The Complexities of Diagnosis with Co-Existing Gaucher Disease and Hemato-Oncology-A Case Report and Review of the Literature.

Hematological abnormalities are the most common early symptoms of Gaucher disease (GD), with an increased risk of hematopoietic system malignancies reported in patients with GD. GD may be associated with monoclonal and polyclonal gammopathies; however, the mechanism of association of GD with multiple myeloma (MM) remains uncertain. Enzyme replacement therapy (ERT) has been shown to improve patients' cytopenia and it seems to facilitate anti-myeloma therapy in patients with co-occurring GD and MM. Although it is necessary to demonstrate the deficiency of enzymatic activity, as well as using genetic tests to finally diagnose GD, due to changes in the blood count image, bone marrow biopsy is still a frequent element of the GD diagnosis procedure. The diagnosis of GD is often delayed, mainly due to the heterogeneity of the histopathological picture of bone marrow biopsy or overlapping hematological abnormalities. Unrecognized and untreated GD worsens the response of a patient with an oncological disease to targeted treatment. We present a literature review, inspired by the case of a Caucasian patient initially diagnosed with MM and later confirmed with comorbid GD type 1 (GD1). We would like to point out the problem of underdiagnosis and delay in patients with GD.

Lack of major impact of implementation of the Advanced Hybrid Closed Loop System in technologically-naïve patients with Type 1 Diabetes mellitus on their food choices or weight - a one year follow-up.

INTRODUCTION AND OBJECTIVE: The purpose of this follow-up study on the implementation of advanced closed-loop hybrid insulin pumps in people with type 1 diabetes was to assess the impact of introducing this advanced technology on quantitative and qualitative parameters of diet. MATERIAL AND METHODS: 18 patients (8 women and 10 men, mean age 40.9 years) patients using the CE-marked MiniMed 780G AHCL system who completed 1 year of follow-up were included into the study. The research tool was the KomPAN questionnaire with several own questions added, asked in three study periods, concerning the number of meals consumed, general and night snacking, carbohydrate counting, frequency of consumption of various groups of products that affect postprandial glycaemia. RESULTS: Although the mean body weight of the examined group did not increase significantly (from 75.1 kg at the beginning to 75,9 kg at the end), five various individual scenarios of weight change were observed. The eating habits has not changed, but patients began to consume less products containing simple sugars, e.g. fruit preserves, milk chocolate or fish in sauces (p<0.05). No statistically significant correlation was found between the change in body weight at the end of the study and the average amount of carbohydrates entered into the pump from the entire 12 months (p = 0.460). CONCLUSIONS: The implementation of AHCL system in technology naïve patients, despite offering more freedom of food choices due to better glycaemic control, did not have a significant impact on patients' dietary patterns, also did not result in weight gain. This is important since AHCL system offers more freedom of food choices due to better glycaemic control. However, the longer follow up and the study based on larger population is required to finally address the issue of the impact of AHCL on body mass.

Quality of life in the course of a one-year use of an advanced hybrid closed-loop system in adults with type 1 diabetes previously naïve to advanced diabetes technology.

Aim: To evaluate the effect of a one-year use of an advanced hybrid closed-loop (AHCL) system on the quality of life, level of anxiety, and level of self-efficacy in adults with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI) and naïve to advanced diabetes technology. Methods: A total of 18 participants of a previously published 3-month randomized trial (10 men, 8 women; age 40.9 ± 7.6 years) who were switched directly from MDI/BMG to AHCL completed 12 months of MiniMed 780G™system use (a 3-month randomized trial followed by a 9-month follow-up phase). At month 6 of the study, patients were switched from the sensor GS3 (Continuous Glucose Monitoring) system, powered by Guardian™ Sensor 3) to GS4. Quality of life was assessed using the Polish validated version of the 'QoL-Q Diabetes' questionnaire. The level of anxiety was evaluated with the use of the State-Trait Anxiety Inventory (STAI). Self-efficacy was assessed with the General Self-Efficacy Scale (GSES). Results were obtained at baseline and at the end of the study. Results: Significant increase in QoL was reported in the global score (p=0.02, Cohen d=0.61) and in as many as 11 out of 23 analyzed areas of life: being physically active (p=0.02, Cohen d = 0.71); feeling well (p<.01, Cohen d = 0.73); feeling in control of my body (p<.01, Cohen d = 0.72); looking good (p<.01, Cohen d = 1.07); working (p<.01, Cohen d = 1.12); sleeping (p=0.01, Cohen d = 0.66); eating as I would like (p<.01, Cohen d = 0.79); looking after or being useful to others (p= 0.02, Cohen d = 0.65); being active with pets/animals (p<.01, Cohen d = 0.95); being spontaneous (p=0.02, Cohen d = 0.67); and doing "normal" things (p=0.02, Cohen d = 0.67). Both state (p=0.04, Cohen d = 0.56) and trait (p=0.02, Cohen d = 0.60) anxiety decreased while the general self-efficacy increased (p=0.03, Cohen d = 0.76). No participant stopped the use of the pump. Conclusion: Adult patients with T1D previously treated with MDI and naïve to modern technologies experienced significant improvement in their psychological well-being after transitioning to the AHCL system after 12 months of treatment.

