RESUMEN
BACKGROUND: Up to 20% of patients undergoing total knee arthroplasty (TKA) remain dissatisfied with their outcome, leading to the identification of risk factors for poor outcomes. The purpose of this study was to analyze the effect of chronic sleep disorders on patient-reported outcomes after primary TKA. METHODS: A retrospective review of patients undergoing primary TKA was conducted using a prospectively collected database of patients from a single institution between 2018 and 2022. The cohort was split based on the presence of documented chronic sleep disorders, identified preoperatively from the electronic medical record using current procedural terminology codes. The sample was further restricted to include all patients who have sleep disorders (SDs), as well as a 3:1 propensity-matched (on age, sex, body mass index, and American Society of Anesthesiologists class) cohort of patients who had no documented SDs (NSDs) prior to surgery. The final sample included 172 patients (SD: 43; NSD: 129). Repeated-measures linear mixed model analysis was used to analyze the progression of Knee Injury and Osteoarthritis Outcome Score (KOOS) through time between groups. RESULTS: Those who had SDs had a lower preoperative mean total KOOS score (40.2) than the NSD group (44.1); however, this was not significantly different (P = .108). At 1 year postoperatively, those who had an SD had a significantly higher mean total KOOS score (87.2) than the NSD group (80.4), P = .005. When comparing total KOOS scores by group, over each time period, the SD group showed a better progression when compared to the NSD group, P = .001. CONCLUSIONS: Compared to patients who did not have documented chronic sleep disorders, patients who had a prior history of chronic sleep disorders reported significantly greater improvements in most KOOS domains in the 12-month period following TKA.
RESUMEN
Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749.