Andrew A. Shinar

Bulk structural autogenous grafts and allografts for reconstruction of the acetabulum in total hip arthroplasty : Sixteen-year-average follow-up

Acetabular reconstruction with bulk structural autogenous grafts and allografts from the femoral head in complex total hip arthroplasty was highly successful at an average of five years postoperatively but was much less so by 11.8 years. To assess the longer-term fate of such grafts, we reviewed the results of eighty-one consecutive total hip arthroplasties performed by the senior one of us with use of these grafts. Nine hips in nine patients who had died and two hips that were infected in two patients were excluded. Therefore seventy hips (sixty-two patients) were included in this study. The average duration of follow-up was 16.5 years (range, 14.1 to 21.4 years). Sixty-one arthroplasties were performed to treat various forms of congenital dysplasia. Fifteen arthroplasties, ten of which were revision operations, were performed with allograft, and fifty-five were performed with autogenous graft. The average age of the patients at the time of the index operation was 45.2 years (range, sixteen to sixty-nine years). All of the sockets, which had an average outer diameter of forty millimeters (range, thirty-four to fifty millimeters), were inserted with cement. The average coverage of the acetabular component by the bulk graft was 49 per cent (range, 15 to 100 per cent). All of the grafts united. At the latest follow-up examination, twenty-five acetabular components (36 per cent) had been revised for aseptic loosening, eighteen (26 per cent) had radiographic evidence of loosening, and twenty-seven (39 per cent) were rigidly fixed and in place. The average Harris hip score for the hips in which the implant remained rigidly fixed was 74 points, while that for the hips in which the implant was loose but had not been revised was 69 points. Nine of the fifteen acetabular components supported by allograft and sixteen (29 per cent) of the fifty-five supported by autogenous graft were revised (p = 0.03). However, the total rate of acetabular components that were either loose or revised was ten of fifteen and thirty-three (60 per cent) of fifty-five, respectively. This difference was not significant (p = 0.4), with the numbers available. Regression analysis revealed that a younger age at the time of the operation and the extent of coverage of the acetabular component by the graft were associated with the need for revision. Twenty-one (78 per cent) of the twenty-seven acetabular components that remained rigidly fixed were supported by graft over less than 50 per cent of the contact area, while only nine (36 per cent) of the twenty-five that were revised were so supported (p < 0.05). None of the nine acetabular components with 30 per cent of the contact area or less covered by graft were revised. In nineteen of the twenty-two revisions of the acetabular component performed after the index operation, the socket was inserted without cement; the average outer diameter of the socket was fifty-three millimeters (range, forty to fifty-eight millimeters). Both the structural autogenous grafts and the structural allografts used in acetabular reconstruction in total hip replacement functioned well for the initial five to ten years. By an average of 16.5 years, nine of the fifteen hips treated with allograft and sixteen (29 per cent) of the fifty-five treated with autogenous graft had been revised. The greater the extent of the coverage of the acetabular component by the graft, the greater the rate of late failure.

Cemented Total Hip Arthroplasty Following Previous Femoral Osteotomy An Average 16-Year Follow-up Study

The indications for proximal femoral osteotomy would be substantially limited if it significantly compromised the outcome of a subsequent hip arthroplasty. Previous reports have followed only early cementing techniques over intermediate duration. This study comprised 22 primary cemented total hip arthroplasties performed by a single surgeon following failed proximal femoral osteotomies at an average follow-up period of 15.8 years. Three patients who died prior to the 11-year minimum follow-up period are not included, leaving 19 hips for long-term review. All stems were cemented with second-generation techniques. Stem placement and collar-calcar contact, however, were substantially worse compared with historical control subjects. Eight reconstructions required custom miniature or calcar replacement components, and in 6 hips, the stems were inserted only in the diaphysis. Two of 19 femoral components (10.5%) were revised for aseptic loosening and 2 additional femoral components were loose. The average Harris hip score of those not revised was 80.4. Five acetabular components (26.3%) required revision. Four additional cups were loose, yielding a total acetabular loosening rate of 47.4% at 15.5 years. Intertrochanteric osteotomy in general did not affect the expected excellent results of the femoral component using modern cementing techniques. Severe deformity following subtrochanteric osteotomy, however, did adversely affect the outcome.

