Comparison of Adult and Pediatric Cochlear Implant Wound Complications: A Meta-Analysis.

OBJECTIVE: To compare age-related differences in wound complications following cochlear implantation (CI). METHODS: We performed a systematic review of PubMed, Cochrane Database, and Web of Science databases to identify original research evaluating the patient-level factors (demographics and medical history) associated with wound complications following CI. Outcomes were expressed as relative risk (RR) with 95% confidence intervals using the inverse variance method. Studies without comparison groups were described qualitatively. RESULTS: Thirty-eight studies representing 21,838 cochlear implantations were included. The rate of wound complications ranges from 0% to 22%. Patient age (adult versus pediatric) was the only factor with comparison groups appropriate for meta-analysis. The 10 studies (n = 9547 CI's) included in the meta-analysis demonstrated that adults had a higher incidence of overall wound complications (2.94%) than in children (2.44%) (RR 1.31, 95% CI 1.01-1.69). Adults had a higher incidence of general/unclassified wound complications (2.07%) than in children (1.34%) (RR 1.68, 95% CI 1.12-2.52). There was no difference between adults and children for specific complications such as hematoma, infection, or seroma. Elderly patients (over age 75) have wound complication rates that range from 1% to 4%. No studies contained comparison groups regarding other patient-level factors and CI wound complications. CONCLUSION: CI wound complication rates reported in the literature are low; however, adults have a higher risk of these complications than pediatric patients. The reported complication rate in elderly adults is low. There is a gap in CI research in consistently reporting wound complications and rigorous research investigating the impact of patient-level factors and wound complications. LEVEL OF EVIDENCE: NA Laryngoscope, 133:218-226, 2023.

Communities Helping the Hearing of Infants by Reaching Parents (CHHIRP) through patient navigation: a hybrid implementation effectiveness stepped wedge trial protocol.

INTRODUCTION: As the most common neonatal sensory disorder in the USA, infant hearing loss has an incidence of 1.7 per 1000 births. The consequences of delayed diagnosis and failure to obtain timely intervention include significant communication impairment and negative socioeconomic effects. Early Hearing Detection and Intervention (EHDI) national standards dictate that all infants should be screened and diagnosed by 3 months of age and there is a need for interventions that promote adherence to timely diagnosis. Patient navigation (PN) has been shown to be efficacious to decrease non-adherence with infant hearing diagnostic care; however, PN has yet to be tested in diverse communities or implemented into real-world settings. METHODS AND ANALYSIS: The proposed research is a community-engaged, type 1 hybrid effectiveness-implementation trial of a PN intervention aimed at decreasing infant hearing diagnosis non-adherence after failed newborn hearing screening, delivered in state-funded EHDI clinics. Guided by our community advisory board and partners, we aim to (1) test the effectiveness of PN to decrease non-adherence to receipt of infant hearing diagnosis within 3 months after birth using a stepped-wedge trial design, (2) investigate implementation outcomes and factors influencing implementation and (3) determine the cost-effectiveness of PN from the perspective of third-party payers. The study will be conducted from April 2019 until March 2024. ETHICS AND DISSEMINATION: This protocol was approved by the University of Kentucky Institutional Review Board. Although all research involving human subjects contains some risk, there are no known serious risks anticipated from participating in this study. We will seek to disseminate our results in a systematic fashion to patients, key stakeholder, policymakers and the scientific community. Our results will impact the field by partnering with communities to inform the scale-up of this innovative patient supportive intervention to create efficient and effective EHDI programmes and maximise public health impact. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (Pre-results phase): NCT03875339.

Accumulation of γδ T cells in visceral fat with aging promotes chronic inflammation.

Adipose tissue dysfunction is strongly linked to the development of chronic inflammation and cardiometabolic disorders in aging. While much attention has been given to the role of resident adipose tissue immune cells in the disruption of homeostasis in obesity, age-specific effects remain understudied. Here, we identified and characterized a population of γδ T cells, which show unique age-dependent accumulation in the visceral adipose tissue (VAT) of both mice and humans. Diet-induced obesity likewise increased γδ T cell numbers; however, the effect was greater in the aged where the increase was independent of fat mass. γδ T cells in VAT express a tissue-resident memory T cell phenotype (CD44hiCD62LlowCD69+) and are predominantly IL-17A-producing cells. Transcriptome analyses of immunomagnetically purified γδ T cells identified significant age-associated differences in expression of genes related to inflammation, immune cell composition, and adipocyte differentiation, suggesting age-dependent qualitative changes in addition to the quantitative increase. Genetic deficiency of γδ T cells in old age improved the metabolic phenotype, characterized by increased respiratory exchange ratio, and lowered levels of IL-6 both systemically and locally in VAT. Decreased IL-6 was predominantly due to reduced production by non-immune stromal cells, primarily preadipocytes, and adipose-derived stem cells. Collectively, these findings suggest that an age-dependent increase of tissue-resident γδ T cells in VAT contributes to local and systemic chronic inflammation and metabolic dysfunction in aging.

