Prevalence of Cochlear Nerve Deficiency and Hearing Device Use in Children With Single-Sided Deafness.

OBJECTIVE: This study aimed to assess the prevalence of cochlear nerve deficiency (CND) in a cohort of pediatric patients with single-sided deafness (SSD). A secondary objective was to investigate trends in intervention and hearing device use in these children. STUDY DESIGN: Case series with chart review. SETTING: Pediatric tertiary care center. METHODS: Children ages 0 to 21 years with SSD (N = 190) who underwent computerized tomography (CT) and/or magnetic resonance imaging (MRI) were included. Diagnostic criteria for SSD included unilateral severe-to-profound sensorineural hearing loss with normal hearing sensitivity in the contralateral ear. Diagnostic criteria for CND included neuroradiologist report of an "aplastic or hypoplastic nerve" on MRI or a "stenotic cochlear aperture" on CT. RESULTS: The prevalence of CND was 42% for children with CT only, 76% for children with MRI only, and 63% for children with both MRI and CT. Of the children with MRI and CT, there was a 90% concordance across imaging modalities. About 36% of children with SSD had hearing devices that routed sound to the normal hearing ear (ie, bone conduction hearing device/contralateral routing of signal), while only 3% received a cochlear implant. Approximately 40% did not have a hearing device. Hearing device wear time averaged 2.9 hours per day and did not differ based on cochlear nerve status. CONCLUSION: There is a high prevalence of CND in children with SSD. Cochlear nerve status should be confirmed via MRI in children with SSD. The limited implementation and use of hearing devices observed for children with SSD reinforce the need for increased support for early and continuous intervention.

The Relationship between Croup and Gastroesophageal Reflux: A Systematic Review and Meta-Analysis.

OBJECTIVE: The mechanism by which recurrent croup occurs is unknown. Gastroesophageal reflux is commonly implicated, although this relationship is only loosely documented. We conducted a systematic review with a meta-analysis component to evaluate the relationship between recurrent croup and gastroesophageal reflux disease (GERD), and to assess for evidence of improvement in croup symptoms when treated. STYLE DESIGN: Systematic Review and Meta Analysis. METHODS: We searched five separate databases. Studies were included if they discussed the relationship between croup and GERD in children, >5 subjects, and available in English. Literature retrieved was assessed according to pre-specified criteria. Retrieved articles were reviewed by two independent authors and decisions mediated by a third author. If there was a difference of opinion after first review, a second review was performed to obtain consensus. Heterogeneity was calculated and summarized in forest plots. RESULTS: Of 346 initial records, 15 met inclusion criteria. These were two retrospective cohort and 13 cross-sectional studies. Thirteen of 15 articles support an association between recurrent croup and GERD. Although heterogeneity is high among studies that reported prevalence of GERD, there is less uncertainty in results for improvement to recurrent croup after GERD treatment. Most studies lacked a control group and all carry a moderate-to-high risk of bias. CONCLUSION: There is limited evidence linking GERD to recurrent croup; Further research is needed to assess for causality as most studies are retrospective, lack a control group, and have a study design exposing them to bias. Patients treated with reflux medication appear to demonstrate a reduced incidence of croup symptoms. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:209-217, 2021.

Local and Visiting Physician Perspectives on Short Term Surgical Missions in Guatemala: A Qualitative Study.

OBJECTIVE: To explore the impact of short-term surgical missions (STMs) on medical practice in Guatemala as perceived by Guatemalan and foreign physicians. SUMMARY BACKGROUND DATA: STMs send physicians from high-income countries to low and middle-income countries to address unmet surgical needs. Although participation among foreign surgeons has grown, little is known of the impact on the practice of foreign or local physicians. METHODS: Using snowball sampling, we interviewed 22 local Guatemalan and 13 visiting foreign physicians regarding their perceptions of the impact of Guatemalan STMs. Interviews were transcribed verbatim, iteratively coded, and analyzed to identify emergent themes. Findings were validated through triangulation and searching for disconfirming evidence. RESULTS: We identified 2 overarching domains. First, the delivery of surgical care by both Guatemalan and foreign physicians was affected by practice in the STM setting. Differences from usual practice manifested as occasionally inappropriate utilization of skills, management of postoperative complications, the practice of perioperative care versus "pure surgery," and the effect on patient-physician communication and trust. Second, both groups noted professional and financial implications of participation in the STM. CONCLUSIONS: While Guatemalan physicians reported a net benefit of STMs on their careers, they perceived STMs as an imperfect solution to unmet surgical needs. They described missed opportunities for developing local capacity, for example through education and optimal resource planning. Foreign physicians described costs that were manageable and high personal satisfaction with STM work. STMs could enhance their impact by strengthening working relationships with local physicians and prioritizing sustainable educational efforts.

