The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma.

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.

Development of the Soft X-ray AGM-AGS RIXS beamline at the Taiwan Photon Source.

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

Characterization and virus susceptibility of a continuous cell line derived from the brain of Aequidens rivulatus (Günther).

Cell cultures derived from the brain tissues of Aequidens rivulatus (Günther) have been characterized previously. In this study, a continuous cell line ARB8 was further established, and its growth characteristics, transcription and susceptibility to fish viruses-including chum salmon reovirus (CSV), marbled eel infectious pancreative necrosis virus (MEIPNV), grouper nervous necrosis virus (GNNV), giant seaperch iridovirus (GSIV), red seabream iridovirus (RSIV), koi herpesvirus (KHV), herpesvirus anguilla (HVA) and marbled eel polyoma-like virus (MEPyV)-were examined. ARB8 cells that showed epithelioid morphology and were passaged >80 times grew well at temperatures ranging from 25°C to 30°C in L-15 medium containing 5%-15% foetal bovine serum. The cells constitutively transcribed connexion 43, glutamine synthetase, nestin and nkx6-2, which are markers for neural progenitor cells. The cells were highly susceptible to CSV, MEIPNV, GSIV and RSIV and showed the typical cytopathic effect (CPE). However, the cells were resistant to GNNV, KHV, HVA and MEPyV because no significant CPE was noted after infection. Optimal temperatures for virus production ranged from 25°C to 30°C. The results revealed that the neural progenitor cell line ARB8 can potentially serve as a useful tool for investigating fish viruses and isolating new viruses in ornamental cichlid fishes.

Reproductive biology of female striped marlin Kajikia audax in the western Pacific Ocean.

Length and mass data for 1260 (536 females, 683 males, 41 sex unknown) striped marlin Kajikia audax were collected at the fish markets of Tungkang, Singkang and Nanfangao from July 2004 to September 2010. Of these samples, 534 gonads (236 females and 298 males) ranging from 95 to 206 cm in eye-to-fork length (LEF ) and 8 to 88 kg in round mass (MR ), were collected. Chi-square tests indicated sex ratios were homogeneous among months in 2004 and 2006-2008, but not in 2005, 2009 and 2010; and there were significant differences in sex ratio by size. The overall sex ratio (RS ) differed significantly from the expected 0·5. Kajikia audax are sexually dimorphic and the proportions of females increased with size between 140 and 210 cm LEF . Reproductive activity was assessed using a gonado-somatic index (IG ), external appearance of the gonads and histological examination and results indicated that the spawning season occurred from April to August with a peak in June to July. Based on histological observations and the distribution of oocyte diameters, K. audax are multiple spawners and their oocytes develop asynchronously. The estimated length-at-50% maturity (LEF50 ) was c. 181 cm (c. 4·8 years of age) for females. The proportion of reproductively active females in the spawning season with ovaries containing postovulatory follicles (0·27) indicated that they spawned every 3·7 days on average. The hydrated oocyte method estimated mean ± S.D. batch fecundity (FB ) to be 4·4 ± 2·02 million eggs; average relative fecundity was 53·6 ± 13·9 oocytes g-1 MR ; and the average annual fecundity was 181·3 ± 48·3 million eggs. The parameters estimated in this study are key information for stock assessments of K. audax in the north-western and central Pacific and will contribute to the conservation, management and sustainable yield of this species.

Selection of GP. Mur antigen-negative RBC for blood recipients with anti-'Mia ' records decreases transfusion reaction rates in Taiwan.

