The Lasting Impact of the COVID-19 Pandemic on Surgical Key Indicator Cases for Otolaryngology Residency Education.

OBJECTIVES: Early on during the COVID-19 pandemic, the US Centers for Medicare & Medicaid Services (CMS) and other government as well as medical institutions recommended that surgeons postpone nonessential surgeries. The aim of our study is to examine the impact of the COVID-19 pandemic on otolaryngology surgical training by evaluating changes in surgical volumes through various time points relative to the height of the pandemic. METHODS: We performed a retrospective review of all surgical cases performed by the Otolaryngology-Head and Neck Surgery department at a tertiary care academic center from 3 time periods: July 1st, 2018, to June 30th, 2019; July 1st, 2019, to June 30th, 2020; and July 1st, 2020, to June 30th, 2021. RESULTS: From the 2018-19 period to the 2020-21 period, the total number of overall cases decreased by 9.9%, from 2386 to 2148 cases. During this same time duration, the number of key indicator cases decreased by 13.4%, from 1715 to 1486 cases. Relative to other cases, ethmoidectomy, rhinoplasty, and stapes/OCR cases decreased the most during the 2019-20 period by 41.9%, 41.8%, and 29.5%, respectively. From the 2018-19 period to the 2020-21 period, thyroid/parathyroid cases decreased the most by 35.4%. Only ethmoidectomy and oral cavity cases showed increases during this period at 9.7% and 24.4%, respectively. CONCLUSIONS: Although case volumes have stayed relatively constant, key indicator case volumes at the present tertiary care academic center have not yet fully recovered from the COVID-19 pandemic. Efforts must be made to determine how this has impacted residency surgical education.

The Predictive Value of a Modified Frailty Index on Perioperative Morbidity and Mortality Following Otologic Surgery.

Objectives: Recently, determinants of frailty have become an increasingly recognized perioperative risk stratification tool. This study examines the predictive value of a 5-factor modified frailty index (mFI-5) on perioperative morbidity and mortality in patients undergoing otologic surgery, with a subgroup analysis based on surgery site. Study Design: Cross-sectional analysis. Setting: National surgical quality improvement program dataset 2005-2019. Patients: Current procedural terminology (CPT) codes were used to identify patients undergoing all otologic surgeries. Interventions: Otologic surgeries as indicated by CPT codes, including external ear, middle ear/mastoid, implants, and inner ear/facial nerve subgroups. Main Outcome Measures: Primary outcomes examined in this study included rates of overall complications and life-threatening complications within 30 days after surgery. Overall complications included superficial surgical site infections (SSI), deep incisional SSI, readmission, deep vein thrombosis, life-threatening complications, and mortality. Life-threatening complications included those classified as Clavien-Dindo grade IV: cerebrovascular accident, mechanical ventilation for more than 48 hours, reintubation, pulmonary embolism, acute renal failure, cardiac arrest, and myocardial infarction. Results: A total of 16,859 patients who underwent otologic surgery were identified, resulting in a cohort that was 47.5% male with an average age of 47.6 years (17.1 SD). Multivariable regression analysis of the entire cohort demonstrated a score of 3 or more on the mFI-5 was independently predictive of all postoperative complications (odds ratio (OR): 2.02, P < 0.0001). However, subgroup analysis showed that only "external ear" surgery correlated with mFi-5 (OR 8.03, P = 0.013). Conclusions: Higher frailty scores as measured by the mFI-5 correlate with postoperative morbidity and mortality after otologic surgery, though subgroup analysis reveals an association only with cases performed on the external ear. These findings suggest that for most otologic surgery, the mFI-5 frailty score is not predictive of postoperative complications.

The Curious Rise and Incomplete Fall of "Paracusis Willisii".

In 1672, Dr. Thomas Willis, a founder of the Royal Society and accomplished anatomist, described a peculiar phenomenon he had heard about "from a Credible Person" wherein two people with hearing loss appreciated some recovery of hearing when in the presence of increased background noise. Over time, this clinical entity came to bear his name, and Paracusis of Willis (or Paracusis Willisii) became a subject of both clinical interest as well as contention. In the early 1900s, a burgeoning appreciation for the diseases of the middle and inner ear heralded a boom in the study of paracuses, with many incorporating it as one of the diagnostic criteria of otosclerosis. At its peak interest, several potential etiologies were hypothesized in an effort to explain this puzzling entity-some plausible by today's understanding, many not. In the 1950s, however, its prominence in medical literature began to decline, though over the subsequent six decades it has yet to completely disappear. References to this peculiar phenomenon can still be found in prominent textbooks, review articles, and teaching resources. The fascinating story arc of paracusis of Willis serves as an illustration of how and why other questionable eponymic clinical descriptions can persist in conventional wisdom.

Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood.

BACKGROUND: Genetically modified pigs are a promising potential source of lung xenografts. Ex vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. METHODS: Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had one genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 h of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. RESULTS: Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 h generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55, or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. CONCLUSION: This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury and explore why some genes apparently exhibit neutral (hTBM, HLA-E) or inconclusive (CD39) effects, GalTKO, hCD46, HO-1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival.