Correlation of Measured Range of Hip Motion Following Total Hip Arthroplasty and Responses to a Questionnaire

Twenty-eight patients (with 30 primary and 8 revision total hip arthroplasties) completed a standardized questionnaire containing the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Harris hip score questions prior to an office visit a minimum of 1 year after surgery. The range of hip motion measured by an orthopaedic surgeon was compared with the responses to questions on stiffness and function as well as with global scores in the WOMAC osteoarthritis index. Patient responses to the questions asking if they could cut their toenails on the operated side and the Harris hip score question asking if they could put on socks and tie a shoe correlated significantly with postoperative hip motion (P < .005). The WOMAC global pain and stiffness scores did not correlate with range of motion. The WOMAC physical function score correlated significantly only with hip flexion (P < .05). Of the WOMAC physical function questions, difficulty bending to pick an object off the floor (P < .05) and getting on and off the toilet (P < .05) correlated with the sum of the range of motion in all planes and weighted Harris hip score range of motion calculation. These data suggest that the points allocated in the Harris hip score for range of motion can be estimated reasonably accurately from questionnaire or phone response to a series of questions on a standardized questionnaire. The question on ability to cut toenails or the Harris hip score question regarding ability to put on socks and tie a shoe correlated with the most individual planes of motion, but several WOMAC physical function questions also correlated with total and weighted range of motion calculations.

Enhancement of the value of hip questionnaires by telephone follow-up evaluation

Errors, omissions, false understanding, and contradictory answers can compromise the use of questionnaires to generate follow-up data. To assess the utility of and effort involved in adding routinely a telephone interview to clarify the questionnaire, a study of total hip arthroplasty patients was carried out. Thirty-six patients with 37 primary and 13 revision total hip arthroplasties filled out a standardized questionnaire (which asks a number of demographic questions as well as questions that allow calculation of the Medical Outcome Studies [MOS] 36-Item Short-form Health Survey [SF-36], Western Ontario MacMaster Arthritis Center [WOMAC] osteoarthritis index, and Harris hip score) prior to returning for routine follow-up evaluation a minimum of 1 year after surgery. Two hundred thirty-two of a possible 4,350 responses (5.3%) were missing, contradictory, or answered with two or more answers on the questionnaire. Only eight such defects occurred following the telephone interview by a skilled orthopaedic surgeon, representing a significant reduction in these defects (P < .005). The average time of the telephone call was 2.8 minutes (range, 1-12 minutes), and the average number of attempts to contact the patient was 1.4 (range, 1-6). All questionnaire data and questionnaire data plus telephone data were compared with data obtained from a subsequent face-to-face interview by a different skilled orthopaedic surgeon who was blinded to the data from both the questionnaire and the telephone interview. It is demonstrated that a telephone call to follow up a standardized, self-administered questionnaire is a very effective way to augment the quality and quantity of questionnaire responses.

Human Mesenchymal Stromal Cells: Identifying Assays to Predict Potency for Therapeutic Selection

Multipotent mesenchymal stromal cells (MSCs) have the potential to repair and regenerate damaged tissues, making them attractive candidates for cell‐based therapies. To maximize efficacy of MSCs, prediction of their therapeutic abilities must be made so that only the best cells will be used. Our goal was to identify feasible and reproducible in vitro assays to predict MSC potency. We generated cell lines from 10 normal human bone marrow samples and used the International Society for Cellular Therapys minimal criteria to define them as MSCs: plastic adherence, appropriate surface marker expression, and trilineage differentiation. Each MSC line was further characterized by its growth, proliferation, and viability as determined by cell count, bromodeoxyuridine incorporation, and cellular ATP levels, respectively. To determine whether these tests reliably predict the therapeutic aptitude of the MSCs, several lines were implanted in vivo to examine their capacity to engraft and form granulation tissue in a well‐established murine wound model using polyvinyl alcohol sponges. Long‐term engraftment of MSCs in the sponges was quantified through the presence of the human‐specific Alu gene in sponge sections. Sections were also stained for proliferating cells, vascularity, and granulation tissue formation to determine successful engraftment and repair. We found that high performance in a combination of the in vitro tests accurately predicted which lines functioned well in vivo. These findings suggest that reliable and reproducible in vitro assays may be used to measure the functional potential of MSCs for therapeutic use.

Acute Kidney Injury After Placement of an Antibiotic-Impregnated Cement Spacer During Revision Total Knee Arthroplasty

We performed a retrospective cohort study of 84 patients to determine the incidence and predictors of acute kidney injury after antibiotic-impregnated cement spacer (ACS) placement for infected total knee arthroplasties. Acute kidney injury was defined as a more than 50% rise in serum creatinine from a preoperative baseline to a level greater than 1.4 mg/dL within 90 days postoperatively. Total incidence was 17% (n = 14; 95% confidence interval [CI], 10%-26%), and acute kidney injury was significantly associated with ACS tobramycin dose as both a dichotomous variable (>4.8 g; odds ratio, 5.87; 95% CI, 1.43-24.19; P = .01) and linear variable (odds ratio, 1.24 for every 1-g increase; 95% CI, 1.00-1.52; P = .049). Routine monitoring of serum creatinine and measurement of serum aminoglycoside levels in response to a threshold creatinine rise may be warranted after the placement of an aminoglycoside-containing ACS.