Operative Versus Nonoperative Management of Appendicitis: A Long-Term Cost Effectiveness Analysis.

Background. Recent clinical trials suggest that nonoperative management (NOM) of patients with acute, uncomplicated appendicitis is an acceptable alternative to surgery. However, limited data exist comparing the long-term cost-effectiveness of nonoperative treatment strategies. Design. We constructed a Markov model comparing the cost-effectiveness of three treatment strategies for uncomplicated appendicitis: 1) laparoscopic appendectomy, 2) inpatient NOM, and 3) outpatient NOM. The model assessed lifetime costs and outcomes from a third-party payer perspective. The preferred strategy was the one yielding the greatest utility without exceeding a $50,000 willingness-to-pay threshold. Results. Outpatient NOM cost $233,700 over a lifetime; laparoscopic appendectomy cost $2500 more while inpatient NOM cost $7300 more. Outpatient NOM generated 24.9270 quality-adjusted life-years (QALYs), while laparoscopic appendectomy and inpatient NOM yielded 0.0709 and 0.0005 additional QALYs, respectively. Laparoscopic appendectomy was cost-effective compared with outpatient NOM (incremental cost-effectiveness ratio $32,300 per QALY gained); inpatient NOM was dominated by laparoscopic appendectomy. In one-way sensitivity analyses, the preferred strategy changed when varying perioperative mortality, probability of appendiceal malignancy or recurrent appendicitis after NOM, probability of a complicated recurrence, and appendectomy cost. A two-way sensitivity analysis showed that the rates of NOM failure and appendicitis recurrence described in randomized trials exceeded the values required for NOM to be preferred. Limitations. There are limited NOM data to generate long-term model probabilities. Health state utilities were often drawn from single studies and may significantly influence model outcomes. Conclusion. Laparoscopic appendectomy is a cost-effective treatment for acute uncomplicated appendicitis over a lifetime time horizon. Inpatient NOM was never the preferred strategy in the scenarios considered here. These results emphasize the importance of considering long-term costs and outcomes when evaluating NOM.

Saliva: An all-rounder of our body.

Saliva is a multifaceted bodily fluid that is often taken for granted but is indispensable for oral health and overall well-being in humans. Although mainly comprised of water (99.5%), proteins, ions and enzymes turn saliva into a viscoelastic solution that performs a variety of vital tasks. This review article gives a brief overview of the salivary gland system, as well as the composition, output and functions of saliva. It also addresses the current applications of saliva for diagnostic purposes, the clinical relevance of saliva in oral diseases as well as current treatment options.

Retrograde parotidectomy under local anesthesia for benign, malignant, and inflammatory lesions.

OBJECTIVE: To report the patient selection, surgical technique, and outcomes of parotidectomy using local anesthesia under monitored anesthesia care (MAC). METHODS: A retrospective chart review was performed for patients undergoing parotidectomy under local anesthesia at an academic head and neck surgery center. RESULTS: Six patients deemed high risk for general anesthesia (GA) due to medical comorbidities or with a strong preference to avoid GA underwent parotidectomy using local anesthesia and MAC. Parotidectomy was performed for several indications, including benign tumors, malignant tumors, and chronic sialadenitis. Mean age of patients was 78.0 ±â€¯7.9 years, and all had an American Society of Anesthesia score ≥ 2 and Charlson comorbidity index ≥4. Mean operative time was 102.8 ±â€¯38.3 min, comparable to that of parotidectomy under general anesthesia. No major complications occurred. Minor complications included three cases of temporary postoperative facial nerve weakness limited to 1-2 lower division branches. At most recent follow up (10 to 48 months), all patients were medically stable and disease free. CONCLUSION: In carefully selected patients, parotidectomy under local anesthesia is a viable treatment alternative that can be offered to patients. Successful outcomes require preoperative counseling, meticulous technique, and close collaboration with anesthesia colleagues.

