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Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin system (RAS) inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF), its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/day), spironolactone (80 mg/kg/day), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared to that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced HF.
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An investigation of the chemical composition of a Formosan soft coral Cespitularia sp. led to the discovery of one new verticillene-type diterpenoid, cespitulactam M (1); one new eudesmane sesquiterpenoid, cespilamide F (2); and three new hydroperoxysteroids (3-5) along with twelve known analogous metabolites (6-17). In addition, one new derivative, cespitulactam M-6,2'-diacetate (1a), was prepared from compound 1. The structures were determined by detailed spectroscopic analyses, particularly HRESIMS and NMR techniques. Moreover, the in vitro cytotoxicity, anti-inflammatory, and antibacterial activity of 1-17 and 1a were evaluated.
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Antozoários , Diterpenos , Sesquiterpenos de Eudesmano , Sesquiterpenos , Animais , Antozoários/química , Sesquiterpenos de Eudesmano/química , Espectroscopia de Ressonância Magnética , Diterpenos/química , Sesquiterpenos/química , Estrutura MolecularRESUMO
Liver cancers, such as hepatocellular carcinoma (HCC), are a highly prevalent cause of cancer-related deaths. Current treatments to combat liver cancer are limited. (-)-Agelasidine A, a compound isolated from the methanol extract of Agelasnakamurai, a sesquiterpene guanidine derived from sea sponge, has antibacterial activity. We demonstrated its anticancer capabilities by researching the associated mechanism of (-)-agelasidine A in human liver cancer cells. We found that (-)-agelasidine A significantly reduced viability in Hep3B and HepG2 cells, and we determined that apoptosis was involved in the (-)-agelasidine A-induced Hep3B cell deaths. (-)-Agelasidine A activated caspases 9, 8, and 3, as well as PARP. This effect was reversed by caspase inhibitors, suggesting caspase-mediated apoptosis in the (-)-agelasidine A-treated Hep3B cells. Moreover, the reduced mitochondrial membrane potential (MMP) and the release of cytochrome c indicated that the (-)-agelasidine A-mediated mitochondrial apoptosis was mechanistic. (-)-Agelasidine A also increased apoptosis-associated proteins (DR4, DR5, FAS), which are related to extrinsic pathways. These events were accompanied by an increase in Bim and Bax, proteins that promote apoptosis, and a decrease in the antiapoptotic protein, Bcl-2. Furthermore, our results presented that (-)-agelasidine A treatment bridged the intrinsic and extrinsic apoptotic pathways. Western blot analysis of Hep3B cells treated with (-)-agelasidine A showed that endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated PERK, phosphorylated eIF2α, ATF4, truncated ATF6, and CHOP) were upregulated. Moreover, 4-PBA, an ER stress inhibitor, could also abrogate (-)-agelasidine A-induced cell viability reduction, annexin V+ apoptosis, death receptor (DR4, DR5, FAS) expression, mitochondrial dysfunction, and cytochrome c release. In conclusion, by activating ER stress, (-)-agelasidine A induced the extrinsic and intrinsic apoptotic pathways of human HCC.
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Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Guanidinas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Sulfonas/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Guanidinas/isolamento & purificação , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Poríferos/química , Sulfonas/isolamento & purificaçãoRESUMO
Further chemical investigation of the EtOAc extract of the soft coral Lobophytum varium resulted in the discovery of eleven new diterpenoids lobovarols F-P (1-11) of lobane- and prenyleudesmane-types, along with two known metabolites (12 and 13). The structures of the new metabolites were established by spectroscopic analyses, including 2D NMR experiments. The absolute configuration of 1 was determined using Mosher's method. The complete assignment of 1H and 13C NMR spectroscopic data of 12 and 13 and the identification of pyran-derived moieties in the prenyleudesmanes were reported for the first time. Anti-inflammatory activities of the isolated compounds in suppressing elastase release and superoxide anion generation in human neutrophils were disclosed for 1, 2, 4, 12, and 13. A stereospecific biosynthesis for lobanes and prenyleudesmanes from the related prenylgermacranes could explain the coexistence of lobanes and prenylgermacranes in L. varium.
