Protocol for electroporating and isolating murine (sub)ventricular zone cells for single-nuclei omics.

In vivo genetic modification of neural stem cells is necessary to model the origins and pathogenesis of neurological disorders. Electroporation is a technique that applies a transient electrical field to direct charged molecules into living cells to genetically modify the mouse brain. Here, we provide a protocol to electroporate the neural stem cells surrounding the neonatal ventricles. We describe subsequent steps to isolate and prepare nuclei from the cells and their cellular progeny for single-nuclei omics. For complete details on the use and execution of this protocol, please refer to Riley et al.1.

State-of-the-art imaging for children with central lymphatic disorders.

Lymphatic imaging plays a crucial role in novel lymphatic interventions, offering valuable insights into central lymphatic drainage. Lymphatic system abnormalities may appear in various pediatric disorders, and accurate imaging is crucial for effective diagnosis and tailored therapeutic interventions. Traditional imaging modalities have offered valuable insights, but the demand for non-invasive, high-resolution techniques has fueled the development of innovative lymphatic imaging methods. In this review, we explore the state of the art in lymphatic imaging specifically within the context of pediatric surgery.

Diagnosis and management of food allergy-induced constipation in young children-An EAACI position paper.

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review.

Factors influencing central nervous system medication deprescribing and behavior change in hospitalized older adults.

BACKGROUND: Central nervous system (CNS) medications are linked to higher morbidity and mortality in older adults. Hospitalization allows for deprescribing opportunities. This qualitative study investigates clinician and patient perspectives on CNS medication deprescribing during hospitalization using a behavioral change framework, aiming to inform interventions and identify recommendations to enhance hospital deprescribing processes. METHODS: This qualitative study focused on hospitalists, primary care providers, pharmacists, and patients aged ≥60 years hospitalized on a general medicine service and prescribed ≥1 CNS medications. Using semi-structured interviews and focus groups, we aimed to evaluate patient medication knowledge, prior deprescribing experiences, and decision-making preferences, as well as provider processes and tools for medication evaluation and deprescribing. Rapid qualitative analysis applying the Capability, Opportunity, Motivation, and Behavior (COM-B) framework revealed themes influencing deprescribing behavior in patients and providers. RESULTS: A total of 52 participants (20 patients and 32 providers) identified facilitators and barriers across deprescribing steps and generated recommended strategies to address them. Clinicians and patients highlighted the opportunity for CNS medication deprescribing during hospitalizations, facilitated by multidisciplinary teams enhancing clinicians' capability to make medication changes. Both groups also stressed the importance of intensive patient engagement, education, and monitoring during hospitalizations, acknowledging challenges in timing and extent of deprescribing, with some patients preferring decisions deferred to outpatient clinicians. Hospitalist and pharmacist recommendations centered on early pharmacist involvement for medication reconciliation, expanding pharmacy consultation and clinician education on deprescribing, whereas patients recommended enhancing shared decision-making through patient education on medication adverse effects, tapering plans, and alternatives. Hospitalists and PCPs also emphasized standardized discharge instructions and transitional care calls to improve medication review and feedback during care transitions. CONCLUSIONS: Clinicians and patients highlighted the potential advantages of hospital interventions for CNS medication deprescribing, emphasizing the necessity of addressing communication, education, and coordination challenges between inpatient and outpatient settings.

Occupancy of the HbYX hydrophobic pocket is sufficient to induce gate opening in the archaeal 20S proteasomes.

Enhancing proteasome function has been a long-standing but challenging target of interest for the potential treatment of neurodegenerative diseases, emphasizing the importance of understanding proteasome activation mechanisms. Most proteasome activator complexes use the C-terminal HbYX motif to bind and trigger gate-opening in the 20S proteasome. This study defines a critical molecular interaction in the HbYX mechanism that triggers gate opening. Here, we focus on the Hb site interaction and find it plays a surprisingly central and crucial role in driving the allosteric conformational changes that induce gate opening in the archaeal 20S. We examined the cryo-EM structure of two mutant archaeal proteasomes, αV24Y T20S and αV24F T20S. These two mutants were engineered to place a bulky aromatic residue in the HbYX hydrophobic pocket and both mutants are highly active, though their mechanisms of activation are undefined. Collectively, our findings indicate that the interaction between the Hb group of the HbYX motif and its corresponding hydrophobic pocket is sufficient to induce gate opening in a mechanistically similar way to the HbYX motif. The involved activation mechanism appears to involve expansion of this hydrophobic binding site affecting the state of the IT switch to triggering gate-opening. Furthermore, we show that the canonical αK66 residue, understood to be critical for proteasome activator binding, plays a key role in stabilizing the open gate, irrespective of activator binding. This study differentiates between the residues in the HbYX motif that support binding interactions ("YX") versus those that allosterically contribute to gate opening (Hb). The insights reported here will guide future drug development efforts, particularly in designing small molecule proteasome activators, by targeting the identified hydrophobic pocket.

Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19.

Background: The impact of COVID-19 on gastrointestinal (GI) outcomes in children during the post-acute and chronic phases of the disease is not well understood. Methods: We conducted a retrospective cohort study across twenty-nine healthcare institutions from March 2020 to September 2023, including 413,455 pediatric patients with confirmed SARS-CoV-2 infection and 1,163,478 controls without infection. Infection was confirmed via polymerase chain reaction (PCR), serology, antigen tests, or clinical diagnosis of COVID-19 and related conditions. We examined the incidence of predefined GI symptoms and disorders during the post-acute (28 to 179 days post-infection) and chronic (180 to 729 days post-infection) phases. The adjusted risk ratios (aRRs) were calculated using stratified Poisson regression, with stratification based on propensity scores. Results: Our cohort comprised 1,576,933 patients, with females representing 48.0% of the sample. The analysis revealed that children with SARS-CoV-2 infection had an increased risk of developing at least one GI symptom or disorder in both the post-acute (8.64% vs. 6.85%; aRR 1.25, 95% CI 1.24-1.27) and chronic phases (12.60% vs. 9.47%; aRR 1.28, 95% CI 1.26-1.30) compared to uninfected peers. Specifically, the risk of abdominal pain was higher in COVID-19 positive patients during the post-acute phase (2.54% vs. 2.06%; aRR 1.14, 95% CI 1.11-1.17) and chronic phase (4.57% vs. 3.40%; aRR 1.24, 95% CI 1.22-1.27). Interpretation: Children with a history of SARS-CoV-2 infection are at an increased risk of GI symptoms and disorders during the post-acute and chronic phases of COVID-19. This highlights the need for ongoing monitoring and management of GI outcomes in this population. Research in Context: Evidence before this study: We searched PubMed, Scopus, and Google Scholar databases up to September 2023 for studies assessing the incidence and risk of gastrointestinal (GI) symptoms and disorders in children following viral infections, including COVID-19. We included studies published in any language and involving various methodologies (observational studies, cohort studies, and clinical trials). Our search terms included "COVID-19," "SARS-CoV-2," "gastrointestinal symptoms," "children," "post-acute," and "chronic." The evidence prior to this study suggested an increased risk of GI disorders in adults after viral infections but was less definitive for the pediatric population.Added value of this study: This study significantly extends the existing literature by specifically examining the risk of GI symptoms and disorders in the pediatric population during the post-acute and chronic phases of COVID-19. Using a large retrospective cohort design encompassing over 1.5 million children and adolescents from 29 healthcare institutions, our analysis provides robust evidence of increased GI symptoms like abdominal pain, diarrhea, and constipation among COVID-19 positive patients compared to non-infected peers. It is one of the largest studies of its kind and the first to provide such comprehensive data for the U.S. pediatric population, with follow-up extending up to two years post-infection.Implications of all the available evidence: The findings underscore the importance of monitoring children and adolescents for persistent GI symptoms following COVID-19, suggesting that these symptoms may be more common and prolonged than previously recognized. These insights are crucial for pediatric healthcare providers and could influence guidelines for the follow-up care of children recovering from COVID-19. The study also highlights the need for future research to explore the underlying mechanisms of post-acute and chronic GI symptoms in children to develop targeted interventions and improve long-term outcomes. Authorship Statement: Authorship has been determined according to ICMJE recommendations.

Sequencing by Binding rivals error-corrected Sequencing by Synthesis technology for accurate detection and quantification of minor (<0.1%) subpopulation variants.

Detecting very minor (< 1%) subpopulations using next-generation sequencing is a critical need for multiple applications including detection of drug resistant pathogens and somatic variant detection in oncology. To enable these applications, wet lab enhancements and bioinformatic error correction methods have been developed for 'sequencing by synthesis' technology to reduce its inherent sequencing error rate. A recently available sequencing approach termed 'sequencing by binding' claims to have higher base calling accuracy data "out of the box." This paper evaluates the utility of using 'sequencing by binding' for the detection of ultra-rare subpopulations down to 0.001%.

