Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

Comparison of outcomes of treatment for ranula: a proportion meta-analysis.

Treatment for ranula is classified into three categories depending on how the leaking saliva is managed: removal of the leaking site by intraoral or transcervical resection of the sublingual gland; formation of a drainage tract through the wall of the pseudocyst by micromarsupialisation or marsupialisation; or sealing of the site of the leak by inducing fibrosis with a sclerosing agent. Resection of the sublingual gland is probably the option most likely to be curative for both oral and plunging ranula considering their pathophysiology. Although alternative treatments have been introduced to avoid the invasiveness of resection of the gland, their outcomes have been inconsistent. The objective of this study therefore was to help decision-making by providing more integrated rates of cure, consistency of treatment, and morbidity, depending on types of treatment used in previous series of cases. We used proportion meta-analysis of 39 such published series, and the most curative treatment for oral ranula was intraoral resection of the sublingual gland. Micromarsupialisation and its modification showed cure rates comparable with those of resection of the gland, but these were moderately inconsistent. In the treatment of plunging ranula, there was no significant difference in cure rate between the intraoral and transcervical approaches, although they both showed higher cure rates than injection of OK-432. Comparisons of morbidity were available for patients who had developed nerve dysfunction and haematoma after the intraoral and transcervical approaches and there was no significant difference between the two, though the morbidity was higher after the transcervical than that after the intraoral approach. In conclusion, intraoral resection of the sublingual gland is sufficient treatment with a tendency to have fewer complications than that in the transcervical approach.

Initial Experience With Hand-Assisted Laparoscopic Living Donor Nephrectomy: Training and Clinical Practice as a General Surgeon.

BACKGROUND: To analyze our initial results of hand-assisted laparoscopic living donor nephrectomy, executed by a skilled gastrointestinal surgeon. METHODS: A total of 22 consecutive patients underwent the hand-assisted laparoscopic living donor nephrectomy between December 2014 and January 2017. We retrospectively analyze the patient's perioperative clinical data, which were collected prospectively. RESULTS: The right kidney was harvested in 12 patients. The mean operative time and intraoperative blood loss was 241.0 ± 43.4 minutes (range, 140-310 min) and 293.2 ± 203.1 mL (range, 50-700 mL), respectively. The mean warm ischemic time was 288.4 ± 103.4 seconds (range, 179-610 s). Postoperative complications included chyle leakage in 2 patients who were left kidney donors and oliguria in 1 patient who was a right kidney donor. All patients recovered with conservative care, and the mean hospital stay was 7.5 ± 1.7 days. The mean creatinine level was 0.7 ± 0.2 mg/dL before surgery, 1.1 ± 0.3 mg/dL at postoperative day (POD) 1, and 1.0 ± 0.2 mg/dL after discharge. The mean glomerular filtration rate was 97.9 ± 18.2 mL/min/1.73 m2 before surgery, 60.7 ± 10.4 at POD 1, and 67.3 ± 11.1 after discharge. Operation time was not associated with patient body mass index and case number. No significant differences, other than postoperative complications, were found in the perioperative data for the side of kidney donation. CONCLUSION: A skilled surgeon with experience in laparoscopic abdominal surgery (such as gastrectomy or colectomy) might safely perform hand-assisted donor nephrectomy. However, we could not identify a clear case number to complete the learning curve.

Importance of Timed and Detailed Evaluation of Kidney Transplantation Candidates.

