Combined therapy with CD4+ CD25highCD127- T regulatory cells and anti-CD20 antibody in recent-onset type 1 diabetes is superior to monotherapy: Randomized phase I/II trial.

AIMS: Monotherapy with autologous expanded CD4+ CD25high CD127- T regulatory cells (Tregs) or rituximab has been documented to slow disease progression in patients with recent-onset type 1 diabetes mellitus (T1DM). Whether a combined therapy including both drugs would further benefit this patient population is unknown. MATERIALS AND METHODS: We conducted a three-arms clinical trial to explore the efficacy and safety of the combined treatment with Tregs and rituximab in paediatric patients with T1DM. The patients were allocated to three groups: Tregs only (n = 13), Tregs + rituximab (n = 12) and control (n = 11). The key primary efficacy analyses were C-peptide levels (mixed meal tolerance test) and the proportion of patients in remission at 12 and 24 months. RESULTS: At month 24, as compared with the control, both treatment groups remained superior in the area under the curve of C-peptide mixed meal tolerance test, whereas in the analysis of all visits only the combined therapy improved area under the curve at 12 and 24 months. The proportion of patients in remission was significantly higher in the combined group than in the control group at 3, 6, 9 and 21 months but not at 18 and 24 months. There was no significant difference between the Tregs only group and control group. Adverse events occurred in 80% patients, mostly in the combined group and Tregs only group. No adverse events led to the withdrawal of the intervention or death. All comparisons were performed with alpha level of 5%. CONCLUSIONS: Over 2 years, combined therapy with Tregs and rituximab was consistently superior to monotherapy in delaying T1DM progression in terms of C-peptide levels and the maintenance of remission.

How does a predictive low glucose suspend (PLGS) system tackle pediatric lifespan challenges in diabetes treatment? Real world data analysis.

OBJECTIVES: The aim of the study was to assess the benefits of a predictive low glucose suspend (PLGS) system in real-life in children and adolescents with type 1 diabetes of different age and age-related clinical challenges. METHODS: Real life retrospective and descriptive analysis included 44 children (26 girls) with type 1 diabetes who were introduced to PLGS system. We divided them in three age groups: I (3-6 years old, n = 12), II (7-10 y/o, n = 16), III (11-19 y/o, n = 16). All children and their caregivers received unified training in self-management during PLGS therapy. Patients' data included: age, HbA1C levels, sex. While from the CGM metric, we obtained: time of sensor use (SENSuse), time in range (TiR): in, below and over target range and average blood glycemia (AVG), insulin suspension time (INSsusp). RESULTS: SENSuse was 93% in total, with 92%, 94%, and 87% in age groups I, II, III, respectively. In total the reduction of mean HbA1C from 7.61% to 6.88% (P < .05), while for the I, II, and III it was 7.46% to 6.72%, 6.91% to 6.41%, and 8.46 to 7.44%, respectively (P < .05). Although we observed a significant reduction of HbA1C, the time below target range was minimal. Specific findings included: group I-longest INSsusp (17%), group II-lowest glycemic variability (CV) (36%), and group III-highest AVG (169 mg/dL). There was a reverse correlation between suspend before low and age (-0.32, P < .05). In group I CV reduced TiR in target range (TiRin) (-0.82, P < .05), in group II use of complex boluses increased TiRin (0.52, P < .05). In group III higher CV increased HbA1C (0.64, P < .05) while reducing TiRin (-0.72, P < .05). CONCLUSIONS: PLGS is a suitable and safe therapeutic option for children with diabetes of all age and it is effective in addressing age-specific challenges. PLGS improves glycemic control in children of all age, positively affecting its different parameters.

PD-1 Receptor (+) T cells are associated with the efficacy of the combined treatment with regulatory t cells and rituximab in type 1 diabetes children via regulatory t cells suppressive activity amelioration.

An imbalance between exaggerated autoaggressive T cell responses, primarily CD8 + T cells, and impaired tolerogenic mechanisms underlie the development of type 1 diabetes mellitus. Disease-modifying strategies, particularly immunotherapy focusing on FoxP3 + T regulatory cells (Treg), and B cells facilitating antigen presentation for T cells, show promise. Selective depletion of B cells may be achieved with an anti-CD20 monoclonal antibody (mAb). In a 2-year-long flow cytometry follow-up, involving 32 peripheral blood T and B cell markers across three trial arms (Treg + rituximab N = 12, Treg + placebo N = 13, control N = 11), we observed significant changes. PD-1 receptor (+) CD4 + Treg, CD4 + effector T cells (Teffs), and CD8 + T cell percentages increased in the combined regimen group by the end of follow-up. Conversely, the control group exhibited a notable reduction in PD-1 receptor (+) CD4 + Teff percentages. Considering clinical endpoints, higher PD-1 receptor (+) expression on T cells correlated with positive responses, including a higher mixed meal tolerance test AUC, and reduced daily insulin dosage. PD-1 receptor (+) T cells emerged as a potential therapy outcome biomarker. In vitro validation confirmed that successful Teff suppression was associated with elevated PD-1 receptor (+) Treg levels. These findings support PD-1 receptor (+) T cells as a reliable indicator of treatment with combined immunotherapy consisting of Tregs and anti-CD20 mAb efficacy in type 1 diabetes mellitus.

