Post-transcriptional splicing can occur in a slow-moving zone around the gene.

Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.

Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

Child Health Needs and the Developmental-Behavioral Pediatrics Workforce Supply: 2020-2040.

Developmental-behavioral pediatrics (DBP) subspecialists care for children with complex neurodevelopmental and behavioral health conditions; additional roles include education and training, advocacy, and research. In 2023, there were 1.0 DBP subspecialists per 100 000 US children aged 0 to 17 years (range 0.0-3.8), with wide variability in DBP subspecialist distribution. Given the prevalence of DB conditions, the current workforce is markedly inadequate to meet the needs of patients and families. The American Board of Pediatrics Foundation led a modeling project to forecast the US pediatric subspecialty workforce from 2020 to 2040 using current trends in each subspecialty. The model predicts workforce supply at baseline and across alternative scenarios and reports results in headcount (HC) and HC adjusted for percent time spent in clinical care, termed "clinical workforce equivalent." For DBP, the baseline model predicts HC growth nationally (+45%, from 669 to 958), but these extremely low numbers translate to minimal patient care impact. Adjusting for population growth over time, projected HC increases from 0.8 to 1.0 and clinical workforce equivalent from 0.5 to 0.6 DBP subspecialists per 100 000 children aged 0 to 18 years by 2040. Even in the best-case scenario (+12.5% in fellows by 2030 and +7% in time in clinical care), the overall numbers would be minimally affected. These current and forecasted trends should be used to shape much-needed solutions in education, training, practice, policy, and workforce research to increase the DBP workforce and improve overall child health.

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

Transposon Removal Reveals Their Adaptive Fitness Contribution.

Transposable elements are molecular parasites that persist in their host genome by generating new copies to outpace natural selection. Transposable elements exert a large influence on host genome evolution, in some cases providing adaptive changes. Here we measure the fitness effect of the transposable element insertions in the fission yeast Schizosaccharomyces pombe type strain by removing all insertions of its only native transposable element family, the long terminal repeat retrotransposon Tf2. We show that Tf2 elements provide a positive fitness contribution to its host. Tf2 ablation results in changes to the regulation of a mitochondrial gene and, consistently, the fitness effect are sensitive to growth conditions. We propose that Tf2 influences host fitness in a directed manner by dynamically rewiring the transcriptional response to metabolic stress.

Animal assisted therapy in pediatric mental health conditions: A review.

Animal assisted therapy (AAT) has been explored as a treatment option for children with mental health disorders and associated symptoms. AAT can be implemented in inpatient, outpatient, and residential care settings. Some studies demonstrate significant improvement in symptom severity while others report only modest results. In this review, we summarize previous studies that have investigated the applications of AAT for pediatric mental health treatment, focusing on management of symptoms related to post-traumatic stress disorder, depression, anxiety, attention-deficit/hyperactivity disorder, and internet gaming disorder. Current studies on AAT and mental health care tend to lack generalizability due to being single-site studies, and comparisons between studies are difficult because studies tend to adopt different definitions of AAT. Future studies examining the effects of AAT on mental health in general and on symptoms for specific conditions are needed before AAT is widely recommended for the pediatric population.

Frailty as a Predictor of Outcomes in Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

Frailty is an emerging concept in clinical practice used to predict outcomes and dictate treatment algorithms. Frail patients, especially older adults, are at higher risk for adverse outcomes. Aneurysmal subarachnoid hemorrhage (aSAH) is a neurosurgical emergency associated with high morbidity and mortality rates that have previously been shown to correlate with frailty. However, the relationship between treatment selection and post-treatment outcomes in frail aSAH patients is not established. We conducted a meta-analysis of the relevant literature in accordance with PRISMA guidelines. We searched PubMed, Embase, Web of Science, and Google Scholar using "Subarachnoid hemorrhage AND frailty" and "subarachnoid hemorrhage AND frail" as search terms. Data on cohort age, frailty measurements, clinical grading systems, and post-treatment outcomes were extracted. Of 74 studies identified, four studies were included, with a total of 64,668 patients. Percent frailty was 30.4% under a random-effects model in all aSAH patients (p < 0.001). Overall mortality rate of aSAH patients was 11.7% when using a random-effects model (p < 0.001). There was no significant difference in mortality rate between frail and non-frail aSAH patients, but this analysis only included two studies and should be interpreted cautiously. Age and clinical grading, rather than frailty, independently predicted outcomes and mortality in aSAH patients.

Descriptive Analysis of Documentation Time for the National Developmental-Behavioral Pediatric Physician Workforce Using a Commercial Electronic Health Record System.

