We aimed to evaluate the accuracy of transnasal small-caliber esophagogastroduodenoscopy (TNSC-EGD) compared with peroral conventional EGD (POC-EGD) for evaluating varices in unsedated patients with ...liver cirrhosis. The success rate, safety, endoscopist satisfaction, and patient tolerability of TNSC-EGD were also addressed.
One hundred patients with liver cirrhosis participated in this randomized crossover trial, and 84 subjects completed both procedures. Of the 84 patients, 28 had marked bleeding diathesis (platelet count ≤ 50000/mm (3) and/or prothrombin time ≥ 1.7 INR). Endoscopists and patients answered questionnaires using a 100-mm visual analog scale about, respectively, their satisfaction and their tolerance of the procedure.
The success rate of TNSC-EGD was comparable to that of POC-EGD (96% vs. 99%). Nasal mucosal hemorrhages induced by TNSC-EGD occurred in 5 patients (6%), but were easily controlled. Compared to the POC-EGD reference test, diagnostic accuracies of TNSC-EGD for detecting esophageal varices, gastric varices, and red color signs were 98%, 98%, and 96%, respectively. Concordance rates on grading esophageal varices and gastric varices were excellent at 93% (κ = 0.85) and 96% (κ = 0.87). Endoscopist satisfaction was not significantly different between TNSC-EGD and POC-EGD, whereas patient tolerance of TNSC-EGD was significantly greater than that of POC-EGD (79.0 ± 14.4 vs. 69.5 ± 16.1; P = 0.001).
TNSC-EGD without sedation was found to be feasible, safe, and accurate for evaluating esophageal varices, gastric varices, and red color signs in patients with cirrhosis - even in those with marked bleeding diathesis. Furthermore, it was significantly better tolerated by patients, without altering endoscopist satisfaction. Our findings indicate that TNSC-EGD without sedation might be viewed as a potential alternative to POC-EGD for evaluation of varices.
Tigecycline non-susceptible Acinetobacter nosocomialis (TNAN) has been discovered in clinical isolates. The resistance-nodulation-cell division (RND)-type efflux system plays a major role in ...tigecycline non-susceptible Acinetobacter baumannii, but the mechanism in A. nosocomialis remains unknown. Our aim was to analyse the contribution of efflux-based tigecycline resistance in clinical A. nosocomialis isolates collected from multiple medical centres in Taiwan.
A total of 57 A. nosocomialis isolates, including 46 TNAN and 11 tigecycline-susceptible A. nosocomialis (TSAN) isolates, were analysed. Of these, 46 TNAN isolates were clustered to ST410 (43 isolates) and ST68 (three isolates) by multi-locus sequence typing.
The relationship between the RND efflux pump and tigecycline resistance was indirectly verified by successfully reducing tigecycline resistance with NMP, an efflux pump inhibitor. The three RND efflux systems (AdeABC, AdeIJK and AdeFGH) were detected in all clinical isolates. The transcript level of adeB gene increased significantly and was correlated with tigecycline resistance. Moreover, the AdeRS two-component system was further classified into four different types of AdeRS patterns considering the amino acid sequence. Further analysis showed that tigecycline resistance was related to the transcript level of adeB gene and the AdeRS pattern.
This study showed that the dissemination of TNAN isolates in Taiwan is attributable mainly to the spread of ST410. The AdeABC efflux pump appeared to play an important role in the tigecycline resistance of A. nosocomialis.
Background and purpose: Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) have been known to be anti‐inflammatory in Korea. Anti‐inflammatory effects of torilin, ...isolated from this plant and the underlying mechanisms were examined by using lipopolysaccharide (LPS)‐stimulated microglial BV2 cells.
Experimental approach: The cells were treated with torilin prior to LPS exposure and the effects on pro‐inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2), and a pro‐inflammatory cytokine, interleukin‐1β (IL‐1β) were analysed by RT‐PCR, Western blot or elisa. To reveal the mechanism of action of torilin we investigated the involvement of mitogen‐activated protein kinase (MAPK) cascades and their downstream transcription factors, nuclear factor‐κB (NF‐κB) and cyclic AMP‐responsive element (CRE)‐binding protein (CREB).
Key results: Torilin significantly reduced the LPS‐induced expression of iNOS, COX‐2 and IL‐1β, and the subsequent release of NO, prostaglandin E2 and IL‐1β into culture medium. LPS stimulation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and p38 MAPK was inhibited by torilin. In addition, the inhibitory effect of torilin on NF‐κB and CREB was shown by torilin‐mediated recovery of LPS‐induced degradation of inhibitor κB‐α and suppression of LPS‐induced phosphorylation of CREB respectively.
Conclusion and implications: This study indicates that torilin inhibited LPS‐induced iNOS, COX‐2 and IL‐1β via down‐regulation of ERK1/2, p38 MAPK, NF‐κB and CREB and suggests that torilin has a potential as an anti‐inflammatory drug candidate.
With its tropical rainforest climate, rapid urbanization, and changing demography and ecology, Singapore experiences endemic dengue; the last large outbreak in 2013 culminated in 22,170 cases. In the ...absence of a vaccine on the market, vector control is the key approach for prevention.