Analysis of induced pluripotent stem cells from a BRCA1 mutant family.

Understanding BRCA1 mutant cancers is hampered by difficulties in obtaining primary cells from patients. We therefore generated and characterized 24 induced pluripotent stem cell (iPSC) lines from fibroblasts of eight individuals from a BRCA1 5382insC mutant family. All BRCA1 5382insC heterozygous fibroblasts, iPSCs, and teratomas maintained equivalent expression of both wild-type and mutant BRCA1 transcripts. Although no difference in differentiation capacity was observed between BRCA1 wild-type and mutant iPSCs, there was elevated protein kinase C-theta (PKC-theta) in BRCA1 mutant iPSCs. Cancer cell lines with BRCA1 mutations and hormone-receptor-negative breast cancers also displayed elevated PKC-theta. Genome sequencing of the 24 iPSC lines showed a similar frequency of reprogramming-associated de novo mutations in BRCA1 mutant and wild-type iPSCs. These data indicate that iPSC lines can be derived from BRCA1 mutant fibroblasts to study the effects of the mutation on gene expression and genome stability.

Huntingtin-interacting protein 1 phosphorylation by receptor tyrosine kinases.

Huntingtin-interacting protein 1 (HIP1) binds inositol lipids, clathrin, actin, and receptor tyrosine kinases (RTKs). HIP1 is elevated in many tumors, and its expression is prognostic in prostate cancer. HIP1 overexpression increases levels of the RTK epidermal growth factor receptor (EGFR) and transforms fibroblasts. Here we report that HIP1 is tyrosine phosphorylated in the presence of EGFR and platelet-derived growth factor ß receptor (PDGFßR) as well as the oncogenic derivatives EGFRvIII, HIP1/PDGFßR (H/P), and TEL/PDGFßR (T/P). We identified a four-tyrosine "HIP1 phosphorylation motif" (HPM) in the N-terminal region of HIP1 that is required for phosphorylation mediated by both EGFR and PDGFßR but not by the oncoproteins H/P and T/P. We also identified a tyrosine residue (Y152) within the HPM motif of HIP1 that inhibits HIP1 tyrosine phosphorylation. The HPM tyrosines are conserved in HIP1's only known mammalian relative, HIP1-related protein (HIP1r), and are also required for HIP1r phosphorylation. Tyrosine-to-phenylalanine point mutations in the HPM of HIP1 result in proapoptotic activity, indicating that an intact HPM may be necessary for HIP1's role in cellular survival. These data suggest that phosphorylation of HIP1 by RTKs in an N-terminal region contributes to the promotion of cellular survival.

Separate checkpoints regulate splenic plasma cell accumulation and IgG autoantibody production in Lyn-deficient mice.

Accumulation of plasma cells and autoantibodies against nuclear antigens characterize both human and murine lupus. Understanding how these processes are controlled may reveal novel therapeutic targets for this disease. Mice deficient in Lyn, a negative regulator of B and myeloid cell activity, develop lupus-like autoimmune disease. Here, we show that lyn(-) (/) (-) mice exhibit increased splenic plasmablasts and plasma cells and produce IgM against a wide range of self-antigens. Both events require Btk, a target of Lyn-dependent inhibitory pathways. A Btk-dependent increase in the expression of the plasma cell survival factor IL-6 by lyn(-) (/) (-) splenic myeloid cells was also observed. Surprisingly, IL-6 was not required for plasma cell accumulation or polyclonal IgM autoreactivity in lyn(-/-) mice. IL-6 was, however, necessary for the production of IgG autoantibodies, which we show are focused towards a limited set of nucleic acid-containing and glomerular autoantigens in lyn(-) (/) (-) mice. A similar uncoupling of plasma cell accumulation from IgG autoantibodies was seen in lyn(+/-) mice. Plasma cell accumulation and polyclonal IgM autoreactivity are therefore controlled separately from, and are insufficient for, the production of IgG against lupus-associated autoantigens. Regulators of either of these two checkpoints may be attractive therapeutic targets for lupus.