Genome-wide nucleosome and transcription factor responses to genetic perturbations reveal chromatin-mediated mechanisms of transcriptional regulation.

Epigenetic mechanisms contribute to gene regulation by altering chromatin accessibility through changes in transcription factor (TF) and nucleosome occupancy throughout the genome. Despite numerous studies focusing on changes in gene expression, the intricate chromatin-mediated regulatory code remains largely unexplored on a comprehensive scale. We address this by employing a factor-agnostic, reverse-genetics approach that uses MNase-seq to capture genome-wide TF and nucleosome occupancies in response to the individual deletion of 201 transcriptional regulators in Saccharomyces cerevisiae , thereby assaying nearly one million mutant-gene interactions. We develop a principled approach to identify and quantify chromatin changes genome-wide, observing differences in TF and nucleosome occupancy that recapitulate well-established pathways identified by gene expression data. We also discover distinct chromatin signatures associated with the up- and downregulation of genes, and use these signatures to reveal regulatory mechanisms previously unexplored in expression-based studies. Finally, we demonstrate that chromatin features are predictive of transcriptional activity and leverage these features to reconstruct chromatin-based transcriptional regulatory networks. Overall, these results illustrate the power of an approach combining genetic perturbation with high-resolution epigenomic profiling; the latter enables a close examination of the interplay between TFs and nucleosomes genome-wide, providing a deeper, more mechanistic understanding of the complex relationship between chromatin organization and transcription.

Increased endothelial sclerostin caused by elevated DSCAM mediates multiple trisomy 21 phenotypes.

Trisomy 21 (T21), a recurrent aneuploidy occurring in 1:800 births, predisposes to congenital heart disease (CHD) and multiple extracardiac phenotypes. Despite a definitive genetic etiology, the mechanisms by which T21 perturbs development and homeostasis remain poorly understood. We compared the transcriptome of CHD tissues from 49 patients with T21 and 226 with euploid CHD (eCHD). We resolved cell lineages that misexpressed T21 transcripts by cardiac single-nucleus RNA sequencing and RNA in situ hybridization. Compared with eCHD samples, T21 samples had increased chr21 gene expression; 11-fold-greater levels (P = 1.2 × 10-8) of SOST (chr17), encoding the Wnt inhibitor sclerostin; and 1.4-fold-higher levels (P = 8.7 × 10-8) of the SOST transcriptional activator ZNF467 (chr7). Euploid and T21 cardiac endothelial cells coexpressed SOST and ZNF467; however, T21 endothelial cells expressed 6.9-fold more SOST than euploid endothelial cells (P = 2.7 × 10-27). Wnt pathway genes were downregulated in T21 endothelial cells. Expression of DSCAM, residing within the chr21 CHD critical region, correlated with SOST (P = 1.9 × 10-5) and ZNF467 (P = 2.9 × 10-4). Deletion of DSCAM from T21 endothelial cells derived from human induced pluripotent stem cells diminished sclerostin secretion. As Wnt signaling is critical for atrioventricular canal formation, bone health, and pulmonary vascular homeostasis, we concluded that T21-mediated increased sclerostin levels would inappropriately inhibit Wnt activities and promote Down syndrome phenotypes. These findings imply therapeutic potential for anti-sclerostin antibodies in T21.

Nanoparticle delivery of Tat synergizes with classical latency reversal agents to express HIV antigen targets.

Limited cellular levels of the HIV transcriptional activator Tat are one contributor to proviral latency that might be targeted in HIV cure strategies. We recently demonstrated that lipid nanoparticles containing HIV tat mRNA induce HIV expression in primary CD4 T cells. Here, we sought to further characterize tat mRNA in the context of several benchmark latency reversal agents (LRAs), including inhibitor of apoptosis protein antagonists (IAPi), bromodomain and extra-Terminal motif inhibitors (BETi), and histone deacetylase inhibitors (HDACi). tat mRNA reversed latency across several different cell line models of HIV latency, an effect dependent on the TAR hairpin loop. Synergistic enhancement of tat mRNA activity was observed with IAPi, HDACi, and BETi, albeit to variable degrees. In primary CD4 T cells from durably suppressed people with HIV, tat mRNA profoundly increased the frequencies of elongated, multiply-spliced, and polyadenylated HIV transcripts, while having a lesser impact on TAR transcript frequencies. tat mRNAs alone resulted in variable HIV p24 protein induction across donors. However, tat mRNA in combination with IAPi, BETi, or HDACi markedly enhanced HIV RNA and protein expression without overt cytotoxicity or cellular activation. Notably, combination regimens approached or in some cases exceeded the latency reversal activity of maximal mitogenic T cell stimulation. Higher levels of tat mRNA-driven HIV p24 induction were observed in donors with larger mitogen-inducible HIV reservoirs, and expression increased with prolonged exposure time. Combination LRA strategies employing both small molecule inhibitors and Tat delivered to CD4 T cells are a promising approach to effectively target the HIV reservoir.