Diagnosis and Management of Mucopolysaccharidosis Type II (Hunter Syndrome) in Poland.

Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is a rare, inherited lysosomal storage disease. The disease is caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase (I2S) due to mutations in the IDS gene, which leads to accumulation of glycosaminoglycans (GAGs). Deficiency of I2S enzyme activity in patients with MPS II leads to progressive lysosomal storage of GAGs in the liver, spleen, heart, bones, joints, and respiratory tract. This process disturbs cellular functioning and leads to multisystemic disease manifestations. Symptoms and their time of onset differ among patients. Diagnosis of MPS II involves assessment of clinical features, biochemical parameters, and molecular characteristics. Life-long enzyme replacement therapy with idursulfase (recombinant human I2S) is the current standard of care. However, an interdisciplinary team of specialists is required to monitor and assess the patient's condition to ensure optimal care. An increasing number of patients with this rare disease reach adulthood and old age. The transition from pediatric care to the adult healthcare system should be planned and carried out according to guidelines to ensure maximum benefit for the patient.

One-Year Follow-Up of Advanced Hybrid Closed-Loop System in Adults with Type 1 Diabetes Previously Naive to Diabetes Technology: The Effect of Switching to a Calibration-Free Sensor.

The aim of this study was to observe the 1-year clinical outcomes of people with type 1 diabetes who switched from multiple daily injection + blood glucose meter to an advanced hybrid closed-loop (AHCL) system (Medtronic MiniMed™ 780G system [MM 780G]). In addition, the effect of changing at month 6 to a calibration-free sensor (Guardian™ 4 Sensor [G4S]) was evaluated. Eighteen participants (10 men, age 40.9 ± 7.6 years) completed 1 year of MM 780G use. Time in range (TIR; 70-180 mg/dL) remained stable and ranged from 83.2% in month 9 to 84.8% in month 3. There was no difference between TIR at 3 months before switching versus 3 months after switching to G4S (P = 0.614). AHCL system in adults significantly improves glycemic outcomes. This improved glycemic control was maintained over the 12 months. Switching to a calibration-free sensor (G4S) did not affect outcomes but required less patient involvement.

Improvement of Selected Psychological Parameters and Quality of Life of Patients With Type 1 Diabetes Mellitus Undergoing Transition From Multiple Daily Injections and Self-Monitoring of Blood Glucose Directly to the MiniMed 780G Advanced Hybrid Closed-Loop System: Post hoc Analysis of a Randomized Control Study.