Kidney transplant recipients are at increased risk of cardiovascular morbidity and malignant neoplasm, and meticulous evaluation of potential recipients is needed to minimize risks of complications after transplantation. The purpose of this study was to analyze the results of preoperative assessments and document the importance of timed and detailed examinations. METHODS: Medical records of patients evaluated as kidney transplant candidates from January 2015 to September 2017 were retrospectively collected and analyzed. RESULTS: Of the 216 patients evaluated during the study period, 135 (62.5%) were male, 112 (51.9%) had diabetes mellitus, 163 (75.5%) had hypertension, 31 (14.4%) had a cardiovascular event history, and 7 (3.2%) had previous history of malignant neoplasms. Mean (SD) patient age was 50.7 (10.8) years. All 216 recipient candidates underwent echocardiography. Mean (SD) ejection fraction was 57.8% (5.9%), and 48 candidates (22.2%) showed regional wall motional abnormality. Coronary angiography was performed on 81 candidates, and in 57 (70.4%) of these, coronary artery disease was detected. Malignant neoplasms were detected in 10 (4.6%) candidates. Kidney transplantation was performed on 55 candidates. One recipient died of Pneumocystis jirovecii pneumonia at 15 months after kidney transplant, but there was no death-censored graft failure, newly detected malignant neoplasm, or cardiovascular event over a mean (SD) follow-up duration of 15.5 (8.6) months. CONCLUSION: Evaluation of kidney transplant candidates resulted in diagnoses of malignant neoplasms in 4.6% of patients and coronary artery disease in 26.4% of patients. The results of this study demonstrate candidates for kidney transplant should undergo detailed preoperative evaluation.

Subjective apnoea symptoms are associated with daytime sleepiness in patients with moderate and severe obstructive sleep apnoea: a retrospective study.

OBJECTIVES: Most previous studies have failed to show a relation between daytime sleepiness and apnoea severity in patients with obstructive sleep apnoea (OSA). We determined the relation between daytime sleepiness and subjective and objective apnoea severity in newly diagnosed patients with moderate-to-severe OSA. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 559 adults with newly diagnosed moderate and severe OSA. MAIN OUTCOME MEASURES: Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Subjective and objective apnoea severities were assessed using the Sleep Breathing Scale (SBS) and polysomnography respectively. Sleep quality and depressive symptoms were evaluated using Medical Outcomes Study-Sleep Scale and Beck Depression Inventory (BDI) respectively. RESULTS: The mean ESS score was 9.8 (SD 5.0). ESS score was correlated with SBS score (P < 0.001), apnoea-hypopnoea index (AHI) (P = 0.027), minimal oxygen saturation (MinSaO2 ) (P = 0.021), body mass index (BMI) (P = 0.007) and BDI score (P < 0.001). Linear regression analysis showed that higher SBS (P = 0.005) and BDI scores (P < 0.001) were associated with higher ESS score after controlling for gender, BMI and AHI. Apnoea-hypopnoea index, MinSaO2 and BMI were not independently related to ESS score. CONCLUSIONS: Daytime sleepiness was related to subjective OSA symptoms but not objective apnoea severity measured by polysomnography in patients with moderate-to-severe OSA. These findings suggest the usefulness of the subjective apnoea severity as an indicator of OSA disease severity.

The Introduction of Human Heme Oxygenase-1 and Soluble Tumor Necrosis Factor-α Receptor Type I With Human IgG1 Fc in Porcine Islets Prolongs Islet Xenograft Survival in Humanized Mice.

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.

Co-delivery of LETM1 and CTMP synergistically inhibits tumor growth in H-ras12V liver cancer model mice.

As hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, development of novel therapeutic approaches for HCC is urgently needed. Two different genes, LETM1 and CTMP, which target mitochondrial functions, were chosen and linked using 2A-peptide sequence. Successful self-cleavage of 2A-peptide induced synergistic antitumor effect in the liver of H-ras12V, the HCC model mice, by simultaneous activation of LETM1 (Leucine zipper/EF hand-containing transmembrane-1) and CTMP (carboxyl-terminal modulator protein). Overexpression of LETM1 and CTMP significantly reduced the incidence of tumorigenesis, which were confirmed by gross and microscopic observations. Morphological changes in mitochondria, such as swelling and loss of cristae, were significant, and the prolonged activation of defects in mitochondrial function led to mitochondria-mediated apoptosis. Furthermore, with CTMP as a direct binding partner of Akt1, and LETM1 as a binding partner of CTMP, LETM1-2A-CTMP downregulated the Akt1 pathway at both Ser473 and Thr308 sites of phosphorylation. Proliferation and angiogenesis, which are important in cancer prognosis, were reduced in tumor sites after introduction of LETM1-2A-CTMP. Taken together, the results indicate that introduction of the mitochondria-targeting genes, LETM1 and CTMP, and self-processing capacity of 2A-peptide sequence exerts an antitumor effect in liver of H-ras12V mice, suggesting its potential as a tool for gene therapy.