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Antozoários/química , Anti-Inflamatórios/isolamento & purificação , Diterpenos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Estereoisomerismo , Superóxidos/metabolismoRESUMO
Esophageal stricture after surgery or trauma is a major reason for poor oral nutrition, body-weight loss, and general damage to health. Patch esophagoplasty, after repeated failed dilation attempts, is recommended for focal esophageal strictures. In this report, we present a case in which a free proximal lateral leg flap was used for reconstruction of focal stricture of the cervical esophagus. A 62-year-old man developed progressive dysphagia after hypopharyngeal cancer ablation and adjuvant radiotherapy. He was referred for surgical interventions after repeated failed dilation attempts. Preoperative evaluation revealed a 3-cm segment stricture of the cervical esophagus without evidence of an additional distal stricture. Patch esophagoplasty with free tissue transfer was planned. After the stricture site had been explored, the fibrotic tissue was resected. A pathology report confirmed no evidence of malignancy. The resultant defect in an otherwise healthy posterior esophageal wall was reconstructed using a proximal lateral leg flap. Recovery was uneventful and the functional outcome was satisfactory at the 6-month follow-up. For the radiated patients with cervical esophageal focal strictures, we introduced a novel use of the proximal lateral leg flap in patch esophagoplasty because of its unnoticeable donor site morbidity and its thin and pliable nature. © 2016 Wiley Periodicals, Inc. Microsurgery 37:426-430, 2017.
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Estenose Esofágica/cirurgia , Esofagoplastia/métodos , Retalhos de Tecido Biológico/transplante , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: First rib fractures and traumatic Horner's syndrome are both quite rare, which can make it difficult to properly diagnose the combination of these 2 conditions in the emergency department. These conditions may be associated with severe medical emergencies, such as ongoing carotid dissection. CASE REPORT: We present the case of a 33-year-old man who sustained fractures to his right second, third, and fourth ribs and a delay in the diagnosis of left Horner's syndrome after he was involved in a traffic accident. Left Horner's syndrome was caused by a left transverse fracture of the first rib. This fracture was not detected on chest radiographs and required a 3-dimensional reconstructed neck computed tomography scan for detection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In the diagnosis of carotid artery dissection, conventional angiography is the criterion standard but is considered invasive. CTA is less invasive, time-saving, and can show more anatomic structures in the neck in addition to the carotid arteries. It is a good screening diagnostic modality in the traumatology department. Although the treatments for Horner's syndrome and first rib fracture are conservative, the early diagnosis of both conditions can resolve the anxiety and uncertainty experienced by both doctors and patients.
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Síndrome de Horner/etiologia , Fraturas das Costelas/complicações , Acidentes de Trânsito , Adulto , Diagnóstico Diferencial , Síndrome de Horner/diagnóstico por imagem , Humanos , Masculino , Fraturas das Costelas/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Aberrant chondroitin sulfate (CS) accumulation in glioblastoma (GBM) tissue has been documented, but the role of excessive CS in GBM progression and whether it can be a druggable target are largely unknown. The aim of this study is to clarify the biological functions of CHST11 in GBM cells, and evaluate therapeutic effects of blocking CHST11-derived chondroitin 4-sulfate (C4S). We investigated the expression of CHST11 in glioma tissue by immunohistochemistry, and analyzed CHST11 associated genes using public RNA sequencing datasets. The effects of CHST11 on aggressive cell behaviors have been studied in vitro and in vivo. We demonstrated that CHST11 is frequently overexpressed in GBM tissue, promoting GBM cell mobility and modulating C4S on GBM cells. We further discovered that CSPG4 is positively correlated with CHST11, and CSPG4 involved in CHST11-mediated cell invasiveness. In addition, GBM patients with high expression of CHST11 and CSPG4 have a significantly shorter survival time. We examined the effects of treating C4S-specific binding peptide (C4Sp) as a therapeutic agent in vitro and in vivo. C4Sp treatment attenuated GBM cell invasiveness and, notably, improved survival rate of orthotopic glioma cell transplant mice. Our results propose a possible mechanism of CHST11 in regulating GBM malignancy and highlight a novel strategy for targeting aberrant chondroitin sulfate in GBM cells.