OBJECTIVES: To evaluate the clinical significance of GP. Mur antigen-negative blood selection for transfusion in patients with anti-'Mia ' records. BACKGROUND: The GP. Mur RBC phenotype is prevalent (7·3%) in Taiwan. Antibodies against GP. Mur (anti-'Mia ') are identified in 1·24% of our population, and anti-'Mia ' screening using GP. Mur RBC has been routine for Taiwan's blood banks. However, due to the lack of commercial antibodies, only cross-matching was used to prevent transfusion of GP. Mur-positive blood to patients with anti-'Mia ' in most hospitals. There is still a risk of GP. Mur-positive RBC exposure and subsequent anti-'Mia '-related transfusion reactions. METHODS: Since February 2014, GP. Mur antigen-negative RBCs identified by reaction with anti-'Mia '-positive serum were selected for blood recipients with anti-'Mia ' records. The transfusion reactions between January 2013 and January 2014 were compared with those that occurred between February 2014 and July 2015. RESULTS: The transfusion reaction rate was significantly higher in anti-'Mia '-positive blood recipients compared to total subjects receiving an RBC transfusion before GP. Mur-negative donor RBC selection. After antigen-negative RBC selection, the transfusion reaction frequency in subjects with anti-'Mia ' became similar to total blood recipients. IgG form anti-'Mia ' antibodies were present in all cases of probable anti-'Mia '-related transfusion reactions. The time required for anti-'Mia ' boosting after transfusion was around 4-21 days. CONCLUSION: Selection of GP. Mur-negative RBC for transfusion to patients with anti-'Mia ' records could decrease the rate of transfusion reaction and antibody boosting. This procedure should be incorporated into blood bank routines in areas where anti-'Mia ' is prevalent.

ENU-induced mutation in the DNA-binding domain of KLF3 reveals important roles for KLF3 in cardiovascular development and function in mice.

KLF3 is a Krüppel family zinc finger transcription factor with widespread tissue expression and no previously known role in heart development. In a screen for dominant mutations affecting cardiovascular function in N-ethyl-N-nitrosourea (ENU) mutagenized mice, we identified a missense mutation in the Klf3 gene that caused aortic valvular stenosis and partially penetrant perinatal lethality in heterozygotes. All homozygotes died as embryos. In the first of three zinc fingers, a point mutation changed a highly conserved histidine at amino acid 275 to arginine (Klf3(H275R) ). This change impaired binding of the mutant protein to KLF3's canonical DNA binding sequence. Heterozygous Klf3(H275R) mutants that died as neonates had marked biventricular cardiac hypertrophy with diminished cardiac chambers. Adult survivors exhibited hypotension, cardiac hypertrophy with enlarged cardiac chambers, and aortic valvular stenosis. A dominant negative effect on protein function was inferred by the similarity in phenotype between heterozygous Klf3(H275R) mutants and homozygous Klf3 null mice. However, the existence of divergent traits suggested the involvement of additional interactions. We conclude that KLF3 plays diverse and important roles in cardiovascular development and function in mice, and that amino acid 275 is critical for normal KLF3 protein function. Future exploration of the KLF3 pathway provides a new avenue for investigating causative factors contributing to cardiovascular disorders in humans.

Heme oxygenase-1 gene promoter polymorphism and the risk of pediatric nonalcoholic fatty liver disease.

BACKGROUND AND OBJECTIVES: Oxidative stress and the insulin-resistant state are thought to be key components in the pathogenesis of pediatric nonalcoholic fatty liver disease (NAFLD). Heme oxygenase (HO) is important in the defense against oxidative stress. This study aimed to assess the association of HO-1 gene promoter polymorphism and insulin resistance with NAFLD among obese children. METHODS: A total of 101 obese children aged 6-17 years were recruited. Anthropometric, serum biochemical variables and biomarkers for glucose and insulin metabolism were measured. We screened the allelic frequencies of (GT)n repeats in the HO-1 gene promoter among these obese children. NAFLD was determined through liver ultrasonography. Because the distribution of numbers of (GT)n repeats was bimodal, we divided the alleles into two classes: class S included shorter (27) repeats, and class L included longer (⩾27) repeats. We assessed the effects of the length of (GT)n repeats in HO-1 gene promoter on pediatric NAFLD. RESULTS: Of the 101 obese subjects, 27 (26.7%) had NAFLD. The alanine aminotransferase level was higher in patients carrying L alleles (L/L and L/S) than patients with S alleles (S/S) (46.2±49.3 IU|(-1) versus 30.2±20.1 IU|(-1); P=0.027). The significant risk factors for pediatric NAFLD were patients carrying L alleles (L/L and L/S) (odds ratio (OR)=18.84; 95% confidence interval (CI): 1.45-245.22; P=0.025), homeostasis model assessment of insulin resistance (OR=1.40; 95% CI: 1.07-1.83; P=0.014) and age (OR=1.24; 95% CI: 1.03-1.50; P=0.025). CONCLUSION: In this hospital-based study, the obese children with longer GT repeats in the HO-1 gene promoter and insulin resistance were susceptible to NAFLD.