OBJECTIVE: The national developmental-behavioral pediatric (DBP) workforce struggles to meet current service demands because of several factors. Lengthy and inefficient documentation processes are likely to contribute to service demand challenges, but DBP documentation patterns have not been sufficiently studied. Identifying clinical practice patterns may inform strategies to address documentation burden in DBP practice. METHODS: Nearly 500 DBP physicians in the United States use a single commercial electronic health record (EHR) system (EpicCare Ambulatory, Epic Systems Corporation, Verona WI). We evaluated descriptive statistics using the US Epic DBP provider data set. We then compared DBP documentation metrics against those of pediatric primary care and selected pediatric subspecialty providers who provide similar types of care. One-way analyses of variance (ANOVAs) were conducted to determine whether outcomes differed among provider specialties. RESULTS: We identified 4 groups for analysis from November 2019 through February 2020: DBP (n = 483), primary care (n = 76,423), pediatric psychiatry (n = 783), and child neurology (n = 8589). Post hoc pairwise comparisons revealed statistically significant differences between multiple outcome-specialty combinations. Time in notes per appointment and progress note length demonstrated the strongest evidence of an increased burden on DBP providers compared with other similar provider groups. CONCLUSION: DBP providers spend a significant amount of time documenting progress notes both during and outside of normal clinic hours. This preliminary analysis highlights the utility of using EHR user activity data to quantitatively measure documentation burden.

Examining Preoperative MRI for Medial Meniscal Ramp Lesions in Patients Surgically Treated for Acute Grade 3 Combined Posterolateral Corner Knee Injury.

Background: While medial meniscocapsular tears (ramp lesions) are commonly associated with isolated anterior cruciate ligament injuries, there are limited descriptions of these meniscal injuries in multiligament knee injuries (MLKIs). Purpose: To (1) retrospectively evaluate preoperative magnetic resonance imaging (MRI) scans for the presence of ramp lesions in patients surgically treated for acute grade 3 combined posterolateral corner (PLC) knee injuries and (2) determine if a preoperative posteromedial tibial plateau (PMTP) bone bruise is associated with the presence of preoperative ramp lesions on MRI in these same patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Data on consecutive patients at a level 1 trauma center with MLKIs between 2001 and 2021 were retrospectively reviewed. Only patients with acute grade 3 combined PLC injuries who received an MRI scan within 30 days of injury were assessed. Two musculoskeletal radiologists retrospectively reviewed each patient's preoperative MRI for evidence of ramp lesions and bone bruises. Intraclass correlation coefficients (ICCs) were used to calculate reliability among the reviewers. Multivariate analysis was used to evaluate the relationship between PMTP bruising and the presence of a ramp lesion on MRI. Results: A total of 68 patients (79.4% male; mean age, 33.8 ± 13.7 years) with an acute grade 3 combined PLC injury were included in the study. On MRI, the ICCs for detection of ramp lesions and PMTP bone bruising were 0.921 and 0.938, respectively. Medial meniscal ramp lesions were diagnosed in 18 of 68 (26.5%) patients. Eleven of 18 (61.1%) patients with ramp lesions also showed evidence of PMTP bruising, while 13 of 50 (26.0%) patients without ramp lesions had PMTP bruising (P = .008). When controlling for age and sex, PTMP bruising was significantly associated with the presence of a ramp lesion in combined PLC injuries (odds ratio, 4.62; P = .012). Conclusion: Preoperative medial meniscal ramp lesions were diagnosed on MRI in 26.5% of patients with acute grade 3 combined PLC injuries. PMTP bone bruising was significantly associated with the presence of a ramp lesion on MRI. These findings reinforce the need to assess for potential ramp lesions at the time of multiligament reconstruction.

High-quality read-based phasing of cystic fibrosis cohort informs genetic understanding of disease modification.

Phasing of heterozygous alleles is critical for interpretation of cis-effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using linked-read sequencing, which display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, demonstrating its utility for understanding complex CF alleles. These are visualized in a Web app, CFTbaRcodes, that enables interactive exploration of CFTR haplotypes present in this cohort. We perform fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus, an intestinal obstruction at birth associated with more severe CF outcomes and pancreatic disease. A 20-kb deletion polymorphism and a PRSS2 missense variant p.Thr8Ile (rs62473563) are shown to independently contribute to meconium ileus risk (p = 0.0028, p = 0.011, respectively) and are PRSS2 pancreas eQTLs (p = 9.5 × 10-7 and p = 1.4 × 10-4, respectively), suggesting the mechanism by which these polymorphisms contribute to CF. The phase information from linked reads provides a putative causal explanation for variation at a CF-relevant locus, which also has implications for the genetic basis of non-CF pancreatitis, to which this locus has been reported to contribute.

Genomic architecture of autism from comprehensive whole-genome sequence annotation.