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Doxorubicin (Dox) is a potent anticancer agent, but its associated organ toxicity, including nephrotoxicity, restricts clinical applications. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been shown to slow the progression of kidney disease in patients with and without diabetes. However, the effect of DAPA to counteract Dox-induced nephrotoxicity remains uncertain. Therefore, in this study, we aimed to elucidate the effects of DAPA in mitigating Dox-induced nephrotoxicity. We analyzed the Taiwan National Health Insurance Database to evaluate the incidence of renal failure among breast cancer patients receiving Dox treatment compared to those without. After adjusting for age and comorbidities, we found that the risk of renal failure was significantly higher in Dox-treated patients (incidence rate ratio, 2.45; confidence interval, 1.41-4.26; p = 0.0014). In a parallel study, we orally administered DAPA to Sprague-Dawley rats for 6 weeks, followed by Dox for 4 weeks. DAPA ameliorated Dox-induced glomerular atrophy, renal fibrosis, and dysfunction. Furthermore, DAPA effectively suppressed Dox-induced apoptosis and reactive oxygen species production. On a cellular level, DAPA in HK-2 cells mitigated Dox-mediated suppression of the endothelial NOS pathway and reduced Dox-induced activities of reactive oxygen species and apoptosis-associated proteins. DAPA improved Dox-induced apoptosis and renal dysfunction, suggesting its potential utility in preventing nephrotoxicity in patients with cancer undergoing Dox treatment.
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Nefropatias , Insuficiência Renal , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Ratos , Animais , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Ratos Sprague-Dawley , Doxorrubicina/efeitos adversos , Nefropatias/induzido quimicamente , Insuficiência Renal/induzido quimicamente , ApoptoseRESUMO
Patient safety is a paramount concern in the medical field, and advancements in deep learning and Artificial Intelligence (AI) have opened up new possibilities for improving healthcare practices. While AI has shown promise in assisting doctors with early symptom detection from medical images, there is a critical need to prioritize patient safety by enhancing existing processes. To enhance patient safety, this study focuses on improving the medical operation process during X-ray examinations. In this study, we utilize EfficientNet for classifying the 49 categories of pre-X-ray images. To enhance the accuracy even further, we introduce two novel Neural Network architectures. The classification results are then compared with the doctor's order to ensure consistency and minimize discrepancies. To evaluate the effectiveness of the proposed models, a comprehensive dataset comprising 49 different categories and over 12,000 training and testing sheets was collected from Taichung Veterans General Hospital. The research demonstrates a significant improvement in accuracy, surpassing a 4% enhancement compared to previous studies.
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Gonadotropin-releasing hormone (GnRH) therapy has been known to increase risks of major adverse cardiovascular and cerebrovascular events (MACCEs). Herein, we aim to estimate whether regular use of aspirin attenuates risks of MACCEs in prostate cancer patients receiving GnRHs. Using Taiwanese National Health Insurance Research Database (NHIRD), we identified 7719 patients diagnosed with prostate cancer who were either aspirin-naïve, received irregular or regular aspirin from 2008 to 2015. Through a multivariable logistic regression model, we investigated the impact of aspirin on MACCEs. Compared with nonusers and irregular users, most patients receiving regular aspirin were older and had more comorbidities. The crude incidence of one-year MACCEs was lowest in aspirin nonusers but highest in irregular users of aspirin compared with regular users of aspirin (2.65% vs. 4.41% vs. 2.85%, p=0.0099). After adjusting for age, cancer stage and comorbidities, irregular aspirin users had a higher risk of one-year MACCEs (adjusted OR: 1.33; 95% CI: 0.93-1.90, p=0.1139) than aspirin nonusers, but conversely, there was a trend of reducing the risk of MACCEs among those who received regular aspirin (adjusted OR: 0.79; 95% CI: 0.44-1.42, p=0.4256). In the subgroup analysis, there were age- and cancer stage-independent higher risks of MACCEs in patients who took aspirin irregularly compared to those in patients who did not take aspirin. The risks were attenuated in patients receiving regular aspirin. Collectively, regular use of aspirin presented a trend of reducing risks of MACCEs in prostate cancer patients receiving GnRHs. However, irregular use of aspirin diminished the benefits.
