Citations

Background: Patient-level value analysis (PLVA) has been applied to several orthopaedic procedures but has not yet been utilized to assess the value of total knee arthroplasty (TKA). The purpose of this study was to evaluate the 1-year episode of care for TKA with use of PLVA to identify characteristics that influence value at both the patient and surgeon level. Methods: The institutional patient-reported outcome (PRO) database was queried for all patients who underwent TKA from 2020 to 2022. Patients were excluded on the basis of an index revision procedure, a pathology other than primary osteoarthritis, unicompartmental knee arthroplasty, robotic-assisted TKA, incomplete baseline or 1-year PROs, concomitant procedures (i.e., bilateral TKA or hardware removal), complications requiring readmission or reoperation, TKA without patellar resurfacing, the use of constrained implants, incomplete cost information, or other hip or knee arthroplasty procedure during the 1-year episode of care. PROs of interest included preoperative and 1-year postoperative Knee injury and Osteoarthritis Outcome Score-Joint Replacement (KOOS-JR) scores. Episode-of-care costs were calculated using time-driven activity-based costing. The 1-year value quotient (V KOOS ) was calculated for each patient as the ratio of the 1-year change in KOOS-JR score to the total episode-of-care cost. Results: A total of 684 patients (62% female; mean age, 68 ± 8 years) met the inclusion criteria. The mean KOOS-JR score significantly increased from baseline (53 ± 11) to 1 year (79 ± 14; p < 0.001), with a mean improvement of 26 ± 16. The mean total episode-of-care cost was $9,563 ± $2,370. There was no significant correlation between episode-of-care costs and the change in KOOS-JR score (r = 0.02; p = 0.581). Surgery performed at an ambulatory surgery center (p < 0.001) and as an outpatient procedure (p = 0.036) were predictive of lower costs. Patient-specific instrumentation (p < 0.001) and a tibial stem extension (p < 0.001) were predictive of higher costs. Older age (p = 0.023) and male sex (p = 0.007) were predictive of less improvement in KOOS-JR scores from baseline to 1 year. Conclusions: Our study identified patient and surgical characteristics that drive costs and PROs in TKA. PLVA can be used to identify “bright spots” in orthopaedic procedures to optimize care delivery. Level of Evidence: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Tuberous sclerosis complex (TSC) is a highly variable autosomal dominant disease characterized by dysregulated organ development and growth. Benign tumors, termed hamartomas, may occur across organ systems but typically involve the kidney, brain, skin, heart, and lung. The diagnosis, surveillance, and clinical management of TSC requires a multidisciplinary approach, adopted by dedicated multispecialty centers worldwide. Nephrology involvement predominantly stems from the morbidity and mortality related to the prototypical kidney lesion, angiomyolipomas, whose presence and degree confers risk of CKD, hypertension, retroperitoneal bleeding, and possibly renal cell carcinoma. Surveillance of kidney structural lesions, kidney function, and BP may enable early interventions that limit kidney-related morbidity and mortality, such as mammalian target of rapamycin inhibitor therapy. We review the epidemiology, genetics, and pathogenesis of TSC and how these inform the evaluation, diagnosis, and clinical management of TSC from the vantage point of the treating nephrologist.