BACKGROUND: While introducing new technologies and methods of treatment for type 1 diabetes mellitus (T1DM), it seems essential to monitor whether modern technologies in diabetes treatment may improve the psychological and emotional status of patients. OBJECTIVE: This study aims to assess the baseline psychological parameters of patients with T1DM during investigation of the direct transition from multiple daily injections (MDI) and self-monitoring of blood glucose (SMBG) to the MiniMed 780G advanced hybrid closed-loop (AHCL) system and to evaluate changes in the psychological well-being and quality of life (QoL) after the transition in these individuals versus the control group. METHODS: The trial was a 2-center, randomized controlled, parallel group study. In total, 41 patients with T1DM managed with MDI or SMBG were enrolled and randomized either to the AHCL or the MDI+SMBG group. Of these, 37 (90%) participants (mean age 40.3 years, SD 8.0 years; mean duration of diabetes 17.3, SD 12.1 years; mean hemoglobin A1c [HbA1c] 7.2%, SD 1.0%) completed the study (AHCL: n=20, 54%; MDI+SMBG: n=17, 46%). Psychological parameters (level of stress, coping mechanisms, level of anxiety, self-efficacy level, acceptance of illness, locus of control of illness, life satisfaction, QoL) were measured at baseline and at the end of the study using 10 psychological questionnaires. RESULTS: At baseline, the general level of stress of the examined patients was higher than in the general healthy Polish population (P=.001), but coping strategies used in stressful situations were significantly more effective and the level of self-efficacy (P<.001) was much higher than in the general population. The patients in this study accepted their illness more than patients with diabetes from the general Polish population (P<.001), but they felt that their health does not depend on them compared to the general population (P<.001). The overall life satisfaction was similar to that of the general population (P=.161). After 3 months from transition, the AHCL group reported an increase in 4 scales of the QoL-feeling well (P=.042), working (P=.012), eating as I would like (P=.011), and doing normal things (P=.034)-in comparison to the control group, where no significant change occurred. The level of both state anxiety and trait anxiety decreased in the AHCL group: State-Trait Anxiety Inventory (STAI) X1 scores (P=.009), STAI X1 stens (P=.013), and STAI X2 scores (P=.022). The AHCL group became more emotion oriented in stressful situations (Coping Inventory for Stressful Situations [CISS] E; P=.043) and significantly less self-blaming after 3 months of the study (P=.020). CONCLUSIONS: The results indicate that the patients who decided to take part in the transition study were characterized by higher levels of stress than the general healthy population but had better coping strategies and self-efficacy. Furthermore, transitioning from MDI+SMBG treatment to the AHCL in patients naive to technology may significantly improve psychological well-being and QoL within 3 months. The rapidity of these changes suggests that they may be related to the significant improvement in glycemic outcomes but also significantly less burdened diabetes self-management. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616391; https://clinicaltrials.gov/ct2/show/NCT04616391.

Type 1 diabetes outpatient care and treatment effectiveness during COVID-19: A single-center cohort study.

PURPOSE: COVID-19 has brought many challenges for providing quality healthcare for type 1 diabetes (T1DM). We evaluated the impact of the COVID-19 pandemic on the medical care, glycemic control, and selected outcomes in T1DM patients. METHODS: We retrospectively analyzed medical records from 357 T1DM adults enrolled in the Program of Comprehensive Outpatient Specialist Care at the University Hospital in Krakow, and assessed differences in patient data from before the COVID-19 period (March 2019-February 2020) and after it started COVID-19 (March 2020-February 2021). RESULTS: The median HbA1c levels and the percentage of patients within the HbA1c target of <7 % (53 mmol/mol) were similar in both periods: before and after the beginning of the pandemic (6.86 % [51.5 mmol/mol], IQR 6.23-7.58 % [44.6-59.3 mmol/mol] vs. 6.9 % [51.9 mmol/mol], IQR 6.2-7.61 % [44.3-59.7 mmol/mol]; p = 0.50 and 56.3 % vs. 57.1 %, p = 0.42, respectively). However, we observed a rise in BMI and body weight (median 24.25, IQR 21.97-27.05 vs. 24.82, IQR 22.17-27.87 and median weight 71.0 IQR 61-82 vs. 72.55, IQR 55-85; p < 0.001 for both comparisons). There was no reduction in the numbers of total diabetes-related visits (median 4, IQR 4-5 vs. 5, IQR 4-5; p = 0.065), but the frequency of other specialist consultations decreased (2, IQR 0-2 vs. 1, IQR 0-2). During the pandemic, telehealth visits constituted of 1191 out of 1609 (71.6 %) total visits. CONCLUSIONS: In this single-center observation, the COVID-19 pandemic did not have a negative impact on glycemic control in T1DM patients, but the patients' weight did increase. Telemedicine proved to be a valuable tool for T1DM care.

Association of short- and long-term metabolic control parameters with personality traits in adult type 1 diabetes treated with personal insulin pumps. / Korelacja krótko- i dlugoterminowych parametrów kontroli metabolicznej z cechami osobowosci u doroslych chorych na cukrzyce typu 1 leczonych za pomoca osobistych pomp insulinowych.

