Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4+ T Cells as Predictors for Response to Integrin α4ß7-Blocking Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response. METHODS: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4ß7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell variable, diversity, and joining sequencing; serum proteomics; and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response. RESULTS: Vedolizumab treatment led to substantial alterations in the abundance of circulating immune cell lineages and modified the T-cell receptor diversity of gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identified a significant increase in proliferating CD4+ memory T cells among nonresponders before treatment compared with responders. This predictive T-cell signature demonstrated an activated T-helper 1/T-helper 17 cell phenotype and exhibited elevated levels of integrin α4ß1, potentially making these cells less susceptible to direct targeting by vedolizumab. CONCLUSIONS: These findings provide a reliable predictive classifier with significant implications for personalized inflammatory bowel disease management.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis in children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan's syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

Which parents provide zero-alcohol beverages to adolescents? A survey of Australian parents' practices and intentions.

OBJECTIVE: Zero-alcohol beverages (<0.5% alcohol by volume) appear and taste similar to alcoholic beverages but are regulated similarly to soft drinks in many countries, blurring the distinction between alcoholic and non-alcoholic beverages. How parents view provision of zero-alcohol beverages to adolescents is likely a key determinant of adolescent consumption. We investigated factors associated with parents' provision of zero-alcohol beverages to adolescents, including attitudes toward zero-alcohol beverages and demographic, knowledge, and behavioural factors known to be associated with provision of alcoholic beverages. METHODS: We conducted an online cross-sectional survey of N = 1197 Australian parents of adolescents aged 12-17 years in April-May 2022. We examined associations with zero-alcohol beverage provision using binomial logistic regression, and with future provision intentions using multinomial logistic regression analyses. RESULTS: Factors significantly associated (p < .001) with parents' provision and future intentions to provide zero-alcohol beverages to their adolescent included beliefs that zero-alcohol beverages had benefits for adolescents (Adjusted Odds Ratio [AOR] 2.69 (provision); 3.72 (intentions)), provision of alcoholic beverages (AOR 2.67 (provision); 3.72 (intentions)), and an incorrect understanding of alcohol guidelines for adolescents (AOR 2.38 (provision); 1.95 (intentions)). CONCLUSIONS: Parents' provision and intentions to provide zero-alcohol beverages were associated with beliefs about zero-alcohol beverages as well as some factors associated with provision of alcoholic beverages. Precautionary advice to parents that the provision of zero-alcohol beverages may serve to normalise alcohol consumption may be warranted.

Mental health in paediatric and adult myositis-related diseases: current state of research, interventions, and future steps from the MIHRA Psychological Impact Scientific Working Group.

Psychological and emotional well-being are critical aspects of overall health for individuals with chronic rheumatologic conditions. Mental health-related literature, however, predominantly focuses on systemic lupus erythematosus or rheumatoid arthritis, with limited emphasis on idiopathic inflammatory myopathies (IIMs). High proportions of those with juvenile myositis report psychological distress at levels warranting mental health referral. Adults with dermatomyositis diagnosed with depression or anxiety do not receive adequate mental health care. Mental health symptoms in those with IIMs are associated with worse health-related quality of life, medication adherence, and disease outcomes. Despite demonstrated high rates of mental health burden, access to mental health care remains severely lacking.Data related to mental health burden is limited by small sample size, limited generalisability, variable methods of assessment, and inconsistent diagnosis codes to define mental health conditions. Additional research is needed to validate current screening tools in myositis populations. Other relevant measurable factors include disease severity, non-health- and health-related trauma exposure, loneliness, isolation, loss of control, sleep difficulties, fatigue, pain, self-esteem, body image, sexual health, and health inequities. Studiesare needed investigating the efficacy of therapeutic and pharmacologic interventions among patients with myositis who experience depression and anxiety. Currently, knowledge and resources are limited around mental health burden and potential intervention for those living with IIMs. The Myositis International Health & Research Collaborative Alliance (MIHRA) Psychological Impact Scientific Working Group offers a preliminary road map to characterise and prioritise the work ahead to understand baseline mental health burden and compare avenues for intervention.

Donor Characteristics and Outcomes of Pediatric Heart Transplantation in South Korea.