Adult dual kidney transplantations obtained from marginal donors: two case reports.

Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts.

The analysis of PM2.5 and associated elements and their indoor/outdoor pollution status in an urban area.

UNLABELLED: In this study, elemental composition of PM2.5 and the status of indoor/outdoor pollution were investigated in a commercial building near a roadside area in Daejeon, Korea. A total of 60 parallel PM2.5 samples were collected both on the roof (outdoor) and in an indoor office of a building near a highly congested road during the spring and fall of 2008. The concentrations of 23 elements were analysed from these PM2.5 samples using instrumental neutron activation analysis. PM2.5 levels in indoor environment (47.6 ± 16.5 µg/m(3)) were noticeably higher than the outdoor levels (37.7 ± 17.2 µg/m(3)) with the I/O concentration ratio of 1.37 ± 0.33 [correlation coefficient (r) = 0.89, P < 0.001]. Principal component analysis results coincidently showed the predominance of sources such as soil dust, traffic, oil/coal combustion and road dust for both indoor and outdoor microenvironments. An isolated source in the indoor environment was assigned to environmental tobacco smoke (ETS) with high factor loading of Ce, Cl, I, K, La and Zn. The overall results of our study indicate that the sources of indoor constituents were strongly dependent on outdoor processes except for the ones affected by independent sources such as ETS. PRACTICAL IMPLICATIONS: An improved understanding of the factors affecting the indoor PM2.5 concentration levels can lead to the development of an efficient management strategy to control health risks from exposure to indoor PM2.5 and related toxic components. A comparison of our comprehensive data sets indicated that most indoor PM2.5 and associated elemental species were strongly enriched by indoor source activities along with infiltration of ambient outdoor air for a naturally ventilated building.

AFT024 cell line in co-culture system using high pore density insert (HPDI) maintains hematopoietic stem/progenitor cells (HSCs/HPCs) as more primitive state through histone modification.

BACKGROUND: It has been shown that the AFT024 stromal cell line sustains the engraftment capacity of human hematopoietic progenitor cells (HPCs) in vitro. However, the process by which AFT024 cell line maintains human HPCs is a more primitive state ex vivo remains unclear. METHODS: Human umbilical cord blood (UCB)-derived fluorescent activated cell sorter (FACS)-purified CD34(+) CD38(-)hsc/HPCs were cultured with cytokines on hpdi (0.4 micron pore size) coated with irradiated AFT024 cells. The HSC/HPC and AFT024 cells contacted each other through 0.4 micron pores on HPDI membranes; the irradiated AFT024 cells could not migrate through the HPDI to contaminate the HSC/HPC. The frequency of CD34(+)Lin(-) cells was determined as HSCs/HPCs using flow cytometry. To evaluate their engraftment potential in vivo, the co-cultured cells were assayed as Long Term Culture-Initiating Cells (LTC-IC). To understand the process whereby AFT024 cells govern enhanced engraftment, we employed Western blot analysis for histone modifications. RESULTS: There was a 30-fold increase in frequency of CD34(+)Lin(-) cells in co-cultures on HPDI coated on the outer bottom surface with irradiated AFT024 cells and cytokines in contrast to 6-fold among controls. Total colonies from LTC-IC increased approximately 1.5-fold among cells cultured with AFT024, compared with controls. More importantly, cells co-cultured with AFT024 showed a more primitive state with over-methylated h3k4 (Me-H3K4), under-methylated h3k9 (Di-Me-H3K4), and over-acetylated h4 (Ac-H4) compared with controls. CONCLUSION: Our results suggested that co-culture of the AFT024 cell line with HPDI maintained hematopoietic progenitors as a more primitive state through histone modification.

Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-ras(LA1) mice.

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras(LA1) lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.

Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features.

OBJECTIVES: To evaluate patient outcome and investigate the prognostic factors of high-grade meningiomas by adopting the 2000 World Health Organization (WHO) classification system. METHODS: Between 1986 and 2004, 74 patients were diagnosed with high-grade meningioma: 33 with atypical and 41 with anaplastic meningioma. The mean follow-up was 58.5 months. We reclassified all surgical specimens, according to the 2000 WHO classification system, using two expert neuropathologists. RESULTS: Forty of 74 meningiomas were reclassified as atypical meningioma and 24 as anaplastic meningioma. Overall and recurrence-free survivals were significantly longer in patients with atypical than in those with anaplastic meningioma: 142.5 versus 39.8 months and 138.5 versus 32.2 months, respectively (p<0.001). In patients with atypical meningiomas, brain invasion and adjuvant radiotherapy were not associated with survival; however, in the brain invasion subgroup, adjuvant radiotherapy improved patients' survival. In patients with anaplastic meningioma, the prognostic factors were brain invasion, adjuvant radiotherapy, malignant progression, p53 overexpression and extent of resection. The p53 overexpression was the only factor associated with malignant progression (p = 0.009). CONCLUSIONS: The 2000 WHO classification has identified the truly aggressive meningiomas better than did the previous criteria. A precise meningioma grading system may help to avoid over-treatment of patients with an atypical meningioma as, once the tumour has "declared itself" by recurrence and histological features, it becomes a tumour that is poorly amenable to current therapies.

Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice.

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the nose-only inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirus-mediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.

Silencing E1A mRNA by RNA interference inhibits adenovirus replication.

The adenovirus family contains 51 human serotypes, and most human adenoviruses cause widespread respiratory tract infections. Adenovirus infections can result in severe complications in some cases, such as in adenovirus type 11 infection in immunocompromised patients. However, effective treatment methods for adenovirus infections are currently unavailable. This prompted the search for antiviral agents effective against adenovirus infections. In the present study, adenovirus E1A was targeted by RNA interference (RNAi) using synthetic small interfering RNAs (siRNAs) in an attempt to inhibit viral replication, since adenovirus E1A proteins are known to be involved in the transcriptional activation of the viral and cellular genes necessary for controlling the cell cycle and viral replication. The results indicated that the siRNAs effectively reduced the amount of adenovirus E1A mRNA and the levels of replicative intermediates. Additionally, siRNA-mediated gene silencing inhibited adenovirus replication by suppressing the E1A mRNA. These results suggest that the RNAi-mediated targeting of adenovirus E1A may have a potentially therapeutic effect in controlling adenovirus infections.

High isolation rate of adenovirus serotype 7 from South Korean military recruits with mild acute respiratory disease.

Adenovirus is a major cause of acute respiratory disease (ARD) in military recruits. When South Korean military recruits with ARD were surveyed, adenovirus was identified in 122 (61.0%) of the 200 recruits studied. Moreover, all cases of ARD involving adenovirus were caused by serotype 7.

Clinical analysis of vertebrobasilar dissection.

