Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

KBG syndrome; Missense variants; Neurodevelopmental disordersSíndrome KBG; Variants de missense; Trastorns del neurodesenvolupamentSíndrome KBG; Variantes de missense; Trastornos del neurodesarrolloPurpose Although haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants. Methods We collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants through in silico analyses and cell-based experiments. Results We identified 20 unique, mostly de novo, ANKRD11 missense variants in 29 individuals, presenting with syndromic neurodevelopmental disorders similar to KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in repression domain 2 at the ANKRD11 C-terminus. Of the 10 functionally studied missense variants, 6 reduced ANKRD11 stability. One variant caused decreased proteasome degradation and loss of ANKRD11 transcriptional activity. Conclusion Our study indicates that pathogenic heterozygous ANKRD11 missense variants cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges because the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping

A preliminary study of telemedicine for patients with hepatic glycogen storage disease and their healthcare providers:from bedside to home site monitoring

BackgroundThe purpose of this project was to develop a telemedicine platform that supports home site monitoring and integrates biochemical, physiological, and dietary parameters for individual patients with hepatic glycogen storage disease (GSD). Methods and resultsThe GSD communication platform (GCP) was designed with input from software developers, GSD patients, researchers, and healthcare providers. In phase 1, prototyping and software design of the GCP has occurred. The GCP was composed of a GSD App for patients and a GSD clinical dashboard for healthcare providers. In phase 2, the GCP was tested by retrospective patient data entry. The following software functionalities were included (a) dietary registration and prescription module, (b) emergency protocol module, and (c) data import functions for continuous glucose monitor devices and activity wearables. In phase 3, the GSD App was implemented in a pilot study of eight patients with GSD Ia (n=3), GSD IIIa (n=1), and GSD IX (n=4). Usability was measured by the system usability scale (SUS). The mean SUS score was 64/100 [range: 38-93]. ConclusionsThis report describes the design, development, and validation process of a telemedicine platform for patients with hepatic GSD. The GCP can facilitate home site monitoring and data exchange between patients with hepatic GSD and healthcare providers under varying circumstances. In the future, the GCP may support cross-border healthcare, second opinion processes and clinical trials, and could possibly also be adapted for other diseases for which a medical diet is the cornerstone

Dichotomy between the transcriptomic landscape of naturally versus accelerated aged murine hearts

We investigated the transcriptomic landscape of the murine myocardium along the course of natural aging and in three distinct mouse models of premature aging with established aging-related cardiac dysfunction. Genome-wide total RNA-seq was performed and the expression patterns of protein-coding genes and non-coding RNAs were compared between hearts from naturally aging mice, mice with cardiac-specific deficiency of a component of the DNA repair machinery, mice with reduced mitochondrial antioxidant capacity and mice with reduced telomere length. Our results demonstrate that no dramatic changes are evident in the transcriptomes of naturally senescent murine hearts until two years of age, in contrast to the transcriptome of accelerated aged mice. Additionally, these mice displayed model-specific alterations of the expression levels of protein-coding and non-coding genes with hardly any overlap with age-related signatures. Our data demonstrate very limited similarities between the transcriptomes of all our murine aging models and question their reliability to study human cardiovascular senescence

Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia

Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest. A prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined. In total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C. Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest. ClinicalTrials.gov NCT01020916, registered 25 November 200

A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance:A retrospective, single-center study and the generation of www.emergencyprotocol.net

Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long‐term data on outcomes using emergency letters are lacking. This is a retrospective, observational, single‐center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results, and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions, and translations. Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128 (42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration 5 years. Convulsions, coma, or death was not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in nine different languages. Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in‐hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium‐chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD