Private Equity Investment in Surgical Care.

OBJECTIVE: To characterize the extent of private equity investment affecting surgical care. SUMMARY BACKGROUND DATA: Over the last decade, investor-backed, for-profit private equity groups have invested in healthcare at an unprecedented rate, but the breadth of these investments affecting surgical practice remains largely unknown. METHODS: Four nationally representative databases were used to identify all merger/acquisitions involving surgical practices between 2015-2019, determine private equity investment in those transactions, and link the acquisitions with a physician dataset. RESULTS: 1,542 unique transactions were identified, of which 539 were financed by private equity. 58 transactions were then classified into their respective categories within surgical care: digestive disease, orthopedics, urology, vascular surgery, and plastic/cosmetic surgery. These transactions accounted for 199 practice sites and 1,405 physicians, averaging 24.2 physicians per transaction. Acquisition activity peaked in 2017 with a total of 63 practices involved. Digestive disease, urology, and orthopedic surgery accounted for the most activity. General surgeons were involved in a small share of the digestive disease practice acquisitions. Three "surgery-adjacent" categories were also identified: anesthesiology, ambulatory surgery centers, and surgical staffing firms. Among these, anesthesia was the largest category in terms of practices (194) and physicians (2,660) involved in transactions across the study period. Medical Service Organizations (MSOs) were a key mechanism through which private equity firms invested in surgical care. CONCLUSIONS: Private equity has engaged in substantial investment within surgical specialties, creating increased practice consolidation. These investments affect all levels of medical care and have notable implications for patients, practitioners, and policymakers.

Serial Intralesional Steroid Injection for Subglottic Stenosis: Systemic Side Effects and Impact on Surgery-Free Interval.

OBJECTIVES: In-office serial intralesional steroid injections (SILSIs) have become a commonly used treatment for subglottic stenosis. We characterized the impact of SILSIs on the time between operating room visits and incidence of glucocorticoid systemic side effects. STUDY DESIGN: Retrospective case series. SETTING: Academic tertiary care center. METHODS: All patients with subglottic stenosis receiving SILSIs at 1 institution from 2016 to 2020 were included. Surgery-free interval was compared using paired t tests. Side effect incidence was calculated with Kaplan-Meier methodology for visualization. RESULTS: Nineteen patients and 207 procedures were included. The majority of patients were White (95%) and female (95%) and had idiopathic subglottic stenosis (53%). Mean surgery-free interval for all patients was 8.7 months (95% CI, 5.6-11.8) before initiating SILSIs. Of 11 patients with calculable surgery-free interval, 10 experienced improvement, with a mean surgery-free interval increase of 4.6 months (95% CI, 2.4-6.7). Seven patients have not required surgery since initiation of SILSIs, with a mean follow-up time of 28 months (95% CI, 25-31). Noncutaneous systemic side effects occurred at a mean 3.2 months (95% CI, 2.4-4.0) from first injection and included Cushing's syndrome, increased intraocular pressure, central serous chorioretinopathy, and new insulin requirement in the setting of diabetes. CONCLUSIONS: Ninety-one percent of patients who initiated SILSIs and had a subsequent return to the operating room experienced a mean 4.6-month increase in surgery-free interval. Systemic side effects of glucocorticoids occurred in 32% of patients after initiating SILSIs. This should be considered in preprocedure counseling and side effect monitoring during treatment.

Postacute COVID-19 Laryngeal Injury and Dysfunction.

OBJECTIVE: Patients with COVID-19 are at risk for laryngeal injury and dysfunction secondary to respiratory failure, prolonged intubation, and other unique facets of this illness. Our goal is to report clinical features and treatment for patients presenting with voice, airway, and/or swallowing concerns postacute COVID-19. STUDY DESIGN: Case series. SETTING: Academic tertiary care center. METHODS: Patients presenting with laryngeal issues following recovery from COVID-19 were included after evaluation by our laryngology team. Data were collected via retrospective chart review from March 1, 2020, to April 1, 2021. This included details of the patient's COVID-19 course, initial presentation to laryngology, and subsequent treatment. RESULTS: Twenty-four patients met inclusion criteria. Twenty (83%) patients were hospitalized, and 18 required endotracheal intubation for a median (range) duration of 14 days (6-31). Ten patients underwent tracheostomy. Patients were evaluated at a median 107 days (32-215) after their positive SARS-CoV-2 test result. The most common presenting concerns were dysphonia (n = 19, 79%), dyspnea (n = 17, 71%), and dysphagia (n = 6, 25%). Vocal fold motion impairment (50%), early glottic injury (39%), subglottic/tracheal stenosis (22%), and posterior glottic stenosis (17%) were identified in patients who required endotracheal intubation. Patients who did not need intubation were most frequently treated for muscle tension dysphonia (67%). CONCLUSION: Patients may develop significant voice, airway, and/or swallowing issues postacute COVID-19. These complications are not limited to patients requiring intubation or tracheostomy. Multidisciplinary laryngology clinics will continue to play an integral role in diagnosing and treating patients with COVID-19-related laryngeal sequelae.