Type 1 Myocardial Infarction in Patients With Acute Ischemic Stroke.

Importance: Elevated values of high-sensitivity cardiac troponin (hs-cTn) are common in patients with acute ischemic stroke and are associated with poor prognosis. However, diagnostic and therapeutic implications in patients with ischemic stroke remain unclear. Objective: To identify factors indicative of myocardial infarction (MI) in patients with acute ischemic stroke and hs-cTn elevation. The primary hypothesis was that a dynamic change of hs-cTn values (>50% change) in patients with acute ischemic stroke indicates MI. Design, Setting, and Participants: This cross-sectional study was a prospective, observational study with blinded end-point assessment conducted across 26 sites in Germany. Patients were included if they had acute ischemic stroke within 72 hours and either (1) highly elevated hs-cTn values on admission (>52 ng/L) or (2) hs-cTn levels above the upper limit of normal and a greater than 20% change at repeated measurements. Patients were enrolled between August 2018 and October 2020 and had 1 year of follow-up. Statistical analysis was performed between April 2022 and August 2023. Exposure: Standardized electrocardiography, echocardiography, and coronary angiography. Main Outcome and Measures: Diagnosis of MI as adjudicated by an independent end-point committee based on the findings of electrocardiography, echocardiography, and coronary angiography. Results: In total, 254 patients were included. End points were adjudicated in 247 patients (median [IQR] age, 75 [66-82] years; 117 were female [47%] and 130 male [53%]). MI was present in 126 of 247 patients (51%) and classified as type 1 MI in 50 patients (20%). Dynamic change in hs-cTn value was not associated with MI in univariable (32% vs 38%; χ2 P = .30) or adjusted comparison (odds ratio, 1.05; 95% CI, 0.31-3.33). The baseline absolute hs-cTn value was independently associated with type 1 MI. The best cutoffs for predicting type 1 MI were at hs-cTn values 5 to 10 times the upper limit normal. Conclusions and Relevance: This study found that in patients with acute ischemic stroke, a dynamic change in hs-cTn values did not identify MI, underscoring that dynamic changes do not identify the underlying pathophysiological mechanism. In exploratory analyses, very high absolute hs-cTn values were associated with a diagnosis of type 1 MI. Further studies are needed how to best identify patients with stroke who should undergo coronary angiography.

Temperature Control After Cardiac Arrest-A Rational Approach.

This Viewpoint discusses hypothermic temperature control for neuroprotection among survivors of out-of-hospital cardiac arrest and offers a rational approach to treating such patients as investigations continue.

Evaluation of germicidal UV-C light for suppression of grape powdery mildew and Botrytis bunch rot in Western Oregon.

Germicidal ultraviolet light (UV-C) has been shown to effectively suppress several plant pathogens, as well as some arthropod pests. Recent reports describe the efficacy of nighttime applications of UV-C at doses from 100 to 200 J/m2 in vineyards to reduce grape powdery mildew (Erysiphe necator). Our in vitro studies confirmed efficacy of UV-C to inhibit germination of E. necator and Botrytis cinerea conidia, demonstrated a range of tolerances to UV-C within a collection of E. necator isolates, and showed growth stage-specific effects of UV-C on B. cinerea. Nighttime use of UV-C was evaluated at 48 to 96 J/m2 in small plot trials (<1,000 vines) from 2020 to 2023. Once or twice weekly UV-C applications significantly reduced the incidence of foliar powdery mildew compared to non-UV-C-treated controls (P < 0.02). Suppression of powdery mildew on fruit was less consistent, where once or twice weekly UV-C exposure reduced powdery mildew disease severity in 2020 (P = 0.04), 2021 (P = 0.02) and 2023 (P =0.003), but less so in 2022 (P = 0.07). Bunch rot severity was not significantly reduced with UV-C treatment in any year of the study. Application of UV-C until the onset of fruit color change (veraison) also had a minimal effect on the fruit soluble solids, pH, anthocyanins, or phenolics in harvested fruit at any UV-C dose or frequency (P > 0.10). Suppression of powdery mildew by nighttime application UV-C at lower doses in small plots suggests that such treatments merit further evaluation in larger-scale studies in Western Oregon.