Surgical Factors Influencing Wound Complication After Cochlear Implantation: A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify perioperative surgical factors associated with wound complications following cochlear implantation (CI). DATA SOURCES: PubMed, Web of Science, and Cochrane databases. STUDY SELECTION: Eligible studies included peer-reviewed research in English evaluating wound complications (wound infection, skin flap breakdown/dehiscence, seroma/hematoma) following CI. Studies with paired samples were included in the meta-analysis. DATA EXTRACTION: Surgical factors (techniques and perioperative management) in CI and reported wound complications were examined. Level of evidence was assessed using the Oxford Centre for Evidence-based Medicine guidelines and bias was assessed using the NIH Quality Assessment Tool. DATA SYNTHESIS: Twenty-six studies representing 10,214 cochlear implantations were included. The overall wound complications rate was 3.1% (range 0.03-13.9%). Eleven studies contained paired data and were used for meta-analysis regarding three different surgical factors: incision length, implant placement method, and antibiotic usage. Longer incision lengths (≥7 cm) demonstrated a higher risk of wound complications (risk ratio 2.27, p = 0.02, CI 1.16-4.43). Different implant placement techniques (suture fixation versus periosteal pocket) (p = 0.08, CI 0.92-3.69) and postoperative antibiotic regimens (postoperative use versus none) (p = 0.68, CI = 0.28-7.18) were not associated with differences in wound complication rates following CI. CONCLUSIONS: Overall rate of wound complications following CI is low. Shorter incision length is associated with lower risk of wound complications. Differences in perioperative techniques and practices regarding implant placement and antibiotic use were not associated with differences in wound complication rates. Considering the low number and quality of studies, there is a need for research in CI outcomes using paired sample prospective designs and standardized reporting.

Adipose-Derived Inflammatory and Coagulant Mediators in Patients With Sepsis.

ABSTRACT: Results from preclinical sepsis studies using rodents are often criticized as not being reproducible in humans. Using a murine model, we previously reported that visceral adipose tissues (VAT) are highly active during the acute inflammatory response, serving as a major source of inflammatory and coagulant mediators. The purpose of this study was to determine whether these findings are recapitulated in patients with sepsis and to evaluate their clinical significance. VAT and plasma were obtained from patients undergoing intra-abdominal operations with noninflammatory conditions (control), local inflammation, or sepsis. In mesenteric and epiploic VAT, gene expression of pro-inflammatory (TNFα, IL-6, IL-1α, IL-1ß) and pro-coagulant (PAI-1, PAI-2, TSP-1, TF) mediators was increased in sepsis compared with control and local inflammation groups. In the omentum, increased expression was limited to IL-1ß, PAI-1, and PAI-2, showing a depot-specific regulation. Histological analyses showed little correlation between cellular infiltration and gene expression, indicating a resident source of these mediators. Notably, a strong correlation between PAI-1 expression in VAT and circulating protein levels was observed, both being positively associated with markers of acute kidney injury (AKI). In another cohort of septic patients stratified by incidence of AKI, circulating PAI-1 levels were higher in those with versus without AKI, thus extending these findings beyond intra-abdominal cases. This study is the first to translate upregulation of VAT mediators in sepsis from mouse to human. Collectively, the data suggest that development of AKI in septic patients is associated with high plasma levels of PAI-1, likely derived from resident cells within VAT.

Chronic muscle weakness and mitochondrial dysfunction in the absence of sustained atrophy in a preclinical sepsis model.

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of survivors. Our data suggest that sustained mitochondrial dysfunction, rather than atrophy alone, underlies chronic sepsis-induced muscle weakness. This study emphasizes that conventional efforts that aim to recover muscle quantity will likely remain ineffective for regaining strength and improving quality of life after sepsis until deficiencies in muscle quality are addressed.