Timing of symptomatic subsequent vertebral compression fracture associated with different demographic factors.

BACKGROUND: Symptomatic subsequent vertebral compression fracture (VCF; SVCF) is a common complication associated with poor outcomes. Accumulating evidence shows that demographic factors and incidences of symptomatic SVCFs differ during different periods after the primary vertebroplasty (VP). PURPOSE: To investigate the incidence and demographic factors of symptomatic SVCFs after the primary VP in different periods using registry data in the Taiwan National Health Insurance Research Database. METHODS: This retrospective cohort study included 28,343 patients aged ≥ 50 years with painful VCF treated with VP from 2002 to 2016. Symptomatic SVCF was defined as SVCF requiring another VP or re-admission. During the 2-year follow-up, 1955 patients received subsequent VP while 1,407 were readmitted. Cox proportional hazard models were used to compare the risks of subsequent VP or readmission. RESULTS: The cumulative incident rate of subsequent VP and re-hospitalization was 0.87 [95% confidence interval (CI), 0.82 ~ 0.92] and 0.62 (95% CI, 0.58 ~ 0.66) per 100 person-months, respectively, within the first 6 months after the primary VP, and it decreased over time. A multiple Cox regression model showed that age, osteopenia or osteoporosis, Charlson comorbidity index (CCI) were significant independent risk factors of subsequent VP or readmission within the first 6 months. CONCLUSIONS: This study demonstrated that the incidence of symptomatic SVCF peaked in the first 6 months after the primary VP. Age, osteoporosis or osteopenia, and CCI were determined to be risk factors in the first 6 months, but only osteoporosis or osteopenia and CCI were risk factors thereafter.

Understanding the Future Prospects of Synergizing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery with Ceramics and Regenerative Cellular Therapies.

Transforaminal lumber interbody fusion (TLIF) is the last resort to address the lumber degenerative disorders such as spondylolisthesis, causing lower back pain. The current surgical intervention for these abnormalities includes open TLIF. However, in recent years, minimally invasive TLIF (MIS-TLIF) has gained a high momentum, as it could minimize the risk of infection, blood loss, and post-operative complications pertaining to fusion surgery. Further advancement in visualizing and guiding techniques along with grafting cage and materials are continuously improving the safety and efficacy of MIS-TLIF. These assistive techniques are also playing a crucial role to increase and improve the learning curve of surgeons. However, achieving an appropriate output through TLIF still remains a challenge, which might be synergized through 3D-printing and tissue engineering-based regenerative therapy. Owing to their differentiation potential, biomaterials such as stem/progenitor cells may contribute to restructuring lost or damaged tissues during MIS-TLIF, and this therapeutic efficacy could be further supplemented by platelet-derived biomaterials, leading to improved clinical outcomes. Thus, based on the above-mentioned strategies, we have comprehensively summarized recent developments in MIS-TLIF and its possible combinatorial regenerative therapies for rapid and long-term relief.

Teriparatide Associated with Fewer Refractures and Higher Body Heights of Cemented Vertebrae after Vertebroplasty: A Matched Cohort Study.

Refracture of cemented vertebrae occurs commonly after vertebroplasty (VP) for osteoporotic vertebral compression fracture (OVCF). It can result in severe pain or neurological deficit, but no preventive medication is available. Owing to the bone anabolic benefits of teriparatide (TP), this study was aimed to compare the outcomes of cemented vertebrae with TP to those without TP. Patients who received VP for OVCF with at least 1 year follow-up were included. The anterior body height (ABH) and middle body height (MBH) and kyphotic angle (KA) were measured before VP and 1 week and at least 1 year after VP. Refracture was defined as a 15% decrease in ABH or MBH and 8° decrease in KA compared with those at postoperative 1 week. The clinical outcomes were evaluated. 35 VP procedures in 21 patients treated with TP (TP group), and, matched to that, 29 out of 133 patients treated with VP alone (VP group) were included. One year after VP, ABH and MBH were significantly greater, except KA, in the TP group (VP group vs. TP group: KA - 4.97° ± 12.1 vs. -2.85° ± 12.21°, p = 0.462, ABH 1.56 ± 0.48 cm vs. 1.84 ± 0.56 cm, p = 0.027, MBH 1.49 ± 0.39 cm vs. 1.73 ± 0.41 cm, p = 0.017). The refracture rates of KA, ABH, and MBH were significantly lower in the TP group (VP group vs. TP group: KA 42.11% vs.8.57%, p < 0.001; ABH 76.32% vs. 28.57%, p < 0.0001; MBH 76.32% vs. 28.57%, p < 0.0001). In single-level subgroup comparison, TP was associated with better improvement of pain VAS and better radiological outcomes. TP was associated with higher BHs and fewer refractures than VP alone, with comparable clinical outcomes 1 year after VP. TP may be associated with better improvement of pain VAS in those with single-level VP procedure. Higher BH was due to the better maintenance effect of TP.

