Endobronchial Phenylephrine in Airway Bleeding During Bronchoscopy Does not Cause Hypertension: A Retrospective Observational Study.

BACKGROUND: Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. METHODS: In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. RESULTS: There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29 mm Hg (IQR 19 to 41) compared with 31.8 mm Hg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. CONCLUSIONS: We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.

Early Mobility Index and Patient Outcomes: A Retrospective Study in Multiple Intensive Care Units.

BACKGROUND: Early mobility interventions in intensive care units (ICUs) are safe and improve outcomes in subsets of critically ill adults. However, implementation varies, and the optimal mobility dose remains unclear. OBJECTIVE: To test for associations between daily dose of out-of-bed mobility and patient outcomes in different ICUs. METHODS: In this retrospective cohort study of electronic records from 7 adult ICUs in an academic quarternary hospital, multivariable linear regression was used to examine the effects of out-of-bed events per mobility-eligible day on mechanical ventilation duration and length of ICU and hospital stays. RESULTS: In total, 8609 adults hospitalized in ICUs from 2015 through 2018 were included. Patients were mobilized out of bed on 46.5% of ICU days and were eligible for mobility interventions on a median (IQR) of 2.0 (1-3) of 2.7 (2-9) ICU days. Median (IQR) out-of-bed events per mobility-eligible day were 0.5 (0-1.2) among all patients. For every unit increase in out-of-bed events per mobility-eligible day before extubation, mechanical ventilation duration decreased by 10% (adjusted coefficient [95% CI], -0.10 [-0.18 to -0.01]). Daily mobility increased ICU stays by 4% (adjusted coefficient [95% CI], 0.04 [0.03-0.06]) and decreased hospital stays by 5% (adjusted coefficient [95% CI], -0.05 [-0.07 to -0.03]). Effect sizes differed among ICUs. CONCLUSIONS: More daily out-of-bed mobility for ICU patients was associated with shorter mechanical ventilation duration and hospital stays, suggesting a dose-response relationship between daily mobility and patient outcomes. However, relationships differed across ICU subpopulations.

Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations.

BACKGROUND: The ratio of oxygen saturation index (ROX index; or SpO2 /FIO2 /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death.

MAN VERSUS MACHINE: PROVIDER DIRECTED VERSUS PRECISION AUTOMATED CRITICAL CARE MANAGEMENT IN A PORCINE MODEL OF DISTRIBUTIVE SHOCK.

ABSTRACT: Background: Critical care management of shock is a labor-intensive process. Precision Automated Critical Care Management (PACC-MAN) is an automated closed-loop system incorporating physiologic and hemodynamic inputs to deliver interventions while avoiding excessive fluid or vasopressor administration. To understand PACC-MAN efficacy, we compared PACC-MAN to provider-directed management (PDM). We hypothesized that PACC-MAN would achieve equivalent resuscitation outcomes to PDM while maintaining normotension with lower fluid and vasopressor requirements. Methods : Twelve swine underwent 30% controlled hemorrhage over 30 min, followed by 45 min of aortic occlusion to generate a vasoplegic shock state, transfusion to euvolemia, and randomization to PACC-MAN or PDM for 4.25 h. Primary outcomes were total crystalloid volume, vasopressor administration, total time spent at hypotension (mean arterial blood pressure <60 mm Hg), and total number of interventions. Results : Weight-based fluid volumes were similar between PACC-MAN and PDM; median and IQR are reported (73.1 mL/kg [59.0-78.7] vs. 87.1 mL/kg [79.4-91.8], P = 0.07). There was no statistical difference in cumulative norepinephrine (PACC-MAN: 33.4 µg/kg [27.1-44.6] vs. PDM: 7.5 [3.3-24.2] µg/kg, P = 0.09). The median percentage of time spent at hypotension was equivalent (PACC-MAN: 6.2% [3.6-7.4] and PDM: 3.1% [1.3-6.6], P = 0.23). Urine outputs were similar between PACC-MAN and PDM (14.0 mL/kg vs. 21.5 mL/kg, P = 0.13). Conclusion : Automated resuscitation achieves equivalent resuscitation outcomes to direct human intervention in this shock model. This study provides the first translational experience with the PACC-MAN system versus PDM.