BACKGROUND: Heart transplantation is often limited by the availability of transplantable donor heart and understanding of donor aspects that would influence transplant outcomes becomes important. In this study, donor characteristics and their impact on the outcomes of pediatric heart transplantations performed in South Korea were investigated. METHODS: We reviewed the medical records of patients less than 18 years old who received heart transplantation between 2002 and 2022 in three tertiary hospitals located in South Korea. RESULTS: A total of 139 cases were enrolled. One-year mortality was 10.4% and total mortality was 33.8%. Forty-nine recipients (35.3%) showed biopsy-proven rejections and 20 (14.4%) showed cardiac allograft vasculopathy during mean follow-up of 6.4 ± 4.9 years. Six recipients (4.5%) showed left ventricle ejection fraction of less than 55% post-transplantation. The mean age of the donors was 23.0 ± 15.4 years. The most common cause of death of the donors was unspecified illness (46.4%). Donors with a history of diabetes, hypertension, smoking, and alcohol consumption were 0%, 3.1%, 32.1%, and 34.4%, respectively. Mean total ischemic time was 191.6 ± 72.7 min, while total ischemic time was over 4 h in 37 patients (26.6%). There were no significant relationship between donor factors and survival. However, donor's history of drinking or cardiopulmonary resuscitation was significantly associated with acute rejection and donor's age with cardiac allograft vasculopathy. CONCLUSION: Donor factors did not show significant impact on post-transplant survival but some factors were predictive of post-transplant rejection and cardiac allograft vasculopathy.

Combined Pediatric Rheumatology/Dermatology Clinics: Benefits and Challenges.

BACKGROUND/OBJECTIVES: Integrated care models, like combined rheumatology/dermatology clinics (RDCs), facilitate efficient coordination between specialists and provide comprehensive care. Given the limited literature on pediatric RDC logistics, outcomes, benefits and, challenges, we comprehensively characterized our patient cohort at the UCSF Benioff Children's Hospital RDC and surveyed pediatric dermatologists participating in RDCs. METHODS: We retrospectively reviewed 71 patients new to the UCSF Pediatric RDC between September 2017 and September 2023. A survey was distributed in 2024 to 17 dermatologists in North America, each representing a unique pediatric RDC. RESULTS: 69% of patients (49/71) were female. Seventeen (24%) presented without a known diagnosis; the first RDC visit established a diagnosis for 7 of them (41%). Of patients with a previously established diagnosis, initial RDC evaluation confirmed it in 52 (96%) and revised it for 2 (4%). The most encountered diagnoses were linear morphea (33%), lupus (23%), and psoriasis (13%). New systemic therapy was prescribed for 23% of patients, and additional work-up was recommended via skin biopsy (8%) and imaging (28%). Survey results revealed all pediatric RDCs include trainees, but only 59% (10/17) receive administrative support. All agreed that RDCs are valuable for patient care and most (15/17, 88%) felt that the RDC was a valuable use of their time. CONCLUSIONS: Pediatric RDCs are valuable for consensus diagnosis, streamlined evaluation, and management of complex patients. Though clinical and administrative support for RDCs is generally poor, RDCs are valuable to patients, a good use of time for clinicians, and offer educational opportunities for team members.

Exacerbation-prone pediatric asthma is associated with arginine, lysine, and methionine pathway alterations.

BACKGROUND: The asthma of some children remains poorly controlled, with recurrent exacerbations despite treatment with inhaled corticosteroids. Aside from prior exacerbations, there are currently no reliable predictors of exacerbation-prone asthma in these children and only a limited understanding of the potential underlying mechanisms. OBJECTIVE: We sought to quantify small molecules in the plasma of children with exacerbation-prone asthma through mass spectrometry-based metabolomics. We hypothesized that the plasma metabolome of these children would differ from that of children with non-exacerbation-prone asthma. METHODS: Plasma metabolites were extracted from 4 pediatric asthma cohorts (215 total subjects, with 41 having exacerbation-prone asthma) and detected with a mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects receiving high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. MetaboAnalyst software was used to identify pathways of interest. Concentrations were calculated by reference standardization. RESULTS: We identified 32 unique, cohort-independent metabolites that differed in children with exacerbation-prone asthma compared to children with non-exacerbation-prone asthma. Comparison of metabolite concentrations to literature-reported values for healthy children revealed that most metabolites were decreased in both asthma groups, but more so in exacerbation-prone asthma. Pathway analysis identified arginine, lysine, and methionine pathways as most impacted. CONCLUSIONS: Several plasma metabolites are perturbed in children with exacerbation-prone asthma and are largely related to arginine, lysine, and methionine pathways. While validation is needed, plasma metabolites may be potential biomarkers for exacerbation-prone asthma in children.

