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.

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.

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.

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.

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.

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.

Assessment of optimal insulin administration timing for standard carbohydrates-rich meals using continuous glucose monitoring in children with type 1 diabetes: A cross-over randomized study.

AIMS/INTRODUCTION: The present study was an assessment of postprandial glucose concentration after carbohydrates-rich meals using continuous glucose monitoring in 30 children with type 1 diabetes treated using continuous subcutaneous insulin infusion with a rapid-acting insulin analog. MATERIALS AND METHODS: Over a period of 3 days, participants administered simple boluses with different delay times between insulin administration and the beginning of carbohydrates-rich meal consumption (meal no. 1 containing 197 kcal, no. 2 containing 247 kcal and meal no. 3 containing 323 kcal; containing practically no protein and fat). In the present cross-over randomized study, we analyzed the average glucose concentration profiles in 5-min intervals, mean glucose at insulin administration, mean glucose after 120 and 180 min, mean and peak glucose, glucose peak time, areas under the glucose and glucose increase curves, and time period lengths with glucose <50, 70 mg/dL, and >140 and 200 mg/dL. RESULTS: For test meals at 20-min versus 0-min delay time, the study exposed a longer median time period to reach peak glucose (95 vs 65 min, P = 0.01) after meals. A tendency to the lowest peak and mean glucose, and the longest time with glucose within a normal range was observed in patients who administered bolus insulin 20 min before a meal. CONCLUSIONS: For carbohydrates-rich meals, administration of a proper dose of a rapid-acting insulin analog is crucial. The influence of rapid-acting insulin analog administration timing seems to be of minor importance in comparison with correct insulin dose adjustment; however, a tendency to achieve more balanced glucose profiles was found in a group who administered insulin 20 min before a meal.

Hospitalizations due to alcohol intoxication among children and adolescents - data from one clinical hospital in Poland. / Hospitalizacje z powodu zatruc alkoholem etylowym wsród dzieci i mlodziezy ­ dane pochodzace z jednego szpitala klinicznego w Polsce.

OBJECTIVES: To determine the frequency of hospitalizations due to alcohol intoxication (AI) at the Pediatric Health Center, and to attempt to identify factors contributing to the occurrence of intoxication in the population of children and adolescents. METHODS: Medical documentation of 227 patients hospitalized due to AI. 108 (48%) patients were girls and 119 (52%) patients were boys. The mean age of the study group was 14.9 years ±2.1. Data regarding patients, their families and the circumstances of intoxication underwent analysis. RESULTS: Alcohol intoxication constituted 2.8% of all hospitalizations. The number of hospitalizations between 2000 and 2011 showed an increasing tendency with some fluctuations within years. Spirits were predominant alcohol beverages. Over 10% of patients required a short-term hospital stay at the Department of Anesthesiology and Intensive Care. In 13% of children, coexisting medicine or drug intoxication was observed and 10% of patients presented with alcohol-related injury to the head or extremities. Risky sexual behaviors were noted in 25% of girls. The majority of children were raised by two parents who had received primary education. Alcoholism was present in over 20% of the families. In single-parent families, fathers were more frequently absent and a lack of a regular source of income was more often related to mothers. CONCLUSIONS: There are no uniform standards of multi-specialist medical care for children hospitalized due to AI. Identification of children consuming alcohol is recommended. It should be done by primary physicians, pediatricians, teachers and psychologists. Minor patients hospitalized due to AI should be provided with a long-term and comprehensive care.

Factors influencing high-quality chest compressions during cardiopulmonary resuscitation scenario, according to 2015 American Heart Association Guidelines.

BACKGROUND AND AIM: Recent American Heart Association guidelines from 2010 and 2015 stressed the importance of high-quality chest compression and defined standards for compression rate, depth, recoil, and maximal acceptable time for interruptions. High-quality cardiopulmonary resuscitation (CPR) is the "cornerstone" of a system of care that can optimise outcomes beyond the return of spontaneous circulation. METHODS: One hundred medical students were enrolled to the study. Study participants, after attending a Basic Life Support Course according to American Heart Association 2015 guidelines, performed 2-min CPR on a Resusci Anne® QCPR Mani-kin. The following data were collected: age, sex, and health status. The study made use of a Tanita MC-980 MA for body composition analysis. RESULTS: Mean height of participants was 170.2 ± 8.3 cm, and mean weight was 65 ± 11.8 kg. Mean body mass index was 22.1 ± 2.7, and mean fat-free mass (FFM) was 50.1 ± 10.5 kg. The mean fat mass (FAT%) was 22.9 ± 7.6. Basal metabolic rate, FFM, trunk muscle mass, left arm muscle mass, and right arm muscle mass were positively correlated with compression depth (all p for trend < 0.05). Mean compression depth was 49.7 ± 8.4 (for female 48.7 ± 7.9 mm, for male 42.4 ± 9.5 mm; p = 0.144). Compression rate for males and females was the same, at 114 ×/min (p = 0.769). CONCLUSIONS: In our study, basal metabolic rate, FFM, trunk muscle mass, and left and right arm muscle mass were positively correlated with compression depth. Moreover, an arm muscle mass rise of 1 kg caused a rise of compression depth param-eter of 7.3 mm, while when chest compression was performed by females, a fall of compression depth of 3.3 mm was seen.