Adaptive Phase-Field Modeling of Anisotropic Wetting with Line Tension at the Triple Junction.

Line tension could affect the contact angle at triple junction, especially in micro- to nanoscale wetting. We have developed an adaptive phase-field model to consider the line tension quantitatively. This model is coupled to the smoothed boundary method for treating the contact line with the solid phase, while the volume constraint is imposed. Our calculated contact angles are in good agreement with the modified Young's equation. Further examples are illustrated for the anisotropic wetting on hydrophilic/hydrophobic stripes and rectangular grooves.

Statins can increase the risk of herpes zoster infection in Asia.

This study evaluated whether statin therapy increases the risk of herpes zoster (HZ) infection in Asia. This retrospective cohort study used the Longitudinal Health Insurance Database (LHID2000). From the LHID2000, patients aged 20 years were divided into two cohorts according to their statin use and were matched at a 1:1 ratio according to propensity scores, which were calculated using a logistic regression for estimating the probability of treatment assignment. The primary outcome was HZ infection. All patients were followed from the index date until the date of HZ infection, withdrawal from the insurance system, or the end of 2011. The study included 53,069 patients receiving statin therapy as a statin cohort and 53,069 patients without statin therapy as a nonstatin cohort. The mean follow-up durations for the statin cohort and nonstatin cohort were 4.89 [standard deviation (SD) = 2.86] years and 4.75 (SD = 2.90) years, respectively. The patients in the statin cohort had a 21 % higher risk of contracting HZ infection than the patients in the nonstatin cohort [95 % confidence interval (CI) = 1.13-1.29]. The incidence of HZ infection increased with the Charlson comorbidity index (CCI) score in both cohorts. A high mean defined daily dose of the six types of statins considered in this study was associated with a significantly increased risk of HZ infection. Statin therapy can increase HZ infection in Asia. More benefit-risk evaluations for statin use are necessary in Asia.

Orolingual angioedema after alteplase therapy of acute ischaemic stroke: incidence and risk of prior angiotensin-converting enzyme inhibitor use.

BACKGROUND AND PURPOSE: Orolingual angioedema (OA) is an uncommon but potentially life-threatening complication of treatment with recombinant tissue plasminogen activator (rt-PA; alteplase) during acute ischaemic stroke. This study aimed to determine the incidence of rt-PA-related OA in an Asian stroke population and the risk of pre-stroke anti-hypertensive drug use for development of this complication. METHODS: A multi-center stroke registry was used to identify the pre-stroke medications of acute ischaemic stroke patients receiving intravenous rt-PA from January 2002 to December 2013. The clinical manifestations of rt-PA-related OA were recorded and the incidence of this complication was determined. The risks of pre-stroke use of different anti-hypertensive agents for the occurrence of rt-PA-related OA were determined from this study and from a meta-analysis. RESULTS: A total of 559 patients received intravenous rt-PA over a 12-year period. Five patients (two males) developed OA after rt-PA administration. The incidence of OA amongst these patients was 0.89% (95% confidence interval 0.29%-2.09%), which was lower than that obtained by meta-analysis (1.9%). Amongst pre-stroke anti-hypertensive medications, angiotensin-converting enzyme (ACE) inhibitors were found in this study to have the highest relative risk for rt-PA-related OA (17.1; 95% confidence interval 3.0-96.9). Meta-analysis also revealed that pre-stroke use of ACE inhibitors was associated with a high relative risk of OA after intravenous rt-PA (12.9; 95% confidence interval 4.5-37.0). CONCLUSIONS: The incidence of rt-PA-related OA in the Asian population is lower than that in the Caucasian population. Pre-stroke use of ACE inhibitors significantly increases the risk of this complication.