Cardiovascular Characteristics and Progressions of Hypertrophic Cardiomyopathy and Pulmonary Stenosis in RASopathy Syndrome in the Genomic Era.

INTRODUCTION: To investigate cardiovascular characteristics and progressions of hypertrophic cardiomyopathy (HCM) and pulmonary stenosis (PS) and determine whether any genotype-phenotype correlations exist in patients with gene-confirmed RASopathy syndrome. STUDY DESIGN: Eighty patients (male, 55%) confirmed as having RASopathy syndrome by genetic testing at a single tertiary center were enrolled. Subjects' medical and echocardiography records were reviewed and the changes in the z scores of left ventricular wall thickness (LVWT) and the degree of PS over time were examined during follow-up of 5.7 ± 3.1 and 7.5 ± 5.2 years, respectively. RESULTS: The most common RASopathy gene identified was PTPN11 (56%), followed by RAF1 (10%). Eighty-five percent of patients had cardiovascular diseases, wherein 42% had HCM, and 38% PS. Mean maximal LVWT z score on the initial echocardiography (mean age 5.0 ± 6.0 years) was 3.4 ± 1.3 (median 2.8, range 2.1-6.6) in the HCM group. Overall, the maximal LVWT increased with time, especially in the HCM group (z = 3.4 ± 1.3 to 3.7 ± 1.6, P = .008) and RAF1-variant group (z = 3.7 ± 1.7 to 4.6 ± 1.8, P = .031). Five patients newly developed HCM during the study period. Genotype-phenotype correlation was significant for HCM (P = .002); 31% of patients with PTPN11 and 88% with RAF1 variants had HCM. PS did not progress in this study cohort. CONCLUSIONS: In this study, progression of ventricular hypertrophy was seen in a significant number of patients with genotype correlation. Thus, long-term follow up of cardiovascular problems in patients with RASopathy is necessary.

Implementation of an intravenous sotalol initiation protocol: Implications for feasibility, safety, and length of stay.

INTRODUCTION: Oral sotalol initiation requires a multiple-day, inpatient admission to monitor for QT prolongation during loading. A 1-day intravenous (IV) sotalol loading protocol was approved by the United States Food and Drug Administration in March 2020, but limited data on clinical use and administration currently exists. This study describes implementation of an IV sotalol protocol within an integrated health system, provides initial efficacy and safety outcomes, and examines length of stay (LOS) compared with oral sotalol initiation. METHODS: IV sotalol was administered according to a prespecified initiation protocol to adult patients with refractory atrial or ventricular arrhythmias. Baseline characteristics, safety and feasibility outcomes, and LOS were compared with patients receiving oral sotalol over a similar time period. RESULTS: From January 2021 to June 2022, a total of 29 patients (average age 66.0 ± 8.6 years, 27.6% women) underwent IV sotalol load and 20 patients (average age 60.4 ± 13.9 years, 65.0% women) underwent oral sotalol load. The load was successfully completed in 22/29 (75.9%) patients receiving IV sotalol and 20/20 (100%) of patients receiving oral sotalol, although 7/20 of the oral sotalol patients (35.0%) required dose reduction. Adverse events interrupting IV sotalol infusion included bradycardia (seven patients, 24.1%) and QT prolongation (three patients, 10.3%). No patients receiving IV or oral sotalol developed sustained ventricular arrhythmias before discharge. LOS for patients completing IV load was 2.6 days shorter (mean 1.0 vs. 3.6, p < .001) compared with LOS with oral load. CONCLUSION: IV sotalol loading has a safety profile that is similar to oral sotalol. It significantly shortens hospital LOS, potentially leading to large cost savings.

Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines.

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.

Esophageal temperature management during cryoballoon ablation for atrial fibrillation.

