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Background: To preserve the benefit of atrial sensing without the implantation of an additional lead, a single‐lead ICD system with a floating atrial dipole (DX ICD) has been developed. The purpose of this nationwide survey was to provide an overview of the current key influences of device selection focusing on DX ICD and to test the applicability of a previously published decision‐making flowchart of ICD‐type selection. Methods: An online questionnaire was sent to all implanting centers in Hungary. Eleven centers reported data from 361 DX ICD and 10 CRT‐DX systems implantations between February 2021 and May 2023. Results: The most important influencing clinical factors indicated by the participating doctors were elevated risk of atrial fibrillation (AF)/stroke (56%), risk of sinus/supraventricular tachycardias (SVT) (42%), and a potential need for CRT upgrade in the future (36%). The DX ICD was considered in the majority of cases instead of the VVI system (87%), and only in a small proportion instead of a DDD ICD (13%). 60% of the patients with DX ICDs were also included into remote monitoring‐based follow‐up. In 83% of the cases, good (>2 mV) or excellent (>5) atrial signal amplitude was recorded within 6 weeks after the implantation. Conclusion: In the current national survey, the most important influencing factors indicated by the implanters for selecting a DX ICD were the elevated risk of stroke or sinus/SVT and a potential need for CRT upgrade in the future. These findings support the use of a previously published decision‐making flowchart. [ABSTRACT FROM AUTHOR]

Objective: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure. Methods: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter‐rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment. Results: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA‐Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate‐to‐excellent inter‐rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation. Conclusion: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies. [ABSTRACT FROM AUTHOR]

Aims: Cerebral amyloid angiopathy (CAA)‐related inflammation (CAA‐RI) is a potentially reversible manifestation of CAA, histopathologically characterised by transmural and/or perivascular inflammatory infiltrates. We aimed to identify clinical, radiological and laboratory variables capable of improving or supporting the diagnosis of or predicting/influencing the prognosis of CAA‐RI and to retrospectively evaluate different therapeutic approaches. Methods: We present clinical and neuroradiological observations in seven unpublished CAA‐RI cases, including neuropathological findings in two definite cases. These cases were included in a systematic analysis of probable/definite CAA‐RI cases published in the literature up to 31 December 2021. Descriptive and associative analyses were performed, including a set of clinical, radiological and laboratory variables to predict short‐term, 6‐month and 1‐year outcomes and mortality, first on definite and second on an expanded probable/definite CAA‐RI cohort. Results: Data on 205 definite and 100 probable cases were analysed. CAA‐RI had a younger symptomatic onset than non‐inflammatory CAA, without sex preference. Transmural histology was more likely to be associated with the co‐localisation of microbleeds with confluent white matter hyperintensities on magnetic resonance imaging (MRI). Incorporating leptomeningeal enhancement and/or sulcal non‐nulling on fluid‐attenuated inversion recovery (FLAIR) enhanced the sensitivity of the criteria. Cerebrospinal fluid pleocytosis was associated with a decreased probability of clinical improvement and longer term positive outcomes. Future lobar haemorrhage was associated with adverse outcomes, including mortality. Immunosuppression was associated with short‐term improvement, with less clear effects on long‐term outcomes. The superiority of high‐dose over low‐dose corticosteroids was not established. Conclusions: This is the largest retrospective associative analysis of published CAA‐RI cases and the first to include an expanded probable/definite cohort to identify diagnostic/prognostic markers. We propose points for further crystallisation of the criteria and directions for future prospective studies. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary vein isolation (PVI) is a pivotal part of ablative therapy for atrial fibrillation (AF). Currently, there are multiple techniques available to realize PVI, including: manual‐guided cryoballoon (MAN‐CB), manual‐guided radiofrequency (MAN‐RF), and robotic magnetic navigation‐guided radiofrequency ablation (RMN‐RF). There is a lack of large prospective trials comparing contemporary RMN‐RF with the more conventional ablation techniques. This study prospectively compared three catheter ablation techniques as treatment of paroxysmal AF. Methods: This multicenter, prospective study included patients with paroxysmal AF who underwent their first ablation procedure. Procedural parameters (including procedural efficiency), complication rates, and freedom of AF during 12‐month follow‐up, were compared between three study groups which were defined by the utilized ablation technique. Results: A total of 221 patients were included in this study. Total procedure time was significantly shorter in MAN‐CB (78 ± 21 min) compared to MAN‐RF (115 ± 41 min; p <.001) and compared to RMN‐RF (129 ± 32 min; p <.001), whereas it was comparable between the two radiofrequency (RF) groups (p =.062). A 3% complication rate was observed, which was comparable between all groups. At 12‐month follow‐up, AF recurrence was observed in 40 patients (19%) and was significantly lower in the robotic group (MAN‐CB 19 [24%], MAN‐RF 16 [23%], RMN‐RF 5 [8%] AF recurrences, p =.045) (multivariate hazard ratio of RMN‐RF on AF recurrence 0.32, 95% confidence interval: 0.12–0.87, p =.026). Conclusion: RMN‐guided PVI results in high freedom of AF in patients with paroxysmal AF, when compared to cryoablation and manual RF ablation. Cryoablation remains the most time‐efficient ablation technique, whereas RMN nowadays has comparable efficiency with manual RF ablation. [ABSTRACT FROM AUTHOR]

Objective: Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes. Methods: This proposal is the result of 4 face‐to‐face consensus meetings with a 27‐member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data‐driven decisions. The use of items for each domain as an outcome measure in an open label 12‐month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique. Results: After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda. Conclusion: We reached consensus on multiple domains and items that should be assessed in an open label, 12‐month clinical juvenile SSc trial as well as a research agenda for future development. [ABSTRACT FROM AUTHOR]

Aims: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. Methods: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt‐based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation‐inductively coupled plasma‐mass spectrometry and correlated with clinicopathological features. Results: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of Pt distribution was seen within the tumourous areas. Pt levels correlated neither with the microvessel area nor with apoptosis rate in the tumourous or nontumourous regions. A significant positive correlation was found between serum and both full tissue section and tumourous area mean Pt levels (r = 0.532, P = 0.006, 95% confidence interval [95% CI] 0.161‐0.771 and r = 0.415, P = 0.039, 95% CI 0.011‐0.702, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r = −0.474, P = 0.017, 95% CI −0.738‐−0.084). Serum Pt levels correlated negatively with overall survival (OS) (P = 0.029). Conclusions: There are major differences in drug distribution between tumourous and nontumourous areas of PM specimens. Serum Pt levels significantly correlate with full section and tumourous area average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted. [ABSTRACT FROM AUTHOR]

Objectives: The Future Proofing Study (FPS) was established to examine factors associated with the onset and course of mental health conditions during adolescence. This paper describes the design, methods, and baseline characteristics of the FPS cohort. Methods: The FPS is an Australian school‐based prospective cohort study with an embedded cluster‐randomized controlled trial examining the effects of digital prevention programs on mental health. Data sources include self‐report questionnaires, cognitive functioning, linkage to health and education records, and smartphone sensor data. Participants are assessed annually for 5 years. Results: The baseline cohort (N = 6388, M = 13.9 years) is broadly representative of the Australian adolescent population. The clinical profile of participants is comparable to other population estimates. Overall, 15.1% of the cohort met the clinical threshold for depression, 18.6% for anxiety, 31.6% for psychological distress, and 4.9% for suicidal ideation. These rates were significantly higher in adolescents who identified as female, gender diverse, sexuality diverse, or Aboriginal and/or Torres Strait Islander (all ps < 0.05). Conclusions: This paper provides current and comprehensive data about the status of adolescent mental health in Australia. The FPS cohort is expected to provide significant insights into the risk, protective, and mediating factors associated with development of mental health conditions during adolescence. [ABSTRACT FROM AUTHOR]

