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PURPOSE: To evaluate the clinical effectiveness and safety of drug-coated balloons (DCBs) compared with those of percutaneous transluminal angioplasty (PTA) for arteriovenous fistula (AVF) stenosis via a review of systematic reviews (SRs) and an update of the current meta-analysis. MATERIALS AND METHODS: Literature was searched to retrieve SRs comparing DCBs and PTA for AVFs. A narrative review of SRs and pooled analysis were performed. RESULTS: Eleven SRs were included. DCBs demonstrated favorable outcomes at 6 and 12 months compared with PTA, with improved patency in 7 SRs and a trend toward favorable outcomes without statistical significance in 3 SRs. Target lesion revascularization (TLR) was reported in 3 SRs; 2 reviews reported a significantly lower incidence in the DCB group than in the PTA group, whereas 1 review reported no significant differences at 12 months. Four studies reporting all-cause mortality revealed no significant difference between the 2 treatments. In the updated meta-analysis including 23 studies, DCBs demonstrated improved primary patency at 6 months (risk ratio [RR], 1.27; 95% CI, 1.07-1.50) and 12 months (RR, 1.36; 95% CI, 1.19-1.55) and were associated with a lower incidence of TLR at 6 months (RR, 0.54; 95% CI, 0.41-0.73) and 12 months (RR, 0.78; 95% CI, 0.62-0.99). There was no difference in mortality between the 2 groups for 24 months. CONCLUSIONS: A review of SRs and meta-analysis update revealed the consistent benefits of DCBs over PTA in treating AVFs in terms of primary patency and TLR. Compared with PTA, DCBs do not increase mortality risk.
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Angioplastia com Balão , Derivação Arteriovenosa Cirúrgica , Materiais Revestidos Biocompatíveis , Grau de Desobstrução Vascular , Humanos , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Angioplastia com Balão/mortalidade , Resultado do Tratamento , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/mortalidade , Oclusão de Enxerto Vascular/terapia , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/diagnóstico por imagem , Fatores de Risco , Diálise Renal , Dispositivos de Acesso Vascular , Desenho de Equipamento , Fatores de TempoRESUMO
OBJECTIVE: To investigate the opioid consumption and the healthcare resource utilization in patients with the intrathecal drug delivery system (IDDS) therapy and the comprehensive medical management (CMM) alone. DESIGN: A retrospective cohort study with a customized claims database. SETTING: In a university-based hospital. SUBJECTS: Patients with complex regional pain syndrome, post-laminectomy syndrome, and fibromyalgia. METHODS: Using propensity score matching (1:3), we selected patients with morphine infusion through IDDS (IDDS group) and CMM alone (CMM group). The primary endpoints were comparisons of average morphine equivalents daily dosages (MEDD, mg/day) for 6 and 12 months from an index date. The number of emergency room (ER) visits and hospitalizations and the total medical expenditures were compared as secondary outcomes. RESULTS: In total, 82 patients (N = 23 in the IDDS group and N = 59 in the CMM group) were analyzed. Although a 6-month average MEDD did not reach statistical significance, a 12-month average MEDD was significantly decreased in the IDDS group compared to the CMM group (53.2 ± 46.3 vs 123.9 ± 176.4, respectively; P = 0.008). ER visits were more frequent in the IDDS group than the CMM group at baseline (5.4 vs 0.5, respectively; P = .002), which was maintained for 12 months (P < 0.001). Otherwise, the number of hospitalization and the medical expenditures for pain management were not different between the groups for 12 months. CONCLUSIONS: The combined IDDS therapy had some benefits in reducing opioid consumption for 1-year follow-up compared to the CMM alone in chronic noncancer pain patients.