Cross-Modal Sensory Boosting to Improve High-Frequency Hearing Loss: Device Development and Validation.

BACKGROUND: High-frequency hearing loss is one of the most common problems in the aging population and with those who have a history of exposure to loud noises. This type of hearing loss can be frustrating and disabling, making it difficult to understand speech communication and interact effectively with the world. OBJECTIVE: This study aimed to examine the impact of spatially unique haptic vibrations representing high-frequency phonemes on the self-perceived ability to understand conversations in everyday situations. METHODS: To address high-frequency hearing loss, a multi-motor wristband was developed that uses machine learning to listen for specific high-frequency phonemes. The wristband vibrates in spatially unique locations to represent which phoneme was present in real time. A total of 16 participants with high-frequency hearing loss were recruited and asked to wear the wristband for 6 weeks. The degree of disability associated with hearing loss was measured weekly using the Abbreviated Profile of Hearing Aid Benefit (APHAB). RESULTS: By the end of the 6-week study, the average APHAB benefit score across all participants reached 12.39 points, from a baseline of 40.32 to a final score of 27.93 (SD 13.11; N=16; P=.002, 2-tailed dependent t test). Those without hearing aids showed a 10.78-point larger improvement in average APHAB benefit score at 6 weeks than those with hearing aids (t14=2.14; P=.10, 2-tailed independent t test). The average benefit score across all participants for ease of communication was 15.44 (SD 13.88; N=16; P<.001, 2-tailed dependent t test). The average benefit score across all participants for background noise was 10.88 (SD 17.54; N=16; P=.03, 2-tailed dependent t test). The average benefit score across all participants for reverberation was 10.84 (SD 16.95; N=16; P=.02, 2-tailed dependent t test). CONCLUSIONS: These findings show that vibrotactile sensory substitution delivered by a wristband that produces spatially distinguishable vibrations in correspondence with high-frequency phonemes helps individuals with high-frequency hearing loss improve their perceived understanding of verbal communication. Vibrotactile feedback provides benefits whether or not a person wears hearing aids, albeit in slightly different ways. Finally, individuals with the greatest perceived difficulty understanding speech experienced the greatest amount of perceived benefit from vibrotactile feedback.

Unraveling the Interplay: Soil Biogeochemical Factors Shaping the Efficacy of Anaerobic Soil Disinfestation in Suppressing Fusarium Root Rot of Strawberry.

Non-toxic alternatives to chemical soil fumigants for suppressing soilborne pathogens such as Fusarium oxysporum (Fo), one causative agent of strawberry black root rot complex prevalent in the southeastern U.S., are urgently needed. A promising alternative is anaerobic soil disinfestation (ASD), in which soil is amended with labile organic materials, irrigated to field capacity, and tarped to induce anaerobic fermentation for a brief period before planting. Pathogen-suppression mechanisms of ASD include anaerobic conditions and generation of reduced metal cations (Fe2+ and Mn2+) and volatile fatty acids (VFAs; e.g., acetic, n-butyric, isovaleric, and others). However, little is known about how the interaction between VFAs, reduced metals, soil texture, and liming influences suppression of Fo. We investigated Fo suppression by VFAs and reduced metal cations in both aqueous and soil-based incubation trials. Inoculum containing Fo chlamydospores was added to aqueous medium containing either 5 or 10 mmol/liter VFAs and either 0.01% or 0.05% (w/w) reduced metals. In soil-based incubations, chlamydospore-containing inoculum was applied to sandy, sandy loam, and silty clay soil saturated by solutions containing 10 or 20 mmol/liter VFAs with or without 0.05% (w/w) reduced metals. VFAs, particularly in combination with Fe2+ in aqueous solutions and Mn2+ in soils significantly reduced Fo viability. At the same time, liming and higher soil clay content reduced the effectiveness of VFAs and reduced metals for suppressing Fo, highlighting the influence of soil pH and soil texture on ASD effectiveness.