AIM: Several studies have assessed the association between personality traits and metabolic outcomes in children and adolescents with type 1 diabetes (T1DM). The aim of this observational single-visit study was to investigate whether specific personality traits were related to the degree of metabolic control/diabetes duration in adult T1DM patients. METHOD: Data were collected from 56 adults (40 men) with T1DM treated in a tertiary care center. "Big Five" personality traits were assessed using the NEO-Five Factor Inventory questionnaire. Several variables were obtained from the insulin pumps, glucometers and blinded continuous glucose monitoring system. RESULTS: All personality traits but neuroticism (low level of the trait) showed average intensity. Agreeableness was associated with most variables from CGMS data. Higher conscientiousness was associated with longer diabetes duration. Higher neuroticism was correlated with greater glycemic variability (GV), while high Extraversion was associated with lower GV. Lower Openness was associated with prolonged time in clinically significant hypoglycaemia. CONCLUSIONS: Our study suggest that personality traits manifest in individual approach to diabetes management and emotion regulation, translating also into the attitude to treatment. On the other hand, T1DM patients' overall trait scores were consistent with healthy nonpsychiatric norms, which debunks myths and stereotypes suggesting that chronic disease is usually associated with psychopathology.

Assessment of the spectrum of depression and bipolarity in patients with type 1 diabetes.

AIMS: The aim of the study was to check the prevalence of unipolarity (depression), bipolarity, as well as the quality of sleep and temperament traits in patients with type 1 diabetes (T1DM) who are provided with optimal conditions of diabetes care and to identify possible risk factors connected with affective traits. MATERIALS AND METHODS: Out of the 107 T1DM patients, 78 (54 females, 24 males) were included for the analysis (HbA1c [%] 7.11 ± 1.0, BMI [kg/m2 ] 25.3 ± 5.6; Years of disease duration [N] 13.7 ± 8.3). The patients filled in a set of questionnaires during their regular visit to the outpatient clinic. Three patients from the whole group were on intensive insulin therapy with Multiple Daily Injections (MDI) and Self-Monitoring of Blood Glucose (SMBG), all the rest were on various types of personal insulin pumps (years on insulin pump [N] 9.1 ± 4.5). All the patients were on regular diabetologist care, with regular visits in a Centre for Advanced Technologies in Diabetes (at least every 6 months). RESULTS: In QIDS-S (full explanation and abbreviation 26 patients (33.8%) were screened positive for depression, in PHQ (full explanation and ab 57.7% of the patients (45 patients) had symptoms of depression (age was negatively correlated with PHQ score [r = -0.26; p = 0.023]). In CES-D 16 (20%) of the patients assessed their present affect as depressed. None of the analysed clinical variables correlated with depression scores. In the Mood Disorder Questionnaire (MDQ), 16 patients reported having symptoms of bipolarity (20.5% vs. 79.5%). Hypomania Checklist (HCL) analysis indicated 10 patients with bipolar traits (>14) (14.9% vs. 85.1%). None of the analysed clinical variables correlated with HCL results. 11.5% of patients were indicated to be of morning type. Morningness was more often seen in younger patients (r = 0.39; p = 0.001). As many as 46.6% declared that they had poor sleep quality. The temperament traits analysis correlated with clinical parameters: Cyclothymic temperament trait was negatively correlated with age (r = -0.30; p = 0.007) and positively with HbA1c level (r = 0.30; p = 0.025). Hyperthymic temperament was positively correlated with (BMI r = 0.28; p = 0.016). Quality of sleep was highly correlated with depressive symptoms CESD (r = 0.61, p = 0.001), PHQ Score (r = 0.62; p = 0.001), QISD (r = 0.68; p = 0.001) and bipolarity MDQ (p = 0.50, p = 0.001) and HCL (r = 0.42, p = 0.001). In addition, QIDS was shown to be correlated with the following features of temperament: depressive factor (r = 0.41; p = 0.001), irritable factor (r = 0.53; p = 0.001), cyclothymic factor (r = 0.59; p = 0.001), anxious factor (r = 0.58, p = 0.001). CONCLUSIONS: The prevalence of affective disorders and poor sleep quality in the examined T1DM patients was much higher than in the general population. Even if the patients have in general good glycaemic control, their mental health condition should not be neglected. Well organised cooperation between patients, diabetologists, psychiatrists and psychotherapists is needed (Clinical Trials Identifier: NCT04616391).

Higher scanning frequency is correlated with less fear of hypoglycemia in type 1 diabetes patients using isCGM.

