Inhaled Nitric Oxide Is Associated with Improved Oxygenation in a Subpopulation of Infants with Congenital Diaphragmatic Hernia and Pulmonary Hypertension.

OBJECTIVES: To determine which patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PH) benefit from inhaled nitric oxide (iNO) treatment by comparing characteristics and outcomes of iNO responders to nonresponders. STUDY DESIGN: We performed a retrospective chart review of infants with CDH treated at our center between 2011 and 2016. In a subset of patients, iNO was initiated for hypoxemia or echocardiographic evidence of extrapulmonary right to left shunting. Initial post-treatment blood gases were reviewed, and patients were classified as responders (increased PaO2 >20 mm Hg) or nonresponders. Baseline characteristics, echocardiograms and outcomes were compared between groups with Fisher exact tests and Mann-Whitney t tests, as appropriate. RESULTS: During the study period, 95 of 131 patients with CDH (73%) were treated with iNO. All patients with pretreatment echocardiograms (n = 90) had echocardiographic evidence of PH. Thirty-eight (40%) patients met treatment response criteria. Responders had significant improvements in PaO2 (51 ± 3 vs 123 ± 7 mm Hg, P < .01), alveolar-arterial gradient (422 ± 30 vs 327 ± 27 mm Hg, P < .01), and PaO2 to FiO2 ratio (82 ± 10 vs 199 ± 15 mm Hg, P < .01). Nonresponders were more likely to have left ventricular systolic dysfunction (27% vs 8%, P = .03) on echocardiogram. Responders were less likely to require extracorporeal membrane support (50 vs 24%, P = .02). CONCLUSIONS: iNO treatment is associated with improved oxygenation and reduced need for ECMO in a subpopulation of patients with CDH with PH and normal left ventricular systolic function.

Premature Lambs Exhibit Normal Mitochondrial Respiration after Long-Term Extrauterine Support.

BACKGROUND: In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants. OBJECTIVES: We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level. METHODS: Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105-107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3-4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128-134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured. RESULTS: There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed. CONCLUSIONS: Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity.

Predicting Adherence to Topical Medications in Chronic Rhinologic Disease: A Systematic Review.

OBJECTIVE: To determine risk factors of medical adherence and describe strategies to increase adherence in patients with chronic rhinologic disease. DATA SOURCES: PubMED, SCOPUS, CINAHL, and Cochrane. REVIEW METHODS: Systematic review of 4 databases (PubMED, SCOPUS, CINAHL, Cochrane) from inception of databases to September 1, 2022 to identify studies that evaluated factors related to and affected by medical adherence in patients with chronic rhinologic disease. RESULTS: Of 1491 studies screened, 25 studies met inclusion criteria. Of these, 7 studies described how sensory attributes of intranasal sprays affect adherence, including odor, taste, aftertaste, and side effects. Five studies described record keeping diaries/notification systems to improve adherence, with demonstration of web-based platforms to send reminders as well as keep record of medication usage to improve adherence. Eight studies described patient-specific risk factors to nonadherence, with demonstration of increased age and conscientious personalities correlating with medical adherence. Five studies looked at pediatric patients specifically, with adherence rates in children parallelling that of adults. Additionally, nonadherence in children may have greater implications for school performance. CONCLUSION: Overall, adherence to topical medical therapy in patients with chronic rhinologic disease is affected by patient-related and medication-specific factors which should be considered when counseling patients. Web-based diary or notification systems may help increase adherence. Additionally, children are equally adherent to topical medical therapy as adults and nonadherence may have negative implications for school performance.

Comparing adverse events associated with LigaSure and Harmonic devices in head and neck surgery.

OBJECTIVE: To characterize adverse events, provide a safety profile, and understand patient outcomes after complications arising from LigaSure and Harmonic use in the head and neck region. METHODS: Retrospective analysis of adverse events from the Manufacturer and User Facility Device Experience (MAUDE) between January 2013 and 2023. RESULTS: A total of 158 LigaSure and 159 Harmonic events were extracted. There were significantly more reports of Harmonic device overheating (6.9% vs. 0.6%, p = 0.003) and spontaneous self-activation (4.4% vs. 0%, p = 0.032). Although intra-operative and post-operative complications were similar among both groups, there were significantly more intra-operative bleeding events for LigaSure as compared to Harmonic (8.2% vs. 0.0%, p = 0.001). CONCLUSION: Understanding technical complications and adverse events attributable to LigaSure and Harmonic devices enables the development of clinically relevant risk mitigation strategies. Surgeons should avoid improper use by remaining vigilant of device functionality and temperature changes.

Management of the Difficult Airway: An Appraisal of Clinical Practice Guidelines.

OBJECTIVE: Management of the difficult airway can be a challenging process, which necessitates actionable recommendations from well-established guidelines. Herein, clinical practice guideline (CPG) quality is evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. STUDY DESIGN: A systematic literature search was performed using Scopus, EMBASE, and MEDLINE via PubMed. SETTING: Literature database. METHODS: Data were abstracted from relevant guidelines and appraised by 4 expert reviewers in the 6 domains of quality defined by AGREE II. Intraclass correlation coefficients (ICC) were calculated across domains to quantify interrater reliability. RESULTS: Twelve guidelines met the inclusion criteria. With a mean quality score of 83.1%, the highest quality guideline was authored by the American Society of Anesthesiologists (ASA). Low-quality content was observed in CPGs authored by the Japanese Society of Anesthesiologists (JSA) and the Chinese Collaboration Group for Emergency Airway Management (CCGEAM). Overall, deficits were most pronounced in domains describing the involvement of stakeholders, developmental rigor, and editorial independence. These findings were consistent among the panel of independent reviewers, with high ICC inter-rater reliability scores of 58.0% to 70.0% for the referenced domains. CONCLUSION: By providing a comprehensive appraisal of guidelines, this report may serve as a reference for clinicians seeking to understand and improve upon the developmental quality of difficult airway management resources. According to AGREE II criteria for the quality of the guideline creation process, the 2022 ASA guideline outperforms its predecessors.

Radioactive Iodine in Differentiated Thyroid Carcinoma: A Systematic AGREE II Clinical Practice Guideline Appraisal.

OBJECTIVE: Identify and appraise clinical practice guidelines (CPGs) for radioactive iodine (RAI) indications in differentiated thyroid carcinoma (DTC), and the treatment for radioactive iodine refractory (RAI-R) DTC using the Appraisal of Guidelines for Research and Evaluation II tool. DATA SOURCES: MEDLINE (Pubmed), Ovid (EMBASE), and Scopus. REVIEW METHODS: A systematic literature search was conducted to identify CPGs addressing RAI in DTC. CPGs were appraised by 4 independent reviewers in 6 distinct areas of quality. Scaled domain scores were subsequently calculated for each domain. Intraclass correlation coefficients were calculated for each domain to assess interrater reliability. RESULTS: Sixteen guidelines were found addressing RAI indications for DTC. Of these 16, 9 also addressed the treatment of RAI-R DTC. A further 6 unique guidelines were identified that exclusively address RAI-R DTC, bringing the total number of guidelines to 22. The American Thyroid Association (ATA) guidelines for adult thyroid cancer were the highest scoring with a mean score of 83.5%. Two guidelines scored >60% in 5 or more domains, qualifying as "high" quality: ATA and British Thyroid Association. The highest scoring domain was domain 4: clarity of presentation (80.4%) while the lowest scoring domain was domain 5: applicability (38.6%). CONCLUSION: Of the 22 guidelines identified, only two were "high quality." CPGs exclusively addressing the treatment of RAI-R DTC were weak with most guidelines scoring in the "low" quality range. This report reveals an unmet need for rigorously developed guidelines addressing indications for RAI in DTC, as well as the treatment for RAI-R DTC.

Medico-legal liability of injuries arising from laryngoscopy.

OBJECTIVE: Dental and mucosal injuries from laryngoscopy in the peri-operative period are common medico-legal complaints. This study investigated lawsuits arising from laryngoscopy. METHODS: Westlaw, a legal database containing trial records from across the USA, was retrospectively reviewed. Plaintiff and/or defendant characteristics, claimed injuries, legal outcomes and awards were extracted. RESULTS: Of all laryngoscopy-related dental or mucosal injuries brought before a state or federal court, none (0 per cent) resulted in a defence verdict against the provider or monetary gain for the patient. Rulings in the patient's favour were observed only when laryngoscopy was found to be the proximate cause of multiple compounding complications that culminated in severe medical outcomes such as exsanguination, septic shock or cardiopulmonary arrest. CONCLUSION: Proper laryngoscopy technique and a robust informed-consent process that accurately sets patients' expectations reduces litigation risk. Future litigation pursuits should consider the low likelihood of malpractice allegation success at trial.

Long-term core outcomes of patients with simple gastroschisis.