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Aging is a major risk factor for ischemic hypoxia-related diseases, including peripheral artery diseases (PADs). Signal transducer and activator of transcription 3 (STAT3) is a critical transcription activator in angiogenesis. Nevertheless, the effect of aging on endothelial cells and their responses to hypoxia are not well studied. Using a hindlimb hypoxic/ischemic model of aged mice, we found that aged mice (80-100-week-old) expressed significantly lower levels of angiogenesis than young mice (10-week-old). In our in vitro study, aged endothelial cells (≥30 passage) showed a significant accumulation of ß-galactosidase and a high expression of aging-associated genes, including p16, p21, and hTERT compared with young cells (<10 passage). After 24 hours of hypoxia exposure, proliferation, migration and tube formation were significantly impaired in aged cells compared with young cells. Notably, STAT3 and angiogenesis-associated proteins such as PI3K/AKT were significantly downregulated in aged mouse limb tissues and aged cells. Further, using STAT3 siRNA, we found that suppressing STAT3 expression in endothelial cells impaired proliferation, migration and tube formation under hypoxia. Correspondingly, in patients with limb ischemia we also observed a higher expression of circulating STAT3, associated with a lower rate of major adverse limb events (MALEs). Collectively, STAT3 could be a biomarker reflecting the development of MALE in patients and also a regulator of age-dependent angiogenesis post limb ischemia. Additional studies are required to elucidate the clinical applications of STAT3.
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Células Endoteliais , Fator de Transcrição STAT3 , Envelhecimento/metabolismo , Animais , Células Endoteliais/metabolismo , Humanos , Hipóxia/metabolismo , Isquemia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de SinaisRESUMO
With an increasing prevalence, peripheral arterial disease (PAD), cause by atherosclerosis is a new threat to public health beyond coronary artery disease and involves aberrant vascular endothelial cell proliferation and angiogenesis. The degree of vascular remodeling is influenced by the processes described. MicroRNA-21 (miR-21) has been found to play a critical role in cellular functions, including angiogenesis. Nevertheless, the effect of miR-21 on endothelial cells in response to hypoxia is largely unknown. Using wild-type C57BL/6J and miR-21-/- mice, we compared the capability of angiogenesis in response to hindlimb hypoxic/ischemia. In an in vitro study, we further studied whether overexpression of miR-21 mitigates hypoxia-induced apoptosis and impaired angiogenesis. Also, we prospectively collected the sera of patients with limb ischemia and followed the clinical information, including major adverse limb events (MALEs). Using laser Doppler perfusion imaging and CD31 staining, compared with miR-21-/- mice, wild-type mice expressed a significantly higher capability of angiogenesis and less apoptosis following 28 days of hindlimb hypoxic/ischemic surgery. In our in vitro study, after 24 h of hypoxia, proliferation, migration, and tube formation were significantly impaired in cells treated with the miR-21 inhibitor but rescued by the miR-21 mimic. Mechanistically, by suppressing PTEN/PI3K/AKT, miR-21 promoted angiogenesis and suppressed apoptosis in endothelial cells post hypoxia. In patients with limb ischemia, the high expression of circulating miR-21 was associated with less subsequent MALE. Collectively, miR-21 could be a biomarker associated with the endogenous ability of angiogenesis and reflect subsequent MALE in patients. Additionally, abolishing miR-21 impairs angiogenesis and promotes apoptosis post limb ischemia. Further studies are required to elucidate the clinical applications of miR-21.
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Chemical investigation of the soft coral Cespitularia sp. led to the discovery of twelve new verticillane-type diterpenes and norditerpenes: cespitulins H-O (1-8), one cyclic diterpenoidal amide cespitulactam L (9), norditerpenes cespitulin P (10), cespitulins Q and R (11 and 12), four new sesquiterpenes: cespilins A-C (13-15) and cespitulolide (16), along with twelve known metabolites. The structures of these metabolites were established by extensive spectroscopic analyses, including 2D NMR experiments. Anti-inflammatory effects of the isolated compounds were studied by evaluating the suppression of pro-inflammatory protein tumor necrosis factor-α (TNF-α) and nitric oxide (NO) overproduction, and the inhibition of the gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide-induced dendritic cells. A number of these metabolites were found to exhibit promising anti-inflammatory activities.