Background: Frequent scanning of intermittently scanned continuous glucose monitoring (isCGM) devices is associated with improvements in glycemic indices. Limited data is available for its correlation with fear of hypoglycemia (FOH), an established factor affecting quality of life and glycemic control in type 1 diabetes (T1DM). Aim: The aim of the study was to analyze the association of sensor scanning frequency with FOH and glycemic indices in T1DM patients using isCGM. Subjects and methods: T1DM patients using isCGM were eligible. Clinical data and Ambulatory Glucose Profile (AGP) reports were obtained from medical records. At outpatient visits, AGP of last 14 days prior to visit were analyzed and FOH was assessed using Hypoglycemia Fear Survey II (HFS II). Results: We included 77 consecutive T1DM patients (58 females, 19 males). Mean age was 34.1 ± 10.2 years and mean T1DM duration was 14.7 ± 12.0 years. Baseline mean glycemic indices were as follows: mean glucose - 155.8 ± 29.8 mg/dL; GMI - 53.3 ± 7.5 mmol/mol; TIR - 66.4 ± 17.8%; TBR70 - 4.5 ± 4.1%; TBR54 - 0.6 ± 1.2%; TAR180 - 29.2 ± 17.9%; TAR250 - 9.6 ± 10.4%; %CV - 36.7 ± 8.3. Average scanning frequency was 13.8 ± 7.8 scans/day. Mean HFS II scores were 16.1 ± 7.2 and 18.7 ± 12.2 in behavior and worry subscale, respectively. Correlation was confirmed between scanning frequency and mean glucose, GMI, TIR, TBR70, TAR180, TAR250, %CV and HFS II total, and HFS II - B (p<0.05 for all statistics). Conclusions: For the first time, we report that higher scanning frequency is associated not only with better glycemic indices but also with less FOH in T1DM adult patients using isCGM.

Nephropathic cystinosis in Poland: a 40-year retrospective study.

INTRODUCTION: Nephropathic cystinosis (NC) is a rare, autosomal recessive disorder leading to lysosomal accumulation of cystine. It is caused by mutations in the CTNS gene encoding a cystine cotransporter cystinosin. The infantile (INC) and juvenile (JNC) forms are distinguished. The former, responsible for 95% of cases, is characterized by development of renal Fanconi syndrome, end-stage kidney disease (ESKD), and extrarenal complications. A therapy with cysteamine significantly improves outcomes. There are limited data on NC in the Central Eastern European countries. OBJECTIVES: We aimed to evaluate the prevalence, genetic background, and clinical course of NC in the Polish population. PATIENTS AND METHODS: We performed a retrospective analysis of data of all identified NC patients in Poland. RESULTS: Between 1982 and 2017, 15 patients with NC (13 ICN, 2 JCN) were identified. The most common mutations of the CTNS gene were c.18_c.21delGACT and c.681+1G>A, whereas only 2 patients carried the 57 kb deletion. The majority (11/13) of INC patients with limited access to the cysteamine therapy developed ESKD at a median age of 11 years and 9 of them received kidney transplants. Three INC patients died at a median age of 24 years. In contrast, 2 INC patients treated adequately present normal kidney function and growth at the age of 13 and 11 years. Two JNC patients presented a milder course. CONCLUSIONS: The prevalence of NC in Poland is much lower than in the Western countries and its molecular background appears to be different. The unfavorable course in the majority of INC patients was caused by a limited access to the cysteamine treatment.

Transitioning of People With Type 1 Diabetes From Multiple Daily Injections and Self-Monitoring of Blood Glucose Directly to MiniMed 780G Advanced Hybrid Closed-Loop System: A Two-Center, Randomized, Controlled Study.