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

Repair of Acute Grade 3 Combined Posterolateral Corner Avulsion Injuries Using an Enhanced Fixation Technique.

Background: Previous studies have suggested that surgical repair of the posterolateral corner (PLC) may be inferior to reconstruction. Hypothesis: We hypothesized that acute repair (<3 weeks) of avulsion-type PLC multiligament knee injuries with no midsubstance injury would lead to lower failure rates than previously reported for PLC repair. Study Design: Case series; Level of evidence, 4. Methods: A total of 28 patients with multiligament knee injuries who underwent acute repair between January 2007 and June 2018 of a PLC avulsion injury with no evidence of midsubstance tearing were included. All PLC avulsion injuries were treated using a transosseous Krackow suture pull-through technique without graft augmentation. Outcome metrics included lateral joint-space widening with varus stress, patient-reported clinical varus instability, patient-reported outcome measures (PROMs), and any subsequent revision or salvage procedure. Results: The mean time from injury to repair was 8.1 ± 5 days. At a mean follow-up of 2 years (range, 3-90 months), clinical varus stress examination at 30° demonstrated a significant reduction in lateral compartment opening, from 9 ± 3 mm preoperatively to 0 ± 3 mm (P < .0001). The failure rate was calculated to be 10.7% (3/28), which was significantly lower than the failure rate from a 2016 systematic review (38%, 17/45; P = .015). Of the 28 patients, 21 (75%) had PROM scores. Patients who underwent staged bi-cruciate reconstructions (n = 5) had significantly higher subjective International Knee Documentation Committee (IKDC) (87.2 vs 65.5; P = .014) and Lysholm (90.5 vs 75.2; P = .029) scores compared to patients with untreated bi-cruciate injuries (n = 9). Patients with peroneal nerve injury (n = 4) had significantly lower IKDC (58.2 vs 80.8; P = .0045) and Tegner (3.2 vs 5.4; P = .047) scores than those without peroneal nerve injury (n = 17). The mean IKDC and Lysholm scores at final follow-up were 73.4 ± 24.0 and 80.8 ± 23.1 at 7.1 years (range, 2.3-10.6 years) of follow-up. Conclusion: Repair of acute grade 3 combined PLC avulsion injuries using a transosseous Krackow suture pull-through technique demonstrated a failure rate of 10.7%. Patients who underwent a staged cruciate reconstruction(s) had higher subjective outcome scores than those who had cruciate injuries left untreated. Peroneal nerve injury was associated with lower outcome scores.

Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder.

Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian children with ASD into dysmorphic and nondysmorphic subgroups. We develop a method for calculating a patient-level, genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD have a significantly higher GRVS compared to those with nondysmorphic ASD (P = 0.03). Using the polygenic transmission disequilibrium test, we observe an over-transmission of ASD-associated common variants in nondysmorphic ASD probands (P = 2.9 × 10-3). These findings replicate using WGS data from 442 ASD probands with accompanying morphology data from the Simons Simplex Collection. Our results provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.

Computing contact angles for oil-water-rock systems via thermodynamic integration.

Wettability of rock surfaces with respect to oil and water, which is characterized by the contact angle, is an important factor that determines the efficacy of enhanced oil recovery operations. Experimental determination of contact angles for oil-water-rock systems is expensive and time-consuming due to the extremely long times needed for the establishment of adsorption equilibrium at the liquid-solid interface. Hence, molecular simulations form an attractive tool for computing contact angles. In this work, we use the cleaving wall technique that was developed previously in our group [R. K. R. Addula and S. N. Punnathanam, J. Chem. Phys. 153, 154504 (2020)] to compute solid-liquid interfacial free energy, which is then combined with Young's equation to compute the oil-water contact angle on silica surfaces. The silica surface is modeled with the INTERFACE force field that has been developed to accurately reproduce experimental data. We have considered three different surface chemistries of silica, namely, Q2, Q3, and Q4, in this study. Our calculations reveal that while the Q2 and Q3 surfaces are completely wetted by water, the Q4 surface is partially non-wetted by water. All the simulations needed for this calculation can be performed using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) molecular package. This should facilitate wider adoption of the Young's equation route to compute contact angles for systems comprised of complex molecules.

Disaggregation of Asian American and Pacific Islander Women With Stage 0-II Breast Cancer Unmasks Disparities in Survival and Surgery-to-Radiation Intervals: A National Cancer Database Analysis From 2004 to 2017.