Diagnostic performance of point-of-use ultrasound of resuscitation outcomes: A systematic review and meta-analysis of 3265 patients.

BACKGROUND: Echocardiography in the setting of resuscitation can provide information as to the cause of the cardiac arrest, as well as indicators of futility. This systematic review and meta-analysis were performed to determine the value of point-of-care ultrasonography (PoCUS) in the assessment of survival for adult patients with cardiac arrest. METHODS: This meta-analysis was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Web of Science, Cochrane have been searched from databases inception until March 2nd 2021. The search was limited to adult patients with cardiac arrest and without publication dates or country restrictions. Papers were chosen if they met the required criteria relating to the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this diagnostic technique concerning resuscitation outcomes. RESULTS: This systematic review identified 20 studies. Overall, for survival to hospital discharge, PoCUS was 6.2% sensitivity (95% confidence interval [CI] 4.7-8.0%) and 2.1% specific (95% CI 0.8-4.2%). PoCUS sensitivity and specificity for return of spontaneous circulation were 23.8% (95% CI 21.4-26.4%) and 50.7% (95% CI 45.8-55.7%) respectively, and for survival to admission 13.8% (95% CI 12.2-15.5%) and 20.1% (95% CI 16.2-24.3%), respectively. CONCLUSIONS: The results do not allow unambiguous recommendation of PoCUS as a predictor of resuscitation outcomes and further studies based on a large number of patients with full standardization of operators, their training and procedures performed were necessary.

[Acute alcohol intoxication among children and adolescents admitted to the Department of Pediatrics, Pediatric Endocrinology and Diabetes, Medical University of Silesia, Katowice during 2000-2010--preliminary study]. / Zatrucia alkoholem etylowym wsród dzieci i mlodziezy hospitalizowanych w Klinice Pediatrii, Endokrynologii i Diabetologii Dzieciecej Górnoslaskiego Centrum Zdrowia Dziecka w Katowicach w latach 2000-2010--doniesienie wstepne.

The alcohol drinking at the young age is a risk factor of alcohol addiction later in life, and is connected with school problems, binge drinking, tobacco addiction, illegal drug use, violence, crime commitment, and risky sexual behaviors. Alcohol drinking in the last 12 months is declared by 78% Polish children. The aim of the study was to evaluate the frequency of admissions due to alcohol intoxication to the Department of Pediatrics, Pediatric Endocrinology and Diabetes, Pediatric Center of Silesia and the identification of the risk factors of the acute alcohol intoxication among Polish children and adolescents. Ten-year retrospective study includes investigation of patients medical records from the Department of Pediatrics. Among 8048 patients hospitalized in the Department of Pediatrics between the years 2000-2010, 220 (2.7%) cases of acute alcohol poisoning occurred The detailed data analysis from 139 patients [66 (47.5%) girls, 73 (52,5%) boys] was done. In the years 2006-2010 the number of girls admitted to the department increased in comparison to boys. The largest group of patients was at age between 14 and 16 years [61 (44%) children]. The blood alcohol concentration at the moment of admission to the hospital was 0.1 to 4.0 per thousand. In most cases (92.8%) the alcohol intoxication was intentional. Five percent of them were suicide attempts. In the youngest group of children alcohol abuse was unintentional. 23 (16.5%) of patients initially needed admission to the intensive care unit. In 30 (21.6%) patient the family was incomplete and five times more often father was absent. The alcohol addiction occurs in 18 (13.0%) fathers and 10 (7.2%) mothers of our patients. It is concluded that over the last decade the number of girls admitted due to alcohol abuse increased. Children at school grade between 7-9 are intoxicated most often. One six of intoxicated patents needed hospitalization at intensive care unit.

Reference Ranges of Glycemic Variability in Infants after Surgery-A Prospective Cohort Study.

