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Purpose of Review: Symptoms/complications related to extraesophageal reflux (EER) are increasingly prevalent presentations and pose significant challenges for clinicians. We summarize and discuss clinical advances and developments in pathophysiology, testing and treatment algorithms of upper/lower airway manifestations of EER., Recent Findings: Growing evidence supports likely multifactorial causes of laryngeal symptoms, including EER, oropharyngeal pathologies, allergic conditions, and cognitive-affective processes (brain-larynx interaction). Diagnostic paradigm for laryngopharyngeal reflux (LPR) is shifting towards a personalized approach with noninvasive strategies/prediction tools to risk-stratify patients for upfront reflux testing over empiric acid suppression trials. Management should be multipronged to include antireflux therapies and treatments targeting other causes. Lower airway complications of EER may result in lung dysfunction and poor transplant outcomes. Esophageal symptoms are often absent and routine esophageal/reflux testing to guide timely antireflux therapies may lead to improved outcomes. Modalities that leverage impedance technology may be important, given the potential role of nonacidic reflux. Novel impedance-based metrics such as mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index may provide adjunctive diagnostic values., Summary: Standardized approach to diagnosis/management of EER should include multidisciplinary care teams and consider different phenotypes, nonreflux contributors, and the complex gut-airway relationships. Prompt antireflux therapies after careful candidate selection may improve outcomes of these airway complications., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Background: The Pediatric Anesthesia COVID-19 Collaborative (PEACOC) is a research network to advance the care of children during the pandemic. Here we calculate the prevalence of coronavirus disease 2019 (COVID-19) among children undergoing anesthesia, look at prevalence in the population data from the Centers for Disease Control and Prevention (CDC), and assess independent risk factors for infection., Methods: This was a multicenter, retrospective, observational study. Children aged 28 days to 18 years scheduled for anesthesia services at 12 centers requiring universal COVID-19 testing from March 29, 2020 to June 30, 2020 were included. COVID-19 positivity rates among those tested were plotted and trends were assessed using the Cochran Armitage test of trend. Independent risk factors were explored using multivariable logistic regression., Results: Data were collected and analyzed on 33,320 anesthesia encounters including 265 children with COVID-19. Over the study period, the rates of infections in the pediatric anesthesia population did not demonstrate a significant trend. In the general population, there was a significant downward trend in infection rates ( P < .001). In exploratory analysis, multivariable risk factors for a COVID-19 positive test were Black/African American race, Hispanic ethnicity, American Society of Anesthesiologists (ASA) physical status III or above, overweight and obese body mass index (BMI), orthopedic cases, abdominal cases, emergency cases, absence of injury and trauma, and West region (all P < .05)., Conclusions: Rates of COVID-19 in pediatric anesthesia patients were consistently lower than in the general population. Independent risk factors of a positive test for children were identified. This is the first time universal testing for a single infectious disease was undertaken on a wide scale. As such, the association of infection with surgical case type or emergency case status is unprecedented., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Competing Interests: Conflicts of Interest: V. T. Raman shares in Johnson/Johnson, 2 Honarium from Merck, NDS Kalstars/Face2Face equity, none of which contribute any financial conflicts to this project. Remaining authors declare no conflicts of interest.

Since the approval of immune checkpoint anti-programmed cell death protein 1 antibodies (pembrolizumab and nivolumab) and anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) in combination or monotherapy, significant advances have been made in the treatment of metastatic melanoma. The nonspecific immune stimulation resulting from these drugs can case a wide range of side effects in many organs including the nervous system, named immune-related adverse events. Few immune-related encephalitis associated with these antibodies have been described in the literature. It is a rare complication (<1% of the total of immune-related adverse events) but it can be fatal if not diagnosed and treated on time. We describe 3 cases of patients with melanoma, which were treated with a combination of ipilimumab-nivolumab (case 1), ipilimumab monotherapy (case 2), and nivolumab monotherapy (case 3), who developed an encephalitis which was related to immune checkpoint therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Craniosynostosis is the premature fusion of ≥1 cranial sutures and often requires surgical intervention. Surgery may involve extensive osteotomies, which can lead to substantial blood loss. Currently, there are no consensus recommendations for guiding blood conservation or transfusion in this patient population. The aim of this study is to develop a machine-learning model to predict blood product transfusion requirements for individual pediatric patients undergoing craniofacial surgery., Methods: Using data from 2143 patients in the Pediatric Craniofacial Surgery Perioperative Registry, we assessed 6 machine-learning classification and regression models based on random forest, adaptive boosting (AdaBoost), neural network, gradient boosting machine (GBM), support vector machine, and elastic net methods with inputs from 22 demographic and preoperative features. We developed classification models to predict an individual's overall need for transfusion and regression models to predict the number of blood product units to be ordered preoperatively. The study is reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist for prediction model development., Results: The GBM performed best in both domains, with an area under receiver operating characteristic curve of 0.87 ± 0.03 (95% confidence interval) and F-score of 0.91 ± 0.04 for classification, and a mean squared error of 1.15 ± 0.12, R-squared (R) of 0.73 ± 0.02, and root mean squared error of 1.05 ± 0.06 for regression. GBM feature ranking determined that the following variables held the most information for prediction: platelet count, weight, preoperative hematocrit, surgical volume per institution, age, and preoperative hemoglobin. We then produced a calculator to show the number of units of blood that should be ordered preoperatively for an individual patient., Conclusions: Anesthesiologists and surgeons can use this continually evolving predictive model to improve clinical care of patients presenting for craniosynostosis surgery.