Voice-Related Quality of Life Is Associated with Postoperative Change in Subglottic Stenosis.

OBJECTIVES: To characterize the impact of subglottic stenosis (SGS) on voice-related quality of life (V-RQOL) and quantify the effect of treatment on voice outcomes. STUDY DESIGN: Case series. METHODS: Retrospective review of SGS patients treated from 1996 to 2018 at a single institution to assess for 1) V-RQOL association with individual patient cumulative treatment number and 2) V-RQOL correlation with treatment type, time between treatments, and degree of stenosis. Analysis included both parametric and nonparametric statistical comparison across treatment types and multivariable and univariate linear regression. RESULTS: Sixty-one patients, predominantly white (93%) and female (93%), were included. Etiology of SGS included idiopathic (61%), iatrogenic (16%), granulomatosis with polyangiitis (16%), and other (7%). The plurality of patients had four or more treatments (44%), with the remainder having one (28%), two (13%), or three treatments (15%). Analysis of change between pre- and postoperative V-RQOL scores was completed for 130 treatments. These included dilation with laser incision (52%), in-office injection (34%), dilation without division (8%), cricotracheal resection (1%), and all other treatment (8%). For every 10% improvement in airway caliber postoperatively, there was a 1.3-point improvement in calculated V-RQOL (r = 0.27, P = .02). After adjustment for treatment type, age, sex, and SGS etiology, this association held (beta = 1.5, P = .02). Change in V-RQOL was not associated with treatment type, treatment number, or time between treatments. CONCLUSION: Patients with subglottic stenosis who have greater degree of change in airway caliber experience greater improvement in V-RQOL scores following treatment. V-RQOL scores are not associated with treatment type or time between individual treatments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:360-365, 2021.

Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes.

Nef is an HIV-encoded accessory protein that enhances pathogenicity by down-regulating major histocompatibility class I (MHC-I) expression to evade killing by cytotoxic T lymphocytes (CTLs). A potent Nef inhibitor that restores MHC-I is needed to promote immune-mediated clearance of HIV-infected cells. We discovered that the plecomacrolide family of natural products restored MHC-I to the surface of Nef-expressing primary cells with variable potency. Concanamycin A (CMA) counteracted Nef at subnanomolar concentrations that did not interfere with lysosomal acidification or degradation and were nontoxic in primary cell cultures. CMA specifically reversed Nef-mediated down-regulation of MHC-I, but not CD4, and cells treated with CMA showed reduced formation of the Nef:MHC-I:AP-1 complex required for MHC-I down-regulation. CMA restored expression of diverse allotypes of MHC-I in Nef-expressing cells and inhibited Nef alleles from divergent clades of HIV and simian immunodeficiency virus, including from primary patient isolates. Lastly, we found that restoration of MHC-I in HIV-infected cells was accompanied by enhanced CTL-mediated clearance of infected cells comparable to genetic deletion of Nef. Thus, we propose CMA as a lead compound for therapeutic inhibition of Nef to enhance immune-mediated clearance of HIV-infected cells.

Hematopoietic Stem and Progenitor Cells Are a Distinct HIV Reservoir that Contributes to Persistent Viremia in Suppressed Patients.

Long-lived reservoirs of persistent HIV are a major barrier to a cure. CD4+ hematopoietic stem and progenitor cells (HSPCs) have the capacity for lifelong survival, self-renewal, and the generation of daughter cells. Recent evidence shows that they are also susceptible to HIV infection in vitro and in vivo. Whether HSPCs harbor infectious virus or contribute to plasma virus (PV) is unknown. Here, we provide strong evidence that clusters of identical proviruses from HSPCs and their likely progeny often match residual PV. A higher proportion of these sequences match residual PV than proviral genomes from bone marrow and peripheral blood mononuclear cells that are observed only once. Furthermore, an analysis of near-full-length genomes isolated from HSPCs provides evidence that HSPCs harbor functional HIV proviral genomes that often match residual PV. These results support the conclusion that HIV-infected HSPCs form a distinct and functionally significant reservoir of persistent HIV in infected people.