Can Tibial Shaft Fractures Bear Weight After Intramedullary Nailing? A Randomized Controlled Trial.

OBJECTIVE: To examine the potential benefits and risks associated with weight-bearing after intramedullary (IM) nailing of unstable tibial shaft fractures. DESIGN: Randomized controlled trial. SETTING: Two New York State level 1 trauma centers, one level 2 trauma center, and 1 tertiary care orthopaedic hospital in a large urban center in New York City. PATIENTS/PARTICIPANTS: Eighty-eight patients with 90 tibial shaft fractures were enrolled. The following were used as inclusion criteria: (1) skeletally mature adult patients 18 years of age or older, (2) displaced fractures of tibial diaphysis (OTA type 42) treated with operative intervention, and (3) radiographs, including injury, operative, and completion of follow-up. Sixty-eight patients with 70 tibial shaft fractures completed follow-up. INTERVENTION: All patients were treated with locked IM nailing. Patients were randomized to 1 of 2 groups: immediate weight-bearing-as-tolerated (WBAT) or non-weight-bearing for the first 6 postoperative weeks (NWB). MAIN OUTCOME MEASURES: Fracture union or treatment failure/revision surgery. RESULTS: There was no statistical difference in the observed time to union between groups (WBAT = 22.1 ± 11.7 weeks vs. NWB = 21.3 ± 9.9 weeks; P = 0.76). Rates of complications did not statistically differ between groups. No fracture loss of reduction leading to malunion was encountered. Short Musculoskeletal Function Assessment scores for all domains did not statistically differ between groups. CONCLUSIONS: Immediate weight-bearing after IM nailing of tibial shaft fractures is safe and is not associated with an increase in adverse events or complications. Patients should be allowed to bear weight as tolerated after IM nailing of OTA subtype 42-A and 42-B tibial shaft fractures. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

The Role of Arthroscopy in the Management of Tibial Plateau Fractures.

Arthroscopy has been advocated as a possible adjunct to the operative treatment of tibial plateau fractures. This review article provides a historical perspective on the development of the technique while focusing on its current role in the management of these injuries. Topics include the possible utility of employing arthroscopy in the diagnosis and management of associated soft tissue lesions and potential for arthroscopic assistance to facilitate achieving fracture reduction without an open arthrotomy. Pertinent literature is reviewed and discussed, with an emphasis on the data related to patient outcomes.

Ankle fracture surgery on a pregnant patient complicated by intraoperative emergency caesarian section.

We report the case of a woman in the third trimester of pregnancy who sustained an ankle fracture dislocation that could not be adequately closed reduced. After discussions with the patient, her obstetrician, and the anesthesiologists, she was indicated for surgical fixation. A heart tone monitor was used to assess fetal health during the procedure. During surgical incision, the fetus went into distress, and an emergency caesarian section was performed. After delivery of the infant and abdominal closer, surgery was completed. Due to a cohesive team effort, both the patient and her infant had excellent outcomes. There are many important considerations in the surgical management of the pregnant patient with traumatic orthopaedic injuries. Of especial importance to the orthopaedic surgeon is the impact of patient positioning on uteroplacental blood flow. This report discusses factors that should be taken into account by any orthopaedist who plans to operate on a pregnant patient.

Barbed sutures for arthroplasty closure--does it decrease the risk of glove perforation?

Recent resurgence in the interest of barbed suture has extended its application to wound closures in total joint surgery. Improved suture biomaterials and barb geometry has lead to consideration for its use in various orthopedic procedures including arthroplasty. The reported superior wound tensile stress distribution, no need for knots, and ability to close multiple layers with one suture make it an attractive option for deep wound closure after total joint surgery. However, inherent to the design of this suture are barbs that pose a risk of glove perforation and the potential for the transmission of blood borne pathogens. This study reports no increase in the incidence of glove perforation with use of barbed suture for deep wound closure after total joint arthroplasty.

Forty-eight-hour pH monitoring increases sensitivity in detecting abnormal esophageal acid exposure.

Ambulatory 24-hour esophageal pH measurement is the standard for detecting abnormal esophageal acid exposure (AEAE), but it has a false negative rate of 15% to 30%. Wireless 48-hour pH monitoring (Bravo; Medtronic, Shoreview, MN) may allow more accurate detection of AEAE versus 24-hour pH monitoring. Forty-eight-hour wireless data were reviewed from 209 patients at three different tertiary care referral centers between 2003 and 2005. Manometric or endoscopic determination of the lower esophageal sphincter helped place the Bravo probe 5 to 6 cm above the lower esophageal sphincter. A total of 190 studies in 186 patients had sufficiently accurate data. There were 114 women and 72 men with an average age of 51 years. AEAE was defined by a Johnson-DeMeester score greater than 14.7 and was obtained in 115 of 190 studies (61%). Only 64 of 115 patients (56%) demonstrated AEAE for both days of the study, whereas 51 of 115 patients (44%) demonstrated AEAE in a single 24-hour period. There was no difference in the prevalence of AEAE on day 1 versus day 2 only (26% vs. 18%, P = .26). Compared with 24-hour alone data, 48-hour data showed 22% more patients with AEAE. Frequent day-to-day variability in patients with AEAE may be missed by a single 24-hour pH test. Forty-eight-hour pH testing may increase detection accuracy and sensitivity for AEAE by as much as 22%.

FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis.

Fatty acid synthase (FAS), a key enzyme of the fatty acid biosynthetic pathway, has been shown to be overexpressed in various types of human cancer and is, therefore, considered to be an attractive target for anticancer therapy. However, the exact mechanism of overexpression of the FAS gene in tumor cells is not well understood. In this report, we demonstrate that the expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression in the case of prostate cancer in the clinical setting, and inhibition of the PTEN gene leads to the overexpression of FAS in vitro. We also found that the combination of the expression status of these two genes is a better prognostic marker than either gene alone. Furthermore, our results indicate that the specific inhibition of FAS gene by siRNA leads to apoptosis of prostate tumor cells, and inhibition of PI 3-kinase pathway synergizes with FAS siRNA to enhance tumor cell death. These results provide a strong rationale for exploring the therapeutic use of an inhibitor of the PTEN signaling pathway in conjunction with the FAS siRNA to inhibit prostate tumor growth.

Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression.

The differentiation-related gene-1 (Drg-1) was first identified as a gene strongly upregulated by induction of differentiation in colon carcinoma cells in vitro, and later the same gene was shown to suppress tumorigenicity of human bladder cancer cells in vivo. On the other hand, we and others have demonstrated that the Drg-1 gene suppresses prostate and colon cancer metastases in mouse models. In the context of such potential organ-specific differential function of the Drg-1 gene, the present study was designed to clarify the expression status, regulation and function of Drg-1 in the case of human breast cancer. We found that the expression of the Drg-1 protein was significantly reduced in breast tumor cells, particularly in patients with lymph node or bone metastasis as compared to those with localized breast cancer. Drg-1 expression also exhibited significant inverse correlation with the disease-free survival rate of patients and emerged as an independent prognostic factor. The downregulation of the Drg-1 gene appeared to be largely at the RNA level, and the DNA methylation inhibitor, 5-Azacytidine, significantly elevated the Drg-1 gene expression in various breast tumor cell lines. Furthermore, we found that overexpression of the Drg-1 gene suppresses the invasiveness of breast cancer cells in vitro, and this suppression was also achieved by treatment of cells with 5-Azacytidine. Together, our results strongly suggest functional involvement of the Drg-1 gene in suppressing the metastatic advancement of human breast cancer.

The Drg-1 gene suppresses tumor metastasis in prostate cancer.

Drg-1 was previously identified (N. van Belzen et al., Lab. Investig., 77: 85-92, 1997) as a gene that was up-regulated by the induction of differentiation in a colon carcinoma cell line in vitro. Subsequently, this gene was found to be regulated by several factors including hypoxia, androgen, p53, and N-myc. Recently, Drg-1 has also been shown to be involved in tumor progression in animals, although the clinical significance of its involvement remains to be investigated. To clarify the functional role of Drg-1 in prostate cancer, we examined a clinical archive of cancer specimens for the expression of Drg-1 by immunohistochemistry. We found that the expression of Drg-1 had a significant inverse correlation with the Gleason grading and the overall survival rate of patients. In particular, the gene expression in patients with lymph node or bone metastasis was significantly reduced as compared with those with localized prostate cancer, suggesting that the function of Drg-1 is negatively involved in metastatic progression of the disease. To further clarify the function of this gene in the advancement of prostate cancer, a spontaneous metastasis assay was performed in a severe combined immunodeficient (SCID) mouse model. We found that Drg-1 almost completely inhibited lung colonization of highly metastatic prostate cancer cells without affecting the growth of the primary tumors. These results strongly suggest that Drg-1 is a candidate metastasis suppressor gene for prostate cancer and may serve as a useful prognostic marker.

Antineoplastic activity of Solidago virgaurea on prostatic tumor cells in an SCID mouse model.

Solidago virgaurea (goldenrod) has traditionally been used as an anti-inflammatory herbal medicine for the treatment of various symptoms, including prostatic diseases. The plant has also been reported to have antibacterial, spasmolytic, and carminative properties. During the course of our screening for antineoplastic activities in various herbal plants, we found that the extract of S. virgaurea exhibits strong cytotoxic activities on various tumor cell lines. The active component mostly resides in the leaves of the plant and is soluble in water. When the extract was fractionated by a Sephadex G-100 column, the active fraction corresponded to a molecular weight of approximately 40,000. This cytotoxic activity is effective on various tumor cell lines, including human prostate (PC3), breast (MDA435), melanoma (C8161), and small cell lung carcinoma (H520). To examine the effect of the cytotoxic activity on tumor cells in vivo, we used the rat prostate cell line (AT6.1) and an SCID mouse model. AT6.1 cells were injected into the flank of SCID mice, and then the G-100 fraction of S. virgaurea was administered intraperitoneally or subcutaneously every 3 days. The size of the tumor was measured for up to 25 days. The growth of the tumor was significantly suppressed by the G-100 fraction at 5 mg/kg without any apparent side effects. Therefore, S. virgaurea is considered to be promising as an antineoplastic medicine with minimal toxicities.