Trophic size-structure of sailfish Istiophorus platypterus in eastern Taiwan estimated by stable isotope analysis.

To examine trophic dynamics over different size classes, an isotopic study of sailfish Istiophorus platypterus life-history stages was carried out. Samples were collected from eastern Taiwan and the South China Sea during April 2009 and February 2012. A total of 263 samples (111-245 cm, lower jaw fork length, LLJFL ) were examined for changes in trophic structure in relation to LLJFL by using stable isotope analysis of carbon (δ(13) C) and nitrogen (δ(15) N). The δ(15) N values for I. platypterus ranged from 7·51 to 14·19‰ (mean ± s.d. = 12·06 ± 1·16‰) and the δ(13) C values ranged from -22·04 to -15·48‰ (mean ± s.d. = -17·62 ± 1·10‰). The δ(15) N values were positively dependent on LLJFL (r(2) = 0·377), whereas δ(13) C were negatively dependent on LLJFL (r(2) = 0·063). There were significantly different seasonal changes in nitrogen and carbon isotopic concentration, but no significant differences in concentrations between eastern Taiwan and the South China Sea were reported. The trophic level (TL ) of each LLJFL class was correlated, starting from 2·84 TL for size class I (LLJFL < 140 cm) and reaching 5·03 TL for size class VI (LLJFL > 221 cm). The mean ± s.d. TL was 4·43 ± 0·19 for all samples. The results reveal that I. platypterus occupies a wide range of trophic levels and different size classes occupy different trophic positions in the pelagic ecosystem.

Pre-ICH warfarin use, not antiplatelets, increased case fatality in spontaneous ICH patients.

BACKGROUND AND PURPOSE: Anticoagulant and antiplatelets for prevention of ischaemic stroke and cardiovascular diseases may increase the risk of intracerebral hemorrhage (ICH). This study aimed to investigate the influence of pre-ICH use of anticoagulant and antiplatelets on ICH patients. METHODS: Consecutive patients with acute spontaneous ICH registered in a single-center stroke registry during 2001 to 2010 were analyzed and categorized according to their pre-ICH use of warfarin (Group I), antiplatelets (Group II), or neither (Group III). Survival analysis and the Cox proportional hazard model were used to compare between the three groups and the predictors. RESULTS: Of 2021 ICH patients (male, 63.3%; mean age, 62.6 ± 14.4 years) included, there were 94 (4.7%) in Group I, 232 (11.4%) in Group II, and 1695 (83.9%) in Group III. Warfarin users had larger hematoma volume, more intraventricular extension, higher frequencies of lobar ICH, and higher case fatality than non-warfarin users (Groups II and III). The Cox proportional hazard model showed increased 6-month case fatality in pre-ICH warfarin users (adjusted hazard ratio 2.75, 95% confidence interval 2.04-3.72, P < 0.001), but not in pre-ICH antiplatelet users (adjusted hazard ratio 0.95, 95% confidence interval 0.72-1.26). CONCLUSIONS: Intracerebral hemorrhage patients with prior warfarin use, but not antiplatelet use, had significantly higher case fatality at 6 months.

First Report of Sweet potato virus G Infecting Sweet Potato in Taiwan.