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Alteration of extracellular glycosylation is a hallmark of malignant characteristics. In this study, we revealed that fucosyltransferase 8 (FUT8), an enzyme that mediates the core fucosylation of N-linked glycosylation, is an important regulator of malignant characteristics in human glioma that acts by modifying the activities of both the HGF receptor (MET) and epidermal growth factor receptor (EGFR). mRNA and protein expression levels of FUT8 were frequently upregulated in gliomas, and these events were showed positive correlations with advanced tumor grade, recurrence, and decreased overall survival. Silencing FUT8 expression in glioma cells suppressed cell growth, migration, and invasion, whereas overexpression of FUT8 was sufficient to enhance these phenotypes. Mechanistic investigations revealed that FUT8 was involved in the alteration of fucosylation status that was attached to MET and EGFR, changing MET responses after HGF stimulation, as well as in the transactivation of EGFR. Importantly, altering FUT8 expression or using the fucosylation inhibitor 2F-peracetyl-fucose sensitized the efficacy of of temozolomide (TMZ) therapy. Collectively, these results suggested that FUT8 dysregulation contributed to the malignant behaviors of glioma cells and provide novel insights into the significance of fucosylation in receptor tyrosine kinase activity and TMZ resistance.
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PURPOSE: Accurate diagnosis of small bowel obstruction (SBO) remains challenging. The evidence of the diagnostic accuracy of ultrasound varies among studies, with reporting sensitivity ranging from 82 % to 100 % and specificity ranging from 54 % to 100 %. The aim of our study is to perform a systematic review and meta-analysis to investigate the accuracy of ultrasound for diagnosing SBO. METHOD: The PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were searched from database inception to March 2020. Randomized controlled trials, quasi randomized studies, and prospective or retrospective cohort studies that evaluated the diagnostic performance of ultrasound for the diagnosis of bowel obstruction in adult patients (age ≥ 16 years) were eligible. The QUADAS-2 tool was used to assess the quality of the included studies. The pooled sensitivities, specificities were analyzed using a bivariate random-effects model. (PROSPERO ID: CRD42020170010). RESULTS: Fifteen studies, with most rating as a moderate risk of bias, met the inclusion criteria. The pooled sensitivity and specificity were 92 % (95 % CI: 89%-95%) and 93 % (95 % CI: 85%-97%), respectively. Subgroup analysis revealed no significant differences in sensitivity when ultrasound was performed on different continents, in different settings, and under different reference standards. However, the specificity was significantly lower when ultrasound was performed in the North America, in the emergency department, and when computed tomography was used as the only reference standard. CONCLUSIONS: Overall, ultrasound is a highly sensitive and specific tool for the diagnosis of SBO. Using ultrasound to rule in patients with SBO should be used with caution, as variations in the specificity were observed in different study setting, operators from different continents and reference standards used.
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Obstrução Intestinal , Adolescente , Adulto , Humanos , Obstrução Intestinal/diagnóstico por imagem , América do Norte , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Sensibilidade e Especificidade , UltrassonografiaRESUMO
BACKGROUND: The trends in computed tomography (CT) scan uses in Taiwan were examined in different age and sex groups and compared between catastrophic illness and noncatastrophic illness groups. METHODS: This retrospective cohort study used data from the National Health Insurance Research Database (NHIRD) in Taiwan to analyze CT scan uses from the beginning of 2000 to the end of 2013. The number, annual growth rate, and cumulative fold change ratio were estimated in different groups classified by sex, age, or disease category (catastrophic illness, noncatastrophic illness). RESULTS: The number of CT scan uses per million people per year in Taiwan increased 2.5 times from 24 257 in 2000 to 60 351 in 2013, at the average annual growth rate of 7.4% ± 5.9%. The annual number of CT scan uses in different age groups and disease category groups was significantly higher in males than in females. However, the average annual growth rate and the cumulative fold change ratio were slightly higher in females than in males. The majority of CT scan uses were in middle age and young adult groups. The annual number of CT scan uses in the young adult, child/adolescent, and middle age groups increased 3.7-, 3.5-, and 2.7-fold from 2000 to 2013, but decreased 0.8-fold in the old-age group. The annual number of CT scan uses was highest in the noncatastrophic illness group, followed by the catastrophic illness cancer group and catastrophic illness others group. CONCLUSION: CT scan uses in Taiwan increased continuously from 2000 to 2013, even in the groups with higher radiation-related cancer risk. Therefore, clinicians, radiologists, and medical policy makers should weigh diagnostic benefit against sex-specific and age-specific risks in the future.