Background: Rates of depression are increasing among adolescents. A novel way to reduce depression is by improving sleep. We evaluated whether an app‐based intervention for insomnia improved sleep and depression, and whether changes in insomnia mediated changes in depression. Methods: We conducted a 2‐arm single‐blind randomised controlled trial at the Black Dog Institute in Australia. Adolescents 12–16 years experiencing insomnia symptoms were randomly allocated to receive Sleep Ninja, an app‐delivered cognitive behavioural therapy program for insomnia, or to an active control group involving weekly text message sleep tips. Assessments took place at baseline, 6 weeks (post‐intervention) and 14 weeks (post‐baseline). Co‐primary outcomes were symptoms of insomnia and depression at post‐intervention (primary endpoint). Intent‐to‐treat analyses were conducted. The trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12619001462178. Results: Between October 25, 2019, and September 6, 2020, 264 participants were randomised to receive Sleep Ninja (n = 131) or to the control group (n = 133). Relative to the control group, those allocated to the intervention reported a greater reduction in insomnia symptoms at 6 weeks (95% CI: −2.96 to −0.41, d =.41) and 14 weeks (95% CI: −3.34 to −0.19, d =.39), and a greater reduction in depression symptoms at 6 weeks (95% CI: −3.46 to −0.56, d =.28) but not 14 weeks (p < 1). Change in insomnia mediated change in depression. No adverse events were reported. Conclusions: An app‐delivered program for insomnia could be a practical, non‐stigmatising and scalable way to reduce symptoms of insomnia and depression among adolescents experiencing difficulties getting enough good quality sleep. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation (CA) remains challenging due to suboptimal success rates in persistent atrial fibrillation (AF). Existing mapping technologies cannot reliably distinguish sources in this patient population. Recently, the novel electrographic flow (EGF) mapping system was developed using a modified Horn‐Schunk optical flow algorithm to detect and quantify patterns of electrical wavefront propagation in the atria. Objectives: To test the hypothesis that targeted source ablation based on EGF mapping is superior to empiric AF ablation. Methods: We included all consecutive patients undergoing EGF guided ablation for persistent AF. All patients underwent pulmonary vein isolation (PVI) and were treated with the same EAM system (CARTO). The outcome of PVI+EGF guided CA was compared with data of PVI‐only procedures (PVI‐only group) and PVI plus additional empiric adjunctive linear and substrate ablations (PVI+LINES group). 12‐months outcome as freedom from AF and atrial tachycardia/flutter (AT/AFL), procedural safety and efficiency characterized by procedure duration, fluoroscopy use, radiofrequency applications and duration, were analyzed. Both intention‐to‐treat and per protocol analysis were conducted. Results: A total number of 70 patients (39 in PVI+EGF, 16 in PVI‐only and 15 patients in PVI+LINES group) were enrolled. Intention‐to‐treat analysis showed fewer AF recurrences in PVI+EGF as compared with the PVI‐only or PVI+LINES groups at 12 months (25.6% vs. 62.5% vs. 53.3%, p =.02). There were no differences in AT/AFL recurrence (17.9% vs. 37.5% vs. 20.0%, p =.37). Procedure times were longer in PVI+EGF group (p <.01), and there were no differences in fluoroscopy use (p =.67). Conclusion: Our data suggest that patients treated with EGF‐guided CA developed fewer AF recurrences. Although the procedure times are longer, it seems to be safe and offers a more targeted, patient‐specific ablation strategy beyond PVI than adjunctive empiric lines and substrate ablation in this complex group of patients. [ABSTRACT FROM AUTHOR]

Background: The Localized Scleroderma Quality of Life Instrument (LoSQI) is a disease‐specific patient‐reported outcome (PRO) measure designed for children and adolescents with localized scleroderma (LS; morphea). This tool was developed using rigorous PRO methods and previously cognitively tested in a sample of paediatric patients with LS. Objective: The purpose of this study was to evaluate the psychometric properties of the LoSQI in a clinical setting. Methods: Cross‐sectional data from four specialized clinics in the US and Canada were included in the analysis. Evaluation included reliability of scores, internal structure of the survey, evidence of convergent and divergent validity, and test–retest reliability. Results: One hundred and ten patients with LS (age: 8–20 years) completed the LoSQI. Both exploratory and confirmatory factor analysis supported the use of two sub‐scores: Pain and Physical Functioning, and Body Image and Social Support. Correlations with other PRO measures were consistent with pre‐specified hypotheses. Limitations: This study did not evaluate longitudinal validity or responsiveness of scores. Conclusion: Results from a representative sample of children and adolescents with LS continue to support the validity of the LoSQI when used in a clinical setting. Future work to evaluate the responsiveness is ongoing. [ABSTRACT FROM AUTHOR]

Background: Poor engagement has hindered the dissemination of self‐guided digital therapeutics for mental health. Evidence on the efficacy of technology‐supported strategies designed for increasing engagement with these interventions is currently inconclusive. Few studies have examined user perceptions of such strategies, which could yield key insights for enhancing their effectiveness. Methods: Two hundred and eleven participants completed a cross‐sectional online survey. All participants were aged 18 years and above, living in Australia, fluent in English, and self‐reported prior use of digital therapeutics for mental health needs. Survey items elicited participants' views on factor(s) contributing to their engagement/disengagement with digital therapeutics, and perceptions of engagement strategies, including: automated electronic reminders, fun facts, quizzes, and social media platforms. χ2 tests of independence were used to analyse nominal data. Inductive thematic analysis was used to analyse free‐text data. Results: Factors facilitating engagement included digestible content, assurance of confidentiality, and esthetically appealing design. Factors hindering engagement included lack of time, forgetfulness, and lack of perceived intervention efficacy. Participants had mixed views over the feasibility and acceptability of the strategies explored toward promoting engagement. Conclusions: Regardless of strategy type, succinct and easily applicable content was identified as an important feature for promoting engagement. Conversely, content that could trigger psychological distress among intervention users should be avoided. Overall, the diverse range of user perspectives highlighted that engagement strategies for any specific digital intervention should be co‐designed with individuals with lived experience of mental health difficulties. [ABSTRACT FROM AUTHOR]

Dogs have served as one of the most reliable preclinical models for a variety of diseases and treatments, including stem/progenitor cell transplantation. At the genetic epicenter of dog transplantation models, polymorphic major histocompatibility complex (MHC) genes are most impactful on transplantation success. Among the canine class I and class II genes, DLA‐88 has been best studied in transplantation matching and outcomes, with 129 DLA‐88 alleles identified. In this study we developed and tested a next generation (NGS) sequencing protocol for rapid identification of DLA‐88 genotypes in dogs and compared the workflow and data generated with an established DLA‐88 Sanger sequencing protocol that has been in common prior use for clinical studies. By testing the NGS protocol on a random population of 382 dogs, it was possible to demonstrate superior efficacy based on laboratory execution and overall cost. In addition, NGS proved far more effective at discovering new alleles and detecting multiple alleles associated with gene duplication. A total of 51 new DLA‐88 alleles are reported here. This rate of new allele discovery indicates that a large pool of yet un‐discovered DLA‐88 alleles exists in the domestic dog population. In addition, more than 46% of dogs carried three or more copies of DLA‐88, further emphasizing the need for more sensitive and cost‐effective DLA typing methodology for the dog clinical model. [ABSTRACT FROM AUTHOR]