INTRODUCTION: Esophageal thermal injury (ETI) is a well-recognized complication of atrial fibrillation (AF) ablation. Previous studies have demonstrated that direct esophageal cooling reduces ETI during radiofrequency AF ablation. The purpose of this study was to evaluate the use of an esophageal warming device to prevent ETI during cryoballoon ablation (CBA) for AF. METHODS: This prospective, double-blinded study enrolled 42 patients with symptomatic AF undergoing CBA. Patients were randomized to the treatment group with esophageal warming (42°C) using recirculated water through a multilumen, silicone tube inserted into the esophagus (EnsoETM®; Attune Medical) (WRM) or the control group with a luminal single-electrode esophageal temperature monitoring probe (LET). Patients underwent upper endoscopy esophagogastroduodenoscopy (EGD) the following day. ETI was classified into four grades. RESULTS: Baseline patient characteristics were similar between groups. Procedural characteristics including number of freezes, total freeze time, early freeze terminations, coldest balloon temperature, procedure duration, posterior wall ablation, and proton pump inhibitor and transesophageal echocardiogram use before procedure were not different between groups. The EGD was completed in 40/42 patients. There was significantly more ETI in the WRM group compared to the LET group (n = 8 [38%] vs. n = 1 [5%], p = 0.02). All ETI lesions were grade 1 (erythema) or 2 (superficial ulceration). Total freeze time in the left inferior pulmonary vein was predictive of ETI (360 vs. 300 s, p = 0.03). CONCLUSION: Use of a luminal heat exchange tube for esophageal warming during CBA for AF was paradoxically associated with a higher risk of ETI.

Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study.

OBJECTIVES: High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes. METHODS: Youth <18 years with pAAV, biopsy-confirmed pauci-immune glomerulonephritis and 12-month follow-up data were included from an international paediatric vasculitis registry. Presenting features and 12-month outcomes (eGFR, glucocorticoid-related adverse effects), were compared between patients receiving no, low-moderate (≤90mg/kg) and high (>90mg/kg) cumulative intravenous methylprednisolone (IVMP), and low (<0.5mg/kg/day prednisone equivalent), moderate (0.5-1.5mg/kg/day) and high (>1.5mg/kg/day) starting doses of oral glucocorticoids. RESULTS: Among 131 patients (101 granulomatosis with polyangiitis, 30 microscopic polyangiitis), 27 (21%) received no IVMP, 64 (49%) low-moderate and 29 (22%) high-dose IVMP, while 9 (7%) received low, 75 (57%) moderate and 47 (36%) high initial doses of oral glucocorticoids. Renal failure at diagnosis (p=0.022) and plasmapheresis use (p=0.0001) were associated with high-dose IVMP. Rates of glucocorticoid-related adverse effects ranged from 15-31% across dose levels, and glucocorticoid dosing did not associate with 12-month outcomes. CONCLUSIONS: Glucocorticoid dosing for pAAV-related renal disease was highly variable, and rates of adverse effects were high across all dosing groups. A significant proportion of patients received oral glucocorticoid or IVMP doses that were discordant with current adult guidelines. Higher glucocorticoid doses did not associate with improved outcomes.

Elements at the 5' end of Xist harbor SPEN-independent transcriptional antiterminator activity.

The Xist lncRNA requires Repeat A, a conserved RNA element located in its 5' end, to induce gene silencing during X-chromosome inactivation. Intriguingly, Repeat A is also required for production of Xist. While silencing by Repeat A requires the protein SPEN, how Repeat A promotes Xist production remains unclear. We report that in mouse embryonic stem cells, expression of a transgene comprising the first two kilobases of Xist (Xist-2kb) causes transcriptional readthrough of downstream polyadenylation sequences. Readthrough required Repeat A and the ∼750 nucleotides downstream, did not require SPEN, and was attenuated by splicing. Despite associating with SPEN and chromatin, Xist-2kb did not robustly silence transcription, whereas a 5.5-kb Xist transgene robustly silenced transcription and read through its polyadenylation sequence. Longer, spliced Xist transgenes also induced robust silencing yet terminated efficiently. Thus, in contexts examined here, Xist requires sequence elements beyond its first two kilobases to robustly silence transcription, and the 5' end of Xist harbors SPEN-independent transcriptional antiterminator activity that can repress proximal cleavage and polyadenylation. In endogenous contexts, this antiterminator activity may help produce full-length Xist RNA while rendering the Xist locus resistant to silencing by the same repressive complexes that the lncRNA recruits to other genes.