Distinct Site Motifs Activate O2 and H2 on Supported Au Nanoparticles in Liquid Water.

Au nanoparticles catalyze the activation and conversion of small molecules with rates and kinetic barriers that depend on the dimensions of the nanoparticle, composition of the support, and presence of catalytically culpable water molecules that solvate these interfaces. Here, molecular interpretations of steady-state rate measurements, kinetic isotope effects, and structural characterizations reveal how the interface of Au nanoparticles, liquid water, and metal oxide supports mediate the kinetically relevant activation of H2 and sequential reduction of O2-derived intermediates during the formation of H2O2 and H2O. Rates of H2 consumption are 10-100 fold greater on Au nanoparticles supported on metal oxides (e.g., titania) compared to more inert and hydrophobic materials (carbon, boron nitride). Similarly, Au nanoparticles on reducible and Lewis acidic supports (e.g., lanthana) bind dioxygen intermediates more strongly and present lower barriers (<22 kJ mol-1) for O-O bond dissociation than inert interfaces formed with silica (>70 kJ mol-1). Selectivities for H2O2 formation increase significantly as the diameters of the Au nanoparticles increase because differences in nanoparticle size change the relative fractions of exposed sites that exist at Au-support interfaces. In contrast, site-normalized rates and barriers for H2 activation depend weakly on the size of Au nanoparticles and the associated differences in active site motifs. These findings suggest that H2O aids the activation of H2 at sites present across all surface Au atoms when nanoparticles are solvated by water. However, molecular O2 preferentially binds and dissociates at Au-support interfaces, leading to greater structure sensitivity for barriers of O-O dissociation across different support identities and sizes of Au nanoparticles. These insights differ from prior knowledge from studies of gas-phase reactions of H2 and O2 upon Au nanoparticle catalysts within dilute vapor pressures of water (10-4 to 0.1 kPa H2O), in which catalysis occurs at the perimeter of the Au-support interface. In contrast, contacting Au catalysts with liquid water (55.5 M H2O) expands catalysis to all surface Au atoms and enables appreciable H2O2 formation.

Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment.

Individuals with Williams syndrome (WS), a neurodevelopmental disorder caused by hemizygous loss of 26-28 genes at 7q11.23, characteristically portray a hypersocial phenotype. Copy-number variations and mutations in one of these genes, GTF2I, are associated with altered sociality and are proposed to underlie hypersociality in WS. However, the contribution of GTF2I to human neurodevelopment remains poorly understood. Here, human cellular models of neurodevelopment, including neural progenitors, neurons, and three-dimensional cortical organoids, are differentiated from CRISPR-Cas9-edited GTF2I-knockout (GTF2I-KO) pluripotent stem cells to investigate the role of GTF2I in human neurodevelopment. GTF2I-KO progenitors exhibit increased proliferation and cell-cycle alterations. Cortical organoids and neurons demonstrate increased cell death and synaptic dysregulation, including synaptic structural dysfunction and decreased electrophysiological activity on a multielectrode array. Our findings suggest that changes in synaptic circuit integrity may be a prominent mediator of the link between alterations in GTF2I and variation in the phenotypic expression of human sociality.

Direct propylene epoxidation via water activation over Pd-Pt electrocatalysts.

Direct electrochemical propylene epoxidation by means of water-oxidation intermediates presents a sustainable alternative to existing routes that involve hazardous chlorine or peroxide reagents. We report an oxidized palladium-platinum alloy catalyst (PdPtOx/C), which reaches a Faradaic efficiency of 66 ± 5% toward propylene epoxidation at 50 milliamperes per square centimeter at ambient temperature and pressure. Embedding platinum into the palladium oxide crystal structure stabilized oxidized platinum species, resulting in improved catalyst performance. The reaction kinetics suggest that epoxidation on PdPtOx/C proceeds through electrophilic attack by metal-bound peroxo intermediates. This work demonstrates an effective strategy for selective electrochemical oxygen-atom transfer from water, without mediators, for diverse oxygenation reactions.