Lung xenotransplantation: recent progress and current status.

Xenotransplantation has undergone important progress in controlling initial hyperacute rejection in many preclinical models, with some cell, tissue, and organ xenografts advancing toward clinical trials. However, acute injury, driven primarily by innate immune and inflammatory responses, continues to limit results in lung xenograft models. The purpose of this article is to review the current status of lung xenotransplantation--including the seemingly unique challenges posed by this organ-and summarize proven and emerging means of overcoming acute lung xenograft injury.

The NIMH Research Domain Criteria (RDoC) Project: implications for genetics research.

Heterogeneity of disorders, comorbidity across diagnoses, and reification of existing disease classifications are some of the challenges facing psychiatry in the twenty-first century. NIMH's Research Domain Criteria (RDoC) Project seeks to address these issues by defining basic dimensions of function that cut across disorders as traditionally defined and can be studied across multiple units of analysis, from genes to neural circuits to behaviors. The intent is to translate rapid progress in basic genetic, neurobiological, and behavioral research to an improved integrative understanding of psychopathology. In so doing, RDoC seeks to facilitate the development of new and/or optimally targeted treatments for mental disorders. The RDoC project would not have been possible without NIMH's long-term investment in basic research. Without the continuation of basic research, both related and unrelated to current RDoC domains and constructs, it will not be possible to sustain the RDoC effort. This article seeks to outline the relationship between RDoC and NIMH's ongoing support for broad-based basic research, from genetics to behavior.

Developing constructs for psychopathology research: research domain criteria.

There exists a divide between findings from integrative neuroscience and clinical research focused on mechanisms of psychopathology. Specifically, a clear correspondence does not emerge between clusters of complex clinical symptoms and dysregulated neurobiological systems, with many apparent redundancies. For instance, many mental disorders involve multiple disruptions in putative mechanistic factors (e.g., excessive fear, deficient impulse control), and different disrupted mechanisms appear to play major roles in many disorders. The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology. Such integration might be achieved by shifting the central research focus of the field away from clinical description to more squarely examine aberrant mechanisms. RDoC first aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms. This approach will require new methods to ascertain samples, relying on hypothesized psychopathological mechanisms to define experimental groups instead of traditional diagnostic categories. RDoC, by design, uncouples research efforts from clinically familiar categories to focus directly on fundamental mechanisms of psychopathology. RDoC proposes a matrix of domains and levels of analyses and invites the field to test and refine the framework. If RDoC is successful, the domains will ultimately relate to familiar psychopathologies in ways that promote new knowledge regarding etiology and more efficient development of new preventive and treatment interventions.

Social Neuroscience: Progress and Implications for Mental Health.

Social neuroscience is a new, interdisciplinary field devoted to understanding how biological systems implement social processes and behavior. Social neuroscience capitalizes on biological concepts and methods to inform and refine theories of social behavior, and it uses social and behavioral constructs and data to inform and refine theories of neural organization and function. We focus here on the progress and potential of social neuroscience in the area of mental health. Research in social neuroscience has grown dramatically in recent years. Among the most active areas of research we found are brain-imaging studies in normal children and adults; animal models of social behavior; studies of stroke patients; imaging studies of psychiatric patients; and research on social determinants of peripheral neural, neuroendocrine, and immunological processes. We also found that these areas of research are proceeding along largely independent trajectories. Our goals in this article are to review the development of this field, examine some currently promising approaches, identify obstacles and opportunities for future advances and integration, and consider how this research can inform work on the diagnosis and treatment of mental disorders.

Asymmetric total synthesis of rollicosin.

[structure: see text] The first total synthesis of rollicosin, a member of a rare subgroup of Annonaceous acetogenins containing two terminal gamma-lactones, is reported. The approach features a highly regio- and stereoselective tandem ring-closing/cross-metathesis reaction for construction of the east-wing lactone and incorporation of the alkyl spacer. Establishment of the C4 stereocenter and addition of the west-wing lactone were achieved by Sharpless asymmetric dihydroxylation and enolate alkylation.

Concise total synthesis of (-)-muricatacin by tandem ring-closing/cross metathesis.

A strategy for the synthesis of chiral 5-(1-hydroxyalk-2-enyl)-5H-furan-2-ones and its application to the total synthesis of (-)-muricatacin, in four steps and 37% overall yield from (R,R)-hexa-1,5-diene-3,4-diol, are described. The key synthetic step in this approach is a highly regioselective and stereoselective tandem ring-closing/cross metathesis reaction in which both lactone formation and alkyl chain extension are accomplished in an efficient one-pot process.

Tandem Diels-Alder/fragmentation approach to the synthesis of eleutherobin.

[reaction: see text] A synthesis of 28, the carbon framework of the eleutherobin aglycone, is reported in a 15-step sequence from readily available starting materials. The tandem Diels-Alder reaction of 6 and 7 to produce 18, in which three new rings and six new stereocenters are formed, is a key step in the reaction sequence.