The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell lines

We mixed various amounts of methotrexate with bone cement and measured the absorbance daily for 4 weeks. The cytotoxic effects on SaOS2 and MG63 osteosarcoma cells were examined by the MTT assay, and analysed according to the methotrexate concentration and the elapsed time. The amount of eluted methotrexate was greatest during the first day, and then decreased rapidly reaching a plateau in the third week. The number of viable tumour cells decreased significantly after 72 h, and they were hardly seen after 1 week.     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.     

Filiform serrated adenomas: a clinicopathologic and immunophenotypic study of 18 cases

In this study, we describe a previously uncharacterized type of adenomatous polyp of the colorectum that shows prominent, thin, elongated projections of neoplastic epithelium with a serrated contour, which we have termed "filiform serrated adenoma" (SA). Routinely processed polypectomy specimens from 18 patients with filiform SA and 23 controls with traditional (nonfiliform) SA were evaluated for their clinical and pathologic features, and immunohistochemically stained for a variety of markers (O-methylguanine methyltransferase, MLH1, MSH2, CDX2, nuclear beta-catenin, p53, and Ki-67) designed to evaluate their molecular and proliferative characteristics. DNA was extracted from the paraffin-embedded materials, amplified by polymerase chain reaction, and analyzed for microsatellite instability, BRAF, K-ras, and p53 mutational status. Five cases contained sufficient non-neoplastic tissue for dissection and DNA extraction, allowing analysis of loss of heterozygosity. The study group consisted of 7 males and 11 females of mean age 64 years (range: 42 to 89 y). All 18 filiform SAs were located in the left colon, including 15 (83%) that occurred in the rectum, compared with 43% of the control group (P=0.03). Filiform SAs were also larger (1.6 cm) than SAs (mean: 1.2 cm, P=0.02), but no other clinical differences were noted. Most (56%) filiform SAs contained marked stromal edema and tall nonmucinous cells with abundant eosinophilic cytoplasm (61%). High-grade dysplasia was present in 4/18 (22%) cases. Four (22%) filiform SAs also contained nonserrated adenomatous elements with a villous (3 cases) or tubular (1 case) growth pattern. Two (11%) cases contained adjacent areas of sessile SAs and 4 (22%) had hyperplastic areas. None of the polyps in the control group showed stromal edema, high-grade dysplasia, or mixed elements. Polyps in both groups demonstrated comparable staining patterns for O-methylguanine methyltransferase, MLH-1, MSH-2, CDX2, beta-catenin, and Ki-67, and none showed increased nuclear p53 expression. Low-frequency microsatellite instability was present in 5/12 (42%) filiform SAs, 7/12 (58%) were microsatellite stable. Mitogen-activated protein kinase pathway abnormalities were present in 71% of the cases [7/14 (50%) with BRAF and 3/14 (21%) with K-ras mutations]. Four cases showed silent p53 mutations upon direct sequencing and 4 revealed loss of heterozygosity at the loci evaluated, including 1 at D5S346 [adenomatous polyposis coli (APC) gene], 1 at D17S250 (p53 gene), and 2 at MYCL (chromosome 1p34). We conclude that filiform SA potentially represents an unusual variant of SA with a predilection for the left colon, particularly the rectum.     

Porcine PD-L1: cloning, characterization, and implications during xenotransplantation

BACKGROUND: Effective intervention achieved by manipulating cell-mediated xenogeneic immune responses would critically increase the clinical feasibility of xenotransplantation as immediate hyperacute rejections become controllable through genetic modulations of donor organs. Endogenous negative regulatory signals like the programmed death 1 (PD-1)-programmed death ligand 1 (PD-L1) system are candidate targets for the control of cell-mediated xenogeneic immune response. METHODS: A porcine PD-L1 molecule was cloned using RACE (rapid amplification of cDNA ends) technology based on the human PD-L1 sequence. The functional effects of cloned porcine PD-L1 were tested on human CD4(+) T cell activation using porcine PD-L1-transfected bystander cells. Cellular proliferation was monitored by [3H] thymidine incorporation, and human T cell apoptosis was measured by flow cytometry. RESULTS: Porcine PD-L1 (GenBank accession number AY837780) was found to have 73.8% sequence homology with human PD-L1 and to contain two immunoglobulin domains in its extracellular region. Moreover, porcine PD-L1 expressed on Chinese hamster ovary (CHO) cells inhibited human CD4(+) T cell proliferation stimulated with anti-CD3 only or anti-CD3 plus anti-CD28. Percentages of apoptotic activated human T cells increased by over 30% in the presence of porcine PD-L1/CHO cells, and the addition of recombinant human PD-1-Fc fusion proteins during human T cell activation reversed the inhibitory effects of porcine PD-L1. CONCLUSIONS: Cloned porcine PD-L1 showed high sequence homology with human PD-L1 and a similar molecular structure. Moreover, porcine PD-L1 inhibited human CD4(+) T cell activation in human PD-1-dependent manner, and this involved activated T cell apoptosis. The authors suggest that PD-1-PD-L1 might play an important endogenous immune regulatory role during xenogeneic transplantation, and that the effective application of this system would improve transplanted xenogeneic organ survival.     

Tension wire fixation for mallet fracture after extension block pinning failed

Introduction

Various surgical treatments such as extension block pinning have been proposed for acute bony mallet finger. We evaluated the clinical results of tension wire fixation technique for the treatment of nonunion of mallet fracture after failed mallet finger surgery.

Materials and methods

Nine male patients were treated with open tension wire fixation for chronic nonunion of mallet fracture after extension block pinning surgery failed. The mean age was 29.3 years (range 18–47). We assessed bone union in simple radiographs. Crawford’s and Bischoff functional score was used to assess the functional outcome.

