Does Metabolic Syndrome Impact the Risk of Reoperation, Revision, or Complication After Primary Total Knee Arthroplasty?

BACKGROUND: Metabolic syndrome (MetS) is an increasingly frequent condition characterized by insulin resistance, abdominal obesity, hypertension, and dyslipidemia. This study evaluated implant survivorship, complications, and clinical outcomes of primary TKAs performed in patients who have MetS. METHODS: Utilizing our institutional total joint registry, 2,063 primary TKAs were performed in patients with a diagnosis of MetS according to the World Health Organization criteria. MetS patients were matched 1:1 based on age, sex, and surgical year to those who did not have the condition. The World Health Organization's body mass index (BMI) classification was utilized to evaluate the effect of obesity within MetS patients. Kaplan-Meier methods were utilized to determine implant survivorship. Clinical outcomes were assessed with Knee Society scores. The mean follow-up was 5 years. RESULTS: MetS and non-MetS patients did not have significant differences in 5-year implant survivorship free from any reoperation (P = .7), any revision (P = .2), and reoperation for periprosthetic joint infection (PJI; P = .2). When stratifying, patients with MetS and BMI >40 had significantly decreased 5-year survivorship free from any revision (95 versus 98%, respectively; hazard ratio = 2.1, P = .005) and reoperation for PJI (97 versus 99%, respectively; hazard ratio = 2.2, P = .02). Both MetS and non-MetS groups experienced significant improvements in Knee Society Scores (77 versus 78, respectively; P < .001) that were not significantly different (P = .3). CONCLUSION: MetS did not significantly increase the risk of any reoperation after TKA; however, MetS patients with BMI >40 had a two-fold risk of any revision and reoperation for PJI. These results suggest that obesity is an important condition within MetS criteria and remains an independent risk factor. LEVEL OF EVIDENCE: Level 3, Case-control study.

Dynamic Stimulations with Bioengineered Extracellular Matrix-Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy.

Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, and time. Compared to static mechanical signals such as stiffness, porosity, and topography, the current understanding on the effects of dynamic mechanical stimulations on cells remains limited, attributing to a lack of access to devices, the complexity of experimental set-up, and data interpretation. Yet, in the pursuit of emerging translational applications (e.g., cell manufacturing for clinical treatment), it is crucial to understand how cells respond to a variety of dynamic forces that are omnipresent in vivo so that they can be exploited to enhance manufacturing and therapeutic outcomes. With a rising appreciation of the extracellular matrix (ECM) as a key regulator of biofunctions, researchers have bioengineered a suite of ECM-mimicking hydrogels, which can be fine-tuned with spatiotemporal mechanical cues to model complex static and dynamic mechanical profiles. This review first discusses how mechanical stimuli may impact different cellular components and the various mechanobiology pathways involved. Then, how hydrogels can be designed to incorporate static and dynamic mechanical parameters to influence cell behaviors are described. The Scopus database is also used to analyze the relative strength in evidence, ranging from strong to weak, based on number of published literatures, associated citations, and treatment significance. Additionally, the impacts of static and dynamic mechanical stimulations on clinically relevant cell types including mesenchymal stem cells, fibroblasts, and immune cells, are evaluated. The aim is to draw attention to the paucity of studies on the effects of dynamic mechanical stimuli on cells, as well as to highlight the potential of using a cocktail of various types and intensities of mechanical stimulations to influence cell fates (similar to the concept of biochemical cocktail to direct cell fate). It is envisioned that this progress report will inspire more exciting translational development of mechanoresponsive hydrogels for biomedical applications.

Mechano-Activated Cell Therapy for Accelerated Diabetic Wound Healing.

Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. A powerful platform technology combining magneto-responsive hydrogel, cells, and wireless magneto-induced dynamic mechanical stimulation (MDMS) is developed to accelerate diabetic wound healing. The hydrogel encapsulates U.S. Food and Drug Administration (FDA)-approved fibroblasts and keratinocytes to achieve ∼3-fold better wound closure in a diabetic mouse model. MDMS acts as a nongenetic mechano-rheostat to activate fibroblasts, resulting in ∼240% better proliferation, ∼220% more collagen deposition, and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto-responsive property also enables on-demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, a mechanosensitive fibroblast subpopulation is identified that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. The "all-in-one" system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types.

Materials for Improving Immune Cell Transfection.

Chimeric antigen receptor T cell (CAR-T) therapy holds great promise for preventing and treating deadly diseases such as cancer. However, it remains challenging to transfect and engineer primary immune cells for clinical cell manufacturing. Conventional tools using viral vectors and bulk electroporation suffer from low efficiency while posing risks like viral transgene integration and excessive biological perturbations. Emerging techniques using microfluidics, nanoparticles, and high-aspect-ratio nanostructures can overcome these challenges, and on top of that, provide universal and high-throughput cargo delivery. Herein, the strengths and limitations of traditional and emerging materials for immune cell transfection, and commercial development of these tools, are discussed. To enhance the characterization of transfection techniques and uptake by the clinical community, a list of in vitro and in vivo assays to perform, along with relevant protocols, is recommended. The overall aim, herein, is to motivate the development of novel materials to meet rising demand in transfection for clinical CAR-T cell manufacturing.

