIONS: CCT measurement may be helpful in the referral of the asymptomatic pediatric T1D patients to assess an early stage of diabetic neuropathy.

The HD-OCT Study May Be Useful in Searching for Markers of Preclinical Stage of Diabetic Retinopathy in Patients with Type 1 Diabetes.

The aim of the study was to analyze the thickness of individual retinal layers in patients with type 1 diabetes (T1D) in comparison to the control group and in relation to markers of diabetes metabolic control. The study group consisted of 111 patients with an average of 6-years of T1D duration. The control group included 36 gender- and age-matched individuals. In all patients optical coherence tomography (OCT) study was performed using HD-OCT Cirrus 5000 with evaluation of optic nerve head (ONH) parameters, thickness of retinal nerve fiber layer (RNFL) with its quadrants, macular full-thickness parameters, ganglion cells with inner plexus layer (GCIPL) and choroidal thickness (CT). Lower disc area value was observed in the study group as compared to controls (p = 0.0215). Negative correlations were found both between age at examination and rim area (R = -0.28, p = 0.0007) and between superior RNFL thickness and duration of diabetes (R = -0.20, p = 0.0336). Positive correlation between center thickness and SD for average glycemia (R = 0.30, p = 0.0071) was noted. Temporal CT correlated positively with age at examination (R = 0.21, p = 0.0127). The selected parameters the HD-OCT study may in the future serve as potential markers of preclinical phase of DR in patients with T1D.

Measurement of corneal thickness, optic nerve sheath diameter and retinal nerve fiber layer as potential new non-invasive methods in assessing a risk of cerebral edema in type 1 diabetes in children.

AIMS: Some patients with diabetic ketoacidosis develop cerebral edema (CE) in the course of type 1 diabetes mellitus (T1D), which may result in central nervous system disorders and high mortality. The imperfection of existing neuroimaging techniques for early recognition of CE forces us to search for the new and non-invasive methods. The aim of the study was to assess the usefulness of new methods (pachymetry, transorbital ultrasonography-USG, optical coherence tomography-OCT study) in the assessment of the risk of CE occurrence in children with newly diagnosed T1D. METHODS: The study group included 50 children with newly diagnosed T1D, 54 patients with long-term T1D as a reference group and 40 children without glucose tolerance disorders as controls. In all subjects, a corneal thickness (CCT) index with pachymeter, optic nerve sheath diameter (ONSD) using transorbital USG and retinal nerve fiber layer (RNFL) during OCT study were measured and compared with selected clinical parameters of T1D. RESULTS: In patients from a study group at onset of T1D, the higher CCT (p < 0.001) and ONSD (p < 0.001) values were observed as compared to the results obtained after 48 h of metabolic compensation. The ONSD correlated negatively with pH value (r = - 0.64; p < 0.001), BE (r = - 0.54, p < 0.001) and HCO3- (r = - 0.50; p < 0.001). A positive correlation between RNFL and Na+ levels (r = 0.47; p < 0.005) was also observed. CONCLUSIONS: Transorbital USG and pachymetry may serve as the potential promising methods for the non-invasive assessment of the increased risk of development of CE in patients with T1D.