Results

The mean follow-up period was 45.8 months (range 18–74). Clinical and radiographic bone unions were achieved in eight of nine patients with average time of 31 days (range 23–41). Mean extension lag at final follow-up was 7° (range 0–25). Four patients showed excellent, three patients showed good and two patients showed fair results on the Crawford’s score scale. With Bischoff functional score, all patients were categorized as excellent.

Conclusions

Tension wire fixation can be a good second-line reconstructive surgery for the treatment of mallet fracture after extension block failed, so that patients can avoid arthrodesis or complex tendon transfer as a salvage procedure.     

Atypical femoral fractures after anti-osteoporotic medication: a Korean multicenter study

Purpose

Increasing numbers of atypical femoral fractures have been reported among long-term bisphosphonate users. We evaluated clinical characteristics of atypical femoral fractures throughout Korean multicenter studies.

Methods

We retrospectively analysed the bone mineral density, prodromal symptoms before femoral fracture, and medication history of osteoporosis in 76 cases of atypical femoral fracture.

Results

The mean age of cases was 71.4 ± 8.8 (range, 43–89) years old. The mean follow-up period after the fracture operation was 24.5 ± 12.9 (range, 12–79) months. BMI was 23.2 ± 3.0 on average. The mean BMD of femur was −1.9 ± 1.4 (range, −4.8 to 1.3). Prodromal symptoms including thigh pain before femoral fracture appeared in 22 (28.9 %) of 76 patients. All patients included in the study used bisphosphonate. The duration of taking bisphosphonate before fracture was 36.8 ± 50.8 (one–204 months) months. Fifty-seven (75 %) of 76 patients were taking the medication for more than three years. Delayed union occurred in 43 (56.5 %) of 76 patients. Delayed union was defined as a fractured bone that did not completely heal within six months of injury. The group of having taken anti-osteoporotic medication for more than three years showed relatively longer union period compared to that for a shorter period medication group (4.8 ± 2.5 months vs 9.3 ± 3.7 months, p = 0.017). The delayed union developed in 43 (56.5 %) of 76 patients and showed a significantly higher incidence in the group with long-term therapy (five/43 vs 38/43, p = 0.021). The bilateral femoral fractures developed in 23 (30.2 %) of 76 patients and showed a high incidence in the group medicated more than three years (two/23 vs 21/23, p = 0.039).

Conclusions

The longer bisphosphonates are used, the more the cases of delayed union and the more frequent the development of bilateral fractures following unilateral fractures. With regard to the delayed union, the methods of the acceleration of fracture healing may be beneficial in atypical femoral fracture patients who had been receiving long-term bisphosphonates therapy. Careful observation is required for contra-lateral femurs due to a high incidence of bilateral atypical femoral fractures.     

High prevalence of low bone mass and associated factors in Korean HIV-positive male patients undergoing antiretroviral therapy

Introduction

Low bone mass is prevalent in HIV-positive patients. However, compared to Western countries, less is known about HIV-associated osteopenia in Asian populations.

Methods

We performed a cross-sectional survey in Seoul National University Hospital from December 2011 to May 2012. We measured bone mineral density using central dual energy X-ray absorptiometry, with consent, in male HIV-positive patients, aged 40 years and older. Diagnosis of low bone mass was made using International Society for Clinical Densitometry Z-score criteria in the 40–49 years age group and World Health Organization T-score criteria in the >50-year age group. The data were compared with those of a community-based cohort in Korea.

Results

Eighty-four HIV-positive male patients were included in this study. Median age was 49 (interquartile range [IQR], 45–56) years, and median body mass index (BMI) was 22.6 (IQR, 20.9–24.4). Viral suppression was achieved in 75 (89.3%) patients and median duration of antiretroviral therapy was 71 (IQR, 36–120) months. The overall prevalence of low bone mass was 16.7% in the 40–49 years age group and 54.8% in the>50 years age group. Our cohort had significantly lower bone mass at the femur neck and total hip than HIV-negative Koreans in the 40–49 years age group. Low bone mass was significantly associated with low BMI, and a high level of serum carboxy-terminal collagen crosslinks, but was not associated with antiretroviral regimen or duration of antiretroviral therapy.

Conclusions

Low bone mass is prevalent in Korean HIV-positive males undergoing antiretroviral therapy, and may be associated with increased bone resorption.     

Does Well Maintained Graft Provide Consistent Return to Play after Medial Ulnar Collateral Ligament Reconstruction of the Elbow Joint in Elite Baseball Players?

Background

Several studies have reported the clinical outcomes of medial ulnar collateral ligament (MUCL) reconstruction of the elbow joint in throwing athletes, including the rate of return to sports. However, little has been known about the imaging outcomes after MUCL reconstruction. The aim of this study is to report the clinical and imaging outcomes after MUCL reconstruction using figure of eight fashion in the elite and professional baseball players.

Methods

This study included 17 baseball players, who underwent MUCL reconstruction between July 2007 and May 2010. The average follow-up period was 48.6 months. Imaging assessment consisted of preoperative plain and stress radiographs, magnetic resonance imaging, and postoperative serial ultrasonography. The clinical assessments were composed of visual analogue scale (VAS) for pain, range of motion, and the Conway scale.

Results

The mean VAS score was 6.4 (range, 3 to 8) preoperatively and 2.2 (range, 0 to 4) postoperatively (p < 0.05). There were nine players (53%) classified as excellent who returned to sports at the same or higher level compared to preinjury. Serial ultrasonography revealed well-maintained grafts at 3 and 12 months in all of the players. Five out of 17 players showed decreased echogenecity in the common flexor tendon at 3 months, which was considered as remaining tissue swelling and resolved completely at 12 months.

Conclusions

All grafts are well-maintained until 12-months based on the ultrasonographic findings, although only 53% of the players returned to preinjury level.