We aimed to define reference ranges of glycemic variability indices derived from continuous glucose monitoring data for non-diabetic infants during post-operative intensive care treatment after cardiac surgery procedures. We performed a prospective cohort intervention study in a pediatric intensive care unit (PICU). Non-diabetic infants aged 0-12 months after corrective cardiovascular surgery procedures were fitted upon arrival to the PICU with a continuous glucose monitoring system (iPro2, Medtronic, Minneapolis, MN, USA). Thirteen glycemic variability indices were calculated for each patient. Complete recordings of 65 patients were collected on the first postoperative day. During the first three postsurgical days 5%, 24% and 43% of patients experienced at least one hypoglycemia episode, and 40%, 10% and 15%-hyperglycemia episode, respectively, in each day. Due to significant differences between the first postoperative day (mean glycemia 130 ± 31 mg/dL) and the second and third day (105 ± 18 mg/dL, 101 ± 22.2 mg/dL; p < 0.0001), we proposed two separate reference ranges-for the acute and steady state patients. Thus, for individual glucose measurements, we proposed a reference range between 85 and 229 mg/dL and 69 and 149 mg/dL. For the mean daily glucose level, ranges between 122 and 137 mg/dL and 95 and 110 mg/dL were proposed. In conclusion, rt-CGM revealed a very high likelihood of hyperglycemia in the first postsurgical day. The widespread use of CGM systems in a pediatric ICU setting should be considered as a safeguard against dysglycemic episodes; however, reference ranges for those patients should be different to those used in diabetes care.

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.

A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease primarily affecting the respiratory tract, however due to the nature of the pathogenesis it is able to affect the whole body. So far, no causative treatment has been found and the main strategy when dealing with COVID-19 relies on widespread vaccination programs and symptomatic treatment. Vitamin D due to its ability to modulate the immunological system has been proposed as a factor playing role in the organism response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, we decided to perform this meta-analysis which aimed to establish a connection between vitamin D status and COVID-19 infection. METHODS: Study was designed as a systematic review and meta-analysis. PubMed, EMBASE, Web of Science, Cochrane Collaboration Databases and Scopus electronic databases were searched for relevant studies from database inception to May 10th, 2021. Mean differences (MDs) with their 95% confidence intervals (CI) were calculated. RESULTS: Thirteen studies providing data for 14,485 participants met the inclusion criteria. Mean vitamin D levels in SARS-CoV-2 negative patients was 17.7 ± 6.9 ng/mL compared to SARS-CoV-2 positive patients 14.1 ± 8.2 ng/mL (MD = 3.93; 95% CI 2.84-5.02; I2 = 99%; p < 0.001). CONCLUSIONS: Low serum vitamin D levels are statistically significantly associated with the risk of COVID-19 infection. Supplementation of vitamin D especially in the deficiency risk groups is indicated.

Impact of diabetes mellitus on in-hospital mortality in adult patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has spread worldwide since the beginning of 2020, placing the heavy burden on the health systems all over the world. The population that particularly has been affected by the pandemic is the group of patients suffering from diabetes mellitus. Having taken the public health in considerations, we have decided to perform a systematic review and meta-analysis of diabetes mellitus on in-hospital mortality in patients with COVID-19. METHODS: A systematic literature review (MEDLINE, EMBASE, Web of Science, Scopus, Cochrane) including all published clinical trials or observational studies published till December 10, 2020, was performed using following terms "diabetes mellitus" OR "diabetes" OR "DM" AND "survival" OR "mortality" AND "SARS-CoV-2" OR "COVID-19". RESULTS: Nineteen studies were included out of the 7327 initially identified studies. Mortality of DM patients vs non-DM patients was 21.3 versus 6.1%, respectively (OR = 2.39; 95%CI: 1.65, 3.64; P < 0.001), while severe disease in DM and non-DM group varied and amounted to 34.8% versus 22.8% (OR = 1.43; 95%CI: 0.82, 2.50; P = 0.20). In the DM group, the complications were observed far more often when compared with non-DM group, both in acute respiratory distress (31.4 vs. 17.2%; OR = 2.38; 95%CI:1.80, 3.13; P < 0.001), acute cardiac injury (22.0% vs. 12.8%; OR = 2.59; 95%CI: 1.81, 3.73; P < 0.001), and acute kidney injury (19.1 vs. 10.2%; OR = 1.97; 95%CI: 1.36, 2.85; P < 0.001). CONCLUSIONS: Based on the findings, we shall conclude that diabetes is an independent risk factor of the severity of COVID-19 in-hospital settings; therefore, patients with diabetes shall aim to reduce the exposure to the potential infection of COVID-19.