PURPOSE: Aggregation of Asian Americans (AAs) with Native Hawaiians and Other Pacific Islanders (NHPIs) masks significant health disparities. We evaluated overall survival (OS) and surgery-to-radiation intervals (STRIs) among AA and NHPI women with early-stage breast cancer. METHODS: This National Cancer Database study included women with stage 0-II breast cancer diagnosed between 2004 and 2017. STRI was defined as days from surgery to radiation. Patients were stratified by adjuvant treatment. AAs were disaggregated into geographically relevant subpopulations: East, South, and Southeast Asians. Kaplan-Meier estimates and log-rank tests assessed survival. Cox proportional hazard and linear regression were adjusted for clinical and sociodemographic factors. RESULTS: In total, 578,927 women were included (median age 61 years, median follow-up 65 months, and 10-year OS 83%). AA and NHPI 10-year OS was 91% overall; subpopulation 10-year OS was 92% for East Asian, 90% for South Asian, 90% for Southeast Asian, and 83% for NHPI. On multivariable analysis, compared with non-Hispanic White, NHPI women had worse survival (adjusted hazard ratio [aHR] = 1.38; 95% CI, 1.09 to 1.77); all AA subpopulations had improved survival: East Asian (aHR = 0.57; 95% CI, 0.48 to 0.69), South Asian (aHR = 0.66; 95% CI, 0.51 to 0.84), and Southeast Asian (aHR = 0.78; 95% CI, 0.65 to 0.94). The AA and NHPI median STRI for was 73 days overall; the disaggregated median STRI was 68 days for East Asian, 80 days for South Asian, 77 days for Southeast Asians, and 81 days for NHPI. On adjusted analysis, compared with non-Hispanic White, Southeast Asians and NHPI had longer STRI by 6.6 (95% CI, 4.3 to 8.9) and 10.0 (95% CI, 5.8 to 14) days, respectively. CONCLUSION: Breast cancer disparities exist among disaggregated AA and NHPI subpopulations. Data disaggregation insights may lead to interventions to overcome these disparities, such as optimizing time-to-treatment for select populations.

Autonomic Dysreflexia After Hip Fractures Managed by Regional Anesthesia: A Case Report.

Autonomic dysreflexia occurs after a spinal cord injury usually at the level of T6 or above, and its hallmark feature is exaggerated autonomic response to noxious stimuli resulting in uncontrolled hypertensive episodes with reflexive bradycardia that can be fatal if not controlled. We present a case highlighting regional anesthetic techniques, including peripheral nerve blocks, to ameliorate the symptoms of autonomic dysreflexia triggered by hip fractures in a 57-year-old woman with an old C5-C6 spinal cord injury before definitive hip surgery. The regional techniques described provide anesthesiologists with a simple strategy to potentially mitigate a life-threatening situation.

Hidden in Plain Sight: A Case of Arrhythmic Mitral Valve Prolapse Presenting as Cardiac Arrest.

Mitral valve prolapse (MVP) is a well-studied, mostly benign, phenomenon; however, arrhythmic mitral valve prolapse (AMVP) is a rare subtype that can precipitate sudden cardiac death (SCD). Herein, we present a case of a young female with sudden cardiac arrest. Extensive multimodality imaging and follow-up helped establish the diagnosis of AMVP.

Herb-Induced Liver Injury by Cimicifuga racemosa and Thuja occidentalis Herbal Medications for Fertility.

Herb-induced liver injury (HILI) is often an underreported sequela for many herbal remedies due to the lack of safety measurements involving these supplements. Cimicifuga racemosa and Thuja occidentalis are two herbal medications commonly used by women for fertility purposes. Many herbal preparations of these two supplements do not specify the risks behind their individual usage. We present a case of a 40-year-old woman who developed acute liver injury after concomitant use of these two products assessed for causality using the updated RUCAM. Upon a detailed investigation, the patient did not have evidence of underlying liver disease or any other risk factors to explain her presentation. After discontinuation of both herbal supplements, the patient had complete resolution of her symptoms and a significant improvement of transaminitis. This report highlights the importance of potential risk of hepatotoxicity induced by concomitant use of Cimicifuga racemosa and Thuja occidentalis.

Strategies to Prevent Cardiac Implantable Electronic Device Infection.

The association between the risk of mortality and cardiovascular implantable electronic device (CIED) infections has been well-established in the literature. As CIED implantations have increased in frequency in the past few decades, the incidence of CIED-related infections has also risen. Given the morbidity, mortality, and health-care costs associated with CIED infections, the prevention of device-related infection is a critical goal. Risk factors for developing CIED infections can be categorized as patient-, procedure-, or device-related. Numerous studies have highlighted different strategies for preventing CIED-related infections, which include patient optimization, device selection, and periprocedural preparation and treatment. Nonetheless, as the comorbidity burden of patients undergoing CIED implantation continues to increase, significant challenges in the successful elimination of CIED-related infections remain. This review provides a comprehensive overview of available evidence-based approaches and strategies to reduce the risk of CIED infections.