Cleft Lip and Palate Surgery at a Rural African Hospital: A 13-Year Experience From Western Kenya.

INTRODUCTION: Most studies on the treatment of cleft lip and palate (CLP) in low-income and middle-income countries have reported on the experience of urban centers or surgical mission trips to rural locations. There is a paucity of literature on the experience of local teams providing orofacial cleft surgery in rural Sub-Saharan Africa. This study reports the efficacy and cost-effectiveness of cleft surgery performed by an all-local team in rural Kenya. METHODS: A retrospective chart review was performed on all patients who received CLP repair at Kapsowar Hospital between 2011 and 2023. Information regarding patient age, sex, cleft etiology, surgical management, and home location was retrieved. For the most recent year of study (2023), the authors performed a financial audit of all costs related to the performance of unilateral cleft lip surgery. Descriptive statistics were performed. RESULTS: The authors identified 381 CLP surgeries performed on 311 patients (197 male, 63.3%). The most common etiology of the cleft was left unilateral (28.3%). The average age of primary lip repair decreased from 46.3 months in 2008 to 2009 to 20.2 months in 2022 to 2023 (P<0.001). The average age of primary cleft palate repair decreased from 38.0 months in 2008 to 2009 to 25.3 months in 2022 to 2023 (P<0.001). Patients traveled from 23 districts to receive treatment. Age of treatment was not different when distinguished by sex, county poverty level, or travel time from the hospital. The total costs associated with cleft lip repair was $201.6. CONCLUSIONS: Adequately staffed hospitals in rural locations can meaningfully address a regional CLP backlog more cost-effectively than surgical mission trips.

Co-aggregation with Apolipoprotein E modulates the function of Amyloid-ß in Alzheimer's disease.

Which isoforms of apolipoprotein E (apoE) we inherit determine our risk of developing late-onset Alzheimer's Disease (AD), but the mechanism underlying this link is poorly understood. In particular, the relevance of direct interactions between apoE and amyloid-ß (Aß) remains controversial. Here, single-molecule imaging shows that all isoforms of apoE associate with Aß in the early stages of aggregation and then fall away as fibrillation happens. ApoE-Aß co-aggregates account for ~50% of the mass of diffusible Aß aggregates detected in the frontal cortices of homozygotes with the higher-risk APOE4 gene. We show how dynamic interactions between apoE and Aß tune disease-related functions of Aß aggregates throughout the course of aggregation. Our results connect inherited APOE genotype with the risk of developing AD by demonstrating how, in an isoform- and lipidation-specific way, apoE modulates the aggregation, clearance and toxicity of Aß. Selectively removing non-lipidated apoE4-Aß co-aggregates enhances clearance of toxic Aß by glial cells, and reduces secretion of inflammatory markers and membrane damage, demonstrating a clear path to AD therapeutics.

A comparison of screw and suture button fixation in the management of adolescent ankle syndesmotic injuries.

Purpose: Ankle injuries involving the tibiofibular syndesmosis often necessitate operative fixation to restore stability to the ankle. Recent literature in the adult population has suggested that suture button fixation may be superior to screw fixation. There is little evidence as to which construct is preferable in the pediatric and adolescent population. This study investigates outcomes of suture button and screw fixation in adolescent ankle syndesmotic injuries. Methods: A retrospective matched cohort study over 10 years of pediatric patients who underwent ankle syndesmotic fixation at a large Level 1 Trauma Center was conducted. Both isolated syndesmotic injuries and ankle fractures with syndesmotic disruption were included. Preoperative variables collected include basic patient demographics, body mass index, and fracture type. Suture button and screw cohorts were matched based on age, race, sex, and open fracture utilizing propensity scores. Outcomes assessed include reoperation and implant failure. Results: A total of 44 cases of operative fixation of the ankle syndesmosis were identified with a mean age of 16 years. After matching cohorts based on age, sex, race, and open fracture status, there were 17 patients in the suture button and screw cohorts, respectively. Patients undergoing screw fixation had a six times greater risk of reoperation (p = 0.043) and 13 times greater risk of implant failure (p < 0.001). Out of six cases of reoperation in the screw cohort, five were unplanned. Conclusion: Our findings favor suture button fixation in operative management of adolescent tibiofibular syndesmotic injuries. Compared with screws, suture buttons are associated with lower risk of both reoperation and implant failure. Level of evidence: level III therapeutic.