Improving the precision of shock resuscitation by predicting fluid responsiveness with machine learning and arterial blood pressure waveform data.

Fluid bolus therapy (FBT) is fundamental to the management of circulatory shock in critical care but balancing the benefits and toxicities of FBT has proven challenging in individual patients. Improved predictors of the hemodynamic response to a fluid bolus, commonly referred to as a fluid challenge, are needed to limit non-beneficial fluid administration and to enable automated clinical decision support and patient-specific precision critical care management. In this study we retrospectively analyzed data from 394 fluid boluses from 58 pigs subjected to either hemorrhagic or distributive shock. All animals had continuous blood pressure and cardiac output monitored throughout the study. Using this data, we developed a machine learning (ML) model to predict the hemodynamic response to a fluid challenge using only arterial blood pressure waveform data as the input. A Random Forest binary classifier referred to as the ML fluid responsiveness algorithm (MLFRA) was trained to detect fluid responsiveness (FR), defined as a ≥ 15% change in cardiac stroke volume after a fluid challenge. We then compared its performance to pulse pressure variation, a commonly used metric of FR. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), confusion matrix metrics, and calibration curves plotting predicted probabilities against observed outcomes. Across multiple train/test splits and feature selection methods designed to assess performance in the setting of small sample size conditions typical of large animal experiments, the MLFRA achieved an average AUROC, recall (sensitivity), specificity, and precision of 0.82, 0.86, 0.62. and 0.76, respectively. In the same datasets, pulse pressure variation had an AUROC, recall, specificity, and precision of 0.73, 0.91, 0.49, and 0.71, respectively. The MLFRA was generally well-calibrated across its range of predicted probabilities and appeared to perform equally well across physiologic conditions. These results suggest that ML, using only inputs from arterial blood pressure monitoring, may substantially improve the accuracy of predicting FR compared to the use of pulse pressure variation. If generalizable, these methods may enable more effective, automated precision management of critically ill patients with circulatory shock.

Modern Trends in Otologic Surgery and Implications for Residency Training.

OBJECTIVE: Placing a middle ear prosthesis is considered a key competency for the general otolaryngologist, but surgeons struggle to obtain and maintain this skill. The current study aims to characterize pre-coronavirus disease 2019 trends in stapedectomy and ossiculoplasty. STUDY DESIGN: Database review. SETTING: Tricare beneficiaries are treated at civilian and military facilities. METHODS: The Department of Defense beneficiary population of more than nine million persons per year was reviewed for patients undergoing either stapedectomy or ossiculoplasty between 2010 and 2019, identified by the current procedural terminology code. RESULTS: A total of 3052 stapedectomies and 7197 ossiculoplasties were performed. Over the 10-year study period, stapedectomy decreased by 23%, with an average annual rate of -2.7% per year (Pearson r = -.91, P = .0003). Ossiculoplasties declined by 18%, an average annual rate of -1.9% (r = -.8, P = .006). In combination, cases declined by 20%, an average annual rate of -2.2% (r = -.87, P = .001). CONCLUSION: While declines in stapedectomy surgery have been well reported, here we show steady declines in ossiculoplasty as well. If these trends continue, more cochlear implantations may be performed annually than stapedectomy and ossiculoplasty combined, with cochlear implantation likely to overtake ossicular chain surgery in the near future. These changes in surgical volume have a direct implication on resident education and general otolaryngology expectations after graduation. Strong consideration should be made to replace "Stapedectomy/Ossiculoplasty" as resident key indicator with "Cochlear Implantation," a more professionally meaningful skill.

Department of Defense Medical Examination Review Board Audiogram Screening Comparative Analysis.

