Screening of Fracture Risk and Osteoporosis Among Older Long-term Care Residents: A Prospective Study.

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.

Increased risk of end-stage renal disease in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organs, including the kidneys. There is a lack of long-term renal prognosis studies on patients with SSc. The aim of this study was to assess the risk of end-stage renal disease (ESRD) in patients with SSc. METHOD: We designed a prospective cohort study based on the National Health Insurance Research Database of Taiwan. Patients with SSc and a non-SSc control group were selected from 1 January 2000 to 31 December 2013. The SSc cohort and control group were matched on the propensity score in a 1:2 ratio. The primary outcome was development of ESRD. Cox proportional hazard regression was performed to assess the effects of SSc on ESRD. RESULTS: After propensity score matching, we enrolled 2012 patients in the SSc group and 4024 patients in the control group. During a mean follow-up of 6.5 years, 86 individuals [SSc group, n = 41 (2.04%); control group, n = 45 (1.12%)] had developed ESRD. The risk of ESRD in the SSc group was approximately two times higher than that in the control group [hazard ratio (HR) = 2.12, 95% confidence interval (CI) 1.39-3.24]. Subgroup analysis revealed that the higher risk of ESRD was predominantly in males (HR = 4.14, 95% CI 1.97-8.71) and the younger population (HR = 7.09, 95% CI 2.31-21.80). CONCLUSION: There was a significantly higher risk of ESRD among SSc patients than among the general population, with males and younger generations being the most vulnerable groups.

Management of colorectal anastomotic stricture with multidiameter balloon dilation: long-term results.

BACKGROUND: Postoperative colorectal anastomotic strictures are quite common. As such, many techniques have been available to address such a problem, one of which is endoscopic dilation. The aim of the present study was to evaluate the long-term outcomes following endoscopic dilation using a multidiameter balloon. METHODS: A retrospective study was conducted on patients with postoperative anastomotic stenosis treated with endoscopic dilation using a multidiameter balloon at our institution, in January 2005-December 2019 were retrospectively reviewed, excluding those with tumor recurrence. Perioperative factors, complications, and recurrence rates were analyzed. RESULTS: There were 40 patients, (22 males and 18 females, mean age 64.6 ± 10.7 years, range 33-84 years). The median follow-up period was 56 months (interquartile range 22.5-99 months). Only 1 complication occurred, micro-perforation due to guided wire injury, which was managed conservatively. Five (12.5%) patients developed restenosis and underwent repeat balloon dilation. None of the five recurrences required more aggressive management, such as redo anastomosis. CONCLUSIONS: Endoscopic multidiameter balloon dilation is a safe and effective method for treating benign colorectal anastomotic strictures.

Romosozumab or alendronate for fracture prevention in East Asian patients: a subanalysis of the phase III, randomized ARCH study.

Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. Among high-risk postmenopausal East Asian women, romosozumab followed by alendronate was associated with lower incidences of fractures vs alendronate alone. Romosozumab demonstrates potential to address an unmet need in osteoporosis management in Asia. INTRODUCTION: Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. The global ARCH study demonstrated superiority of romosozumab followed by alendronate in reducing fracture risk in high-risk postmenopausal osteoporotic women vs alendronate alone. We report outcomes among ARCH East Asian patients. METHODS: In ARCH, 4093 postmenopausal osteoporotic women with fragility fracture were randomized 1:1 to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, both followed by open-label alendronate. Primary endpoints were incidence of new vertebral fracture (VF) at 24 months and clinical fracture at primary analysis (confirmed fractures in ≥ 330 patients and all patients had opportunity to attend month 24 visit). This post hoc analysis was not powered to detect fracture-rate differences. RESULTS: This analysis included 275 patients from Hong Kong, Korea, and Taiwan. Romosozumab followed by alendronate reduced risk of new VFs at 24 months by 60% (P = 0.11) and clinical fractures at primary analysis by 44% (P = 0.15) vs alendronate alone. Romosozumab followed by alendronate significantly increased mean bone mineral density at 24 months from baseline by a further 9.0%, 3.3%, and 3.0% at the lumbar spine, total hip, and femoral neck vs alendronate alone. Adverse event (AE) rates, including positively adjudicated serious cardiovascular AEs (1.6% vs 1.4% at 12 months for romosozumab vs alendronate), were similar across treatment groups. CONCLUSIONS: Consistent with the global analysis, romosozumab followed by alendronate was associated with lower incidences of new vertebral, clinical, non-vertebral, and hip fractures vs alendronate alone among East Asian patients.

