Integrin‐mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin‐mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM‐111 and LM‐511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM‐binding integrins was quantified for human NP cells using flow cytometry. The cell‐ECM attachment mechanism was determined by quantifying cell attachment to LM‐111, LM‐511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM‐111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell‐based therapeutics. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1661–1667, 2013     

Histological evaluation of a free medial femoral condyle flap at 21 months

Recalcitrant nonunions typically require vascularized bone for reconstruction. In this report, we present a case of an index finger middle phalanx nonunion that was successfully treated with a free medial femoral condyle corticocancellous flap. Nearly 2 years after the free tissue transfer, the patient underwent debulking of the bone flap. This gave us the unique opportunity to examine the histology of the vascularized bone. © 2013 Wiley Periodicals, Inc. Microsurgery 33:567–571, 2013.     

Operative Treatment of Early Peri-Prosthetic Femur Fractures Following Primary Total Hip Arthroplasty

The risk factors for and results of operatively treated peri-prosthetic femoral fractures sustained within 90 days following primary THA were evaluated. 5,313 consecutive THAs were reviewed and 32 (0.60%) fractures were identified which included 9 A_g, 2 B₁, 18 B₂, 1 B₃, and 2 A_g/B₂ fractures. 19 (61%) patients sustained 23 complications including 9 greater trochanter non-unions, 2 femoral shaft non-unions, 3 patients with Brooker III HO, and 2 deep infections. 7 patients (23%) required a second operative procedure and one patient required a third. Peri-prosthetic fractures were associated with advancing age, female gender, developmental hip dysplasia, and cementless metaphyseal engaging components, particularly flat wedge tapers. Overall, operative treatment of acute peri-prosthetic fractures is associated with a high rate of complications (61%) and re-operation (23%).     

Trends in hip fracture rates in Canada: An age‐period‐cohort analysis

Age‐standardized rates of hip fracture in Canada declined during the period 1985 to 2005. We investigated whether this incidence pattern is explained by period effects, cohort effects, or both. All hospitalizations during the study period with primary diagnosis of hip fracture were identified. Age‐ and sex‐specific hip fracture rates were calculated for nineteen 5‐year age groups and four 5‐year calendar periods, resulting in 20 birth cohorts. The effect of age, calendar period, and birth cohort on hip fracture rates was assessed using age‐period‐cohort models as proposed by Clayton and Schiffers. From 1985 to 2005, a total of 570,872 hospitalizations for hip fracture were identified. Age‐standardized rates for hip fracture have progressively declined for females and males. The annual linear decrease in rates per 5‐year period were 12% for females and 7% for males (both p < 0.0001). Significant birth cohort effects were also observed for both sexes (p < 0.0001). Cohorts born before 1950 had a higher risk of hip fracture, whereas those born after 1954 had a lower risk. After adjusting for age and constant annual linear change (drift term common to both period and cohort effects), we observed a significant nonlinear birth cohort effect for males (p = 0.0126) but not for females (p = 0.9960). In contrast, the nonlinear period effect, after adjustment for age and drift term, was significant for females (p = 0.0373) but not for males (p = 0.2515). For males, we observed no additional nonlinear period effect after adjusting for age and birth cohort, whereas for females, we observed no additional nonlinear birth cohort effect after adjusting for age and period. Although hip fracture rates decreased in both sexes, different factors may explain these changes. In addition to the constant annual linear decrease, nonlinear birth cohort effects were identified for males, and calendar period effects were identified for females as possible explanations.     

Molecular Staging of Surgical Margins in Oral Squamous Cell Carcinoma Using Promoter Methylation of p16INK4A, Cytoglobin, E-cadherin, and TMEFF2

Background

Local recurrence in oral squamous cell carcinoma (OSCC) despite clear surgical margins may indicate the presence of residual, sub-microscopic disease. Molecular assessment of surgical margins may provide a greater prognostic sensitivity compared to histopathology. We aimed to determine whether promoter methylation in deep and mucosal resection margins can predict recurrence in OSCC.

Methods

Forty-eight consecutive OSCC cases were recruited and a 5 mm³ tumor sample plus 5 deep and 5 mucosal margin samples were snap frozen. Clinical, pathological, adjuvant therapy, and outcome data were recorded. Tumors were informative if >5 % promoter methylation was found for ≥1 of 4 genes using qMSP. Margins were declared molecularly positive if >1 % promoter methylation was found in any margin.

Results

Thirty (63 %) of 48 cases were methylation informative. Mucosal margin samples were largely positive for methylation (26 of 30, 87 %), indicating the presence of field cancerization. Methylation at ≥1 gene promoters in ≥1 deep margin correlated with the presence of close/involved mucosal margins (P = 0.027) and increased pT status (P = 0.027) but not the status of deep margins, recurrence, or survival.

Conclusions

The current gene panel did not add prognostic information to histopathological reporting of resection margins. Future efforts should concentrate on improving gene selection, informativity, and assay performance in the patient group with intermediate indications for adjuvant therapy.     

Lifestyle Risk Factors Associated with Arm Swelling Among Women with Breast Cancer

Background

Breast cancer-related lymphedema (BCRL) is a feared complication for breast cancer patients who have undergone axillary surgery. Although clinical risk factors for BCRL are defined, data are sparse regarding common exposures that might induce incident arm swelling. The goal of this study was to quantify the association between common exposures thought to be potential risk factors and the occurrence of incident arm swelling among breast cancer survivors with or at risk for BCRL.

Methods

This is a prospective subanalysis of the Physical Activity and Lymphedema (PAL) trial, a randomized controlled trial of 295 breast cancer survivors. Participants reported their exposure to 30 different potential risk factors at 3 month intervals for 1 year. Incident arm swelling was defined as a ≥5 % increase in interlimb water volume difference between two consecutive time points.

Results

Twenty-seven participants (9 %) experienced incident arm swelling and 268 patients (91 %) did not. Sauna use was the only exposure that was significantly predictive of incident arm swelling (p = 0.05). Nonwhite and nonblack participants had a significantly increased risk for experiencing incident arm swelling (p = 0.005 for both comparisons).

Conclusions

In our patient cohort, many common exposures that have been reported to be risk factors did not prove to have a significant predictive relationship for incident arm swelling. This study supports the recommendation that breast cancer patients who have had axillary surgery should avoid sauna use. The results do not confirm the need for other restrictions that may interfere with the quality of life in women with breast cancer.