INTRODUCTION: The Department of Defense Medical Examination Review Board (DoDMERB) plays a pivotal role in the assessment of medical fitness for aspiring military officers. A crucial component of this process is the screening audiogram, designed to evaluate hearing capabilities. However, recent observations of high disqualification rates following screening audiograms led to concerns about their accuracy. MATERIALS AND METHODS: This quality improvement project, conducted between 2017 and 2019, aimed to assess the concordance between screening audiograms and reference-standard audiometry, as well as to investigate the relationship between disqualification status and hearing thresholds at different frequencies. A sample of 134 candidates, drawn from various locations across the United States, was analyzed. RESULTS: Results revealed that the screening audiogram mean thresholds were twice that of the reference-standard audiogram, particularly in the lower frequencies. Additionally, we found that 84% of candidates were incorrectly disqualified by the screening exam when followed up by the reference-standard. Overall, Bland-Altman analysis revealed significant disagreement between these two tests. This discrepancy prompted a fundamental policy shift in 2020, where candidates who fail screening audiograms now automatically undergo reference-standard audiometry before any disqualification decision. This policy change reflects the commitment of DoDMERB to refining the medical screening process. It reduces the burden on candidates, provides a more comprehensive assessment, and ensures that qualified individuals are not erroneously disqualified.In addition to policy changes, this quality improvement project explored potential courses of action to enhance the screening audiogram process. Among these, improving contract specifications for testing facilities to minimize ambient noise emerged as the most practical and cost-effective approach. CONCLUSION: In conclusion, the project underscores the importance of refining medical screening processes to accurately assess candidates' qualifications while retaining the utility of screening audiograms. These efforts not only benefit aspiring military officers but also contribute to maintaining the high standards required for military service.

National Trends in Cochlear Implantation Across the Department of the Defense: A Case for Inclusion as a General Otolaryngology Core Competency.

OBJECTIVE: With ongoing national expansions in cochlear implantation (CI) candidacy criteria, more patients qualify for CI today than ever before. Among US veterans and military service members, the prevalence of qualifying degrees of hearing loss secondary to occupational noise exposure exceeds the general population. The primary aim of the current work was to evaluate CI trends across the military health system. STUDY DESIGN: Database review. SETTING: Military and civilian practices. PATIENTS: Department of Defense (DoD) beneficiaries who underwent CI. MAIN OUTCOME MEASURES: CI rates between 2010 and 2019. RESULTS: A total of 3,573 cochlear implant operations were performed among DoD beneficiaries from 2010 to 2019. A majority of patients (55%) were older than 64 years, with the next most commonly implanted age group being 0 to 4 years of age (14%). From 2010 to 2019, annual CI increased at a rate of 7.9% per year for all implantation over the study period ( r = 0.97, p < 0.0001); there was a statistically significant difference of this rate compared with tympanoplasty, which was used as a reference procedure (rate, -1.9%; p = 0.03). This trend was similar for beneficiaries implanted both in military (11.9% per year, r = 0.77, p = 0.009) and civilian facilities (7.7% per year, r = 0.96, p < 0.0001); there was no statistically significant difference between the annual growth rates of these groups ( p = 0.68). CONCLUSIONS: Although the number of devices implanted is rapidly increasing among DoD beneficiaries, reported national utilization rates remain low. This disparity likely exists in the general public, considering the aging demographic in the West and continual expansions in US Federal Drug Administration labeling. These data suggest that widespread expansion of the procedure to general otolaryngology practices will be required to meet current and future demands for CI. For this reason, CI should be considered for "key indicator" designation among residency training programs.

Timely Diagnosis of Basilar Artery Occlusion Leading to Improved Outcomes: A Case Report.

This is a case report of an 83-year-old female who presented to the emergency department within eight hours of symptom onset. A CT angiogram revealed a distal basilar artery occlusion, as well as a perfusion deficit in the right superior cerebellar artery. Her symptoms fluctuated, and she was started on a heparin drip, but later in the evening her symptoms worsened. A mechanical thrombectomy was performed by interventional radiology. The following morning, most of the patient's deficits had resolved, and, when seen in the clinic several weeks later, she continued to be asymptomatic. This case report highlights the importance of timely diagnosis and intervention in the management of distal basilar artery occlusion.

Precision Automated Critical Care Management: Closed-loop critical care for the treatment of distributive shock in a swine model of ischemia-reperfusion.