Sweet potato, Ipomoea batatas (L.) Lam., is an important root crop grown mainly in the counties of Changhua, Yunlin, Tainan, and Pingtung in Taiwan where Sweet potato feathery mottle virus (SPFMV) and Sweet potato latent virus (SPLV) have been reported. Commercial sweet potato grown in Nantou in 2009 and in Hualian in 2010 exhibited downward leaf curling and vein clearing, indicative of viral infection, yet symptoms were distinct from those caused by SPFMV, SPLV, or mixed infection of both viruses. Total RNA was extracted from two symptomatic plants from each county with RNeasy Plant Mini Kit (Qiagen, Hilden, Germany) and analyzed by reverse transcription (RT)-PCR using the potyvirusdegenerate primer Hrp5 (1) and oligo-dT18 with BamHI site at the 5' end (5'-GGATCCTTTTTTTTTTTTTTTTTT-3'). Two healthy plants served as negative controls. An approximately 1.5-kb amplicon covering the region from the 3'-end of the nuclear inclusion protein b (NIb) gene to the 3'-untranslated region (3'-UTR) was amplified from all symptomatic plants, while the healthy controls remained negative. Subsequently, one sample from each location was cloned and sequenced (GenBank Accession No. HQ171932-TW1 [Nantou] and JN205346-TW2 [Hualian]). Based on sequence comparison, the two isolates shared only 86.7% nucleotide identity. BLAST analysis of the CP gene of the isolate TW1 revealed 99% nucleotide identity with the corresponding sequence of Sweet potato virus G (SPVG)-CH2 from China (Z83314). Isolate TW2, however, only shared 86% nucleotide identity with SPVG-CH2, indicating isolate TW2 is genetically different from other isolates and probably represents a new strain of SPVG. The presence of SPVG was further confirmed in symptomatic plants by indirect ELISA using SPVG antiserum developed by Y.-H. Cheng of the Agricultural Research Institute. Since co-infection of different viruses in sweet potato can cause severe leaf symptoms and significant yield reduction (3), a preliminary field survey was also conducted to determine the extent of co-infection with more than one potyvirus using three different primer pairs, SPVGup (5'-ACCGAGCTTTACCCCAGGTAGAGAG-3')/SPVdw (5'-CGCGCAAGACTCATRTCAGTCAAAT-3') for SPVG, FM16 (5'-GAATTTAAAGATGCAGGTGTGAAC-3')/FM895 (5'-GAGGTTATGTATATTTCTAGTAAC-3') for SPFMV, and L166 (5'-GACAGAGATATCAACACTGGCACC-3')/L841 (5'-TCCAAGTAGTGTGTGTATGTTCCG-3') for SPLV. Forty-six of 128 (36%) sweet potato samples collected from Nantou, Hualian, Yunlin, Tainan, and Chiayi counties during 2010 and 2011 tested positive for SPVG. Of the 46 samples that tested positive for SPVG, six were co-infected with SPLV, 19 were co-infected with SPFMV, and two were co-infected with all three viruses. Of the samples that tested negative for SPVG, 10 were infected with SPLV, eight were infected with SPFMV, and two were infected with both SPLV and SPFMV. To date, SPVG has been detected in China, the United States, Peru, Egypt, Ethiopia, Zimbabwe, South Africa, Spain, Java, New Zealand, Hawaii, French Polynesia, and Easter Island (2). To our knowledge, this is the first report of SPVG infecting sweet potato in Taiwan. SPVG could become a new and potentially serious threat to sweet potato production in Taiwan. References: (1) C. C. Chen et al. Bot. Stud. 47:369, 2006. (2) M. Rännäli et al. Plant Dis. 92:1313, 2008. (3) M. Untiveros et al. Plant Dis. 91:669, 2007.

Reproductive biology of female bigeye tuna Thunnus obesus in the western Pacific Ocean.