This article discusses the role of ultrasound screening in identifying false negative results in non-invasive prenatal testing (NIPT). The study, conducted at a tertiary center in Hungary, collected cases where ultrasound examinations and invasive diagnostic testing were performed following NIPT. The results showed that ultrasound was able to detect abnormalities in cases where the NIPT results were negative, preventing the birth of children with severe genetic disorders. The study highlights the importance of expert ultrasound in preventing diagnostic errors in NIPT. [Extracted from the article]

This article, titled "EP14.26: Outcome of monochorionic twin pregnancies complicated with selective intrauterine growth restriction," discusses the outcomes of pregnancies with selective intrauterine growth restriction (sIUGR) in monochorionic (MC) twins. The study, conducted at a tertiary referral center between 2018 and 2022, analyzed cases of sIUGR and focused on factors such as fetal status, gestational age at delivery, birthweight discordance, perinatal mortality, neonatal death, neonatal morbidity, and long-term follow-up data. The results showed a strong association between the subtypes of sIUGR in MC twins and perinatal outcomes. [Extracted from the article]

This article, published in the journal Ultrasound in Obstetrics & Gynecology, discusses two cases in which the diagnosis of DiGeorge microdeletion syndrome was made based on fetal ultrasound. DiGeorge syndrome is a common microdeletion syndrome caused by the deletion of a specific region on chromosome 22. The article emphasizes the importance of extended fetal cardiac examination in the first trimester. The families in the case reports made decisions about their pregnancies based on the diagnosis and consultation with medical professionals. [Extracted from the article]

Background: The propagation and spread of pathology in Alzheimer's disease (AD) results from the interplay of many complex biological processes. Two key hypotheses have been proposed to help explain the characteristic Braak stageing patterns that define typical AD tau pathology1: network spread, which posits that trans‐synaptic spread of tau determines how pathology progresses2, and selective vulnerability, which states that the regions most affected by tau pathology contain high densities of cell types particularly sensitive to the presence of tau3. Here we explore the explanatory power of each hypothesis in the context of mouse tauopathy models. Methods: We implemented a mathematical network spread model that extends the Network Diffusion Model2 by adding a linear accumulation term (sNDM). We also utilized the cell type distributions recently made available by the MISS algorithm, which deconvolves spatial transcriptomic data into cell type densities using scRNAseq information4. We fit the sNDM to the Iba, et al. PS19 tauopathy model seeded at the hippocampus5 (IbaHippInj) and the Hurtado, et al. unseeded PS19/PDAPP model6 (Hurtado). Results: We find that although network spread is the single‐best correlate of tau pathology, there are many cell types that are highly correlated at the regional level, particularly Layer‐2/3 glutamatergic neurons and Lamp5‐expressing GABAergic neurons (Figure 1). A combined linear model using sNDM predictions and these two cell types (Figure 2) yields higher R2 values than the sNDM predictions alone (Figure 3). Conclusion: We demonstrate that both the network spread and selective vulnerability hypotheses contribute meaningful information for explaining tau pathology in mouse models, indicating that more sophisticated modeling approaches taking into account the full biological complexity of AD have more explanatory power. References: 1. Braak, H. & Braak, E. Acta Neuropathol. 82, 239‐259 (1991). 2. Raj, A., Kuceyeski, A. & Weiner, M. Neuron (2012). 3. Fu, H., Hardy, J. & Duff, K. E. Nat. Neurosci. 21, 1350‐1358 (2018). 4. Mezias, C., Torok, J., Maia, P. D., Markley, E. & Raj, A. PNAS. (In press). 5. Iba, M. et al. J. Neurosci. 33, 1024‐1037 (2013). 6. Hurtado, D. E. et al. Am. J. Pathol. 177, E4376–E4385 (2010). [ABSTRACT FROM AUTHOR]

Background: Insertable cardiac monitors (ICMs) are increasingly used to evaluate the atrial fibrillation (AF) burden after catheter ablation of AF. BioMonitor III (BM3) is an ICM with a long sensing vector, which enhances sensing capabilities. The AF detection algorithm of the BM3 is based on R–R interval variability. Objective: To evaluate the performance of the AF detection algorithm of BM3 in patients before and after catheter ablation of AF using simultaneous Holter recordings. Methods: In this prospective study, we enrolled patients scheduled for catheter ablation of paroxysmal or persistent AF. After BM3 implantation, patients had a 4 days Holter registration before and 3 months after ablation. All true AF episodes ≥2 min on the Holter were annotated and matched with BM3 detected AF detections. Results: Thirty‐one patients were enrolled (mean age 60 ± 8, 74% male, 68% paroxysmal AF). Fifty‐six Holter registrations were performed in 30 patients. Twelve patients demonstrated at least one true AF episode with a total AF duration of 570 h. The AF burden accuracy of BM3 before catheter ablation was 99.6%, with a duration sensitivity of 98.6% and a duration specificity of 99.9%. The AF burden accuracy of BM3 after catheter ablation was 99.8%, with a duration sensitivity of 90.2% and a duration specificity of 99.9%. Overall, the AF burden detected on the Holter and BM3 demonstrated a high Pearson correlation coefficient of 0.996. Conclusion: BM3 accurately detects AF burden in patients before and after catheter ablation of AF. [ABSTRACT FROM AUTHOR]

Aims: The need for permanent pacemakers (PMs) after heart transplantation (HT) is increasing. The aim was to determine the influence of cardiac allograft vasculopathy (CAV), donor age, and other risk factors on PM implantations early and late after HT and its effect on survival. Methods and results: A retrospective, single‐centre study was performed including HTs from 1984 to July 2018. Early PM was defined as PM implantation ≤90 days and late PM as PM > 90 days. Risk factors for PM and survival after PM were determined with (time‐dependent) multivariable Cox regression. Out of 720 HTs performed, 62 were excluded (55 mortalities ≤30 days and 7 retransplantations). Of the remaining 658 patients, 95 (14%) needed a PM: 38 (6%) early and 57 (9%) late during follow‐up (median 9.3 years). Early PM risk factors were donor age [hazard ratio (HR) 1.06, P < 0.001], ischaemic time (HR 1.01, P < 0.001), and in adults amiodarone use before HT (HR 2.02, P = 0.045). Late PM risk factors were donor age (HR 1.03, P = 0.024) and CAV (HR 3.59, P < 0.001). Late PM compromised survival (HR 2.05, P < 0.001), while early PM did not (HR 0.77, P = 0.41). Conclusions: Risk factors for early PM implantation were donor age, ischaemic time, and in adults amiodarone use before HT. Late PM implantation risk factors were donor age and CAV. Late PM diminished survival, which is probably a surrogate marker for underlying progressive cardiac disease. [ABSTRACT FROM AUTHOR]