Central venous catheter use increases ischemic stroke risk: a nationwide population-based study.

BACKGROUND: Central venous catheter (CVC) placement is a common procedure used for the treatment of critically ill patients. However, ischemic stroke is a complication after CVC placement. AIM: This study investigated the association between CVC placement and ischemic stroke risk in an Asian population. DESIGN: Population-based retrospective study. METHODS: We enrolled 37 623 patients who ever-received CVC placement over 2000-10 and propensity score-matched individuals without CVC placement as the comparison cohort from the Taiwan National Health Insurance Research Database. We determined the cumulative incidence rates and adjusted hazard ratios (aHRs) for ischemic stroke. RESULTS: We finally identified and enrolled 34 164 propensity score-matched pairs of individuals. Compared with the comparison group, CVC placement increased the average annual ischemic stroke incidence [19.5 vs. 11.6 per 10 000 person-years; crude HR=1.28, 95%, confidence interval (CI)=1.21-1.35; adjusted subhazard ratio (aSHR)=1.4, 95% CI = 1.33-1.47; P<0.001). In addition, compared with those aged >35 years, stroke risk was significantly higher in <35-year-old patients with CVC placement (aSHR=14.3, 95% CI=6.11-33.4; P<0.001). After <1-year follow-up, the ischemic stroke incidence rate in the CVC placement group was ∼3.25-fold higher than that in the comparison group (aHR=3.25, 95% CI=2.9-3.63; P<0.0001). CONCLUSION: CVC placement increases ischemic stroke risk, particularly in those aged ≤35 years; this trend warrants further investigation.

Randomized trial of oral versus enteral feeding for patients with postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Whether continued oral feeding may have a negative impact on healing of postoperative pancreatic fistula (POPF) is unclear. The aim was to test the hypothesis that oral feeding is non-inferior to enteral feeding in closure of POPF after pancreatoduodenectomy, and to clarify the effects of oral feeding on the duration and grade of POPF. METHODS: This multicentre, non-inferiority randomized trial of oral or enteral feeding of patients with POPF after pancreatoduodenectomy recruited patients between August 2013 and September 2016. The primary efficacy outcome was the 30-day fistula closure rate. The prespecified non-inferiority margin was 15 per cent. Other efficacy outcomes included grade of fistula, and hospital stay and costs. RESULTS: A total of 114 patients were included, and received oral (57) or enteral (57) feeding. The two groups were balanced in baseline characteristics and no patient was lost to follow-up. In intention-to-treat analysis, oral feeding was non-inferior to enteral feeding in terms of 30-day fistula closure rate (88 versus 89 per cent respectively; difference -1·8 per cent, lower limit of 95 per cent c.i. -14·4 per cent; P = 0·020 for non-inferiority). Compared with enteral feeding, oral feeding significantly reduced hospital costs and duration of stay. No significant differences were noted in the number of patients whose POPF evolved into grade B/C, or other outcomes. CONCLUSION: Oral feeding in patients with POPF after pancreatoduodenectomy did not increase the duration or grade of POPF, and was associated with reduced duration of stay and hospital costs. Registration number: NCT01755260 (http://www.clinicaltrials.gov).

Chopart amputation with tibiotalocalcaneal arthrodesis and free flap reconstruction for severe foot crush injury.

