Manipulation Under Anesthesia is Safe After Cementless Total Knee Arthroplasty: A Multicenter Study.

BACKGROUND: Cementless total knee arthroplasty (TKA) is thought to facilitate durable, biological fixation between the bone and implant. However, the 4-12 weeks required for osseointegration coincides with the optimal timeframe to perform a manipulation under anesthesia (MUA) if a patient develops postoperative stiffness. This study aims to determine the impact of early MUA on cementless fixation by comparing functional outcomes and survivorship of cementless and cemented TKAs. METHODS: A consecutive series of patients who underwent MUA for postoperative stiffness within 90 days of primary, unilateral TKA at 2 academic institutions between 2014 and 2018 were identified. Cases involving extensive hardware removal were excluded. Cementless TKAs undergoing MUA (n = 100) were propensity matched 1:1 to cemented TKAs undergoing MUA (n = 100) using age, gender, body mass index, and year of surgery. Both groups had comparable baseline Knee Injury and Osteoarthritis Outcome Scores (KOOS), Short Form (SF)-12 Physical, and SF-12 Mental scores. MUA-related complications as well as postoperative KOOS and SF-12 scores were compared. RESULTS: MUA-related complications were equivalently low in both groups (P = .324), with only 1 patella component dissociation in the cementless group. No tibial or femoral components acutely loosened in the perioperative period. Postoperative KOOS (P = .101) and SF-12 Mental scores (P = .380) were similar between groups. Six-year survivorship free from any revision after MUA was 98.0% in both groups (P = 1.000). CONCLUSION: Early postoperative MUA after cementless TKA was not associated with increased MUA-related complications or worse patient-reported outcomes compared to cemented TKA. Short-term survivorship was also comparable, suggesting high durability of the bone-implant interface.

Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways.

The bark of Cinnamomum cassia (C. cassia) has been used for the management of coronary heart disease (CHD) and diabetes mellitus. C. cassia may target the vasculature, as it stimulates angiogenesis, promotes blood circulation and wound healing. However, the active components and working mechanisms of C. cassia are not fully elucidated. The Shexiang Baoxin pill (SBP), which consists of seven medicinal materials, including C. cassia etc., is widely used as a traditional Chinese patent medicine for the treatment of CHD. Here, 22 single effective components of SBP were evaluated against the human umbilical vein endothelial cells (HUVECs). We demonstrated that in HUVECs, cinnamaldehyde (CA) stimulated proliferation, migration, and tube formation. CA also activated the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, the secretion of vascular endothelial growth factor (VEGF) from HUVECs was increased by CA. In vivo, CA partially restored intersegmental vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for vascular endothelial growth factor receptor (VEGFR). CA also showed pro-angiogenic efficacy in the Matrigel plug assay. Additionally, CA attenuated wound sizes in a cutaneous wound model, and elevated VEGF protein and CD31-positive vascular density at the margin of these wounds. These results illustrate that CA accelerates wound healing by inducing angiogenesis in the wound area. The potential mechanism involves activation of the PI3K/AKT and MAPK signaling pathways. Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction.

How are we measuring clinically important outcome for operative treatments in sports medicine?

OBJECTIVES: Minimal clinically important difference (MCID) and other measures of minimum clinical importance are increasingly recognized as important clinical considerations for evaluating the efficacy of an intervention. As our interpretation of clinical outcome evolves beyond statistical significance, psychometric properties such as MCID will be increasingly important to various stakeholders in the orthopaedic community. The purpose of this study was to: 1) describe the state of clinically important outcome reporting and 2) describe the methods used to derive these psychometric values for sports medicine patients undergoing operative treatments. METHODS: A review of the MEDLINE database was performed. Studies primarily deriving and reporting clinically important outcome measures for operative interventions in sports medicine were included. Demographic, methodological and psychometric properties of included studies were extracted. Level of Evidence and the Newcastle Ottawa Scale (NOS) were used to assess study quality. Statistical analysis was primarily descriptive. RESULTS: Fifteen studies met inclusion criteria; 10 of the 15 studies were Level II evidence and mean NOS score was 5.3/9. Minimal detectable change (MDC) was the most commonly derived measure of clinical importance, calculated in 53.3% of studies, followed by MCID, calculated in 40.0% of studies. A combination of distribution and anchor-based methods was the most commonly used method to determine clinical importance (N = 7, 46.7%) followed by distribution only (N = 5, 33.3%). Predictors of clinically important change were reported in four studies and were most commonly related to pre-operative functional score. CONCLUSIONS: MDC and the MCID are the most commonly reported measures of clinically important outcome after operative treatment in sports medicine. A combination of both distribution and anchor-based methods is commonly used to derive these values. More attention should be paid to reporting outcomes that are clinically important and developing guidelines for reporting clinical meaningful outcome.

Asthma discordance in twins is linked to epigenetic modifications of T cells.

T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals and have been suspected to be prone to epigenetic regulation. However, these relationships are not well established from past clinical studies that have had limited capacity to control for the effects of variable genetic predisposition and early environmental exposures. Relying on a cohort of monozygotic twins discordant for asthma we sought to determine if epigenetic modifications in T cells were associated with current asthma and explored whether such modifications were associated with second hand smoke exposures. Our study was conducted in a monozygotic twin cohort of adult twin pairs (n = 21) all discordant for asthma. Regulatory T cell (Treg) and effector T cell (Teff) subsets were assessed for levels of cellular function, protein expression, gene expression and CpG methylation within Forkhead box P3 (FOXP3) and interferon gamma-γ (IFNγ) loci. Comparisons by asthma and current report of exposure to second hand smoke were made. Treg from asthmatic discordant twins demonstrated decreased FOXP3 protein expression and impaired Treg function that was associated with increased levels of CpG methylation within the FOXP3 locus when compared to their non-asthmatic twin partner. In parallel, Teff from discordant asthmatic twins demonstrated increased methylation of the IFNγ locus, decreased IFNγ expression and reduced Teff function when compared to Teff from the non-asthmatic twin. Finally, report of current exposure to second hand smoke was associated with modifications in both Treg and Teff at the transcriptional level among asthmatics. The results of the current study provide evidence for differential function of T cell subsets in monozygotic twins discordant for asthma that are regulated by changes in DNA methylation. Our preliminary data suggest exposure to second hand smoke may augment the modified T cell responses associated with asthma.