Objective: Juvenile localized scleroderma (LS) is an autoimmune disease of the skin whose pathogenesis is not well understood due to the rarity of the disease. This study was undertaken to determine the skin transcriptome in skin biopsy tissue from children with juvenile LS compared to pediatric healthy controls, with identification of significant molecular targets using RNA sequencing (RNA‐Seq). In this study, differentially expressed genes (DEGs) were assessed for correlations with histopathologic and clinical features in children with juvenile LS, and were used to group the children into distinct genetic clusters based on immunophenotype. Methods: RNA‐Seq was performed on sections of paraffin‐embedded skin tissue obtained from 28 children with juvenile LS and 10 pediatric healthy controls. RNA‐Seq was carried out using an Illumina HTS TruSeq RNA Access library prep kit, with data aligned using STAR and data analysis using a DESeq2 platform. A standardized histologic scoring system was used to score skin sections for the severity of inflammation and levels of collagen deposition. Histologic scoring was completed by 2 pathologists who were blinded with regard to the status of each sample. Spearman's rank correlation coefficients were used to assess significant correlations between DEG expression profiles and skin histologic findings in patients with juvenile LS. Results: We identified 589 significant DEGs in children with juvenile LS as compared to healthy controls. Hierarchical clustering was used to demonstrate 3 distinct juvenile LS immunophenotype clusters. The histologic scores of skin inflammation (based on numbers and categories of inflammatory cell infiltrates) were significantly correlated with the expression levels of HLA–DPB1, HLA–DQA2, HLA–DRA, and STAT1 genes (rs > 0.5, P < 0.01). Collagen thickness correlated with the expression levels of collagen organization genes as well as with genes found to be correlated with the severity of inflammation, including genes for major histocompatibility complex (MHC) class I, MHC class II, and interferon‐γ signaling. Conclusion: Among children with juvenile LS, 3 distinct genetic signatures, or clusters, were identified. In one cluster, inflammation‐related pathways were up‐regulated, corresponding to the histologic skin inflammation score. In the second cluster, fibrosis‐related pathways were up‐regulated. In the third cluster, gene expression in the skin corresponded to the patterns seen in healthy controls. Up‐regulation of HLA class II genes was observed within the first cluster (characterized by predominant inflammation), a feature that has also been observed in the peripheral blood of patients with morphea and in the skin of patients with systemic sclerosis. [ABSTRACT FROM AUTHOR]

Ablation procedures using classical sequential mapping systems may fail to eliminate IAST. The AcQMap dipole charge density mapping technique may offer improved accuracy and has a potential added value for the ultimate success of eliminating IAST. The use of the AcQMap should be considered for redo, as well as first line therapy for patients with symptomatic IAST. [ABSTRACT FROM AUTHOR]

Introduction: In May 2020, a novel cryoballoon system (POLARx; Boston Scientific) became available for catheter ablation of atrial fibrillation (AF). The design of the cryoballoon is comparable to the Arctic Front Advance Pro (AFA‐Pro; Medtronic), but it is more compliant during freezing. We compared the procedural efficacy, biophysical parameters, and risk of phrenic nerve palsy (PNP) between the two cryoballoons. Methods: Embase, MEDLINE, Web of Science, Cochrane, and Google Scholar databases were searched until June 1, 2021 for relevant studies comparing POLARx versus AFA‐Pro in patients undergoing pulmonary vein isolation (PVI) for AF. Results: A total of four studies, involving 310 patients were included. There was no difference between the two groups for outcomes regarding procedural efficacy: acute PVI (odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.06 to 3.03; p =.40), procedure time (mean difference [MD]: 8.15 min; 95% CI: −8.09 to 24.39; p =.33), fluoroscopy time (MD: 1.32 min; 95% CI: −1.61 to 4.25; p =.38) and ablation time (MD: 1.00 min; 95% CI: −0.20 to 2.20; p =.10). The balloon nadir temperature was lower for all individual pulmonary veins (PV) in POLARx compared with AFA‐Pro (MD: −9.74°C, −9.98°C, −6.72°C, −7.76°C, for left superior PV, left inferior PV, right superior PV, and right inferior PV, respectively; all p <.001). The incidence of PNP was similar between groups (OR: 0.79; 95% CI: 0.22 to 2.85; p =.72). Conclusion: In AF patients undergoing PVI, POLARx and AFA‐Pro had a similar procedural efficacy. Balloon nadir temperatures were lower with POLARx, however, the incidence of PNP was similar. [ABSTRACT FROM AUTHOR]

Aims: Electrographic flow (EGF) mapping is a method to detect action potential sources within the atria. In a double‐blinded retrospective study we evaluated whether sources detected by EGF are related to procedural outcome. Methods: EGF maps were retrospectively generated using the Ablamap® software from unipolar data recorded with a 64‐pole basket catheter from patients who previously underwent focal impulse and rotor modulation‐guided ablation. We analyzed patient outcomes based on source activity (SAC) and variability. Freedom from atrial fibrillation (AF) was defined as no recurrence of AF, atypical flutter or atrial tachycardia at the follow‐up visits. Results: EGF maps were from 123 atria in 64 patients with persistent or long‐standing persistent AF. Procedural outcome correlation with SAC peaked at >26%. S‐type EGF signature (source‐dependent AF) is characterized by stable sources with SAC > 26% and C‐type (source‐independent AF) is characterized by sources with SAC ≤ 26%. Cases with AF recurrence at 3‐, 6‐, or 12‐month follow‐up showed a median final SAC 34%; while AF‐free patients had sources with significantly lower median final SAC 21% (p =.0006). Patients with final SAC and Variability above both thresholds had 94% recurrence, while recurrence was only 36% for patients with leading source SAC and variability below threshold (p =.0001). S‐type EGF signature post‐ablation was associated with an AF recurrence rate 88.5% versus 38.1% with C‐type EGF signature. Conclusions: EGF mapping enables the visualization of active AF sources. Sources with SAC > 26% appear relevant and their presence post‐ablation correlates with high rates of AF recurrence. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of intimate partner violence (IPV) and frequency of victimisation questioning by hospital staff in women presenting to EDs for suicide‐related complaints and injuries. Methods: A cross‐sectional survey design was used to assess IPV and ED experiences among women with a recent (<18 months) suicide‐related presentation to EDs within six Local Health Districts across New South Wales. Women aged 16 years and over, residing in participating health districts were recruited in‐person by hospital staff, or via Facebook advertisements. Variables assessed included demographic characteristics, psychosocial assessment coverage and exposure to IPV (Composite Abuse Scale [Revised]‐Short‐Form). Binary logistic regression was used to test for independent associations between variables on victimisation questioning by hospital staff. Results: A total of 563 women completed questionnaires following presentation to the ED for a suicide attempt (n = 329; 58%) or suicide crisis (n = 234; 42%). Of these, 200 women (36%) reported IPV exposure in the 18 months prior and 141 women (25%) reported earlier lifetime victimisation. Of the 341 women with a history of IPV, 155 women (45%) were asked about victimisation by hospital staff. Younger age and lower socio‐economic status were significantly associated with questioning (P = 0.03). Conclusion: Findings suggest a large proportion of women seeking support for suicide in the ED are affected by IPV, although few are asked about abuse experiences. Victimisation is associated with complex health issues and heightened mortality risk, which carry important implications for patient‐care. Findings support routine ED screening and can be applied to stratify risk within IPV responses. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have examined the relationship between executive functions and performance on cognitive behavioural therapy (CBT) tasks, such as cognitive restructuring. However, previous studies have used samples of older adults and only traditional measures of executive functions involving non‐emotional stimuli. This study extends previous research to examine the specific executive function of shifting with regard to non‐emotional and emotional stimuli and its relationship with cognitive restructuring, in a sample of young to middle‐aged adults with elevated social anxiety. Design: Cross‐sectional study. Methods: Participants (N = 49) completed a standard Wisconsin Card Sorting Test (WCST), an emotional version of the WCST (eWCST), and a cognitive restructuring task prior to an impromptu speech task. Per cent perseverative errors (an indicator of shifting) from the WCST and eWCST, along with planned covariates, were used to predict three indicators of cognitive restructuring task performance: task response quality (production of helpful alternative thoughts), change in belief in negative thought, and peak anxiety during speech. Results: As expected, higher per cent perseverative errors (i.e., poorer shifting) on the WCST predicted poorer ability during the cognitive restructuring task to produce helpful alternative thoughts to a negative thought about the impending speech task. However, WCST per cent perseverative errors did not predict the other indicators of cognitive restructuring task performance. eWCST per cent perseverative errors did not predict any of the indicators of cognitive restructuring task performance. Conclusions: The standard WCST may be sensitive to capturing the type of mental flexibility which is important for producing helpful alternative thinking during cognitive restructuring. Practitioner points: Poorer shifting ability with regard to non‐emotional stimuli in clients with elevated social anxiety may be related to poorer ability to produce helpful alternative thoughts during cognitive restructuring.For clinicians whose clients with elevated social anxiety are having difficulty with generating alternative thoughts during cognitive restructuring, clinicians should consider poor shifting ability as a potential contributing factor.Clinicians may need to provide further support for such clients during cognitive restructuring (e.g., greater emphasis on Socratic questioning to better facilitate alternative thinking). [ABSTRACT FROM AUTHOR]