AIMS: This study reports the outcomes of a technique of soft-tissue coverage and Chopart amputation for severe crush injuries of the forefoot. PATIENTS AND METHODS: Between January 2012 to December 2016, 12 patients (nine male; three female, mean age 38.58 years; 26 to 55) with severe foot crush injury underwent treatment in our institute. All patients were followed-up for at least one year. Their medical records, imaging, visual analogue scale score, walking ability, complications, and functional outcomes one year postoperatively based on the American Orthopedic Foot and Ankle Society (AOFAS) and 36-Item Short-Form Health Survey (SF-36) scores were reviewed. RESULTS: The mean length of follow-up was 18.6 months (13 to 28). Two patients had a local infection, flap necrosis was seen in one patient, and one patient experienced a skin graft wound healing delay. Of the 12 patients, one had persistent infection and eventually required below-knee amputation, but pain-free walking was achieved in all the other patients. The mean one-year postoperative AOFAS and SF-36 scores were 75.6 (68 to 80) and 82 (74 to 88), respectively. CONCLUSION: Although our sample size was small, we believe that this treatment method may be a valuable alternative for treating severe foot crush injuries. Cite this article: Bone Joint J 2018;100-B:1359-63.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

Identifying characteristics of an effective fracture liaison service: systematic literature review.

Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.

Economic impact and cost-effectiveness of fracture liaison services: a systematic review of the literature.

Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023-$28,800 US dollars (USD) in Japan to $14,513-$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

This corrects the article DOI: 10.1038/onc.2015.168.

Risk and outcomes of fracture in peripheral arterial disease patients: two nationwide cohort studies.

Using national insurance claims data of Taiwan, we found that patients with peripheral arterial disease (PAD) had increased risk of fracture during the follow-up period of 2000-2013. History of PAD was also associated with adverse outcomes in hospitalized fracture patients. Prevention strategies were needed in this susceptible population. INTRODUCTION: Limited information was available on the association between PAD and fracture. The purpose of this study is to evaluate fracture risk and post-fracture outcomes in patients with PAD. METHODS: We identified 6647 adults aged ≥ 20 years with newly diagnosed PAD using the Taiwan National Health Insurance Research Database in 2000-2004. Comparison cohort consisted of 26,588 adults without PAD randomly selected with frequency matching in age and sex. Events of fracture were identified during the follow-up period from January 1, 2000 until December 31, 2013, to evaluate adjusted hazard ratios (HR) and 95% confidence interval (CI) of fracture associated with PAD. Another nested cohort study of 799,463 hospitalized fracture patients analyzed adjusted odds ratios (ORs) and 95% CIs of adverse events after fracture among patients with and without PAD in 2004-2013. RESULTS: Incidences of fracture in people with and without PAD were 22.1 and 15.5 per 1000 person-years, respectively (P < .0001). Compared with control, the adjusted HR of fracture was 1.59 (95% CI, 1.48-1.69) for PAD patients. In the nested cohort study, patients with PAD had higher post-fracture mortality (OR = 1.16; 95% CI, 1.09-1.25) and various complications. PAD patients also had comparatively higher medical expenditure (2691 vs. 2232 USD, P < .0001) and longer hospital stay (10.6 vs. 9.0 days, P < 0.0001) during fracture admission. CONCLUSIONS: Increased risk of fracture and post-fracture adverse outcomes were associated with PAD. This susceptible population needs care to prevent fracture and to minimize adverse outcomes after it occurs.

Transarterial embolisation for congenital renal arteriovenous malformations improves clinical condition even with partial obliteration.

AIM: To evaluate the efficacy and safety of transarterial embolisation (TAE), used to treat congenital renal arteriovenous malformations (CRAVMs). MATERIALS AND METHODS: The medical records were searched retrospectively to identify patients who underwent TAE to treat CRAVM from January 2003 to August 2015. Patient demographics, clinical presentations, and imaging findings were reviewed. TAE outcomes, including complete or partial obliteration, clinical success, complications, renal function changes, and relapse of symptoms or signs after the final TAE, were assessed. RESULTS: Over the 12-year period, 16 patients (nine male, seven female; median age, 47 years) who underwent 21 TAE procedures to treat 16 CRAVMs were enrolled in the study. The most common clinical presentation was haematuria (81.3%). Thirteen patients (81.3%) had cirsoid and three (18.7%) had aneurysmal CRAVMs. Of the 16 CRAVMs, 11 (68.8%) were peripheral, four (25%) were central, and one (6.3%) was both peripheral and central. The complete obliteration rate was 56.3%. The clinical success rate was 87.5% over a median follow-up period of 398.5 days. Two (9.5%) major complications and 14 (66.7%) minor complications were encountered. No statistically significant change in renal function was evident after TAE. CONCLUSION: TAE was safe and effective when used to treat CRAVM; the complication profile was acceptable and renal function was preserved. TAE improved the clinical condition of CRAVM patients even when obliteration was only partial.

Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

Application of Time-Resolved 3D Digital Subtraction Angiography to Plan Cerebral Arteriovenous Malformation Radiosurgery.

BACKGROUND AND PURPOSE: Time-resolved 3D-DSA (4D-DSA) enables viewing vasculature from any desired angle and time frame. We investigated whether these advantages may facilitate treatment planning and the feasibility of using 4D-DSA as a single imaging technique in AVM/dural arteriovenous fistula radiosurgery. MATERIALS AND METHODS: Twenty consecutive patients (8 dural arteriovenous fistulas and 12 AVMs; 13 men and 7 women; mean age, 45 years; range, 18-64 years) who were scheduled for gamma knife radiosurgery were recruited (November 2014 to October 2015). An optimal volume of reconstructed time-resolved 3D volumes that defines the AVM nidus/dural arteriovenous fistula was sliced into 2D-CT-like images. The original radiosurgery treatment plan was overlaid retrospectively. The registration errors of stereotactic 4D-DSA were compared with those of integrated stereotactic imaging. AVM/dural arteriovenous fistula volumes were contoured, and disjoint and conjoint components were identified. The Wilcoxon signed rank test and the Wilcoxon rank sum test were adopted to evaluate registration errors and contoured volumes of stereotactic 4D-DSA and integration of stereotactic MR imaging and stereotactic 2D-DSA. RESULTS: Sixteen of 20 patients were successfully registered in Advanced Leksell GammaPlan Program. The registration error of stereotactic 4D-DSA was smaller than that of integrated stereotactic imaging (P = .0009). The contoured AVM volume of 4D-DSA was smaller than that contoured on the integration of MR imaging and 2D-DSA, while major inconsistencies existed in cases of dural arteriovenous fistula (P = .042 and 0.039, respectively, for measurements conducted by 2 authors). CONCLUSIONS: Implementation of stereotactic 4D-DSA data for gamma knife radiosurgery for brain AVM/dural arteriovenous fistula is feasible. The ability of 4D-DSA to demonstrate vascular morphology and hemodynamics in 4 dimensions potentially reduces the target volumes of irradiation in vascular radiosurgery.

Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

BACKGROUND: Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. METHODS: Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 µg per 10 µL per rat) or HDAC inhibitor (10 µg per 10 µL per rat) was injected once daily for 3 days before CFA injection. RESULTS: Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. CONCLUSION: These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. SIGNIFICANCE: Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic.

Exosomes mediated transfer of lncRNA UCA1 results in increased tamoxifen resistance in breast cancer cells.

OBJECTIVE: In this study, we firstly compared the loading of urothelial carcinoma-associated 1 (UCA1) in exosomes between tamoxifen sensitive and tamoxifen resistant breast cancer cells and further investigated the role of exosomal transfer of UCA1 in the development of tamoxifen resistance in estrogen receptor (ER) positive breast cancer cells. MATERIALS AND METHODS: Exosomes were isolated from the culture medium of tamoxifen sensitive MCF-7 cells and tamoxifen resistant LCC2 cells. QRT-PCR was performed to analyze UCA1 expression in cells and exosomes. CCK-8 assay, immunofluorescence staining of cleaved caspase-3 and flow cytometric analysis of annexin V/PI staining were used to assess tamoxifen sensitivity. RESULTS: UCA1 is significantly increased not only in LCC2 cells, but also in exosomes released from LCC2 cells. The increase in exosomes is more evident than in cells. MCF-7 cells pretreated with exos/LCC2 had a significantly increased cell viability, a decreased expression of cleaved caspase-3 and a lower ratio of apoptosis after tamoxifen treatment. The exos/LCC2 with impaired UCA1 loading had significantly suppressed capability to promote tamoxifen resistance in MCF-7 cells. CONCLUSIONS: UCA1 is significantly loaded in exosomes from tamoxifen resistant LCC2 cells. Exosomes mediated transfer of UCA1 can significantly increase tamoxifen resistance in ER-positive MCF-7 cells.