OBJECTIVE: The aim of this study was to evaluate the outcomes of transitioning to the MiniMed 780G advanced hybrid closed-loop (AHCL) system in adult individuals with type 1 diabetes mellitus (T1DM) naive to continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) technologies. RESEARCH DESIGN AND METHODS: This was a two-center, randomized, controlled, parallel-group trial with evaluation of individuals with T1DM aged 26-60 years managed with multiple daily injections (MDI) and self-monitoring of blood glucose (BGM) with HbA1c <10%. RESULTS: A total of 41 participants were recruited and randomized to either the AHCL (n = 20) or the MDI+BGM (n = 21) group, and 37 participants (mean ± SD age 40.3 ± 8.0 years, duration of diabetes 17.3 ± 12.1 years, BMI 25.1 ± 3.1 kg/m2, HbA1c 7.2 ± 1.0%) completed the study. Time spent with glucose levels in target range increased from 69.3 ± 12.3% at baseline to 85.0 ± 6.3% at 3 months in the AHCL group, while remaining unchanged in the control group (treatment effect 21.5% [95% CI 15.7, 27.3]; P < 0.001). The time with levels below range (<70 mg/dL) decreased from 8.7 ± 7.3% to 2.1 ± 1.7% in the AHCL group and remained unchanged in the MDI+BGM group (treatment effect -4.4% [95% CI -7.4, -2.1]; P < 0.001). Participants from the AHCL group also had significant improvements in HbA1c levels (treatment effect -0.6% [95% CI -0.9, -0.2]; P = 0.005) and in quality of life (QoL) in specific subscales compared with the MDI+BGM group. CONCLUSIONS: People with T1DM naive to CSII and CGM technologies initiating AHCL significantly and safely improved their glycemic control, as well as their QoL and psychological well-being.

Consensus statement on enzyme replacement therapy for mucopolysaccharidosis IVA in Central and South-Eastern European countries.

BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. A progressive systemic skeletal chondrodysplasia, leading to significant morbidity and reduced life expectancy is the main clinical feature of this multisystemic disease. Although enzyme replacement therapy with elosulfase alfa is established in Europe, the rarity of disease and other factors still set hurdles in having patients treated in some countries. Aim of this statement is to provide evidence-based guidance for the enzyme replacement treatment of Morquio A patients, harmonizing recommendations from published guidelines with the real-life clinical practice in the Central and South-Eastern European region. PARTICIPANTS: The Consensus Group, convened by 8 Steering Committee (SC) members from 7 Central and South-Eastern European countries, consisted of a multidisciplinary group of 17 experts in the management of MPS in Central and South-Eastern Europe. CONSENSUS PROCESS: The SC met in a first virtual meeting with an external scientific coordinator, to discuss on clinical issues to be analyzed in guidance statements. Statements were developed by the scientific coordinator, evaluated by the SC members in a first modified-Delphi voting and adapted accordingly, to be submitted to the widest audience in the Consensus Conference. Following discussion and further modifications, all participants contributed to a second round of modified-Delphi voting. RESULTS: Nine of ten statements, concerning general guidelines for management of MPS IVA patients and specific recommendations for treatment, received final consensus. CONCLUSIONS: European guidelines and evidence-based recommendations for Morquio A patients should be considered in the real life of Central and South-Eastern European countries and adapted to unique clinical practice approaches and criteria for patients' access to treatment and reimbursement in the region.

The landscape of Mucopolysaccharidosis in Southern and Eastern European countries: a survey from 19 specialistic centers.

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the picture of disease management in the region and understand ERT implementation. Since the considerable number of MPS IVA patients in the region, particularly adults, the study mainly focused on MPS IVA management and treatment. RESULTS: 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding. CONCLUSIONS: The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions, regarding epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.

Mutation search within monogenic diabetes genes in Polish patients with long-term type 1 diabetes and preserved kidney function.

INTRODUCTION: Some patients with type 1 diabetes (T1DM) are free from advanced complications despite long­standing disease. These patients may be carriers of gene mutations responsible for maturity­onset diabetes of the young and may have been misdiagnosed with T1DM. OBJECTIVES: We aimed to determine the clinical characteristics of patients with long­term T1DM, without advanced microvascular complications, and with well­preserved kidney function. A search for mutations in monogenic diabetes genes was performed. PATIENTS AND METHODS: Patients were recruited at 2 Polish university centers based on the following criteria: T1DM duration of 40 years or longer and absence of advanced complications defined as chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 ), overt proteinuria, blindness, and diabetic foot syndrome. Mutations in the 7 most frequent monogenic diabetes genes were identified using next­generation sequencing. RESULTS: We enrolled 45 patients with T1DM (mean [SD] age at examination, 59.2 [8.0] years; mean [SD] age at T1DM diagnosis, 14.6 [6.7] years). Mean (SD) hemoglobin A1c levels were 7.6% (1.4%); daily insulin dose, 0.48 (0.17) U/kg; high­density lipoprotein (HDL) cholesterol levels, 1.9 (0.6) mmol/l; body mass index (BMI), 26.4 (5.0) kg/m2 ; and eGFR, 82.2 (12.1) ml/min/1.73 m2 . Albuminuria and retinopathy were reported in 7 and 39 patients, respectively. We were not able to assign a causative role to any of 10 genetic variants identified by next­generation sequencing in this cohort. CONCLUSIONS: Patients with long­term T1DM and preserved kidney function have good glycemic control, elevated HDL cholesterol levels, low insulin requirements, near ­normal BMI, and a rare occurrence of mutations in monogenic diabetes genes.

