Association of Total Knee Replacement Removal From the Inpatient-Only List With Outpatient Surgery Utilization and Outcomes in Medicare Patients.

Importance: Little is known about the association of total knee replacement (TKR) removal from the Medicare inpatient-only (IPO) list in 2018 with outcomes in Medicare patients. Objective: To evaluate (1) patient factors associated with outpatient TKR use and (2) whether the IPO policy was associated with changes in postoperative outcomes for patients undergoing TKR. Design, Setting, and Participants: This cohort study included data from administrative claims from the New York Statewide Planning and Research Cooperative System. Included patients were Medicare fee-for-service beneficiaries undergoing TKRs or total hip replacements (THRs) in New York State from 2016 to 2019. Multivariable generalized linear mixed models were used to identify patient factors associated with outpatient TKR use, and with a difference-in-differences strategy to examine association of the IPO policy with post-TKR outcomes relative to post-THR outcomes in Medicare patients. Data analysis was performed from 2021 to 2022. Exposures: IPO policy implementation in 2018. Main Outcomes and Measures: Use of outpatient or inpatient TKR; secondary outcomes included 30-day and 90-day readmissions, 30-day and 90-day postoperative emergency department visits, non-home discharge, and total cost of the surgical encounter. Results: A total of 37 588 TKR procedures were performed on 18 819 patients from 2016 to 2019, with 1684 outpatient TKR procedures from 2018 to 2019 (mean [SD] age, 73.8 [5.9] years; 12 240 female [65.0%]; 823 Hispanic [4.4%], 982 non-Hispanic Black [5.2%], 15 714 non-Hispanic White [83.5%]). Older (eg, age 75 years vs 65 years: adjusted difference, -1.65%; 95% CI, -2.31% to -0.99%), Black (-1.44%; 95% CI, -2.81% to -0.07%), and female patients (-0.91%; 95% CI, -1.52% to -0.29%), as well as patients treated in safety-net hospitals (disproportionate share hospital payments quartile 4: -18.09%; 95% CI, -31.81% to -4.36%), were less likely to undergo outpatient TKR. After IPO policy implementation in the TKR cohort, there were lower adjusted 30-day readmissions (adjusted difference [AD], -2.11%; 95% CI, -2.73% to -1.48%; P < .001), 90-day readmissions ( -3.23%; 95% CI, -4.04% to -2.42%; P < .001), 30-day ED visits ( -2.45%; 95% CI, -3.17% to -1.72%; P < .001), 90-day ED visits (-4.01%; 95% CI, -4.91% to -3.11%; P < .001) and higher cost per encounter ($2988; 95% CI, $415 to $5561; P = .03). However, these changes did not differ from changes in the THR cohort except for increased TKR cost of $770 per encounter ($770; 95% CI, $83 to $1457; P = .03) relative to THR. Conclusions and Relevance: In this cohort study of patients undergoing TKR and THR, we found that older, Black, and female patients and patients treated in safety-net hospitals may have had lesser access to outpatient TKRs highlighting concerns of disparities. IPO policy was not associated with changes in overall health care use or outcomes after TKR, except for an increase of $770 per TKR encounter.

Next-Generation Sequencing for Pathogen Identification in Infected Foot Ulcers.

BACKGROUND: Accurate identification of primary pathogens in foot infections remains challenging due to the diverse microbiome. Conventional culture may show false-positive or false-negative growth, leading to ineffective postoperative antibiotic treatment. Next-generation sequencing (NGS) has been explored as an alternative to standard culture in orthopedic infections. NGS is highly sensitive and can detect an entire bacterial genome along with genes conferring antibiotic resistance in a given sample. We investigated the potential use of NGS for accurate identification and quantification of microbes in infected diabetic foot ulcer (DFU). We hypothesize that NGS will aid identification of dominant pathogen and provide a more complete profile of microorganisms in infected DFUs compared to the standard culture method. METHODS: Data were prospectively collected from 30 infected DFU patients who underwent operative treatment by a fellowship-trained orthopedic foot and ankle surgeon from October 2018 to September 2019. The average age of the patient was 60.4 years. Operative procedures performed were irrigation and debridement (12), toe or ray amputation (13), calcanectomies (4), and below-the-knee amputation (1). Infected bone specimens were obtained intraoperatively and processed for standard culture and NGS. Concordance between the standard culture and NGS was assessed. RESULTS: In 29 of 30 patients, pathogens were identified by both NGS and culture, with a concordance rate of 70%. In standard culture, Staphylococcus aureus (58.6%) was the most common pathogen, followed by coagulase-negative Staphylococcus (24.1%), Corynebacterium striatum (17.2%), and Enterococcus faecalis (17.2%). In NGS, Finegoldia magna (44.8%) was the most common microorganism followed by S. aureus (41.4%), and Anaerococcus vaginalis (24.1%). On average, NGS revealed 5.1 (range, 1-11) pathogens in a given sample, whereas culture revealed 2.6 (range, 1-6) pathogens. CONCLUSION: NGS is an emerging molecular diagnostic method of microbial identification in orthopedic infection. It frequently provides different profiles of microorganisms along with antibiotic-resistant gene information compared to conventional culture in polymicrobial foot infection. Clinical use of NGS for management of foot and ankle infections warrants further investigation. LEVEL OF EVIDENCE: Level II, diagnostic study.