Introduction: Recently a novel cryoballoon system (POLARx, Boston Scientific) became available for the treatment of atrial fibrillation. This cryoballoon is comparable with Arctic Front Advance Pro (AFA‐Pro, Medtronic), however, it maintains a constant balloon pressure. We compared the procedural efficacy and biophysical characteristics of both systems. Methods: One hundred and ten consecutive patients who underwent first‐time cryoballoon ablation (POLARx: n = 57; AFA‐Pro: n = 53) were included in this prospective cohort study. Results: Acute isolation was achieved in 99.8% of all pulmonary veins (POLARx: 99.5% vs. AFA‐Pro: 100%, p = 1.00). Total procedure time (81 vs. 67 min, p <.001) and balloon in body time (51 vs. 35 min, p <.001) were longer with POLARx. After a learning curve, these times were similar. Cryoablation with POLARx was associated with shorter time to balloon temperature −30°C (27 vs. 31 s, p <.001) and −40°C (32 vs. 54 s, p <.001), lower balloon nadir temperature (−55°C vs. −47°C, p <.001), and longer thawing time till 0°C (16 vs. 9 s, p <.001). There were no differences in time‐to‐isolation (TTI; POLARx: 45 s vs. AFA‐Pro 43 s, p =.441), however, POLARx was associated with a lower balloon temperature at TTI (−46°C vs. −37°C, p <.001). Factors associated with acute isolation differed between groups. The incidence of phrenic nerve palsy was comparable (POLARx: 3.5% vs. AFA‐Pro: 3.7%). Conclusion: The novel cryoballoon is comparable to AFA‐Pro and requires only a short learning curve to get used to the slightly different handling. It was associated with faster cooling rates and lower balloon temperatures but TTI was similar to AFA‐Pro. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence indicates that defects in axonal transport, an early feature of AD pathology1, could play a role in how directional biases develop on regional level2. Specifically, kinesin‐1, a motor protein responsible for the anterograde‐directed transport of axonal cargoes including tau, is dysregulated by hyperphosphorylated tau species3,4. Here we demonstrate that a mathematical model of tau‐modified axonal transport can reproduce directional biases in tauopathy spread observed in mouse models of disease. Methods: We implemented a mathematical model incorporating the effects of aggregation and fragmentation of pathological tau complexes of two types, soluble and insoluble, on axonal transport and diffusion. We simulated the spatiotemporal profiles of each tau species in a multicompartment, two‐neuron system using biologically plausible parameters and time scales. Notably, anterograde axonal transport velocity is modeled as being locally enhanced by the presence of soluble pathological tau3 and hindered by insoluble tau4. Results: We find that changing the balance of tau transport feedback parameters can elicit anterograde and retrograde biases in the distributions of soluble and insoluble tau between somatodendritic compartments in our two‐neuron system (Figures 1 & 2). Changing the aggregation and fragmentation parameters perturbs this balance, suggesting complex interplay between these distinct molecular processes (Figures 3 & 4). The model also recreates spread biases comparable to those derived from network spread using AD‐like and non‐AD‐like mouse tauopathy models2 (Figure 5). Conclusion: Our model of tau axonal transport feedback provides a parsimonious, biologically plausible explanation for apparent directionality observed in mouse model tauopathy spread, linking microscopic differences in tau conformational states and variance in clinical presentation. References: (1) Wang, Z.‐X., Tan, L. & Yu, J.‐T. Axonal Transport Defects in Alzheimer's Disease. Mol Neurobiol 51, 1309–1321 (2015). (2) Mezias, C. & Raj, A. The role of directionality in determining spatiotemporal tau pathology differs between AD‐Like and Non‐AD‐Like mouse models. bioRxiv11.06.371625 (2020) doi:10.1101/2020.11.06.371625. (3) Rodríguez‐Martín, T. et al. Tau phosphorylation affects its axonal transport and degradation. Neurobiology of Aging 34, 2146–2157 (2013). (4) Sherman, M. A. et al. Soluble Conformers of Aβ and Tau Alter Selective Proteins Governing Axonal Transport. J Neurosci 36, 9647–9658 (2016). [ABSTRACT FROM AUTHOR]

Due to the high prevalence of ECMs, providers should conduct comprehensive screening of all patients with craniofacial scleroderma and strongly consider aggressive treatment with systemic immunomodulators. Keywords: histology; localized scleroderma; microtia; morphea; pediatric EN histology localized scleroderma microtia morphea pediatric e45 e47 3 12/23/21 20211101 NES 211101 CASE REPORT A 4-year-old boy presented with a 3-month history of an asymptomatic erythematous patch of the right ear. Diagnosis: Linear scleroderma, craniofacial subtype DISCUSSION The patient was initially thought to have cutaneous lupus as the skin biopsy revealed a vacuolar interface dermatitis with a superficial and deep perivascular and perifollicular lymphocytic infiltrate with extension to the subcutaneous fat (Figure 2). [Extracted from the article]

Introduction: Entering US clinical training requires completing requirements and navigating an application process differing from the Japanese system. Additionally, increases to the number of US medical school graduates have increased competition for US residency positions. We examined profiles of Japanese International Medical Graduates (IMGs) who completed US clinical training, the timelines to securing US clinical positions, and the greatest challenges during this process and methods to overcome them. Methods: Individual semistructured interviews were conducted with 35 purposively sampled Japanese IMGs. We performed exploratory thematic analysis using iterative data collection and constant comparison. Results: Twenty percent of participants lived in a native English‐speaking country during childhood. The United States Medical Licensing Examinations were completed at ages 25‐40 years. Challenges were categorized as: (1) English communication, (2) understanding the application process, (3) motivation to persevere through the process, (4) time management to complete Educational Commission for Foreign Medical Graduates requirements, (5) receiving letters of recommendation and overcoming competition for US residency positions, (6) financial cost of the process. Pragmatic generally self‐dependent methods helped overcome challenges 1‐4 and 6. Participants detailed personal or, more commonly, institutional connections to US training programs required to overcome challenge 5. Conclusions: Japanese IMGs pursue US clinical training from diverse backgrounds commonly without the advantage of prior English fluency. Amidst increased competition internationally to enter US residency coupled with cultural and linguistic differences making this challenge often greater for Japanese IMGs, the competition to participate in institutionalized connections to US training programs is anticipated to increase. [ABSTRACT FROM AUTHOR]