COVID-19 Pandemic and Patients with Rare Inherited Metabolic Disorders and Rare Autoinflammatory Diseases-Organizational Challenges from the Point of View of Healthcare Providers.

COVID-19 pandemic is an organisational challenge for both healthcare providers and patients. People with rare inherited metabolic disorders (IMD) and rare autoinflammatory diseases (AD) are vulnerable patients whose well-being is deeply connected with regular follow-ups. This study aimed to assess how e one year of coronavirus pandemic has impacted the treatment of patients with IMD and AD in Poland. Surveys were distributed to all healthcare providers that coordinate the treatment of IMD and AD patients. Thirty-two responders (55%) answered the survey. They provide care to 1726 patients with IMD/AD, including 246 patients on dedicated treatment. In 35% of units, the regular appointments were disrupted, primarily because of patient infection. In 18 hospitals, remote visits were implemented, but only 66.6% of patients used this form of consultation. In 14/32 hospitals, administration of the therapy was delayed (median: 17.4 days). Forty-four patients suffered from SARS-COV-2 infection, in majority with mild symptoms. However, four adult patients developed complications, and one died following a SARS-COV-2 infection. Although most hospitals managed to maintain regular visits during the pandemic, more comprehensive implementation of telemedicine and switch to oral therapy or home infusions would be a reasonable solution for the current epidemic situation.

Gene expression with corresponding pathways analysis in Gaucher disease.

Gaucher disease (GD) caused by mutation in the GBA gene has a wide spectrum of phenotypes. Besides the storage disorder, secondary alteration of various pathways occurs with modification of the expression of many genes. In our work we analysed the expression profile of genes in adult patients with type 1 GD. METHODS: This study was an observational, cross-sectional analysis of a group of twenty patients with type 1 GD and ten healthy volunteers as a control group. First, on the group of ten persons, microarray gene analysis was performed. Afterwards, significantly regulated genes were selected, and the microarray results were confirmed by real-time PCR on the whole study group. RESULTS: Based on the microarray results in the pathway analysis, we focused on genes related to chemokines, inflammatory processes, endocytosis, autophagy, and apoptosis. Patients with GD demonstrated up-regulation of genes related to NFkB pathway (NFkB, NKkBR SQSTM1), inflammation (IL-1b), endocytosis and autophagy (BCN1, SMAD), genes coding proteins involved in apoptosis (CASP, NFkB, BCL2) as well as genes related to proteasome degradation (PSMD2, PSMB9) and SNARE complex (SNAP, STX). Simultaneously, we showed down-regulation of genes coding proteins of chemokines and their receptors (GNB4, CCL5). The qRT-PCR results confirmed changes in expression of selected genes. Parallel microarray results showed inhibition of genes related to neurones development and survival (NTRK1) and stimulation of gene expression related to neurodegeneration and apoptosis (BCN1, IL1B). CONCLUSIONS: The work revealed different pathway activation, especially inflammatory processes followed by autophagy and apoptosis. Our results also pay attention to new pathways leading to disorders of the functioning of the nervous tissue in patients with type 1 GD, which may lead to the development of polyneuropathy and chronic pain. These are clinical symptoms that severely decrease the quality of life in GD patients.

Type 1 Diabetes and COVID-19: the level of anxiety, stress and the general mental health in comparison to healthy control. / Cukrzyca typu 1 i COVID-19: poziom leku, stresu i ogólnego stanu zdrowia psychicznego u pacjentów w porównaniu z grupa kontrolna.