Pediatric Flexible Endoscopic Evaluation of Swallowing: Critical Analysis of Implementation and Future Perspectives.

This study aimed to critically review pediatric swallowing assessment data to determine the future need for standardized procedures. A retrospective analysis of 152 swallowing examinations in 128 children aged 21 days to 18 years was performed. The children were presented at a university dysphagia center between January 2015 and June 2020 for flexible-endoscopic evaluation of swallowing (FEES). Descriptive analysis was conducted for the sample, swallowing pathologies, diagnosis, and missing values. Using binary logistic regression, the relationship between dysphagia and underlying diseases was investigated. The largest group with a common diagnosis in the cohort were children with genetic syndromes (n = 43). Sixty-nine children were diagnosed with dysphagia and 59 without dysphagia. The non-dysphagic group included 15 patients with a behavioral feeding disorder. The presence of an underlying disease significantly increased the chance of a swallowing problem (OR 13.08, 95% CI 3.66 to 46.65, p = .00). In particular, the categories genetic syndrome (OR 2.60, 95% CI 1.15 to 5.88) and neurologic disorder (OR 4.23, 95% CI 1.31 to 13.69) were associated with higher odds for dysphagia. All pediatric FEES were performed without complications, with a completion rate of 96.7%, and with a broad variability of implementation. Several charts lacked information concerning swallowing pathologies, though. Generally, a more standardized protocol and documentation for pediatric FEES is needed to enable better comparability of studies on epidemiology, assessment, and treatment outcomes in future.

Implementation of Pediatric Flexible-Endoscopic Evaluation of Swallowing: A Systematic Review and Recommendations for Future Research.

BACKGROUND: Although pediatric flexible-endoscopic evaluation of swallowing (FEES) has developed into a standard in dysphagia diagnostics, there are no valid protocols and procedures for children available to date. OBJECTIVE: This systematic PROSPERO-registered review aimed to identify implementation protocols for pediatric FEES described in research studies, and to analyze them in detail concerning procedural steps, equipment, and reported outcome. METHODS: Included were all studies reporting a pediatric FEES protocol for children aged 0-18 years, if they described at least two criteria defined in advance. The databases MEDLINE and CINHAL were searched systematically from January 2000 to February 2021. Risk of bias for included studies was assessed using the National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis of the FEES protocols was conducted and the results compared in tabular form. RESULTS: In total 22 studies were included, reporting on FEES in 1547 infants, children, and adolescents with a wide range of diagnoses. It was possible to identify protocols related to all age groups in general as well as to particular groups such as breastfed or bottle-fed infants. None of the included studies demonstrated a good methodological quality; all studies had missing data. Uniform implementation for sub-groups could not be determined. The reported outcome of FEES examinations could not be compared. DISCUSSION: None of the included studies showed good methodological quality and a significant amount of data were missing; the review still offers a systematic basis for future research to close the serious gap in the area of pediatric FEES. A proposal is made for a minimum requirement for pediatric FEES protocols in scientific studies.

Dimensions of depressive symptomatology in mothers derived from factor analyses.

PURPOSE: Subtypes of depression have been under studied in women during the peripartum period and the year after childbirth and delivery. Due to heterogeneity of depression, researchers have attempted to identify phenotypes of maternal and postpartum depression based on key symptoms that may represent underlying genes and biological etiology (Leuchter et al. Dialog Clinic Neurosci 16(4):525, 2014). METHODS: The current study collected self-report data from 587 women and utilized exploratory and confirmatory factor analyses (CFA) to identify subtypes of depression symptoms across two measures. RESULTS: Findings of the study showed that: (1) using the Beck Depression Inventory (BDI-II) and the Postpartum Depression Screening Scale (PDSS), a five-factor solution best fit the data in our sample of mothers with infants aged 4-14 months. The factors included: anxiety/thought disorder; cognitive depression; suicide; somatic/neurovegetative; and sleep [χ2 (454, N = 587) = 1102.61, p < 0.001, comparative fit index (CFI) = 0.93, Tucker Lewis index (TLI) = 0.92, root mean square error of approximation (RMSEA) = 0.05]; and (2) the following factors significantly positively predicted interview-based diagnosis of depression: cognitive symptoms of depression and sleep [χ2 (482, N = 587) = 1170.40, p < 0.001, TLI = 0.91, CFI = 0.93, RMSEA = 0.05]. CONCLUSIONS: Future research could assess the clinical benefits of screening for maternal mood disorders.

