Yoav Mattan

Set7/9 Impacts COL2A1 Expression Through Binding and Repression of SirT1 Histone Deacetylation

Type II collagen is a key cartilaginous extracellular protein required for normal endochondral development and cartilage homeostasis. COL2A1 gene expression is positively regulated by the NAD‐dependent protein deacetylase Sirtuin 1 (SirT1), through its ability to bind chromatin regions of the COL2A1 promoter and enhancer. Although SirT1/Sox9 binding on the enhancer site of COL2A1 was previously demonstrated, little is known about its functional role on the gene promoter site. Here, we examined the mechanism by which promoter‐associated SirT1 governs COL2A1 expression. Human chondrocytes were encapsulated in three‐dimensional (3D) alginate beads where they exhibited upregulated COL2A1 mRNA expression and increased levels of SirT1 occupancy on the promoter and enhancer regions, when compared to monolayer controls. Chromatin immunoprecipitation (ChIP) analyses of 3D cultures showed augmented levels of the DNA‐binding transcription factor SP1, and the histone methyltransferase Set7/9, on the COL2A1 promoter site. ChIP reChIP assays revealed that SirT1 and Set7/9 form a protein complex on the COL2A1 promoter region of 3D‐cultured chondrocytes, which also demonstrated elevated trimethylated lysine 4 on histone 3 (3MeH3K4), a hallmark of Set7/9 methyltransferase activity. Advanced passaging of chondrocytes yielded a decrease in 3MeH3K4 and Set7/9 levels on the COL2A1 promoter and reduced COL2A1 expression, suggesting that the SirT1/Set7/9 complex is preferentially formed on the COL2A1 promoter and required for gene activation. Interestingly, despite SirT1 occupancy, its deacetylation targets (ie, H3K9/14 and H4K16) were found acetylated on the COL2A1 promoter of 3D‐cultured chondrocytes. A possible explanation for this phenotype is the enrichment of the histone acetyltransferases P300 and GCN5 on the COL2A1 promoter of3 D‐cultured chondrocytes. Our study indicates that Set7/9 prevents the histone deacetylase activity of SirT1, potentiating euchromatin formation on the promoter site of COL2A1 and resulting in morphology‐dependent COL2A1 gene transactivation.

Effect of Severe Aortic Stenosis on the Outcome in Elderly Patients Undergoing Repair of Hip Fracture

Background: The perioperative assessment and management of elderly patients with hip fracture and significant aortic stenosis (AS) is an increasingly common clinical problem with little data available to guide perioperative management. Objectives: It was the aim of this study to examine the incidence of perioperative events in an elderly population of patients with severe AS undergoing repair of hip fracture as compared with controls without severe AS. Methods: Patients over the age of 70 with an echocardiographic diagnosis of severe AS defined as an aortic valve area ≤1.0 cm2 who underwent surgery for hip fracture repair were retrospectively identified. An age-matched group of patients without a history of AS who underwent surgical repair of hip fracture was the control group. The primary outcome of the incidence of postoperative cardiac events defined as death, acute coronary syndrome or pulmonary edema within 30 days was compared. Results: Thirty-two patients with AS (median age 84.5 years, range 72–94; 27 females and 5 males) and 88 controls (median age 86 years, range 80–95; 67 females and 21 males) were entered into the study. There were no significant differences between the AS group and controls for 30-day mortality (6.2 vs. 6.8%) or for the total cardiac event rate (18.7 vs. 11.8%). Conclusions: Our results demonstrate that elderly patients with severe AS can safely undergo repair of hip fractures with a mortality and morbidity comparable with a control population. These patients should not be denied surgery on the basis of their aortic valve disease.

Navigation-Assisted Minimally Invasive Two-Incision Total Hip Arthoplasty

Flouroscopy-based navigation can increase accuracy in two-incision minimally invasive THA, a novel technique develop for promoting fast recovery.

Bipolar hip hemiarthroplasty in a patient with an above knee amputation: a case report

The treatment of an above knee amputee who has sustained a fracture of femoral neck is a challenge for both the orthopaedic surgeon and the rehabilitation team. We present a case of such a patient and discuss different difficulties in his treatment.

A Practical Tool for Surveillance of Surgical-Site Infections: A 5-Year Experience in Orthopedic Surgeries

Continuous surveillance of surgical-site infection (SSI) is labor intensive. We developed a semiautomatic surveillance system partly assisted by surgeons. Most patients who developed postdischarge SSI were readmitted, which allowed us to limit postdischarge surveillance to this group. This procedure significantly reduced workload while maintaining high sensitivity and specificity for SSI diagnosis. Infect Control Hosp Epidemiol 2017;38:610-613.

Polyethylene Liner Cementation Technique in Asymptomatic Versus Symptomatic Osteolysis

Osteolysis around a cementless acetabular component can lead to severe bone loss. This study examined whether osteolysis should be treated while still asymptomatic. Thirty-seven liner cementation revisions were performed in 34 patients. Mean patient age was 61 years, and mean time elapsed after index surgery was 85 months (range, 36-168 months). Patients were evaluated by Harris Hip Score (HHS), and mean follow-up was 5 years (range, 43-82 months). Average HHS was 87 with a pain component of 39. In asymptomatic patients, both the HHS and the pain score were significantly higher: 95 and 43, respectively (P<.01). One patient with extensive bone loss had a fracture of the acetabulum and underwent revision at another institution. Revision of the polyethylene liner and cementation of a new one is a useful technique in patients with a stable acetabular shell. This is especially true for asymptomatic patients with osteolysis and thus should be performed early; however, high dislocation rate is still a concern.