Hospital for Special Surgery

BackgroundBrepocitinib is a first-in-class, oral, selective TYK2–JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis.MethodsIn this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence.ResultsA total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, −2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial.ConclusionsIn adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.)

Curve progression to surgical range in patients with adolescent idiopathic scoliosis (AIS) is strongly associated with the initial major curve angle and the degree of skeletal maturity as staged by the modified Proximal Humerus Ossification System (PHOS) and other systems. Our purpose was to (1) develop a prognostic model and risk score to estimate the probability of progression to surgical indications in untreated patients using the PHOS and (2) compare its performance to a model using the Risser stage. Patients from the BrAIST study and 2 other institutions were followed to either skeletal maturity (Risser 4+), a major curve angle of ≥45°, or spinal fusion. Candidate variables for the predictive models included age, sex, major curve angle, Scoliosis Research Society (SRS) curve classification, status of triradiate cartilage, Risser stage, and PHOS. Model calibration and discrimination were evaluated. A probability threshold was set, creating low- and high-risk groups to aid in clinical decision-making. Overall, 164 patients (77% female) were included. The mean age at presentation was 12.2±1.4 years (range: 10 to 16 years), and the mean maximum major curve angle was 24±9° (range: 10° to 43°). Fifty-six (34%) patients progressed to a surgical range or had a spinal fusion. The PHOS model included the major curve angle and the presence/absence of a thoracic apex. The model demonstrated strong discrimination (c-statistic = 0.89) and calibration (ICI = 0.02), performing similarly to one developed in this sample using the Risser stage. The sensitivity was 0.91, the specificity was 0.71, the PPV was 0.62, and the NPV was 0.94 at the probability cut-point of 0.22. This study derived a prognostic model estimating the baseline risk of progression to surgical indications in AIS patients using the PHOS. Estimates from this model can inform the shared decision-making process and motivate compliant bracing. Further validation in larger independent samples and exploration of the PHOS to predict bracing outcomes should be performed. Level II.

Bone quality is a critical determinant of outcomes following spine fusion surgery. However, patients with skeletal deficits are often only identified intra-operatively when there are unexpected problems with hardware placement, or post-operatively, when bone-related complications occur. MRI is routinely performed for diagnosis and surgical planning, making a technique based on clinical MRI ideal to opportunistically evaluate bone health. Texture analysis of trabecular bone from MRI has recently emerged as a biomarker of bone quality. This prospective study related pre-operative MRI-based texture from standard clinical images and areal BMD (aBMD) by DXA to post-operative outcomes following spine fusion. T1-weighted MR images were acquired from patients undergoing instrumented lumbar spine fusion. The following texture features were derived within the L1-L5 vertebral bodies to characterize the local distribution and spatial organization of signal intensity: contrast (variability) and entropy (disorder) for which higher values reflect high heterogeneity; angular second moment (ASM; uniformity) and inverse difference moment (IDM; homogeneity) for which higher values reflect low heterogeneity. Of 72 patients enrolled, mean age was 63 years (54% female). Patients were followed for a median of 13 months after surgery. Skeletal complications occurred in 27 patients (38%); proximal junctional kyphosis and screw loosening were the most common. There was no association between new complications and aBMD at any site. In contrast, patients who developed post-operative complications had greater pre-operative MRI-texture heterogeneity than those who did not, specifically higher contrast (26%) and entropy (12%), lower ASM (-13%) and IDM (-25%, p < 0.01 for all). In summary, greater heterogeneity of pre-operative bone texture from clinical MRIs was associated with skeletal complications following spine fusion. These findings support this novel method as an opportunistic screening technique to foster earlier identification of high-risk patients who would benefit from interventions to improve surgical outcomes.

The ability of a surgeon to provide accurate visual estimates of intraoperative gaps during total knee arthroplasty (TKA) is not well understood. This study evaluated: 1) the accuracy of gap estimation in extension and in flexion; 2) the accuracy of gap estimation in the medial and lateral compartments, also in extension and flexion; 3) the differences in accuracy among surgeons; and 4) the frequency of clinically significant errors in gap estimation, defined as greater than 1 mm. A posterior stabilized TKA was performed on seven cadaveric knees. Five fellowship-trained arthroplasty surgeons and one orthopaedic resident manually stressed each knee, and visually assessed the medial and lateral gaps in full extension and 90° of flexion. Gaps were objectively measured via a motion capture system. Gap estimation error was calculated as the difference between the surgeons' visual assessment and the measured gaps. Across all surgeons and knees, the mean gap estimation error was -0.4 mm (SD 0.7), with the majority (72%) of gaps being underestimated. Errors were greater in extension (-0.7 mm (SD 0.8)) than in flexion (-0.2 mm (SD 1.0)) (p < 0.001). Lateral gap error was less in flexion (-0.1 mm (SD 1.0)) than extension (-0.7 mm (SD 0.8)). Gap estimation error pooled for all assessments differed between surgeons, ranging from a mean error of -0.8 mm (SD 0.8) to 0.2 mm (SD 1.2) (p < 0.001). Clinically significant gap estimation errors (> 1 mm) occurred in 33% of assessments in extension and 26% in flexion (p = 0.315, not statistically different). The frequency of such errors varied by surgeon ranging from 18% to 42% (p = 0.370). Surgeons tend to underestimate intraoperative gaps during TKA, particularly in extension. Clinically meaningful gap estimation errors (> 1 mm) occurred in up to 33% (26/78) of exams, supporting the need to enhance gap assessment accuracy.