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Analgésicos Opioides , Dor Crônica , Humanos , Analgésicos Opioides/efeitos adversos , Morfina , Dor Crônica/tratamento farmacológico , Dor Crônica/induzido quimicamente , Estudos Retrospectivos , Bombas de Infusão Implantáveis , Injeções EspinhaisRESUMO
AIM: The recent IN.PACT AV Access study found drug-coated balloon therapy to be associated with reduced reinterventions compared to percutaneous transluminal angioplasty using standard balloons in the management of arteriovenous fistula stenosis. The economic implications of drug-coated balloon use in Asia, including Japan and Korea, remain unknown. METHODS: A decision-analytic model was developed to calculate strategy-specific costs for Korea and Japan through 5-year follow-up. The analysis assumed maintained therapy benefit beyond current trial follow-up of 1 year in the base case, with several alternative scenarios explored in sensitivity analysis. Costs were derived from claims and reimbursement data, and projections were evaluated at 3 and 5 years post-index procedure. RESULTS: Model-projected access circuit reintervention events for drug-coated versus standard balloons were 1.70 versus 2.76 (-1.06) and 2.53 versus 4.10 (-1.57) at 3 and 5 years in the base case. Corresponding 3- and 5-year costs were â©6 211 103 versus â©7 605 553 (-â©1 394 451) and â©7 766 051 versus â©10 124 954 (-â©2 358 904) in Korea, and ¥1 469 824 versus ¥1 504 161 (-¥34 337) and ¥1 956 931 versus ¥2 106 632 (-¥149 701) in Japan. In scenario analyses, drug-coated balloons remained cost saving at 3- and 5-year follow-up in Korea, but required up to 5 years to reach cost-savings in Japan. Drug-coated balloon use in reinterventions increased projected savings, as did younger treatment age. CONCLUSION: Treatment of arteriovenous fistulas with the IN.PACT AV drug-coated balloon, based on preliminary data, may lead to meaningful reductions in reintervention costs that would render it cost-saving at timeframes of around 1 year in Korea and between 3 and 5 years in Japan.
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Angioplastia com Balão , Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Fármacos Cardiovasculares , Angioplastia com Balão/métodos , Materiais Revestidos Biocompatíveis , Constrição Patológica , Humanos , Japão , Paclitaxel , Diálise Renal/métodos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Cardiovascular disease (CVD) is the second leading cause of death among Korean women, and its incidence is dramatically elevated in middle-aged women. This study aimed to identify the predictors of sleep quality, a CVD risk factor, in middle-aged women with CVD risk factors to provide foundational data for developing intervention strategies for the prevention of CVD. The subjects, 203 middle-aged women (40-65 years old) with one or more CVD risk factors were selected through convenience sampling and included in this descriptive correlational study. The effects of somatic symptoms, depression symptoms, and sedentary time on sleep quality were examined. CVD-related characteristics were analyzed using descriptive statistics, whereas the mean values of the independent variables were analyzed using t-tests and analysis of variance. Predictors of sleep quality were analyzed using multiple regression analysis. The results showed that sleep quality increased with decreasing somatic symptoms (ß = -0.36, p < 0.001), depression symptom score (ß = -0.17, p = 0.023), and daily sedentary time (ß = -0.13, p = 0.041), and the regression model was significant (F = 19.80, p < 0.001). Somatic symptoms are the most potent predictors of sleep quality in middle-aged women. Thus, intervention strategies that improve somatic symptoms are crucial for the enhancement of sleep quality, which deteriorates with advancing age.
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PURPOSE: Drug-coated devices have been widely accepted as one of the most promising therapies for femoropopliteal artery revascularization. A recent meta-analysis showed increased mortality in patients treated with drug-coated devices. We sought to examine the association between mortality and drug-coated devices after the treatment of the femoropopliteal artery based on the Korea national administrative claims data. METHODS: In the National Health Insurance Service database from August 2015 to December 2017, we identified patients with femoropopliteal artery revascularization using percutaneous transluminal angioplasty (PTA), bare metal stents (BMS), drug-coated balloon (DCB), or drug-eluting stents (DES). Kaplan-Meier methods were used to estimate the survival among devices, and log-rank tests were used to evaluate differences between groups. Adjusted hazard ratios (aHRs) were computed using the inverse probability of treatment weightings (IPTW). RESULTS: There were 1,724 patients (mean age, 70.9 ± period was 552 days (interquartile range, 404-688 days). There was a difference in IPTW-adjusted mortality risk among device types (26.3% in PTA, 22.1% in BMS, 17.7% in DCB, and 17.8% in DES; P = 0.004). IPTW-adjusted Cox nproportional hazard analysis showed that drug-coated devices were associated with decreased all-cause mortality risk (aHR, 0.70; 95% confidence interval, 0.58-0.86). CONCLUSION: Our real-world analysis showed that there was no evidence of increased all-cause mortality after femoropopliteal artery revascularization with drug-coated devices compared with non-drug-coated devices.