The reproductive biology of female bigeye tuna Thunnus obesus was assessed by examining 888 fish (ranging from 84·9 to 174·4 cm fork length, LF ) caught by Taiwanese offshore longliners in the western Pacific Ocean from November 1997 to November 1998 and November to December 1999 and 258 gonad samples from these fish. The overall sex ratio of the catch during the sampling differed significantly from 0·5, but males were predominant in sizes >140 cm LF . Reproductive activity (assessed by histology), a gonado-somatic index, and the size-frequency distributions of whole oocytes indicated that spawning occurred throughout the year and the major spawning season appeared to be from February to September. The estimated sizes at 50% maturity (LF50 ) of females was 102·85 cm (95% c.i.: 90·79-110·21 cm) and the smallest mature female was 99·7 cm LF . They are multiple spawners and oocytes develop asynchronously. The proportion of mature (0·63) and reproductively active (0·70) females with ovaries containing postovulatory follicles indicated that they spawn almost daily. Batch fecundity for 15 females with the most advanced oocytes (>730 µm) ranged from 0·84 to 8·56 million eggs (mean ± s.d. = 3·06 ± 2·09). The relationships between batch fecundity (FB , in millions of eggs) and LF (cm) and round mass (MR , kg) were FB=9·91×10-14LF6·38 (r(2) = 0·84) and FB=8·89×10-4MR2·05 (r(2) = 0·80), respectively. The parameters estimated in this study are key information for stock assessments of T. obesus in the western Pacific Ocean and will contribute to the conservation and sustainable yield of this species.

The global distribution of oral and maxillofacial surgeons: a mixed-methods study.

Despite its role in treating the most dominant non-communicable diseases worldwide, the global workforce of oral and maxillofacial (OM) surgeons is not well-characterized. To address the current deficit in understanding of the global OM surgeon workforce and to elevate oral and maxillofacial surgery (OMS) in the global health discourse, we join other surgical specialties in evaluating global surgical capacity with a descriptive analysis of the distribution of OM surgeons worldwide. A mixed-methods study was implemented using a combination of literature review, in-country contacts, internet searches, and survey data. The survey was distributed globally from January to June 2022. Data regarding OM surgeon workforce estimates were obtained for 104 of 195 United Nations-recognized countries (53.3%). Among countries with available estimates, the median global workforce density was 0.518 OM surgeons per 100,000 population. Twenty-eight countries (26.9%) were reported to have two or fewer OM surgeons. The median OM surgeon workforce density for low-income countries was 0.015 surgeons per 100,000 population, compared to 1.087 surgeons per 100,000 population in high-income countries. low and middle-income countries countries have the least workforce density as well as the least data coverage. More work is needed to better understand the capacity of the global OM surgeon workforce and access to OMS care.

Prospective comparison of the therapeutic effect of teriparatide with that of combined vertebroplasty with antiresorptive agents for the treatment of new-onset adjacent vertebral compression fracture after percutaneous vertebroplasty.

UNLABELLED: Most post-vertebroplasty new-onset adjacent vertebral compression fractures (VCFs) occur within 2-3 months, and antiresorptive agents do not significantly reduce the risk of their occurrence. In opposite mechanism, teriparatide directly stimulates bone formation and improves bone strength and quality faster. The therapeutic effect of teriparatide is better than that of vertebroplasty combined with an antiresorptive treatment and is a potentially useful therapy for new-onset adjacent VCFs after vertebroplasty. INTRODUCTION: Following vertebroplasty, patients are at increased risk of new-onset adjacent-level VCFs. The therapeutic effect of antiresorptive agents is too slow, and they are associated with the risk of new VCFs. Teriparatide markedly increases bone formation and strength and reduces the incidence of new-onset VCFs. This prospective cohort study compared the therapeutic effects of teriparatide with those of combined vertebroplasty and an anti-resorber for treating new-onset adjacent VCFs after vertebroplasty. METHODS: Fifty patients with adjacent VCFs were randomly assigned to two groups: teriparatide only (group A) and additional vertebroplasty combined with an antiresorptive agent (group B). Relevant clinical data of the two groups were prospectively compared. RESULTS: The 22 patients in group A were at higher risk of new VCFs than those in group B (22 patients); they were older and had more pre-existing fractures (p < 0.05). Patients treated with teriparatide had a significantly lower incidence of new-onset VCFs (odds ratio = 0.21; 95% confidence interval, 0.02-2.10). Teriparatide-mediated VCF reduction was 78.57%, which was markedly better than that of group B. The teriparatide group had a significant decrease in the visual analog scale and an increase in the Japanese Orthopedic Association low back pain score after 6 months of treatment (p < 0.05). The increase in lumbar spine BMD was marked in the teriparatide group (21.70% vs. 6.87%) after an 18-month treatment. CONCLUSIONS: Treatment of post-vertebroplasty adjacent VCFs with teriparatide (no new vertebroplasty) was more effective than that of repeated vertebroplasties combined with an anti-resorber.