Although clinical outcomes after total joint arthroplasty (TJA) are generally positive and reproducible, certain medical and surgical complications are not insignificant and may negatively affect patient outcomes. Hyponatremia is an often overlooked and preventable electrolyte abnormality in patients undergoing TJA that may lead to adverse clinical consequences, including nausea, dizziness, seizures, and death. Incurring such complications may alter the trajectory of recovery after a routine TJA procedure, requiring additional interventions and prolonged hospital stay, and negatively impacting the value of health care rendered. The Hospital for Special Surgery in New York City is a high-volume, tertiary musculoskeletal care center that performs more than 43,000 orthopedic surgical procedures annually; to sustain this volume and positive hospital performance metrics, optimizing value per episode of care is essential. Therefore, the authors implemented an internal quality-improvement investigation utilizing digital implementation of an artificial intelligence (AI)–driven prediction model into the electronic medical record workflow to identify patients at an elevated risk of hyponatremia presenting for elective TJA between April 1, 2022, and March 31, 2023. This was transformed into a clinical decision support tool utilizing a best practice advisory alert on opening the patient chart, raising awareness for those involved in the episode of care. Among those identified as at risk, an intervention was initiated on behalf of the anesthesiologist of record that represented a deviation from standard of institutional care by changing fluid management from lactated Ringer’s intravenous maintenance rate to a Multiple Electrolytes Injection, Type 1 solution, as well as by discontinuing medications with known associations to hyponatremia (such as duloxetine, hydrochlorothiazide, and nonsteroidal antiinflammatory medications). During the 1-year trial period, comprising a total of 22,271 consecutive TJA episodes of care, the authors observed an institutional reduction in the overall rate of hyponatremia of greater than 50% (from 29% to 14%). This study demonstrates the efficacy and feasibility of integrating a scalable AI-based digital solution into the clinical workflow to help augment clinical care through risk stratification and selective interventions.

Acute Achilles tendon rupture is a common and serious injury in sports medicine. Clinical studies demonstrate that both surgical and nonsurgical interventions can achieve satisfactory outcomes; however, considerable debate exists regarding the optimal treatment modality for this injury. Currently, most animal experimental studies on acute Achilles tendon rupture lack clinical relevance due to inadequate fixation of the ankle joint. This study involved 162 male C57BL/6 mice and 30 Scx-CreERT2; Rosa26-tdTomato transgenic mice. The injury+repair groups underwent Achilles tenotomy followed by Kessler suture repair, while the injury+no repair groups underwent tenotomy alone. Ankle joints were immobilized at 160° (plantar flexion) or 90° (neutral alignment). Samples were collected at 2 and 4 weeks post-injury for biomechanical, histological, and quantitative real-time PCR (qPCR) analyses, including tracing of Scx+ tendon progenitor stem cells. Biomechanical analysis was performed 2 and 4 weeks post-injury. At 2 weeks, the injury+repair group immobilized at a maximum plantar flexion angle of 160° showed significantly higher failure force and stiffness compared with the injury+no repair+160° group. However, there was no significant difference between the groups at 4 weeks (p > 0.05). The failure force in each 160° group was significantly higher than in the corresponding 90° group (p < 0.0001). Histological analysis indicated better collagen fiber alignment and higher expression of collagen type I alpha 1 (COL1A1) in the injury+repair groups. qPCR revealed generally higher expression of tendon repair-related genes (Scx, Tnmd, Tgfb1) in the injury+repair groups, while inflammatory factors (Il1b, Il6) were higher in the injury+no repair+90° group. Scx+ tendon progenitor stem cell tracing showed the greatest percentage in the injury+repair+160° group. Both surgical and nonsurgical treatments for acute Achilles tendon rupture achieved satisfactory tendon healing results when the ankle joint was maintained in maximum plantar flexion. However, surgical treatment yielded superior histological tendon repair. The results suggest that clinical trials may show immobilization in maximum plantar flexion following surgery to be optimal for tendon healing.

Intra-articular steroid injections (IASI) and knee arthroscopies are occasionally performed after total knee arthroplasty (TKA) in patients with persistent pain, inflammation, or mechanical symptoms. Prior studies have raised concern regarding a potential increased risk of periprosthetic joint infection (PJI) following such procedures. Comparative data on infection rates across these post-TKA interventions remain limited. This study evaluates and compares the incidence of PJI in patients who underwent IASI, knee arthroscopy, or both following primary TKA. A retrospective cohort study was conducted using patients who received primary TKA between January 2017 and January 2023. PJI was defined according to the 2018 Musculoskeletal Infection Society (MSIS) criteria. Infection rates were compared using Fisher’s exact test. The control group was propensity score matched on a 5:1 ratio independently for IASI and knee arthroscopy based on age, sex, ASA score, Charlson comorbidity index, and surgical date. 362 patients (372 knees) met inclusion criteria for the treatment groups: 173 received steroid injection only (group 1), 142 underwent arthroscopy only (group 2), and 57 received both (group 3). When comparing all treatment groups (1.34%) to the matched control group of 1850 patients (0.97%), there was no significant difference between infection rates (p = 0.5708) at a minimum 2 year follow up. The infection rate in group 1 was 1.73%, in group 2 was 0.70%, and in group 3 was 1.75%. Two of the 3 infections in group 1 occurred within 30 days of IASI. The 6 month PJI rate in the 230 knees receiving IASI (group 1 and 3) was 0.87%. The fact that two infections occurred within 30 days of IASI suggests a slightly increased risk of infection after IASI. However, reported PJI rates within 6 months of IASI and Arthroscopy are very low and both are considered reasonable treatment options in selected patients.