Background: Tracheal intubation and mechanical ventilation are facilitated by neuromuscular blocking agents. We investigated the effectiveness of subjective clinical evaluation of neuromuscular function on retroglossal area size, since it determines spontaneous ventilation adequacy following tracheal extubation. Secondarily, we correlated changes in retroglossal area and depth of neuromuscular block assessed during both respiratory phases using quantitative neuromuscular monitoring. Methods: Once mechanical ventilation was no longer needed, antagonists were used to reverse the neuromuscular block in 21 consenting patients; adequacy of reversal was assessed subjectively by delivering a sequence of four rapid (2 Hz) electrical stimuli (train-of-four, TOF) to a peripheral nerve and assessing attainment of four equal muscle contractions (TOF ratio = 1.0), signifying normal neuromuscular function. Retroglossal area during both inhalation and exhalation were measured pharyngoscopically at various phases of neuromuscular recovery, including at baseline after anesthesia induction but before neuromuscular block onset and at recovery before tracheal extubation; area changes were correlated with depth of quantitatively measured neuromuscular block. Results: Clinicians’ subjective evaluation of readiness for tracheal extubation failed to identify significant residual block in most patients who required rescue antagonism. Markedly decreased retroglossal areas (inhalation: 39.5% of baseline; exhalation: 20.1% of baseline) were present at extubation, and 11 out of 21 (52.4%) patients needed rescue antagonism. In contrast, in patients with neuromuscular recovery to the currently recommended threshold determined quantitatively (TOF ratio > 0.90), retroglossal areas were only 80% recovered but returned to near baseline values when the TOF ratio ≥ 0.95. Conclusions: Quantitative monitoring should guide the timing of tracheal extubation. Current definitions of the minimal threshold for adequate neuromuscular recovery (TOF ratio > 0.90) after mechanical ventilation in postoperative patients should be re-evaluated. A TOF ratio > 0.95 better correlates with return to normal (baseline) retroglossal area during both inhalation and exhalation.

Mesenchymal dendritic cell neoplasms represent a distinct category of hematologic malignancies that challenge traditional classifications of histiocytic and classical dendritic/Langerhans cell neoplasms. Historically grouped under the broader umbrella of dendritic cell neoplasms, these entities differ significantly in their ontogeny, histopathologic features, molecular alterations, and clinical behavior. They are categorized into three main subtypes including follicular dendritic cell sarcoma, fibroblastic reticular cell tumor, and EBV-positive inflammatory follicular dendritic cell sarcoma/fibroblastic reticular cell tumor. They originate from mesenchymal stromal cells, and genetic alterations activating the NF- κβ pathway are frequent in follicular dendritic cell sarcomas. Immunophenotypic characterization is critical to distinguish these from other hematologic malignancies including histiocytic and classical dendritic/Langerhans cell neoplasms and other solid (non-hematopoietic) cancers. This review recapitulates current knowledge on existing classifications, details their diverse ontogeny from classical dendritic cell neoplasms, and provides insights into their clinicopathologic characteristics to improve diagnostic accuracy. We detail two case studies that demonstrate the challenges involved in the histopathologic diagnosis of these rare tumors, necessitating a comprehensive workup. Integrating developmental biology into practical diagnostic algorithms is essential to improve recognition and classification of these underdiagnosed neoplasms, ultimately guiding timely management.

Henipaviruses are emerging zoonotic viruses that have caused deadly outbreaks in humans and livestock across several regions of the world. The fusion (F) protein of henipaviruses plays a critical role in viral entry into host cells and represents a key determinant of viral pathogenicity. This review provides a comprehensive analysis of current knowledge regarding trafficking, activation, as well as the role in particle assembly, of henipavirus F proteins. We discuss the unique characteristics of henipavirus F proteins compared to other paramyxovirus fusion proteins, with particular emphasis on their distinctive trafficking and activation mechanisms. Attention is also given to novel henipaviruses that have been detected in hosts other than bats, namely rodents and shrews. These viruses are sufficiently different that the International Committee on Taxonomy of Viruses has proposed a new genus for them, the Parahenipaviruses. We discuss how variations in F protein characteristics between Henipaviruses, Parahenipaviruses, and yet-unclassified henipa-like viruses might influence their trafficking and activation. Understanding these molecular mechanisms is crucial for developing effective therapeutic strategies against henipavirus infections and for predicting the emergence of novel henipavirus strains with pandemic potential.

Background/Objective: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with 44Sc (t1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as 89Zr (t1/2 = 78.41 h). Methods: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with 44Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (n = 3) for [44Sc]Sc-B11-IgG and 73.6 ± 12.1% (n = 3) for [44Sc]Sc-B11-nanobody, before purification. Results: Significantly higher uptake in the PD-L1+ cells than PD-L1KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. Conclusions: Due to the high non-specific uptake in vitro, the 44Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with 44Sc, due to their well-matched biological and physical half-life.