BACKGROUND: Goal-directed blood pressure management in the intensive care unit can improve trauma outcomes but is labor-intensive. Automated critical care systems can deliver scaled interventions to avoid excessive fluid or vasopressor administration. We compared a first-generation automated drug and fluid delivery platform, Precision Automated Critical Care Management (PACC-MAN), to a more refined algorithm, incorporating additional physiologic inputs and therapeutics. We hypothesized that the enhanced algorithm would achieve equivalent resuscitation endpoints with less crystalloid utilization in the setting of distributive shock. METHODS: Twelve swine underwent 30% hemorrhage and 30 minutes of aortic occlusion to induce an ischemia-reperfusion injury and distributive shock state. Next, animals were transfused to euvolemia and randomized into a standardized critical care (SCC) of PACC-MAN or an enhanced version (SCC+) for 4.25 hours. SCC+ incorporated lactate and urine output to assess global response to resuscitation and added vasopressin as an adjunct to norepinephrine at certain thresholds. Primary and secondary outcomes were decreased crystalloid administration and time at goal blood pressure, respectively. RESULTS: Weight-based fluid bolus volume was lower in SCC+ compared with SCC (26.9 mL/kg vs. 67.5 mL/kg, p = 0.02). Cumulative norepinephrine dose required was not significantly different (SCC+: 26.9 µg/kg vs. SCC: 13.76 µg/kg, p = 0.24). Three of 6 animals (50%) in SCC+ triggered vasopressin as an adjunct. Percent time spent between 60 mm Hg and 70 mm Hg, terminal creatinine and lactate, and weight-adjusted cumulative urine output were equivalent. CONCLUSION: Refinement of the PACC-MAN algorithm decreased crystalloid administration without sacrificing time in normotension, reducing urine output, increasing vasopressor support, or elevating biomarkers of organ damage. Iterative improvements in automated critical care systems to achieve target hemodynamics in a distributive-shock model are feasible.

Work of Breathing During Proportional Assist Ventilation as a Predictor of Extubation Failure.

BACKGROUND: Despite decades of research on predictors of extubation success, use of ventilatory support after extubation is common and 10-20% of patients require re-intubation. Proportional assist ventilation (PAV) mode automatically calculates estimated total work of breathing (total WOB). Here, we assessed the performance of total WOB to predict extubation failure in invasively ventilated subjects. METHODS: This prospective observational study was conducted in 6 adult ICUs at an academic medical center. We enrolled intubated subjects who successfully completed a spontaneous breathing trial, had a rapid shallow breathing index < 105 breaths/min/L, and were deemed ready for extubation by the primary team. Total WOB values were recorded at the end of a 30-min PAV trial. Extubation failure was defined as any respiratory support and/or re-intubation within 72 h of extubation. We compared total WOB scores between groups and performance of total WOB for predicting extubation failure with receiver operating characteristic curves. RESULTS: Of 61 subjects enrolled, 9.8% (n = 6) required re-intubation, and 50.8% (n = 31) required any respiratory support within 72 h of extubation. Median total WOB at 30 min on PAV was 0.9 J/L (interquartile range 0.7-1.3 J/L). Total WOB was significantly different between subjects who failed or were successfully extubated (median 1.1 J/L vs 0.7 J/L, P = .004). The area under the curve was 0.71 [95% CI 0.58-0.85] for predicting any requirement of respiratory support and 0.85 [95% CI 0.69-1.00] for predicting re-intubation alone within 72 h of extubation. Total WOB cutoff values maximizing sensitivity and specificity equally were 1.0 J/L for any respiratory support (positive predictive value [PPV] 70.0%, negative predictive value [NPV] 67.7%) and 1.3 J/L for re-intubation (PPV 26.3%, NPV 97.6%). CONCLUSIONS: The discriminative performance of a PAV-derived total WOB value to predict extubation failure was good, indicating total WOB may represent an adjunctive tool for assessing extubation readiness. However, these results should be interpreted as preliminary, with specific thresholds of PAV-derived total WOB requiring further investigation in a large multi-center study.

Using a Hybrid Approach to Increase the Impact of Medical Response to Natural Disasters.