The Evolving Story of Autoantibodies in Pemphigus Vulgaris: Development of the "Super Compensation Hypothesis".

Emerging data and innovative technologies are re-shaping our understanding of the scope and specificity of the autoimmune response in Pemphigus vulgaris (PV), a prototypical humorally mediated autoimmune skin blistering disorder. Seminal studies identified the desmosomal proteins Desmoglein 3 and 1 (Dsg3 and Dsg1), cadherin family proteins which function to maintain cell adhesion, as the primary targets of pathogenic autoAbs. Consequently, pathogenesis in PV has primarily considered to be the result of anti-Dsg autoAbs alone. However, accumulating data suggesting that anti-Dsg autoAbs by themselves cannot adequately explain the loss of cell-cell adhesion seen in PV, nor account for the disease heterogeneity exhibited across PV patients has spurred the notion that additional autoAb specificities may contribute to disease. To investigate the role of non-Dsg autoAbs in PV, an increasing number of studies have attempted to characterize additional targets of PV autoAbs. The recent advent of protein microarray technology, which allows for the rapid, highly sensitive, and multiplexed assessment of autoAb specificity has facilitated the comprehensive classification of the scope and specificity of the autoAb response in PV. Such detailed deconstruction of the autoimmune response in PV, beyond simply tracking anti-Dsg autoAbs, has provided invaluable new insights concerning disease mechanisms and enhanced disease classification which could directly translate into superior tools for prognostics and clinical management, as well as the development of novel, disease specific treatments.

Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model.

Pemphigus vulgaris (PV) is an autoimmune skin blistering disease effecting both cutaneous and mucosal epithelia. Blister formation in PV is known to result from the binding of autoantibodies (autoAbs) to keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3, and to a lesser extent, desmoglein 1, cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion, although additional autoAbs, whose role in blister formation is still unclear, are also known to be present in PV patients. Nevertheless, there remain large gaps in knowledge concerning the precise mechanisms through which autoAb binding induces blister formation. Consequently, the primary therapeutic interventions for PV focus on systemic immunosuppression, whose side effects represent a significant health risk to patients. In an effort to identify novel, disease-specific therapeutic targets, a multitude of studies attempting to elucidate the pathogenic mechanisms downstream of autoAb binding, have led to significant advancements in the understanding of autoAb-mediated blister formation. Despite this enhanced characterization of disease processes, a satisfactory explanation of autoAb-induced acantholysis still does not exist. Here, we carefully review the literature investigating the pathogenic disease mechanisms in PV and, taking into account the full scope of results from these studies, provide a novel, comprehensive theory of blister formation in PV.

Multiplexed autoantigen microarrays identify HLA as a key driver of anti-desmoglein and -non-desmoglein reactivities in pemphigus.

Patients with pemphigus vulgaris (PV) harbor antibodies reactive against self-antigens expressed at the surface of keratinocytes, primarily desmoglein (Dsg) 3 and, to a lesser extent, Dsg1. Conventionally, only antibodies targeting these molecules have been thought to contribute to disease pathogenesis. This notion has been challenged by a growing pool of evidence that suggests that antibodies toward additional targets may play a role in disease. The aims of this study were to (i) establish high-throughput protein microarray technology as a method to investigate traditional and putative autoantibodies (autoAbs) in PV and (ii) use multiplexed protein array technology to define the scope and specificity of the autoAb response in PV. Our analysis demonstrated significant IgG reactivity in patients with PV toward the muscarinic acetylcholine receptor subtypes 3, 4, and 5 as well as thyroid peroxidase. Furthermore, we found that healthy first- and second-degree relatives of patients with PV express autoAbs toward desmoglein and non-Dsg targets. Our analysis also identified genetic elements, particularly HLA, as key drivers of autoAb expression. Finally, we show that patients with PV exhibit significantly reduced IgM reactivity toward disease-associated antigens relative to controls. The use of protein microarrays to profile the autoAb response in PV advanced the current understanding of disease and provided insight into the complex relationship between genetics and disease development.