BACKGROUND: The natural history of vertebrobasilar artery dissection (VAD) is not fully known. The purpose of this study was to review the clinical outcome of the patients with VAD, then to propose an appropriate management strategy for VAD. METHOD: From 1992 to 2004, 35 VAD patients admitted to our institutes were retrospectively reviewed. There were 28 men and 7 women, whose age ranged from 4 to 67 years with a mean age of 44 years. Angiography was assessed to document the shape, and location of the dissecting aneurysm with respect to the posterior inferior cerebellar artery (PICA). A modified Rankin score was assigned for functional outcome. The functional outcome scores were analyzed according to the patient's age, gender, hypertension history, the pattern of initial manifestation, angiographic shape of VAD, angiographic location of VAD, treatment modality. FINDINGS: There was no statistically significant difference between the functional outcome with age, gender, trauma history and past medical history of hypertension. Of 35 patients, 22 presented with SAH, 11 with ischemic symptoms and 2 were incidentally detected. The patients without SAH had a better functional outcome than those with SAH (p = 0.029). There was statistical significance between Hunt-Hess (H-H) grade and clinical outcome (p = 0.032). The shape and location of VAD was not significantly related to the functional outcome (p = 0.294, 0.840). But all the cases of rebleeding and mortality (except one case with initially poor H-H grade) developed exclusively in patients with aneurysms. There was no statistically significant correlation between the treatment modality and the outcome (p = 0.691). CONCLUSION: The VAD patients with SAH would be recommended to be managed by either surgical or endovascular treatment, but those without SAH, could be managed conservatively with antiplatelet therapy and/or anticoagulation.

Autoantibody biomarker opens a new gateway for cancer diagnosis.

The list of cancer markers of current interest has grown considerably, but none of the markers used in clinical work is a true tumor marker. These cancer biomarkers are based on the determination of tumor antigens. Here, we report a single method of autoantibody enzyme immunoassay (EIA) screens for a spectrum of serum tumor markers. A comparison of the autoantibody-based EIA to conventional antigen EIA kits, using receiver operating characteristic (ROC) plots, showed that the autoantibody EIA can significantly enhance the sensitivity and specificity of tumor markers. The detection of serum autoantibodies for a spectrum of serum tumor markers, as demonstrated here, suggests that most, if not all, serum cancer biomarkers produce autoantibodies. A unique autoantibody biomarker screening method, as presented here, might therefore facilitate achieving the accurate and early diagnosis of cancer.

DNA drug design for cancer therapy.

DNA (antisense and other oligonucleotides) drug design represents a direct genetic approach for cancer treatment. Such an approach takes advantage of mechanisms that activate genes known to confer a growth advantage to neoplastic cells. The ability to block the expression of these genes allows exploration of normal growth regulation. Progress in DNA drug technology has been rapid, and the traditional antisense inhibition of gene expression is now viewed on a genomic scale. This global view has led to a new vision in antisense technology, the elimination of nonspecific and undesirable side effects, and ultimately the generation of more effective and less toxic nucleic acid medicines. Several antisense oligonucleotides are in clinical trials, are well tolerated, and are potentially active therapeutically. DNA drugs are promising molecular medicines for treating human cancer in the near future.

Extrapedicular approach of percutaneous vertebroplasty in the treatment of upper and mid-thoracic vertebral compression fracture.

PURPOSE: To evaluate the clinical outcome of the extrapedicular approach of percutaneous vertebroplasty (PVP) for upper and mid-thoracic vertebral compression fractures in patients. MATERIAL AND METHODS: Extrapedicular vertebroplasty was performed in painful compression fractures at T4-T8 levels. The assessment criteria were changes over time in visual analog scale (VAS) and mobility score. We evaluated the volume of cement injected, the size of needle required, and complications. RESULTS: Procedures were performed in 27 patients with a total of 34 affected vertebral bodies. Early (within a week) and one year later, clinical follow-ups showed that pain intensity had decreased by 50% one day after operation and later by 70-80%. Mobility scores of all patients were improved immediately after the procedure. Average volume of polymethylmethacrylate (PMMA) per vertebral body was 3.8 +/- 1.2 ml. Leakage of PMMA occurred in one vertebral level (intradiskal space), but did not cause clinical complications. CONCLUSION: PVP of upper and mid-thoracic spine with an extrapedicular approach is an efficient and safe procedure for treating painful thoracic vertebral compression fracture under a cautious patient selection and meticulous technical procedure.