Which position should we take during newborn resuscitation? A prospective, randomised, multicentre simulation trial.

BACKGROUND: Early bystander cardiopulmonary resuscitation (CPR) for cardiac arrest is crucial in the chain of survival. Cardiac arrest in infants is rare, but CPR is also performed in severe bradycardia. European Resuscitation Council and American Heart Association guidelines recommend continuing CPR until the heart muscle is sufficiently oxygenated and regains sufficient contractility and function. The most common and recommended CPR techniques that can be applied in newborns are the two-finger technique and two-thumb technique. AIM: We sought to assess the quality of CPR performed in newborns with the two-finger technique depending on the posi-tion of the rescuer during resuscitation. METHODS: This was a prospective, randomised, crossover, simulated study. It involved 93 nurses who were required to perform a two-minute CPR using the two-finger technique in three scenarios: (A) with the newborn lying on the floor; (B) on a table; and (C) with the newborn on the rescuer's forearm. The Newborn Tory® S2210 manikin was used to simulate a neonatal patient in cardiac arrest. The following parameters were measured: chest compression (CC) depth, CC rate, no-flow time, percentage of full release, ventilation rate, and ventilation volume, as well as the number of effective compressions and effective ventilations. RESULTS: Statistical analysis showed significant differences in CC rates between scenarios A and B (p < 0.001) and between scenarios B and C (p = 0.002). Significant differences were also observed between the median CC depth. The median per-centage of no-flow-fraction was the highest for scenario A (55%), followed by scenario B (48%), and scenario C (46%). There were significant differences between the values of no-flow-fraction between scenarios A and B (p < 0.001), and between scenarios A and C (p < 0.001). The percentage of chest full releases for scenarios A, B, and C amounted to 94%, 1%, and 92%, respectively. Significant differences in the number of effective CCs between scenarios A and B (p < 0.001) as well as B and C (p < 0.001) were revealed. The median ventilation rate was highest for scenario B (13 × min-1), and lowest for scenario A (9 × min-1). The highest tidal volume was obtained in scenario A (27 mL), and the lowest in scenario C (26 mL). The most effective CPR was performed when resuscitation was carried out on the rescuer's forearm. CONCLUSIONS: The quality of CCs in newborns depends on the location of the patient and the rescuer. The optimal form of resuscitation of newborns is resuscitation on the rescuer's forearm.

The impact of the use of a CPRMeter monitor on quality of chest compressions: a prospective randomised trial, cross-simulation.

BACKGROUND: Drowning is a common issue at many pools and beaches, and in seas all over the world. Lifeguards often act as bystanders, and therefore adequate training in high-quality cardiopulmonary resuscitation (CPR) and use of adequate equip-ment by lifeguards is essential. AIM: The aim of this study was to evaluate the impact of the recently introduced CPRMeter (Laerdal, Stavanger, Norway) on quality of CPR, if used by moderately experienced CPR providers. In particular, we tested the hypothesis that using the CPRMeter improves quality of chest compression by lifeguards compared to standard non-feedback CPR. METHODS: The study was designed as prospective, randomised, cross-over manikin trial. Fifty lifeguards of the Volunteer Water Rescue Service (WOPR), a Polish nationwide association specialised in water rescue, participated in this study. Participants were randomly assigned 1:1 to one of two groups: a feedback group and a non-feedback group. Participants swim a distance of 25 m in the pool, and then they were asked to haul a manikin for the second 25 m, simulating rescuing a drowning victim. Once participants finished the second 25-m distance, participants were asked to initiate 2-min basic life support according to the randomisation. RESULTS: The median quality of CPR score for the 2-min CPR session without feedback was 69 (33-77) compared to 84 (55-93) in the feedback group (p < 0.001). Compression score, mean depth, rate of adequate chest compressions/min, and overall mean rate during the CPR session improved significantly in the feedback group, compared to the non-feedback group. CONCLUSIONS: Using the visual real-time feedback device significantly improved quality of CPR in our relatively unexperienced CPR providers. Better quality of bystander CPR is essential for clinical outcomes, and therefore feedback devices should be considered. Further clinical studies are needed to assess the effect of real-time visual devices, especially in bystander-CPR.