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In this article, the operational characteristics of coverage with evidence development (CED) programs in Asia-Pacific regions, focusing on two countries-Japan and South Korea-are reviewed. Both countries recommended the introduction of CED to overcome the barrier of lack of robust clinical evidence in the early stages of the introduction of a medical technology. However, each country has a unique approach to CED implementation that reflects the differences in establishment and healthcare and policy environments. Japan adopted a "Challenge Application (CA)" program in 2018, and South Korea introduced the "Conditional Selective Benefit (CSB)" program in 2014. Despite the positive effects of CED programs, their governance and implementation should be improved to benefit patients in both countries from the improved access to new and innovative medical technologies. To this end, CED practices in the United States (the USA) can provide insights on how to improve CED operations in both countries.
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Poly(A) polymerase (PAP), which adds poly(A) tails to the 3' end of mRNA, can be phosphorylated at several sites in the C-terminal domain. Phosphorylation often mediates regulation by extracellular stimuli, suggesting PAP may be regulated by such stimuli. In this study, we found that phosphorylation of PAP was increased upon growth stimulation and that the mitogen-activated protein kinase ERK was responsible for the increase in phosphorylation. We identified serine 537 of PAP as a unique phosphorylation site by ERK. PAP phosphorylation of serine 537 by ERK increased its nonspecific polyadenylation activity in vitro. This PAP activity was also activated by stimulation of ERK with phorbol-12-myristate-13-acetate in vivo. These data suggest that ERK is a novel regulatory kinase for PAP and further, that PAP activity could be regulated by extracellular stimuli through an ERK-dependent signaling pathway(s).
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MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Polinucleotídeo Adenililtransferase/metabolismo , Animais , Anticorpos Fosfo-Específicos , Células HeLa , Humanos , Camundongos , Fosfosserina/análise , Fosfosserina/imunologia , Polinucleotídeo Adenililtransferase/química , Estrutura Terciária de ProteínaRESUMO
The effects of catalponol (1) on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalponol at concentration ranges of 1-5 microM increased the intracellular levels of dopamine at 12-48 h. Catalponol at concentrations of up to 10 microM did not alter cell viability. Tyrosine hydroxylase (TH) activity was enhanced by 1 at 3 microM in a time-dependent manner, but aromatic L-amino acid decarboxylase activity was not. Catalponol also increased the intracellular levels of cyclic AMP and TH phosphorylation. In addition, catalponol at 3 microM associated with L-DOPA (20-50 microM) further enhanced the increases in dopamine levels induced by L-DOPA (50-100 microM) at 24 h. Catalponol at 2-5 microM inhibited L-DOPA (100-200 microM)-induced cytotoxicity at 48 h. These results suggest that 1 enhanced dopamine biosynthesis by inducing TH activity and protected against L-DOPA-induced cytotoxicity in PC12 cells, which was mediated by the increased levels of cyclic AMP.
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Dopamina/biossíntese , Levodopa/farmacologia , Naftóis/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Naftóis/administração & dosagem , Células PC12 , RatosRESUMO
Testis-specific poly(A) polymerase (TPAP) is a cytoplasmic poly(A) polymerase that is highly expressed in round spermatids. We identified germ cell-specific gene 1 (GSG1) as a TPAP interaction partner protein using yeast two-hybrid and coimmunoprecipitation assays. Subcellular fractionation analysis showed that GSG1 is exclusively localized in the endoplasmic reticulum (ER) of mouse testis where TPAP is also present. In NIH3T3 cells cotransfected with TPAP and GSG1, both proteins colocalize in the ER. Moreover, expression of GSG1 stimulates TPAP targeting to the ER, suggesting that interactions between the two proteins lead to the redistribution of TPAP from the cytosol to the ER.
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Retículo Endoplasmático/enzimologia , Polinucleotídeo Adenililtransferase/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Testículo/enzimologia , Adulto , Animais , Humanos , Imuno-Histoquímica , Imunoprecipitação , Masculino , Camundongos , Microscopia Confocal , Células NIH 3T3 , Ligação ProteicaRESUMO
The GC-rich discriminator sequence between the -10 region and the transcription start site of the rnpB promoter is responsible for stringent control of M1 RNA synthesis. The rnpB promoter also contains a G nucleotide at the previously identified transcription start site. In this study, we examined by mutagenesis of G to A whether this +1G nucleotide is involved in the stringent response. We found that the change did not alter the stringent response. Since the +1 mutation might alter transcription initiation, we compared the transcription start sites of the wt and mutant promoters by primer extension analysis. Surprisingly, we found that wild type rnpB transcription starts at both the +1G position (70%) and the -1C position (30%), and that the +1A mutation led to transcription initiation exclusively at the -1C position. We also generated two transversion mutations at the -1 position, both of which led to transcription starting exclusively at that position. The -1G mutant promoter gave a stringent signal similar to the wild-type, whereas the -1A mutant generated a significantly less stringent signal. Base on these results, we propose that a short sequence, up to 7 bp downstream of the -10 region, is involved in the stringent response of the rnpB promoter.