The United Nations (UN) established an umbrella of organizations to manage distinct clusters of humanitarian aid. The World Health Organization (WHO) oversees the health cluster, giving it responsibility for global, national, and local medical responses to natural disasters. However, this centralized structure insufficiently engages local players, impeding robust local implementation. The Gorkha earthquake struck Nepal on April 25, 2015, becoming Nepal's most severe natural disaster since the 1934 Nepal-Bihar earthquake. In coordinated response, 2 organizations, Empower Nepali Girls and International Neurosurgical Children's Association, used a hybrid approach integrating continuous communication with local recipients. Each organization mobilized its principal resource strengths-material medical supplies or human capital-thereby efficiently deploying resources to maximize the impact of the medical response. In addition to efficient resource use, this approach facilitates dynamic medical responses from highly mobile organizations. Importantly, in addition to future earthquakes in Nepal, this medical response strategy is easily scalable to other natural disaster contexts and other medical relief organizations. Preemptively identifying partner organizations with complementary strengths, continuous engagement with recipient populations, and creating disaster- and region-specific response teams may represent viable variations of the WHO cluster model with greater efficacy in local implementation of treatment in acute disaster scenarios.

Impact of alcohol exposure on neural development and network formation in human cortical organoids.

Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

COVID-19 and transtympanic injections for sudden sensorineural hearing loss.

BACKGROUND: Multiple reports have linked COVID-19 infection with sudden sensorineural hearing loss (SSNHL), although other studies have failed to demonstrate this association. The current study was conceived to examine the rates of SSNHL across a large, principally national, population by characterizing the rate of transtympanic injections for SSNHL during the pandemic. METHODS: Retrospective review of all patients that underwent transtympanic injection from 2019 to 2020. RESULTS: Covering a unique beneficiary population of 9.6 million individuals of all ages in the United States, a statistically significant decrease in transtympanic injections for SSNHL was performed from 2019 to 2020 (p = 0.04, IRR = 0.91, 95 % CI = 0.84-0.99). No patient receiving a transtympanic injection also had a COVID-19 diagnosis. CONCLUSIONS: These findings support the idea that COVID-19 infections do not clinically significantly increase patients' risk of developing SSNHL. In fact, the decreased exposure through social isolation to other common viruses implicated in causing SSNHL may have actually led to a lower rate of SSNHL during the pandemic.

Outcomes of Dexmedetomidine with Local Regional Anesthesia in Carotid Endarterectomy.

BACKGROUND: Adequate sedation to complement regional techniques in carotid endarterectomy (CEA) can be challenging. Dexmedetomidine has both analgesic and amnesic properties and is reported to be a safe and acceptable alternative to conventional general endotracheal anesthesia (GETA). Outcomes observing dexmedetomidine in conjunction with regional anesthesia in CEA are not well described or known. OBJECTIVE: Compare the immediate (during hospitalization) and short-term (within 30 days of hospitalization) postoperative outcomes in patients who underwent CEA using GETA versus local regional anesthesia (LRA) alone versus dexmedetomidine with LRA at a single institution to determine whether dexmedetomidine is a safe adjunct and if there are anesthesia advantages over LRA alone. METHODS: A retrospective cohort study from January 2015 to December 2019 at Saint Joseph Mercy Ann Arbor. Patients were stratified into three groups based on anesthesia type: GETA, LRA, and dexmedetomidine (D) + LRA. Primary outcomes included stroke, myocardial infarction (MI), and death. Patient demographics were characterized and adjusted using propensity score weighting. RESULTS: Three hundred seventy nine patients met inclusion criteria; 182 patients in the GETA group, 66 in the D + LRA, and 131 in LRA. There were no significant differences across anesthesia groups in primary outcomes of stroke, MI, and death during the admission. The GETA group had significantly longer length of stay (LOS) compared to the D + LRA group (LOS = 1.51 days versus 0.85 days; P = 0.011) and the LRA group (LOS = 1.08 days; P = 0.003). However, there was no significant difference in hospital LOS between the D + LRA group and LRA only groups (P = 0.952). There was no significant difference between stroke (LRA 0.87%, GETA 0.85%, and LRA + Dex 3.52%), MI (LRA 0%, GETA 0.49%, LRA + Dex 0%), or death (LRA 5.24%, GETA 1.16%, LRA + Dex 0%), within 30 days between all three of the anesthesia groups. There was no significant difference in postoperative pain scores when comparing the GETA group (mean 1.3, standard deviation [SD] 2.5) to LRA (mean 1.2, SD 2.1) and between LRA and D + LRA (mean 0.9, SD 2.1). Procedure time (time of skin incision to closure) and total room time were comparable among all three anesthesia groups (LRA 2.2 hr, SD 2.2; GETA 2.1 hr, SD 0.5; LRA + Dex 2.1 hr, SD 0.5). CONCLUSIONS: The use of dexmedetomidine in addition to LRA is a safe and acceptable alternative to conventional GETA or LRA alone in CEA with shorter length of hospital stay when compared with GETA, improved patient tolerance based on physician observation, and similar rates of immediate and short-term complications and postoperative pain scores.