Impact of global feminist film curriculum on medical student engagement in women's health.

Film effectvely imparts experiential knowledge of lived experiences especially in cross-cultural settings. Incorporating film into medical education can catalyze awareness of global issues in women's health. Film-based interventions highlighting such topics have not been reported in literature. This study outlines one session of an 8-week elective course for trainees to engage with topics in women's health through global cinema. Quantitative and qualitative data were collected from participants during each session and via post-session surveys. Class discussions and survey data reflected favorable responses and positive engagement with the pre-session film viewings and 75-minute weekly discussions. A feminist, film-based curriculum for medical and graduate students may broaden trainees' knowledge of global women's health. In medical education, film may serve as an effective tool to encourage a life-course and gender equity approach to women's health topics, rather than more traditional sexual-reproductive framings.

Insights from Expanded Adverse Childhood Experiences Screening in a Hospital-Based Outpatient Psychiatry Service.

Adverse childhood experiences (ACEs) are associated with poor mental health in adulthood. Comprehensive prevalence data encompassing all 10 ACE questionnaire items has not previously been described in a hospital-based outpatient psychiatric clinic. This study assessed the prevalence of 10 ACEs in such a clinic and correlated ACEs with indicators of case severity. For 252 patients newly evaluated in an urban clinic, a retrospective chart review was completed and data was collected on ACE questionnaire responses, psychiatric, substance-related, and medical diagnoses, psychiatric hospitalizations, suicide attempts, and suicide and violence risk. Patients in the clinic had an average of 3.4 ACEs, higher than national community sample averages of 1.6. The percentages of patients with at least one, two, and four ACEs were 82% (n = 207), 68% (n = 172), and 42% (n = 106) respectively (compared with 61%, 38%, and 15% nationally). ACEs had statistically significant correlations with an increased number of psychiatric diagnoses, substance use disorders, medical illnesses, suicide attempts, and suicide risk level. This study demonstrated that patients seeking psychiatric care from a hospital-based outpatient clinic are likely to be traumatized to a degree far exceeding what is typical in the general population. While a high prevalence of ACEs in a psychiatric population is an expected finding given the literature to date, this is the first study presenting data on the prevalence of ACEs in such a hospital-based community clinic. Additionally this study reinforces prior research correlating childhood adversity and case severity.

A piggyBac-based toolkit for inducible genome editing in mammalian cells.

We describe the development and application of a novel series of vectors that facilitate CRISPR-Cas9-mediated genome editing in mammalian cells, which we call CRISPR-Bac. CRISPR-Bac leverages the piggyBac transposon to randomly insert CRISPR-Cas9 components into mammalian genomes. In CRISPR-Bac, a single piggyBac cargo vector containing a doxycycline-inducible Cas9 or catalytically dead Cas9 (dCas9) variant and a gene conferring resistance to Hygromycin B is cotransfected with a plasmid expressing the piggyBac transposase. A second cargo vector, expressing a single-guide RNA (sgRNA) of interest, the reverse-tetracycline TransActivator (rtTA), and a gene conferring resistance to G418, is also cotransfected. Subsequent selection on Hygromycin B and G418 generates polyclonal cell populations that stably express Cas9, rtTA, and the sgRNA(s) of interest. We show that CRISPR-Bac can be used to knock down proteins of interest, to create targeted genetic deletions with high efficiency, and to activate or repress transcription of protein-coding genes and an imprinted long noncoding RNA. The ratio of sgRNA-to-Cas9-to-transposase can be adjusted in transfections to alter the average number of cargo insertions into the genome. sgRNAs targeting multiple genes can be inserted in a single transfection. CRISPR-Bac is a versatile platform for genome editing that simplifies the generation of mammalian cells that stably express the CRISPR-Cas9 machinery.