Background: Complex cranial vault reconstruction (CCVR) performed to treat craniosynostosis can be associated with significant blood loss, transfusion, and perioperative complications. The aim of this study was to examine the effect of CCVR surgical case volume on perioperative outcomes. We hypothesized that surgical case volume is not associated with differences in perioperative outcomes. The study primary outcome was total perioperative blood donor exposures. Secondary outcomes included the total perioperative transfusion volume, major complications, and intensive care unit and hospital length of stay., Methods: The multicenter Pediatric Surgery Perioperative Registry was queried for infants and children undergoing CCVR between June 2012 and September 2016. Institutions were categorized into low, middle, or high surgical case volume groups based on tertiles of the average number of cases performed per month. Primary and secondary outcomes were analyzed with respect to these groupings., Results: The query yielded 1814 CCVR cases from 33 institutions. Demographics were similar among the 3 study groups. An inverse relationship between surgical case volume and total perioperative blood donor exposures was observed (P < .001). The low-volume group had higher perioperative transfusion volumes (P = .02 versus middle; P = .01 versus high). There was no significant relationship between surgical case volume and the incidence of major postoperative complications or hospital length of stay., Conclusions: In this study, low surgical case volumes were associated with increased total blood donor exposures and increased perioperative transfusion volumes. Hospital length of stay was homogeneous in the 3 groups, suggesting a limited overall clinical impact of the observed transfusion outcome differences.

Purpose of Review: This review will outline the recent advances in the area of insulin-stimulated skeletal muscle glucose uptake and its effect on whole body glucose homeostasis, using gene-deletion and transgenic mouse models., Recent Findings: Insulin resistance is often the first abnormality detected in cases of type 2 diabetes, and is seen at the level of the peripheral tissues especially muscle. Both the insulin receptor and the insulin-like growth factor I receptor are capable of stimulating glucose uptake into skeletal muscle. One model involves the gene deletion of muscle glucose transport protein 4, which leads to severe insulin resistance and hyperglycemia, and a second model using a transgenic approach abrogates the function of the insulin-like growth factor I receptor and the insulin receptor resulting in severe insulin resistance and progression to diabetes. Both models demonstrate that abrogation of the insulin-like growth factor I receptor and the insulin receptor or a common signalling pathway must be inhibited to cause sufficient insulin resistance to lead to type 2 diabetes; with either glucotoxicity or lipotoxicity being involved in the progression from severe to resistance to full-blown type 2 diabetes., Summary: Thus, abrogation of insulin-stimulated glucose uptake in skeletal muscle, at least in mice, may lead to severe insulin resistance and diabetes.

Previous studies have shown that estradiol induces a transient disconnection of axo-somatic inhibitory synapses in the hypothalamic arcuate nucleus of adult ovariectomized rats. The synaptic disconnection is accompanied by an increase in the levels of insulin-like growth factor-I (IGF-I) in the arcuate nucleus, suggesting that IGF-I signaling may be involved in the estrogen-induced synaptic plasticity. The role of estrogen receptors and IGF-I receptors in the synaptic changes has been studied by assessing the number of axo-somatic synapses in ovariectomized rats treated with intracerebroventricular administration of the estrogen receptor antagonist ICI 182,780 and the IGF-I receptor antagonist JBI to ovariectomized rats. Estradiol administration resulted in a significant decrease in the number of axo-somatic synapses on arcuate neurons in control ovariectomized rats. Both the estrogen receptor antagonist and the IGF-I receptor antagonist blocked the estrogen-induced synaptic decrease. This finding suggest that estrogen-induced synaptic plasticity in the arcuate nucleus is dependent on the activation of both estrogen receptors and IGF-I receptors.