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Tomografia Computadorizada por Raios X/tendências , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Caracteres Sexuais , Taiwan , Fatores de Tempo , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adulto JovemRESUMO
Stevens-Johnson syndrome (SJS) is a life-threatening disease, which is mainly ascribed to drugs, such as sulfonamides and psychoepileptics. In this article, we present a pediatric case of vancomycin-induced SJS and an alternative diagnostic algorithm. The patient presented with multiple target-like rashes and vesicles throughout the whole body after receiving vancomycin. Despite the fact that skin biopsy remains the gold standard for diagnosing SJS, the granulysin rapid test by immunochromatographic assay is a non-invasive option for children. In this article, we describe our use of the Algorithm of Drug causality for Epidermal Necrolysis and a modified T-cell activation assay for granzyme B and interferon gamma to screen for the culprit drug. Moreover, we applied the granulysin rapid test as an early diagnosis method for children with drug-induced SJS.
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BACKGROUND: Although clinical assessment remains the gold standard for monitoring the circulation of free flaps, several adjunct techniques promote timely salvage by detecting circulation compromise early. The objective of this systematic review was to evaluate the efficacy of an implantable Doppler probe for postoperatively monitoring free flaps. MATERIALS AND METHODS: English-language articles evaluating the efficacy of implantable Doppler probes compared with clinical assessment for postoperatively monitoring free flaps were analyzed. The outcome measures were total flap failure rates, salvage rates, sensitivity, false-positive rates, and positive likelihood ratios. RESULTS: Of the 504 citations identified, 6 comparative studies were included for meta-analysis. An implantable Doppler probe significantly lowered the flap failure rate (risk ratio: 0.40; 95% confidence interval: 0.21-0.75) and raised the successful salvage rate (risk ratio: 1.73; 95% confidence interval: 1.16-2.59). Pooled sensitivity was higher (1.00 vs 0.98), the positive likelihood ratio was lower (72.16 vs 220.48), and the false-positive rate was higher (0.01 vs 0) in the implantable Doppler probe group than in the clinical assessment group. CONCLUSION: An implantable Doppler probe is significantly more efficacious than clinical assessment for postoperatively monitoring free flaps.
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Cytochrome P450 2E1 (CYP2E1) is involved in the metabolic activation of various carcinogens. CYP2E1 RsaI/PstI polymorphism has been identified in urologic cancer patients, while studies of the polymorphism have shown inconclusive trends in the risk of urologic cancers. Therefore, we performed this systematic review to provide a complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, Embase and Web of Science to identify eligible studies up to December 15, 2014. 12 studies with 2712 cases and 2977 controls were included in the meta-analysis.The odds ratio with a 95% confidence interval was used to assess the strength of associations. We observed that the c2 allele of CYP2E1 RsaI/PstI polymorphism was associated with a decreased risk of urologic cancer under all genetic models (c2 vs. c1: OR = 0.742, 95% CI = 0.659-0.835); c2c2 vs. c1c1: OR = 0.516, 95% CI = 0.357-0.745; c1c2 vs. c1c1: OR = 0.748, 95% CI = 0.748 (0.648-0.863; c2c2 + c1c2 vs. c1c1: OR = 0.722, 95% CI = 0.629-0.829; c2c2 vs. c1c1 + c1c2: OR = 0.578, 95% CI = 0.401-0.832). In the subgroup analysis by cancer type, statistically significant associations were found in urothelial cancer in all genetic models. When stratified by ethnicity, a same trend was also indicated in Asians in all genetic models.To conclude, our results support the conclusion that the CYP2E1 RsaI/PstI polymorphism may be associated with urologic cancer susceptibility. The c2 allele is a low-penetrance risk factor for urologic cancer development.