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions.

BACKGROUND: Tumors with epicenter in the thalamus occur in about 4 % of pediatric brain tumors. The histological diagnosis is mainly gliomas. Among them, low-grade glioma (LGG) constituted of a significant entity of the tumors (Cuccia et al., Childs Nerv Syst 13:514-521, 1997; Puget et al., J Neurosurg 106:354-362, 2007; Bernstein et al., J Neurosurg 61:649-656, 1984; Bilginer et al., Childs Nerv Syst 30:1493-1498, 2014). Since Kelly's report in 1989, >90 % resection of thalamic tumors were achieved in reported series (Ozek and Ture, Childs Nerv Syst 18:450-6, 2002; Villarejo et al., Childs Nerv Syst 10:111-114, 1994; Moshel et al., Neurosurgery 61:66-75, 2007; Albright, J Neurosurg 100(5 Suppl Pediatrics): 468-472, 2004; Kelly, Neurosurgery 25:185-195, 1989; Drake et al., Neurosurgery 29: 27-33, 1991). MATERIALS AND METHODS: Sixty-nine cases of thalamic tumors in children were retrospectively reviewed. There were 25 cases of LGGs. We analyzed our experience and correlated it with reported series. RESULTS: Summing up of 4 reported series and the present series, there were 267 cases of thalamic tumors in children. Among these tumors, 107 (40.1 %) were LGGs and 91 (34.1 %) were low-grade astrocytomas (LGAs). In the present series, all of the 25 LGGs were LGAs that consisted of 11 pilocytic astrocytomas (PAs) and 14 diffuse astrocytomas (DAs). Six cases received biopsy sampling only. The remaining 19 cases received different degrees of surgical resection via several approaches. Radical (>90 %) resection was achieved better in PAs comparing with DAs. There was no operative mortality. Two patients had increased neurological deficits. In a mean follow-up period of 11.9 years, three patients died of tumor progression and one patient died of anaplastic change. The 5- and 10-year overall survival (OS) was 87.1 and 87.1 %, respectively. CONCLUSION: Thalamic LGGs are mainly LGAs and are indolent. The rate of >90 % resection was relatively low in the present series. By applying contemporary diagnostic MRI studies, surgical facilities, and appropriate approaches in selective cases, we may try maximum neuroprotective radical (>90 %) resection.

Direct human papillomavirus E6 whole-cell enzyme-linked immunosorbent assay for objective measurement of E6 oncoproteins in cytology samples.

A novel, whole-cell enzyme-linked immunosorbent assay (ELISA) based on a non-type-specific anti-human papillomavirus (HPV) E6 antibody was tested on 182 residual cytological specimens. For samples with a designation of more severe than cervical intraepithelial neoplasia grade 3 (CIN3+), 83% tested positive for E6; in a subset with paired testing for E6 ELISA and HPV DNA, 72% tested E6 positive and 92% tested high-risk (HR)-HPV DNA positive (P = 0.2). Among the women with a less than CIN3 diagnosis, 31% and 47% tested positive for E6 and HR-HPV DNA, respectively (P = 0.0006).

Determination of critical power in trained rowers using a three-minute all-out rowing test.

The purpose of this study was to determine whether the hyperbolic relationship between power output and time to exhaustion (work - time and power - [1/time] models) could be estimated from a modified version of a three-minute all-out rowing test (3-min RT), and to investigate the test-retest reliability of the 3-min RT. Eighteen male rowers volunteered to participate in this study and underwent an incremental exercise test (IRT), three constant-work rate tests to establish the critical power (CP) and the curvature constant (W'), and two 3-min RTs against a fixed resistance to estimate the end-test power (EP) and work-done-above-EP (WEP) on a rowing ergometer. Peak VO(2max) and maximal VO(2max) oxygen uptakes were calculated as the highest 30 s average achieved during the 3-min RT and IRT tests. The results showed that EP and WEP determinations, based on the 3-min RT, have moderate reproducibility (P = 0.002). EP (269 ± 39 W) was significantly correlated with CP (work - time, 272 ± 30 W; power - [1/time], 276 ± 32 W) (P = 0.000), with no significant differences observed between the EP and CP values (P = 0.474). However, WEP did not significantly correlate with W' (P = 0.254), and was significantly higher than the W' values. There was a significant correlation between the VO(2max) (60 ± 3 ml kg(-1) min(-1)) and VO(2max) (61 ± 4 ml kg(-1) min(-1)) (P = 0.003). These results indicate that the 3-min RT has moderate reliability, and is able to appropriately estimate the aerobic capacity in rowers, particularly for the CP and VO(2max) parameters.

Simultaneous quantification of flavonoids and triterpenoids in licorice using HPLC.