Introduction: Due to the large language and cultural distances between Japan and the US compared to many countries, Japanese International Medical Graduates (IMGs) may have a different US training experience, including more stress, than many IMGs. We examined the US clinical training experience for Japanese IMGs, including the challenges encountered, how those challenges are overcome, and the benefits of US training. Methods: We performed individual semistructured interviews with 35 purposively sampled Japanese IMGs who had completed US clinical training. Exploratory thematic analysis was conducted using iterative data collection and constant comparison. Results: All participants reported high personal growth and that US clinical training was worth the sacrifices. Commonly fatigue was lower than during Japanese residency. Participants explained medical practice and local culture associated challenges that aligned with literature on US graduates and other IMGs. By contrast, nearly all participants reported that English communication was very challenging, and described specific language related struggles and methods to help overcome them. Communication struggles were contextualized within an American training culture that values verbal assertiveness. Self‐esteem varied among participants and, for some participants, improved with confidence in communication. Several participants reported depression and other mental illness. The training environment varied among residency programs. Conclusions: Japanese IMGs who completed US training report that it was worth it, but describe significant language and culture related struggles and effects on mental health. Further research should address which Japanese IMGs are most likely to struggle, how this will transpire, and how to optimize the US clinical training experience. Individual interviews were conducted with thirty‐five Japanese international medical graduates who had completed US clinical training, in order to understand the challenges during US clinical training and methods used to overcome them, and the self‐esteem, fatigue, and personal growth experienced. Main themes include the consensus that US clinical training was worth the sacrifices, but that English communication was tremendously challenging and exacerbated by an American training culture that values verbal assertiveness. Commonly, Japanese IMGs attempted to compensate by striving to perfect other components to their performance, such as medical knowledge and professionalism. Several participants reported depression and other mental illness. [ABSTRACT FROM AUTHOR]

Brain metastasis (BM), the most common adult brain tumor, develops in 20% to 40% of patients with late-stage cancer and traditionally are associated with a poor prognosis. The management of patients with BM has become increasingly complex because of new and emerging systemic therapies and advancements in radiation oncology and neurosurgery. Current therapies include stereotactic radiosurgery, whole-brain radiation therapy, surgical resection, laser-interstitial thermal therapy, systemic cytotoxic chemotherapy, targeted agents, and immune-checkpoint inhibitors. Determining the optimal treatment for a specific patient has become increasingly individualized, emphasizing the need for multidisciplinary discussions of patients with BM. Recognizing and addressing the sequelae of BMs and their treatment while maintaining quality of life and neurocognition is especially important because survival for patients with BMs has improved. The authors present current and emerging treatment options for patients with BM and suggest approaches for managing sequelae and disease recurrence. [ABSTRACT FROM AUTHOR]

Aims/Purpose: Primary open‐angle glaucoma is the leading cause of blindness worldwide, but no definitive treatment is available. Fibrotic‐like changes of trabecular meshwork (TM) results in increased stiffness and impaired outflow leading to increased IOP. Transforming growth factor‐β2 (TGF‐β2), a main driver of eye fibrosis, is increased in the aqueous humour of glaucoma patients. Recently, we proved that the specific sigma‐1 receptor agonist fluvoxamine (FLU) is antifibrotic in the kidney but its role in the TM is unknown. Therefore, we investigated the effects of FLU on the TGF‐β2‐induced fibrotic response in TM cells. Methods: Fibrosis of the AS was induced in C57BL/6J mice by intracameral TGF‐β2 injection. AS were collected and F‐actin was visualized with Phalloidin and detected with confocal microscopy. The effect of FLU on TGF‐β2‐induced cell proliferation, cytoskeletal rearrangement, and fibrosis‐related proteins was investigated by MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide) assay, Phalloidin staining and Western blotting, respectively. Results: TGF‐β2 injection resulted in F‐actin enhancement in vivo, indicating fibrotic‐like changes. In vitro, TGF‐β2 induced cytoskeletal rearrangement with increased F‐actin‐ bundles and clumps formation (p < 0.001) which were reduced by FLU (p < 0.001). Furthermore, FLU also inhibited cell proliferation (p < 0.05) in TGF‐β2‐treated cells. The profibrotic protein levels of connective tissue growth factor, fibronectin and collagen type IV were elevated by TGF‐β2 treatment (p < 0.001), while FLU prevented the elevation of these elements (p < 0.01; p < 0.001). FLU also hindered the TGF‐β2 caused decrease of Matrix Metalloproteinase‐2 (p < 0.05) thus facilitating ECM degradation. Conclusions: FLU may reduce the fibrotic response of trabecular meshwork and could be a potential candidate for the treatment of fibrosis‐induced ocular hypertension. Grants: OTKA‐ K135398, LP2021‐3/2021, TKP2021‐EGA‐24, Stipendium Hungaricum. [ABSTRACT FROM AUTHOR]

Background: Noncompaction cardiomyopathy (NCCM) is considered to be the result of an arrest in the normal myocardial embryogenesis. The histological, developmental, and electrophysiological explanation of ventricular arrhythmias in NCCM is still unknown. The aim of this study was to determine the origin of premature ventricular contractions (PVCs) in NCCM and to identify any predominant arrhythmic foci.Methods: Retrospective data from our NCCM registry including 101 patients were analyzed. A total number of 2069 electrocardiograms (ECGs) were studied to determine the origin of PVCs. Echocardiographic data were analyzed in patients with PVCs in all 12 leads. Segments affected by noncompaction (NC) were compared with the origin of PVCs.Results: PVCs were documented in 250 ECGs from 55 (54%) patients. Thirty-five ECGs recorded PVCs on all 12 leads and the origin of 20 types of PVCs could be determined. Ninety-five percent of PVCs did not originate from left ventricular NC myocardial areas and two PVCs (10%) had a true myocardial origin. All other PVCs originated from structures such as the outflow tracts (8/20), the fascicles (7/20), especially the posteromedial fascicle (6/20), and the mitral and tricuspid annulus (3/20).Conclusions: Our data suggest that PVCs in NCCM mainly originate from the conduction system and related myocardium. [ABSTRACT FROM AUTHOR]

We present a unique case of a left‐sided phrenic nerve injury (PNI) long after a previous contralateral PNI following pulmonary vein isolation (PVI) procedures. Firstly, right‐sided PNI after cryoballoon ablation, and secondly a left‐sided PNI was observed following a redo PVI extended with box‐lesion and left atrial appendage isolation (LAAI). [ABSTRACT FROM AUTHOR]