Physiowise: A Physics-aware Approach to Dicrotic Notch Identification.

Dicrotic Notch (DN), one of the most significant and indicative features of the arterial blood pressure (ABP) waveform, becomes less pronounced and thus harder to identify as a matter of aging and pathological vascular stiffness. Generalizable and automatic DN identification for such edge cases is even more challenging in the presence of unexpected ABP waveform deformations that happen due to internal and external noise sources or pathological conditions that cause hemodynamic instability. We propose a physics-aware approach, named Physiowise (PW), that first employs a cardiovascular model to augment the original ABP waveform and reduce unexpected deformations, then apply a set of predefined rules on the augmented signal to find DN locations. We have tested the proposed method on in-vivo data gathered from 14 pigs under hemorrhage and sepsis study. Our result indicates 52% overall mean error improvement with 16% higher detection accuracy within the lowest permitted error range of 30ms. An additional hybrid methodology is also proposed to allow combining augmentation with any application-specific user-defined rule set.

A Least Absolute Shrinkage and Selection Operator-Derived Predictive Model for Postoperative Respiratory Failure in a Heterogeneous Adult Elective Surgery Patient Population.

BACKGROUND: Postoperative respiratory failure (PRF) is associated with increased hospital charges and worse patient outcomes. Reliable prediction models can help to guide postoperative planning to optimize care, to guide resource allocation, and to foster shared decision-making with patients. RESEARCH QUESTION: Can a predictive model be developed to accurately identify patients at high risk of PRF? STUDY DESIGN AND METHODS: In this single-site proof-of-concept study, we used structured query language to extract, transform, and load electronic health record data from 23,999 consecutive adult patients admitted for elective surgery (2014-2021). Our primary outcome was PRF, defined as mechanical ventilation after surgery of > 48 h. Predictors of interest included demographics, comorbidities, and intraoperative factors. We used logistic regression to build a predictive model and the least absolute shrinkage and selection operator procedure to select variables and to estimate model coefficients. We evaluated model performance using optimism-corrected area under the receiver operating curve and area under the precision-recall curve and calculated sensitivity, specificity, positive and negative predictive values, and Brier scores. RESULTS: Two hundred twenty-five patients (0.94%) demonstrated PRF. The 18-variable predictive model included: operations on the cardiovascular, nervous, digestive, urinary, or musculoskeletal system; surgical specialty orthopedic (nonspine); Medicare or Medicaid (as the primary payer); race unknown; American Society of Anesthesiologists class ≥ III; BMI of 30 to 34.9 kg/m2; anesthesia duration (per hour); net fluid at end of the operation (per liter); median intraoperative FIO2, end title CO2, heart rate, and tidal volume; and intraoperative vasopressor medications. The optimism-corrected area under the receiver operating curve was 0.835 (95% CI,0.808-0.862) and the area under the precision-recall curve was 0.156 (95% CI, 0.105-0.203). INTERPRETATION: This single-center proof-of-concept study demonstrated that a structured query language extract, transform, and load process, based on readily available patient and intraoperative variables, can be used to develop a prediction model for PRF. This PRF prediction model is scalable for multicenter research. Clinical applications include decision support to guide postoperative level of care admission and treatment decisions.