PURPOSE: To report the long-term core outcome set of patients with simple gastroschisis. METHODS: This was a retrospective chart review of all patients with simple gastroschisis managed at our hospital between August 2008 and July 2016. We collected all data included in the core outcome set developed for the standardization of gastroschisis outcomes reporting. We conducted a phone survey of the patients' parents using the PedsQL™ Pediatric Quality of Life Inventory, Cognitive Functioning Scale, and Gastrointestinal Symptoms Scale (GSS). Additionally, parents reported their subjective evaluation of the patients' cosmetic result and overall quality of life. RESULTS: There were 124 patients included in the study. The majority (76.5%) was born prematurely at a median gestational age of 36 (range 27.6-38) weeks. At neonatal discharge (median 36 days [18-150] days) most patients were below the 10th percentile for height (81.4%) and weight (87%). Their growth, however, normalized during early childhood. Seven patients (5.6%) required at some point an operation for acute abdominal complications. One-third of patients required long-term treatment for constipation and one-third of patients required long-term treatment for gastroesophageal reflux disease (GERD). Thirty-five parents participated in the phone survey. Mean parent-reported quality of life score was better than healthy controls (87.5% vs. 82.3%, p = 0.049). Cognitive functions and gastrointestinal symptoms scores were similar to healthy controls. All patients are alive. CONCLUSION: Growth restriction in patients with simple gastroschisis is common at birth and during the neonatal period, but it improves during the first three years of life. Abdominal operations are rarely needed in patients with simple gastroschisis. GERD and constipation, on the other hand, are common and often require long-term medical management. The overall parent-reported quality of life of patients with simple gastroschisis is excellent. LEVEL OF EVIDENCE: Level II.

The Effects of Nitric Oxide in Oxygenator Sweep Gas During Extracorporeal Circulation in a Neonatal Ovine Model.

Extracorporeal membrane oxygenation is a life-saving intervention, but bleeding complications are frequent. Given that the combination of platelet loss and dysfunction is a major contributor to this acquired bleeding diathesis, efforts to combat these phenomena are of great clinical importance. In this study, we investigated the effects of nitric oxide (NO) added to the sweep gas of an extracorporeal circuit in a neonatal ovine model. Eight lambs (age 9.6 ± 1.9 days) were cannulated via the neck vessels and maintained on a pumpless arteriovenous extracorporeal membrane oxygenation circuit with blood flow restricted to 100 ml/min for 72 hours. All animals were heparinized, and a subset (n = 4) also received NO in the sweep gas at a concentration of 200 ppm. We observed no adverse effects from NO administration, and methemoglobin levels remained unchanged. Platelet counts significantly declined in all animals over the course of the study; however, mean counts were higher in the NO-treated group, and this difference was statistically significant at 24 hours (62 ± 3% vs. 32 ± 7% of baseline, P < 0.01). Likewise, mean plasma levels of beta-thromboglobulin, a marker of platelet activation, were lower in the NO-treated group, and this difference was also significant at the 24 hour time point (9.5 ± 2.2 vs. 19.7 ± 6.5 pg/mL/10 platelets, P < 0.05). We conclude that 200 ppm NO can be safely blended into the oxygenator sweep gas of a low-flow extracorporeal circuit and that it may transiently attenuate platelet consumption and activation.

Growth trajectory and neurodevelopmental outcome in infants with congenital diaphragmatic hernia.

PURPOSE: The purpose of this study was to evaluate the impact of impaired growth on short-term neurodevelopmental (ND) outcomes in CDH survivors. METHODS: Between 9/2005-12/2014, 84 of 215 (39%) CDH survivors underwent ND assessment at 12months of age using the BSID-III. RESULTS: Mean cognitive, language, and motor scores were 92.6±13.5, 87.1±11.6, and 87.0±14.4, respectively (normal 100±15). 51% of patients scored 1 SD below the population mean in at least one domain, and 13% scored 2 SD below the population mean. Group-based trajectory analysis identified two trajectory groups ('high' and 'low') for weight, length, and head circumference (HC) z-scores. (Fig. 1) 74% of the subjects were assigned to the 'high' trajectory group for weight, 77% to the 'high' height group, and 87% to the 'high' HC group, respectively. In multivariate analysis, longer NICU stay (p<0.01) was associated with lower cognitive scores. Motor scores were 11 points higher in the 'high' HC group compared to the 'low' HC group (p=0.05). Motor scores were lower in patients with longer NICU length of stay (p<0.001). CONCLUSIONS: At 1 year, half of CDH survivors had a mild delay in at least one developmental domain. Low HC trajectory was associated with worse neurodevelopmental outcomes. TYPE OF STUDY: Prognosis Study/Retrospective Study. LEVEL OF EVIDENCE: Level II.