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Introduction: The aim of the study was to assess the differences in key parameters of type 1 diabetes (T1D) control associated with treatment and monitoring modalities including newly introduced hybrid closed-loop (HCL) algorithm in children and adolescents with T1D (CwD) using the data from the population-wide pediatric diabetes registry ČENDA., Methods: CwD younger than 19 years with T1D duration >1 year were included and divided according to the treatment modality and type of CGM used: multiple daily injection (MDI), insulin pump without (CSII) and with HCL function, intermittently scanned continuous glucose monitoring (isCGM), real-time CGM (rtCGM), and intermittent or no CGM (noCGM). HbA1c, times in glycemic ranges, and glucose risk index (GRI) were compared between the groups., Results: Data of a total of 3,251 children (mean age 13.4 ± 3.8 years) were analyzed. 2,187 (67.3%) were treated with MDI, 1,064 (32.7%) with insulin pump, 585/1,064 (55%) with HCL. The HCL users achieved the highest median TIR 75.4% (IQR 6.3) and lowest GRI 29.1 (7.8), both p < 0.001 compared to other groups, followed by MDI rtCGM and CSII groups with TIR 68.8% (IQR 9.0) and 69.0% (7.5), GRI 38.8 (12.5) and 40.1 (8.5), respectively (nonsignificant to each other). These three groups did not significantly differ in their HbA1c medians (51.8 [IQR 4.5], 50.7 [4.5], and 52.7 [5.7] mmol/mol, respectively). NoCGM groups had the highest HbA1c and GRI and lowest TIR regardless of the treatment modality., Conclusion: This population-based study shows that the HCL technology is superior to other treatment modalities in CGM-derived parameters and should be considered as a treatment of choice in all CwD fulfilling the indication criteria., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Early mobilization after total hip replacement (THR) is key for fast recovery but is often limited by pain. Oral enzyme combinations (OECs) have demonstrated anti-inflammatory and pain-relieving effects., Objectives and Design: This prospective, randomized, double-blind, placebo-controlled exploratory trial evaluated the effects of pre- and post-operative use of OEC (90 mg bromelain, 48 mg trypsin, 100 mg rutoside) following elective THR, on post-operative recovery., Methods: Candidates for primary elective cementless THR owing to osteoarthritis were eligible for participation [age ⩾50 years, body mass index 25-35 kg/m 2 , C-reactive protein (CRP) ⩽6 mg/L]. Following randomization to OEC or placebo, intervention started pre-operatively and continued onwards until day 42. Main outcomes included post-operative CRP levels (days 1-7), self-reported hip pain at rest (by 0-10 cm visual analogue scale on post-operative days 1-42), post-operative analgesic use [by cumulative analgesic consumption score (CACS) days 7-42], tolerability and adverse events., Results: Patients ( N  = 34) were recruited from a tertiary orthopaedic hospital in the Czech Republic, of whom 33 completed the study (OEC/placebo: n  = 15/18). Baseline characteristics across the groups were comparable. Compared with placebo, the OEC group had numerically lower CRP levels on post-operative days 1-7, including peak level [mean (standard deviation) OEC versus placebo: 81.4 (28.3) versus 106.7 (63.3) mg/L], which translated into a significant 32% lower CRP area under the curve ( p  = 0.034). The OEC group reported significantly less pain during post-operative days 1-7 versus placebo (analysis of variance treatment × visit [ F (4) = 3.989]; p  = 0.005). Analgesic use was numerically reduced as assessed through an accumulated CACS. No deleterious effects on haemorheological parameters were observed in either group., Conclusions: Pre- and post-operative use of OEC significantly reduced CRP levels and patient self-reported pain. OEC may be an efficacious and safe treatment option to facilitate post-operative recovery following THR., Trial Registration: EudraCT number 2016-003078-41., (© The Author(s), 2023.)

Adaptive immunity changes over an individual’s lifetime, maturing by adulthood and diminishing with old age. Epigenetic mechanisms involving DNA and histone methylation form the molecular basis of immunological memory during lymphocyte development. Monocytes alter their function to convey immune tolerance, yet the epigenetic influences at play remain to be fully understood in the context of lifespan. This study of a healthy genetically homogenous cohort of children, adults and seniors sought to decipher the epigenetic dynamics in B-lymphocytes and monocytes. Variable global cytosine methylation within retro-transposable LINE-1 repeats was noted in monocytes compared to B-lymphocytes across age groups. The expression of the human leukocyte antigen (HLA)-DQ alpha chain gene HLA-DQA1*01 revealed significantly reduced levels in monocytes in all ages relative to B-lymphocytes, as well as between lifespan groups. High melting point analysis and bisulfite sequencing of the HLA-DQA1*01 promoter in monocytes highlighted variable cytosine methylation in children and seniors but greater stability at this locus in adults. Further epigenetic evaluation revealed higher histone lysine 27 trimethylation in monocytes from this adult group. Chromatin immunoprecipitation and RNA pulldown demonstrated association with a novel lncRNA TINA with structurally conserved similarities to the previously recognized epigenetic modifier PARTICLE. Seeking to interpret the epigenetic immunological landscape across three representative age groups, this study focused on HLA-DQA1*01 to expose cytosine and histone methylation alterations and their association with the non-coding transcriptome. Such insights unveil previously unknown complex epigenetic layers, orchestrating the strength and weakening of adaptive immunity with the progression of life.

Background: To explore type 1 diabetes incidence patterns during the pandemic years 2020 and 2021 in Czechia, to compare them to the trends from the previous decade, and to test its association with indicators of containment measures and of pandemic severity (school closing and the all-cause excess mortality)., Methods: The Czech Childhood Diabetes Register is a population-based incidence register recording patients age 0-14.99 years at diabetes onset. Type 1 diabetes incidence in the pandemic period (April 2020-end of observation Dec 2021) was compared by Poisson regression models to the incidence patterns over the past decade 2010-2019., Results: During the pandemic years 2020-2021, 956 children 0-14.99 years old manifested with type 1 diabetes in Czechia. The observed incidence (27.2/100,000/year) was significantly higher than what was expected from the trends over 2010-2019 (incidence rate ratio, IRR = 1.16, 95%CI 1.06-1.28, p = 0.0022). The incidence had a trough during the first lockdown (March-May 2020), then it rose above expected values with no usual summer decrease. The assessed pandemic indicators (school closing and all-cause excess mortality) were not associated with the incidence levels., Conclusions: The COVID-19 pandemic was associated with a notable upward inflection of the type 1 diabetes incidence curve; the early months of the first lockdown were however hallmarked by a significant dip in new diabetes diagnoses. Long-term observation will show whether the increased incidence originated only from accelerating an advanced preclinical Stage 2 to overt diabetes, or whether the pandemic triggered new cases of islet autoimmunity., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)