Body Mass Index as a Predictor for Postoperative Complications Following Carpometacarpal Arthroplasty.

Purpose: Carpometacarpal (CMC) arthroplasty is an effective surgical treatment to relieve pain and improve function for osteoarthritis of the CMC joint. The association between body mass index (BMI) and postoperative complications has been studied for other orthopedic procedures, including total knee arthroplasty, total hip arthroplasty, and total shoulder arthroplasty. However, BMI has not been studied as a risk factor for postoperative complications following CMC arthroplasty. The purpose of this study was to determine the postoperative complications associated with different categories of BMI following CMC arthroplasty. We hypothesized that increasing BMI is associated with more severe complications. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent CMC arthroplasty between 2015 and 2020. Patient demographics, comorbidities, surgical characteristics, and 30-day postoperative complication data were collected. Patients were stratified into cohorts based on BMI as follows: underweight (BMI < 18.5 kg/m2), normal/reference (18.5 kg/m2 ≤ BMI < 30.0 kg/m2), obese (30.0 kg/m2 ≤ BMI < 35.0 kg/m2), severely obese (35.0 kg/m2 ≤ BMI < 40.0 kg/m2), and morbidly obese (BMI ≥ 40.0 kg/m2). Multivariate logistic regression was used to identify postoperative complications associated with each cohort. Results: In total, 6,432 patients were included in this study: 3,622 (56.3%) patients were included in the normal/reference cohort, 77 (1.2%) patients were included in the underweight cohort, 1,479 (23.0%) patients were included in the obese cohort, 718 (11.2%) patients were included in the severely obese cohort, and 536 (8.3%) patients were included in the morbidly obese cohort. The obese cohort was independently associated with a higher rate of superficial incisional surgical-site infection (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.00-4.44; P = .050). The morbidly obese cohort was independently associated with readmission (OR, 3.35; 95% CI, 1.15-9.74; P = .026) and reoperation (OR, 3.40; 95% CI, 1.04-1.11; P = .043). Conclusions: Morbid obesity is a clinically significant predictor for readmission and reoperation within 30 days following CMC arthroplasty. Obesity is a clinically significant predictor for superficial incisional surgical-site infection within 30 days following CMC arthroplasty. Clinical relevance: A better understanding of BMI as a risk factor for postoperative complications may allow surgeons to improve preoperative risk stratification and patient counseling. Type of study/level of evidence: Prognostic III.

A Critical Role for DLK and LZK in Axonal Repair in the Mammalian Spinal Cord.

The limited ability for axonal repair after spinal cord injury underlies long-term functional impairment. Dual leucine-zipper kinase [DLK; MAP kinase kinase kinase 12; MAP3K12] is an evolutionarily conserved MAP3K implicated in neuronal injury signaling from Caenorhabditis elegans to mammals. However, whether DLK or its close homolog leucine zipper kinase (LZK; MAP3K13) regulates axonal repair in the mammalian spinal cord remains unknown. Here, we assess the role of endogenous DLK and LZK in the regeneration and compensatory sprouting of corticospinal tract (CST) axons in mice of both sexes with genetic analyses in a regeneration competent background provided by PTEN deletion. We found that inducible neuronal deletion of both DLK and LZK, but not either kinase alone, abolishes PTEN deletion-induced regeneration and sprouting of CST axons, and reduces naturally-occurring axon sprouting after injury. Thus, DLK/LZK-mediated injury signaling operates not only in injured neurons to regulate regeneration, but also unexpectedly in uninjured neurons to regulate sprouting. Deleting DLK and LZK does not interfere with PTEN/mTOR signaling, indicating that injury signaling and regenerative competence are independently controlled. Together with our previous study implicating LZK in astrocytic reactivity and scar formation, these data illustrate the multicellular function of this pair of MAP3Ks in both neurons and glia in the injury response of the mammalian spinal cord.SIGNIFICANCE STATEMENT Functional recovery after spinal cord injury is limited because of a lack of axonal repair in the mammalian CNS. Dual leucine-zipper kinase (DLK) and leucine zipper kinase (LZK) are two closely related protein kinases that have emerged as regulators of neuronal responses to injury. However, their role in axonal repair in the mammalian spinal cord has not been described. Here, we show that DLK and LZK together play critical roles in axonal repair in the mammalian spinal cord, validating them as potential targets to promote repair and recovery after spinal cord injury. In addition to regulating axonal regeneration from injured neurons, both kinases also regulate compensatory axonal growth from uninjured neurons, indicating a more pervasive role in CNS repair than originally anticipated.

Oligodendrocytic but not neuronal Nogo restricts corticospinal axon sprouting after CNS injury.

Recovery from injury to the central nervous system (CNS) is limited in the mammalian adult. Nonetheless, some degree of spontaneous recovery occurs after partial CNS injury. Compensatory axonal growth from uninjured neurons, termed sprouting, contributes to this naturally occurring recovery process and can be modulated by molecular intervention. Extensive studies have depicted a long-held hypothesis that oligodendrocyte-derived Nogo restricts axonal sprouting and functional recovery after CNS injury. However, cell type-specific function of Nogo in compensatory sprouting, spinal axon repair or functional recovery after CNS injury has not been reported. Here we present data showing that inducible, cell type-specific deletion of Nogo from oligodendrocytes led to a ~50% increase in the compensatory sprouting of corticospinal tract (CST) axons in the cervical spinal cord after unilateral pyramidotomy in mice. In contrast to a previously proposed growth-promoting role of neuronal Nogo in the optic nerve, deleting neuronal Nogo did not significantly affect CST axon sprouting in the spinal cord. Sprouting axons were associated with the expression of synaptic marker VGLUT1 in both the oligodendrocytic Nogo deletion and control mice. However, we did not detect any functional improvement in fine motor control associated with the increased sprouting in oligodendrocytic Nogo deletion mice. These data show for the first time with genetic evidence that Nogo specifically expressed by oligodendrocytes restricts compensatory sprouting after CNS injury, supporting a longstanding but heretofore untested hypothesis. While implicating a focus on sprouting as a repair mechanism in the translational potential of targeting the myelin inhibitory pathway, our study illustrates the challenge to harness enhanced structural plasticity for functional improvement.