Numerous bioactive compounds are present in licorice (Glycyrrhizae Radix), including flavonoids and triterpenoids. In this study, a reversed-phase high-performance liquid chromatography (HPLC) method for simultaneous quantification of three flavonoids (liquiritin, liquiritigenin and isoliquiritigenin) and four triterpenoids (glycyrrhizin, 18alpha-glycyrrhetinic acid, 18beta-glycyrrhetinic acid and 18beta-glycyrrhetinic acid methyl ester) from licorice was developed, and further, to quantify these 7 compounds from 20 different licorice samples. Specifically, the reverse-phase HPLC was performed with a gradient mobile phase composed of 25 mM phosphate buffer (pH 2.5)-acetonitrile featuring gradient elution steps as follows: 0 min, 100:0; 10 min, 80:20; 50 min, 70:30; 73 min, 50:50; 110 min, 50:50; 125 min, 20:80; 140 min, 20:80, and peaks were detected at 254 nm. By using our technique, a rather good specificity was obtained regarding to the separation of these seven compounds. The regression coefficient for the linear equations for the seven compounds lay between 0.9978 and 0.9992. The limits of detection and quantification lay in the range of 0.044-0.084 and 0.13-0.25 microg/ml, respectively. The relative recovery rates for the seven compounds lay between 96.63+/-2.43 and 103.55+/-2.77%. Coefficient variation for intra-day and inter-day precisions lay in the range of 0.20-1.84 and 0.28-1.86%, respectively. Based upon our validation results, this analytical technique is a convenient method to simultaneous quantify numerous bioactive compounds derived from licorice, featuring good quantification parameters, accuracy and precision.

Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs in a mouse model of human prostate adenocarcinoma.

Bombesin (BBN), an analog of human gastrin-releasing peptide (GRP), binds to the GRP receptor (GRPR) with high affinity and specificity. Overexpression of GRPR has been discovered in mostly androgen-independent human prostate tissues and, thus, provides a potential target for prostate cancer diagnosis and therapy. We have previously demonstrated the feasibility of the positron emission tomography (PET) imaging using 64Cu-1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA)-[Lys3]BBN to detect GRPR-positive prostate cancer. In this study, we compared the receptor affinity, metabolic stability, tumor-targeting efficacy, and pharmacokinetics of a truncated BBN analog 64Cu-DOTA-Aca-BBN(7-14) with 64Cu-DOTA-[Lys3]BBN. Binding of each DOTA conjugate to GRPR on PC-3 and 22Rv1 prostate cancer cells was evaluated with competitive binding assay using 125I-[Tyr4]BBN as radioligand. In vivo pharmacokinetics was determined on male nude mice subcutaneously implanted with PC-3 cells. Dynamic microPET imaging was performed to evaluate the systemic distribution of the tracers. Metabolic stability of the tracers in blood, urine, tumor, liver and kidney was studied using high-performance liquid chromatography. The results showed that 125I-[Tyr4]BBN has a K(d) of 14.8+/-0.4 nM against PC-3 cells, and the receptor concentration on PC-3 cell surface is approximately 2.7+/-0.1 x 10(6) receptors per cell. The 50% inhibitory concentration value for DOTA-Aca-BBN(7-14) is 18.4 +/- 0.2 nM, and that for DOTA-[Lys3]BBN is 2.2 +/- 0.5 nM. DOTA-[Lys3]BBN shows a better tumor contrast and absolute tumor activity accumulation compared to DOTA-Aca-BBN(7-14). Studies on metabolic stability for both tracers on organ homogenates showed that 64Cu-DOTA-[Lys3]BBN is relatively stable. This study demonstrated that both tracers are suitable for targeted PET imaging to detect the expression of GRPR in prostate cancer, while 64Cu-DOTA-[Lys3]BBN may have a better potential for clinical translation.

Electronic and spectroscopic studies of the non-heme reduced binuclear iron sites of two ribonucleotide reductase variants: comparison to reduced methane monooxygenase and contributions to O2 reactivity.

Circular dichroism (CD), magnetic circular dichroism (MCD), and variable-temperature variable-field (VTVH) MCD have been used to probe the biferrous active site of two variants of ribonucleotide reductase. The aspartate to glutamate substitution (R2-D84E) at the binuclear iron site modifies the endogenous ligand set of ribonucleotide reductase to match that of the binuclear center in the hydroxylase component of methane monooxygenase (MMOH). The crystal structure of chemically reduced R2-D84E suggests that the active-site structure parallels that of MMOH. However, CD, MCD, and VTVH MCD data combined with spin-Hamiltonian analysis of reduced R2-D84E indicate a different coordination environment relative to reduced MMOH, with no mu-(1,1)(eta(1),eta(2)) carboxylate bridge. To further understand the variations in geometry of the active site, which lead to differences in reactivity, density functional theory (DFT) calculations have been carried out to identify active-site structures for R2-wt and R2-D84E consistent with these spectroscopic data. The effects of varying the ligand set, positions of bound and free waters, and additional protein constraints on the geometry and energy of the binuclear site of both R2-wt and variant R2s are also explored to identify the contributions to their structural differences and their relation to reduced MMOH.