OBJECTIVES: Assessment of mental state of patients with T1DM - the level of anxiety, stress and general mental health in the stressful conditions of an epidemic. Moreover, it was checked whether the stress response to the epidemic in the T1DM group differed from that in the control group. This is the first study to address these questions in the type 1 diabetes population in Poland. METHODS: An e-mail was sent to all T1DM patients under the care of a diabetes clinic with information about the possibility of online consultation with a psychologist / psychiatrist, with a set of psychological tests attached. The study included 49 patients with T1DM who responded within the first month and agreed to participate in the study. 38 people from the control group were randomly recruited. Each person completed a set of psychological tools. RESULTS: In both groups, the level of stress was higher than typical for the general population in the situation without stressor. T1DM patients who have been ill for over 10 years more often cope with stress through a task-oriented approach. Patients who have been ill for less than 10 years use avoidance strategies. In the first phase of the epidemic,women with T1DM used avoidance strategies. Patients with diabetes and mental disorders react more anxiously and thus require special care in coping with diabetes. CONCLUSIONS: In a situation of stress such as a epidemic, patients suffering from T1DM require optimization of treatment and cooperation of specialists in the field of diabetes and psychology / psychiatry.

Challenges in Transition From Childhood to Adulthood Care in Rare Metabolic Diseases: Results From the First Multi-Center European Survey.

Inherited Metabolic Diseases (IMDs) are rare diseases caused by genetic defects in biochemical pathways. Earlier diagnosis and advances in treatment have improved the life expectancy of IMD patients over the last decades, with the majority of patients now surviving beyond the age of 20. This has created a new challenge: as they grow up, the care of IMD patients' needs to be transferred from metabolic pediatricians to metabolic physicians specialized in treating adults, through a process called "transition." The purpose of this study was to assess how this transition is managed in Europe: a survey was sent to all 77 centers of the European Reference Network for Hereditary Metabolic Disorders (MetabERN) to collect information and to identify unmet needs regarding the transition process. Data was collected from 63/77 (81%) healthcare providers (HCPs) from 20 EU countries. Responders were mostly metabolic pediatricians; of these, only ~40% have received appropriate training in health issues of adolescent metabolic patients. In most centers (~67%) there is no designated transition coordinator. About 50% of centers provide a written individualized transition protocol, which is standardized in just ~20% of cases. In 77% of centers, pediatricians share a medical summary, transition letter and emergency plan with the adult team and the patient. According to our responders, 11% of patients remain under pediatric care throughout their life. The main challenges identified by HCPs in managing transition are lack of time and shortage of adult metabolic physician positions, while the implementations that are most required for a successful transition include: medical staff dedicated to transition, a transition coordinator, and specific metabolic training for adult physicians. Our study shows that the transition process of IMD patients in Europe is far from standardized and in most cases is inadequate or non-existent. A transition coordinator to facilitate collaboration between the pediatric and adult healthcare teams should be central to any transition program. Standardized operating procedures, together with adequate financial resources and specific training for adult physicians focused on IMDs are the key aspects that must be improved in the rare metabolic field to establish successful transition processes in Europe.

Upgrading the evidence for the use of ambroxol in Gaucher disease and GBA related Parkinson: Investigator initiated registry based on real life data.

Ambroxol hydrochloride is an oral mucolytic drug available over-the-counter for many years as cough medicine. In 2009 it was identified as a pharmacological chaperone for mutant glucocerebrosidase, albeit in a several-fold higher dose. Unfortunately, there have been no pharma-driven clinical trials to establish its use. Thus, real-world observational data are needed on the safety and efficacy of ambroxol for patients with Gaucher disease (GD) and GBA-Parkinson disease (GBA-PD). Clinicians treating patients with ambroxol for GD and GBA-PD were approached to collaborate in an investigator-initiated registry. Anonymized data were collected, including demographics, GD type, GD-specific therapy (when applicable), adverse events (AEs), and, when available, efficacy data. We report the data of the first 41 patients (25 females) at a median (range) age 17 (1.5-74) from 13 centers; 11 with GD type 1(four diagnosed with PD), 27 with neuronopathic GD (nGD), and three GBA mutation carriers with PD. The median (range) treatment period and maximum dose of ambroxol were 19 (1-76) months and 435 (75-1485) mg/day, respectively. One patient with type 2 GD died of her disease. No other severe AEs were reported. Twelve patients experienced AE, including minor bowel discomfort, cough, allergic reaction, mild proteinuria, dizziness and disease progression. Clinical benefits were reported in 25 patients, including stable or improved neurological status, increased physical activity, and reduced fatigue. Until the approval of specific therapies for nGD and disease-modification for GBA-PD, these preliminary data may be encouraging to physicians and patients who consider an off-label use of ambroxol.