Quantitative Assessment of Myeloid Nuclear Differentiation Antigen Distinguishes Myelodysplastic Syndrome From Normal Bone Marrow

By using flow cytometry, we analyzed myeloid nuclear differentiation antigen (MNDA) expression in myeloid precursors in bone marrow from patients with myelodysplastic syndrome (MDS) and control samples from patients undergoing orthopedic procedures. The median percentage of MNDA-dim myeloid precursors in MDS cases was 67.4% (range, 0.7%-97.5%; interquartile range, 44.9%-82.7%) of myeloid cells, with bimodal MNDA expression in most MDS samples. Control samples demonstrated a median MNDA-dim percentage in myeloid precursors of 1.2% (range, 0.2%-13.7%; interquartile range, 0.6%-2.7%), with no bimodal pattern in most samples. The area under the receiver operating characteristic curve for MNDA-dim percentage in myeloid precursors was 0.96 (P = 9 × 10(-7)). Correlation of MNDA-dim levels with World Health Organization 2008 morphologic diagnoses was not significant (P = .21), but correlation with patient International Prognostic Scoring System scores suggested a trend (P = .07). Flow cytometric assessment of MNDA in myeloid precursors in bone marrow may be useful for the diagnosis of MDS.

Innovative Analyses Support a Role for DNA Damage and an Aberrant Cell Cycle in Myelodysplastic Syndrome Pathogenesis

We used flow cytometry to analyze the cell cycle, DNA damage, and apoptosis in hematopoietic subsets in MDS marrow. Subsets were assigned using CD45, side scatter, CD34, and CD71. Cell cycle fractions were analyzed using DRAQ 5 (DNA content) and MPM-2 (mitoses). DNA damage was assessed using p-H2A.X, and apoptosis using Annexin V. Compared to controls, MDS patients demonstrated no increased mitoses in erythroid, myeloid, or CD34+ cells. Myeloid progenitors demonstrated increased G2 cells, which with no increased mitoses suggested delayed passage through G2. Myeloid progenitors demonstrated increased p-H2A.X, consistent with DNA damage causing this delay. Annexin V reactivity was equivalent in MDS and controls. Results for each parameter varied among hematopoietic compartments, demonstrating the need to analyze compartments separately. Our results suggest that peripheral cytopenias in MDS are due to delayed cell cycle passage of marrow progenitors and that this delayed passage and leukemic progression derive from excessive DNA damage.

Inhibition of Wnt/β-catenin signaling ameliorates osteoarthritis in a murine model of experimental osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease involving both cartilage and synovium. The canonical Wnt/β-catenin pathway, which is activated in OA, is emerging as an important regulator of tissue repair and fibrosis. This study seeks to examine Wnt pathway effects on synovial fibroblasts and articular chondrocytes as well as the therapeutic effects of Wnt inhibition on OA disease severity. Mice underwent destabilization of the medial meniscus surgery and were treated by intra-articular injection with XAV-939, a small-molecule inhibitor of Wnt/β-catenin signaling. Wnt/β-catenin signaling was highly activated in murine synovial fibroblasts as well as in OA-derived human synovial fibroblasts. XAV-939 ameliorated OA severity associated with reduced cartilage degeneration and synovitis in vivo. Wnt inhibition using mechanistically distinct small-molecule inhibitors, XAV-939 and C113, attenuated the proliferation and type I collagen synthesis in synovial fibroblasts in vitro but did not affect human OA-derived chondrocyte proliferation. However, Wnt modulation increased COL2A1 and PRG4 transcripts, which are downregulated in chondrocytes in OA. In conclusion, therapeutic Wnt inhibition reduced disease severity in a model of traumatic OA via promoting anticatabolic effects on chondrocytes and antifibrotic effects on synovial fibroblasts and may be a promising class of drugs for the treatment of OA.

Metal-Backed Versus All-Polyethylene Tibias in Megaprostheses of the Distal Femur

In megaprostheses, the tibial component is rarely a source of failure. The evolution of these implants has followed standard arthroplasty trends moving from majority use of all-polyethylene tibias (APT) to high volume use of metal-backed tibial (MBT) components. We report the results of 72 endoprostheses using either MBT (n = 42) or APT (n = 30) implanted between 1994 and 2006. Failures of the implant related to the tibial component were isolated, and 5-year survival of the tibial implant of the MBT cohort was 94%, and for the APT cohort, 87% (P = .39). The difference in tibial component failures between the 2 groups was not statistically significant (Pearson χ(2) = 0.1535, P = .6952). Revision rates for the entire implant and infection rates were not significantly different between the 2 groups.