Comparing genomic and histologic correlations to radiographic changes in tumors: a murine SCC VII model study.

RATIONALE AND OBJECTIVES: To investigate the correlation between the temporal changes in T1- and T2-weighted contrast-enhanced magnetic resonance imaging (MRI), histologic evaluation, and genomic analysis using oligonucleotide microarrays in a murine squamous cell carcinoma tumor models. MATERIALS AND METHODS: The squamous cell carcinoma (SCC VII) cell line was used to initiate subcutaneous tumors in mice. This mouse model has been used as a model for human head and neck carcinomas. Animals were imaged using contrast enhanced MRI (CE-MRI). Different stages of tumor growth were defined based on changes in the T1- and T2-weighted MRI patterns. The contrast enhancing (CE) and nonenhancing (NE) regions of the tumors were marked and biopsied for oligonucleotide microarray and histologic analysis. Tumors with no differential contrast enhancement were used as controls. RESULTS: Distinct temporal stages of tumor progression can be defined using both T1- and T2-weighted CE-MRI and microarray analysis. The early stage tumors show a homogeneous contrast enhancement pattern in the T1- and T2-weighted images with no significant differential gene expression from the center and periphery of the tumor. The more advanced tumors that show discrete regions of contrast enhancement in the post-contrast T1-weighted MRIs and tissues from the CE and NE regions show distinctly differential gene expression profiles. Histologic analysis (hematoxylin-eosin stain) showed that the samples obtained from the periphery and center of the early stage tumors and the CE and NE regions from these more advanced tumors were similar. The gene expression profiles of late-stage tumors that showed changes in T2-weighted MRI signal intensity were consistent with tissue degradation in the NE region, which also showed characteristic signs of tissue necrosis in histologic analysis. CONCLUSION: These results show that temporal changes in T1- and T2-weighted CE-MRI are related to distinct gene expression profiles, and histologic analysis may not be sufficient to detect these detailed changes. As tumors progress, discrete regions of post-contrast T1 enhancement are identified; these regions have distinct gene expression patterns despite similar histologic features. In late-stage tumors, regions of T2 signal changes are observed which correspond with tissue necrosis.

Circular dichroism and magnetic circular dichroism studies of the biferrous form of the R2 subunit of ribonucleotide reductase from mouse: comparison to the R2 from Escherichia coli and other binuclear ferrous enzymes.

Ribonucleotide reductase (RNR) catalyzes the synthesis of the four deoxyribonucleotides needed for DNA synthesis and repair in living organisms. The reduced [Fe(II)Fe(II)] form of the model mammalian enzyme, mouse RNR R2, has been studied using a combination of circular dichroism (CD), magnetic circular dichroism (MCD), and variable-temperature variable-field (VTVH) MCD spectroscopies. Titrations of ferrous ion to the apo-enzyme have been performed and analyzed to investigate the metal binding affinity of the metal-binding site. Spectral features of individual iron sites have been analyzed to obtain detailed geometric and electronic structural information. VTVH MCD data have been collected and analyzed using two complementary models to obtain detailed ground state information including the zero-field splitting (ZFS) of both ferrous centers and the exchange coupling (J) between the two sites. These ground and excited state results provide a complete description of the biferrous site of mouse R2. The biferrous site consists of one 4- and one 5-coordinate iron, with positive and negative ZFS values, respectively. Weak exchange coupling between the two ferrous centers is present, consistent with having carboxylate bridges. The two sites have highly cooperative and weak metal binding affinities. This may be a novel regulatory mechanism for RNR. These results are compared with those from reduced Escherichia coli R2 and reduced acyl-carrier protein Delta(9) desaturase to correlate to similarities and differences in their dioxygen reactivity.

Functional genomics guided with MR imaging: mouse tumor model study.

To gain a better understanding of gene expression patterns in tumors, the authors used contrast material-enhanced magnetic resonance (MR) imaging to noninvasively characterize regions within the same tumor to provide a correlate for genomic analysis. Gene expression profiles of samples from a mouse tumor model obtained from contrast-enhanced and nonenhanced regions within the same tumor were compared with MR imaging and functional genomics. From these samples, 11000 genes were analyzed: 10 genes were up-regulated in the contrast-enhanced areas, and one gene was up-regulated in the nonenhanced regions. Several of these genes encode extracellular matrix proteins. Findings in this study demonstrate that MR imaging can serve as a powerful noninvasive tool for characterizing different regions of tumors to guide genomic analysis with high spatial and temporal resolution.