Introduction: Suicide is a leading cause of death in young people, which may in part be because young people are notoriously poor help-seekers. Improving the identification of at-risk young people and connecting them to appropriate help is needed to prevent suicide in adolescents. The aim of this study is to examine the effectiveness of suicide prevention gatekeeper programs for parents and teachers, which are designed to improve their ability to recognise and respond to risks so that they may intervene before crisis occurs.Methods: Academic databases and reference lists were searched for gatekeeper training programs involving teachers and parents, and which aimed to prevent youth suicide, between journal inception and May 2018. Information directly reporting on suicide literacy (knowledge, confidence, attitudes) and/or gatekeeper behaviours (identification, referral) was extracted and a qualitative synthesis was conducted.Results: Thirteen studies fulfilled inclusion criteria. Significant moderate-to-large intervention effects were reported for suicide literacy outcomes among teachers and parents, with the largest gains among those with lowest baseline scores. No improvements in identification and referral behaviors among gatekeepers were noted. A need to improve evaluation research designs and outcome measurements was evident.Conclusions: While gatekeeper programs lead to increased suicide literacy, there is little evidence for behavioural change. There is need to increase the reach and uptake of gatekeeper training by offering digital versions, which may lead to improved behavioural outcomes, and to employ targeted strategies to engage parents in this training as one of the most trusted sources of support for vulnerable youth. [ABSTRACT FROM AUTHOR]

Both transesophageal echocardiography (TEE) and intracardiac echocardiography have been used to assist transvenous lead extractions. The clinical utility of continuous echocardiographic monitoring during the procedure is still debated, with different reports supporting opposite findings. In cases where the procedure is expected to be difficult, we propose adding a continuous TEE monitoring using a static 3D/multiplane probe in mid‐esophageal position, with digital remote manipulation of the field of view. This approach may improve the chances of a successful extraction, increase safety, or even guide the entire intervention. We present here a short case series where continuous monitoring by TEE played an important role. [ABSTRACT FROM AUTHOR]

Objective: Localized scleroderma (LS) is a chronic inflammatory and fibrosing skin disorder. We present baseline data on the juvenile LS (jLS) cohort from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry, a multicenter observational registry of pediatric rheumatologic disorders. Methods: This is a cross‐sectional analysis of children with jLS enrolled in the CARRA Legacy Registry between May 2010 and April 2014. Descriptive statistics were used for demographic, clinical, and laboratory features. Data analysis included two‐sample t test, χ2 test, Fisher's exact test, linear/logistic regression, and analysis of variance. Results: Of 381 children with jLS, 76% were female and 80% Caucasian. Mean onset age was 8.2 years, with 17% having a 2‐year or greater delay to first pediatric rheumatology (PRH) visit. Linear scleroderma was the most common subtype (54%). Antinuclear antibody (ANA) positivity was associated with joint contracture (P = 0.04), muscle atrophy (P = 0.014), and extremity shortening (P = 0.007). Elevated aldolase was associated with joint contracture (P = 0.008) and elevated creatine kinase (CK) with muscle atrophy (P = 0.028) and extremity shortening (P = 0.016). Children with functional limitation (27%) had earlier first PRH visit compared with those without (P = 0.01). Poorer function correlated with muscle atrophy, joint contracture, and extremity shortening (P < 0.001). Methotrexate (97%) and corticosteroids (68%) were the most common medications used. Conclusion: Children with jLS without joint limitation are referred later, highlighting the insidious onset and need for educating referring providers. Poorer function correlated with muscle atrophy, joint contracture, and limb shortening. ANA positivity and elevated CK or aldolase were associated with muscle atrophy, joint contracture, and/or limb shortening, suggesting predictors of muscle involvement. [ABSTRACT FROM AUTHOR]

Objective: To investigate clinical manifestations of juvenile systemic sclerosis (SSc; scleroderma), including disease characteristics and patient quality of life, using the multinational Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry.Methods: Patients with juvenile SSc were prospectively enrolled between 2010 and 2013. The diagnosis of juvenile SSc was determined by the enrolling pediatric rheumatologist, with the requirement for disease onset prior to age 18 years. Collected data included demographics, disease characteristics, medication exposure, and quality of life metrics.Results: In total, 64 patients with juvenile SSc were enrolled a median of 3.6 years after disease onset, which occurred at a median age of 10.3 years. The most common organ manifestations were dermatologic and vascular, followed by musculoskeletal, gastrointestinal, and pulmonary; in 38% of patients, ≥4 organ systems were affected. Patients with juvenile SSc had significantly more disability at enrollment compared with CARRA Legacy Registry patients with juvenile idiopathic arthritis, dermatomyositis, or systemic lupus erythematosus. Although physician-reported measures correlated most closely with arthritis, dermatologic manifestations, and pulmonary manifestations, poor patient-reported measures were associated with gastrointestinal involvement. During >50 person-years of follow-up, most organ manifestations remained stable, and no mortality or development of new solid organ involvement after enrollment was reported.Conclusion: In the first multicenter prospective cohort of patients with juvenile SSc in North America, the disease burden was high: multiorgan manifestations were common, and functional disability was greater than that observed in patients with other childhood-onset rheumatic diseases. Gastrointestinal involvement had the greatest impact on quality of life. [ABSTRACT FROM AUTHOR]

Background: Hospitalization provides an ideal opportunity for immunization, but few studies have explored provider and parental attitudes toward pediatric inpatient vaccination against influenza. Objectives: The objectives were to determine provider and caregiver attitudes and explore potential barriers to inpatient influenza vaccination. Methods: We developed and distributed two surveys to parents/caregivers as well as providers of general pediatric inpatients at Children's Hospital Colorado between October 2014 and March 2015 assessing attitudes toward influenza and inpatient influenza vaccination. We analyzed the Likert scale responses using univariate analyses and multiple logistic regression to assess associations between responses and vaccination status. Results: The overall response rate was 95% and 58% for parents and providers, respectively. Parents of hospitalized children who agreed that flu vaccines are safe (adjusted OR 2.50 [95%CI 1.76‐3.58]), and that the influenza vaccine is needed every year had higher odds of having a vaccinated child (adjusted OR 3.30 [95%CI 2.30‐4.81]). Most providers (91%) agree that influenza vaccination is an important priority among inpatients, but believe that parental misconceptions and their reluctance for inpatient vaccination are the most important barriers to influenza vaccination. Providers forgetting to ask about vaccination status and order the vaccine are the next most commonly identified barriers. In contrast, most parents surveyed had favorable attitudes toward inpatient influenza vaccination and disagreed that their child was too sick to receive the vaccine during hospitalization. [ABSTRACT FROM AUTHOR]

Pregnant women are prone to iodine deficiency due to the increased need for iodine during gestation. Progress has recently occurred in establishing serum thyroglobulin (Tg) as an iodine status biomarker, but there is no accepted reference range for iodine sufficiency during pregnancy. An observational study was conducted in 164 pregnant women. At week 16 of gestation urinary iodine concentration (UIC), serum Tg, and thyroid functions were measured, and information on the type of iodine supplementation and smoking were recorded. The parameters of those who started iodine supplementation (≥150 μg/day) at least 4 weeks before pregnancy ( n = 27), who started at the detection of pregnancy ( n = 51), and who had no iodine supplementation ( n = 74) were compared. Sufficient iodine supply was found in the studied population based on median UIC (162 μg/L). Iodine supplementation ≥150 μg/day resulted in higher median UIC regardless of its duration (nonusers: 130 μg/L vs. prepregnancy iodine starters: 240 μg/L, and pregnancy iodine starters: 205 μg/L, p < .001, and p = .023, respectively). Median Tg value of pregnancy starters was identical to that of nonusers (14.5 vs. 14.6 μg/L), whereas prepregnancy starters had lower median Tg (9.1 μg/L, p = .018). Serum Tg concentration at week 16 of pregnancy showed negative relationship ( p = .010) with duration of iodine supplementation and positive relationship ( p = .008) with smoking, a known interfering factor of iodine metabolism, by multiple regression analysis. Serum Tg at week 16 of pregnancy may be a promising biomarker of preconceptual and first trimester maternal iodine status, the critical early phase of foetal brain development. [ABSTRACT FROM AUTHOR]