Radioactive impact in South Korea from the damaged nuclear reactors in Fukushima: evidence of long and short range transport.

Traces of long-lived fallout-derived radioisotopes ((134)Cs and (137)Cs) were found in wet and dry deposition samples collected from the west and east coasts of South Korea from March to May 2011 following the release of radionuclides from the damaged nuclear power plants in Fukushima, Japan. The analysis of air mass back trajectory and atmospheric pressure systems indicated that the Fukushima-derived radiocaesium had predominantly reached South Korea from the west by surface westerlies from 11 March to 5 April; however, after 6 April, air masses arrived from Japan directly due to a high pressure system that developed to the east of Japan. Spatial variation of deposition fluxes of radiocaesium in South Korea was partly attributed to the presence of local longitudinal orography.

Long term survival of Enteropathy-associated T-cell Lymphoma (EATL) with intracranial metastasis: letter to the Editor.

We read the article by Chuan YY et al (1) with interest when we searched the literature to guide our care for a patient with Enteropathy-associated T-cell Lymphoma (EATL) with intracranial metastasis. Chuan YY et al (1) reported a patient with EATL developed intracranial involvement and died nine months after the initial diagnosis. They also summarized previous studies and found the survival after initial diagnosis was no longer than sixteen months.

Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging.

The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca2+]e), but the local [Ca2+]e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca2+]e in the mouse calvarial bone marrow, taking into account the pH sensitivity of the calcium probe and the wavelength-dependent optical loss through bone. Unexpectedly, the mean [Ca2+]e in the bone marrow (1.0 ± 0.54 mM) is not significantly different from the blood serum, but the HSCs are found in locations with elevated local [Ca2+]e (1.5 ± 0.57 mM). With aging, a significant increase in [Ca2+]e is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca2+]e and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types.

The interaction between Toxoplasma gondii and mammalian cells. I. Mechanism of entry and intracellular fate of the parasite.

Macrophage, fibroblast, and HeLa cell cultures have been infected with Toxoplasma gondii, and observations have been made on parasite entry and fate. A special procedure was devised for studying the entry of toxoplasmas by electron microscopy. Toxoplasmas were centrifuged onto the cells in the cold; fixation 1-3 min after warming yielded specimens showing numerous examples of parasites in the process of entering cells. The mechanism of entry into macrophages, fibroblasts, and HeLa cells was in all cases by phagocytosis. Micropseudopods were extended by the cells to envelop the attached parasites in a typical phagocytic vacuole. Apparently the toxoplasmas stimulated this response of HeLa cells and fibroblasts, cell types not usually phagocytic. No instance was seen of penetration of toxoplasmas through the cell membrane, or of parasites located free in the cytoplasm. Essentially all of the toxoplasmas that entered HeLa cells divided with a generation time of 9 hr; the parasites formed large rosettes situated in vacuoles, eventually leading to host cell rupture. Macrophages took in larger numbers of toxoplasmas than did HeLa cells, but approximately half of the parasites inside of macrophages degenerated within a few hours. The surviving toxoplasmas in macrophages divided every 8 hr, forming rosettes and eventually rupturing the cells.