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Proteínas de Escherichia coli/metabolismo , Regiões Promotoras Genéticas/genética , Ribonuclease P/genética , Sítio de Iniciação de Transcrição/fisiologia , Sequência de Bases , Proteínas de Escherichia coli/genéticaRESUMO
Factor for inversion stimulation (FIS), the Escherichia coli protein, is a positive regulator of the transcription of genes that encode stable RNA species, such as rRNA and tRNA. Transcription of the rnpB gene encoding M1 RNA, the catalytic subunit of E. coli RNase P, rapidly declines under stringent conditions, as does that of other stable RNAs. There are multiple putative FIS binding sites upstream of the rnpB promoter. We tested whether FIS binds to these sites, and if so, how it affects rnpB transcription. In vitro binding assays revealed specific binding of FIS to multiple sites in the rnpB promoter region. Interestingly, FIS bound not only to the upstream region of the promoter, but also to the region from +4 to +18. FIS activated rnpB transcription in vitro, but the level of activation was much lower than that of the rrnB promoter for rRNA. We also examined the effects of FIS on rnpB transcription in vivo using isogenic fis+ and fis- strains. rnpB transcription was higher in the fis- than the fis+ cells during the transitions from lag to exponential phase, and from exponential to stationary phase.
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Proteínas de Escherichia coli/genética , Fator Proteico para Inversão de Estimulação/genética , Regulação Bacteriana da Expressão Gênica , Regiões Promotoras Genéticas/genética , RNA Bacteriano/genética , Transcrição Gênica/genética , Ativação Transcricional , Sequência de Bases , Sítios de Ligação , Pegada de DNA , Ensaio de Desvio de Mobilidade Eletroforética , Escherichia coli/citologia , Escherichia coli/genética , Dados de Sequência Molecular , Ligação ProteicaRESUMO
Baker cyst is an enlargement of the gastrocnemius-semimembranosus bursa. Neuropathy can occur due to either direct compression from the cyst itself or indirectly after cyst rupture. We report a unique case of a 49-year-old man with left sole pain and paresthesia who was diagnosed with posterior tibial neuropathy at the lower calf area, which was found to be caused by a ruptured Baker cyst. The patient's symptoms resembled those of lumbosacral radiculopathy and tarsal tunnel syndrome. Posterior tibial neuropathy from direct pressure of ruptured Baker cyst at the calf level has not been previously reported. Ruptured Baker cyst with resultant compression of the posterior tibial nerve at the lower leg should be included in the differential diagnosis of patients who complain of calf and sole pain. Electrodiagnostic examination and imaging studies such as ultrasonography or magnetic resonance imaging should be considered in the differential diagnosis of isolated paresthesia of the lower leg.
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Salmonella pathogenicity island 2 (SPI2) encodes a type III secretion system (TTSS) necessary for bacterial survival and replication in intracellular environment of host cells. SPI2 genes are transcribed preferentially after Salmonella enters the host cells. Transcriptional regulation of ssaG encoding the component of SPI2-TTSS apparatus was studied in vivo and in vitro. Fis, one of the major components of bacterial nucleoid, activated the stationary phase-specific expression of ssaG when Salmonella was grown in LB media. Gel-shift and footprinting analysis showed Fis bound to four distinct sites of the ssaG promoter region with different affinities. All four Fis-binding sites were required for timely transcription activation of ssaG after Salmonella entered macrophage cells. Gentamicin protection experiments using bacteria grown to stationary phase prior to infection showed that the ability of the fis mutant strain to replicate within the RAW264.7 macrophage cells was lower than the wild type. These observations confirm that Fis plays an important role in regulations of SPI2 as well as SPI1 for an efficient regulation of the virulence genes.