Mass media campaigns are increasingly seen as an important part of suicide prevention; however, despite their popularity, their efficacy is not well understood. The current review aimed to address key knowledge gaps regarding how mass media campaigns can be optimized to prevent suicide, by looking at their global efficacy, and mechanisms related to successful outcomes. A systematic review of the international literature examined studies which evaluated mass media campaigns targeted at suicide prevention, where suicide behaviors (mortality, attempts) or suicide literacy (knowledge, attitudes, help-seeking) was identified as a primary outcome. Thirteen articles describing 12 unique campaigns met eligibility criteria. For behavioral outcomes, mass media campaigns appear to be most effective when delivered as part of a multicomponent suicide prevention strategy, while "standalone campaigns" were modestly useful for increasing suicide literacy. Level of exposure, repeat exposure, and community engagement appeared to be fundamental to the success of these campaigns; however, these constructs were poorly adhered to in the development and implementation of campaigns. Overall, the mixed quality of the included studies highlights a need for increased quantity, consistency, and quality of evaluations to advance the evidence base. [ABSTRACT FROM AUTHOR]

PRKAG2 encodes the γ2 subunit of AMP-activated protein kinase (AMPK), which is an important regulator of cardiac metabolism. Mutations in PRKAG2 cause a cardiac syndrome comprising ventricular hypertrophy, pre-excitation, and progressive conduction-system disease, which is typically not diagnosed until adolescence or young adulthood. However, significant variability exists in the presentation and outcomes of patients with PRKAG2 mutations, with presentation in infancy being underrecognized. The diagnosis of PRKAG2 can be challenging in infants, and we describe our experience with three patients who were initially suspected to have Pompe disease yet ultimately diagnosed with mutations in PRKAG2. A disease-causing PRKAG2 mutation was identified in each case, with a novel missense mutation described in one patient. We highlight the potential for patients with PRKAG2 mutations to mimic Pompe disease in infancy and the need for confirmatory testing when diagnosing Pompe disease. [ABSTRACT FROM AUTHOR]

The same correlation has been found in the patient age of the operated groups: COVID era patients proved to be older. In contrast during the COVID interval 211 patients (avg: 49.73yrs, 15-7yrs) have been examined of which 13 was followed up at least two times while 40 patients underwent operation. As the outbreak of COVID-19 pandemic started in March 2020 in Hungary, many aspects of life have been changed due to the new regulations and restrictions. [Extracted from the article]

Standalone interventions can be useful, but implementing multi-tiered or staged suicide prevention programs is difficult for schools. As it is estimated that only 29% of adolescents who experience suicidal thoughts seek help from mental health services,6 schools have become important settings for implementing effective, multi-tiered preventive strategies that build mental health literacy in the entire school community. [Extracted from the article]

Major histocompatibility complex ( MHC) genes in mammals include highly polymorphic class I and class II genes that are critical for donor-recipient matching for transplantation. Dogs have served as an effective, directly translatable model for stem/progenitor cell transplantation. Previous analyses of MHC class I genes in dogs point to a single highly polymorphic gene, dog leukocyte antigen ( DLA)-88, as an important factor in the success or failure of hematopoietic stem cell transplants. Fifty-nine DLA-88 alleles have been identified and reported so far. Here, we extend this list by presenting 13 novel DLA-88 alleles found in domestic dogs. [ABSTRACT FROM AUTHOR]

Background There remains controversy about the optimal ablation technique and termination rate of atrial fibrillation (AF) during catheter ablation in patients with persistent AF. The aim of this study was to determine the rate and timing of AF termination during combined pulmonary vein isolation (PVI) and focal impulse and rotor modulation (FIRM)-guided ablation of rotational activity (RoAc). Methods This single-center, prospective cohort study enrolled 38 consecutive patients (63% male, mean age 63 ± 11 years) with persistent AF (mean left atrial size: 46 ± 7 mm), who underwent FIRM mapping and ablation of the identified RoAcs followed by PVI. We systematically evaluated the incidence and timing of AF termination during AF ablation. Results 'Late-onset termination' of AF could be observed in 12 (32%) patients after ablation of the identified RoAcs. In a further 10 (26%) patients, 'abrupt' AF termination during PVI was achieved. In total, the combined technique of conventional PVI and RoAc ablation resulted in AF termination rate of 58%. ECV was performed in 16 'nonterminating' patients. At 1-year follow-up, 76.1% (16 of 21) of patients remained free from AF/AT, 4 of 10 patients (25%) within the 'abruptly' terminated group, 7 of 12 (58.3%) patients among the 'late-terminated' group, and 5 of 16 (31, 25%) patients in the 'nonterminating' group. Conclusion Large area RoAc ablation combined with PVI results in a moderate termination rate of persistent AF with two distinctive timing patterns. More studies are needed to determine the clinical significance of type of AF termination and long-term success rate of RoAc ablation in patients with persistent AF. [ABSTRACT FROM AUTHOR]

Objective Localized scleroderma can negatively affect children's quality of life (QoL), but predictors of impact have not been well described. We sought to identify predictors of QoL impact in juvenile localized scleroderma patients. Methods We analyzed longitudinal data from a single-center cohort of juvenile localized scleroderma patients, using hierarchical generalized linear modeling (HGLM) to identify predictors of QoL impact. HGLM is useful for nested data and allows for evaluation of both time-variant and time-invariant predictors. Results The number of extracutaneous manifestations (ECMs; e.g., joint contracture and hemifacial atrophy) and female sex predicted negative QoL impact, defined as a Children's Dermatology Life Quality Index score >1 ( P = 0.019 for ECMs and P = 0.002 for female sex). As the time since the initial visit increased, the odds of reporting a negative QoL impact decreased ( P < 0.001). Conclusion Our results suggest that ECMs, sex, and time since initial visit are more predictive of QoL impact in localized scleroderma than cutaneous features. Further study is required to determine which ECMs have the most impact on QoL, which factors underlie sex differences in QoL in localized scleroderma, and why increasing the time since the initial visit appears to be protective. An improved understanding of predictors of QoL impact may allow for the identification of patients at risk of poorer outcomes and for the tailoring of treatment and psychosocial support. [ABSTRACT FROM AUTHOR]

We have built up a great deal of insight into the early developmental trajectories that lead to heroin use. These cluster under five domains: social disadvantage, parental drug use/psychopathology, childhood abuse and neglect, early onset psychopathology and antisocial behaviors, and a developmental sequence of drug onsets. While not all heroin users have these risk factors, the broad clinical picture shows these early correlates to be the predominant presentation. We discuss each of the early psychosocial correlates of heroin dependence, as well as possible early interventions. Given the chronicity of heroin dependence, interventions to prevent heroin use emerging would reduce the considerable burden of disease associated with the disorder. [ABSTRACT FROM AUTHOR]