Infrapatellar Saphenous Nerve Is at Risk During Tibial Nailing: An Anatomic Study.

OBJECTIVES: To determine the location and stage of the tibial nailing procedure where infrapatellar saphenous nerve (IPSN) injury may occur. METHODS: Fourteen fresh-frozen right cadaveric knees underwent tibial nailing. Six knees underwent a suprapatellar approach and 8 a medial parapatellar approach. Two proximal medial-to-lateral screws were placed using the aiming guide. The incisions were then closed. After the procedure, medial retinacular and saphenous nerves were dissected under surgical 2.5× loupe magnification from a proximal to distal direction. The branch of the IPSN closest to the locking screws was measured, as was the distance between the IPSN branch and the inferior pole of the patella. RESULTS: Twelve of 14 cadavers had prominent IPSN (main branch from the saphenous proper) with an average of 2.5 sub-branches. The mean (SD) distance from the main branch of the IPSN to the inferior pole of the patella was 40.9 (24.4) mm. Four medial retinacular nerve branches, branching from the femoral nerve and not IPSN, were identified proximal to the patella during the medial parapatellar approach. All were cut after the medial parapatellar arthrotomy. The mean (SD) distance from the IPSN to the nearest locking screw was 10.2 (14.1) mm. Seven of 14 had IPSN injuries, and one had hamstring injury. Two direct screw entrapments occurred, whereas two IPSNs were lacerated by the incision. Suture closure entrapped three nerve branches, and one specimen had injured fibers of the hamstring tendinous insertion. CONCLUSIONS: Injury to the IPSN can occur at different locations and stages of tibial nailing, including approach, proximal locking screw insertion, and closure.

Incidence of Encountering the Infrapatellar Nerve Branch of the Saphenous Nerve During a Midline Approach for Total Knee Arthroplasty.

The infrapatellar nerve branch (IPNB) of the saphenous nerve supplies cutaneous sensation to the anterolateral knee. Given its location and variable course, the IPNB is suspected to be at risk of injury with commonly used incisions around the knee. Nerve injury may lead to painful neuroma formation. To our knowledge, no study has evaluated the incidence at which the IPNB is encountered during the anterior approach incision for a routine total knee arthroplasty (TKA). The purpose of this study was to see whether the general joint arthroplasty surgeon can identify and examine the location of the IPNB encountered during primary TKA and to determine whether these branches would be transected during a standard medial arthrotomy. METHODS: Seventy-three patients (76 knees) underwent primary TKA using a standard midline approach with a medial parapatellar arthrotomy. The IPNB was identified, and the distance was measured from the inferior pole of the patella to the point where the nerve crossed the medial border of the patellar tendon. This distance was then compared with the length of the arthrotomy in the same knee to determine whether the nerve would be transected. RESULTS: The IPNB was encountered in all knees with a mean distance of 2.82 cm (95% confidence interval, 2.58-3.06) distal to the inferior pole of the patella during the arthrotomy. Patient characteristics including sex, height, and body mass index were not markedly associated with nerve location. CONCLUSION: The IPNB of the saphenous nerve is at risk for injury and routinely encountered by the general orthopaedic surgeon during a standard TKA medial parapatellar approach without the aid of magnification or dye.

Intrawound vancomycin in primary hip and knee arthroplasty: a safe and cost-effective means to decrease early periprosthetic joint infection.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication after hip and knee arthroplasty. Intrawound vancomycin has been described extensively in the spine literature; however, information regarding use in arthroplasty is limited. We investigate the efficacy and safety of intrawound vancomycin in arthroplasty surgery. METHODS: All primary total hip and knee arthroplasty cases (n = 460) performed by a single surgeon from April 2016 to October 2017 were reviewed. Starting in October 2016, intrawound vancomycin was used in all total joints. Baseline characteristics, infection rates, 90-day readmission, and other complications were compared between untreated subjects and those who received intrawound vancomycin. In addition, cost data were considered. Mean follow-up durations for the control and vancomycin groups were 11.3 and 7.7 months, respectively. RESULTS: Baseline characteristics and comorbidities were similar for the control (n = 112) and vancomycin groups (n = 348). The vancomycin cohort demonstrated decreased both overall infection rate (0.57% vs 2.7%; P = .031) and PJI rate (0.29% vs 2.7%; P = .009) compared with the untreated group. There was no statistical difference in incidence of ototoxicity or acute kidney injury. Although there was no difference in overall 90-day readmission rate, the vancomycin subset demonstrated lower readmission rate due to infection (0.57% vs 2.7%; P = .031). Based on the cost of vancomycin powder and calculated number needed to treat (NNT = 47.5), the cost to prevent 1 infection with the addition of intrawound vancomycin was $816. CONCLUSIONS: These findings suggest that intrawound vancomycin may be a safe, cost-effective means that shows promise in reducing PJI in early follow-up. Future prospective studies are warranted.