We sought to forecast the evolution of dengue epidemics in Singapore to provide early warning of outbreaks and to facilitate the public health response to moderate an impending outbreak.
We developed a set of statistical models using least absolute shrinkage and selection operator (LASSO) methods to forecast the weekly incidence of dengue notifications over a 3-month time horizon. This forecasting tool used a variety of data streams and was updated weekly, including recent case data, meteorological data, vector surveillance data, and population-based national statistics. The forecasting methodology was compared with alternative approaches that have been proposed to model dengue case data (seasonal autoregressive integrated moving average and step-down linear regression) by fielding them on the 2013 dengue epidemic, the largest on record in Singapore.
Operationally useful forecasts were obtained at a 3-month lag using the LASSO-derived models. Based on the mean average percentage error, the LASSO approach provided more accurate forecasts than the other methods we assessed. We demonstrate its utility in Singapore's dengue control program by providing a forecast of the 2013 outbreak for advance preparation of outbreak response.
Statistical models built using machine learning methods such as LASSO have the potential to markedly improve forecasting techniques for recurrent infectious disease outbreaks such as dengue.
Shi Y, Liu X, Kok SY, Rajarethinam J, Liang S, Yap G, Chong CS, Lee KS, Tan SS, Chin CK, Lo A, Kong W, Ng LC, Cook AR. 2016. Three-month real-time dengue forecast models: an early warning system for outbreak alerts and policy decision support in Singapore. Environ Health Perspect 124:1369-1375; http://dx.doi.org/10.1289/ehp.1509981.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background. Cisplatin is a chemotherapeutic agent used in treatment of malignant tumours. However, cisplatin produces various side effects, such as nephrotoxicity, neurotoxicity, emetogenesis and ...ototoxicity. Inflammation is an important mechanism of cisplatin nephrotoxicity. Alpha-lipoic acid (α-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-κB (NF-κB) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of α-LA during cisplatin-induced renal injury and to examine the mechanisms of protection. Methods. C57BL/6 mice were given cisplatin (20 mg/kg) with or without α-LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of α-LA on NF-κB activity was evaluated by examining nuclear translocation and phosphorylation of NF-κB p65 subunits in kidney tissue. Results. Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by α-LA treatment. α-LA decreased the tissue levels of tumour necrosis factor-α, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. α-LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- κB p65 subunits in kidney tissue. Conclusions. These results suggest that α-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-κB activity.
Mucosal healing is the goal for ulcerative colitis (UC) therapy, but it needs to be confirmed via colonoscopy. Colon capsule endoscopy (CCE) is a noninvasive technique for colon investigation. Our ...study investigated the accuracy of second-generation CCE (CCE-2) in assessing mucosal lesions and disease activity in UC.
In this prospective study, CCE-2 and conventional colonoscopy were performed on the same day. CCE-2 reviewers and colonoscopists used the Mayo endoscopic subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) to assess disease activity, and they were blinded to each other’s findings. Diagnostic parameters of CCE-2 for identifying mucosal lesions were evaluated by using colonoscopy as the reference.
A total of 150 patients were enrolled. Of the 150 patients, 108 were included for per-patient analysis. CCE-2 and colonoscopy showed substantial agreement in measuring MES (intraclass correlation coefficient ICC 0.69; 95% confidence interval CI, 0.46-0.81; P < .001) and UCEIS (ICC 0.64; 95% CI, 0.38-0.78; P < .001). CCE-2 had a sensitivity of 97% and 94% to detect mucosal inflammation (MES >0) and moderate to severe inflammation (MES >1), respectively. In per-segment analysis, the negative predictive values of CCE-2 to detect mucosal inflammation, including vascular pattern loss, bleeding, and erosions reached 94% to 95%. Interobserver agreement between 2 independent CCE-2 readers for both scoring systems was good (ICC > .80). The sensitivity and specificity of CCE-2 in detecting postinflammatory polyps were 100% and 91%, respectively. CCE-2 was better tolerated and preferred by patients than was colonoscopy.
CCE-2 yields high accuracy in detecting mucosal lesions and determining disease severity in UC. It represents a well-tolerated and reliable tool for disease monitoring in UC. (Clinical trial registration number: NCT02469103.)
To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients ...with nerve conduction studies (NCS), HbA(1c) levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group n = 56) and patients with diabetes with neuropathy (DN group n = 52) and further into severity grade 0 (TNS 0-1 n = 35), grade 1 (TNS 2-8 n = 42), and grade 2/3 (TNS 9-24 n = 31). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA(1c) level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction.
Adequate bowel preparation is an important colonoscopy quality indicator. Reinforced education is effective in improving bowel preparation quality of colonoscopy with mixed indications. However, it ...remains unclear whether such improvement can be consistently observed in pre- and post-irrigation during colonoscopy in screening population.
We aimed to study the effectiveness of nurse-led reinforced education delivered via mobile messenger (WhatsApp Messenger) on pre- and post-irrigation bowel preparation adequacy in colonoscopies for positive fecal immunochemical test in a population-based colorectal cancer screening program.
Randomized controlled trial.
A hospital-based endoscopy centre in Hong Kong, China.
Patients undergoing colonoscopy for positive fecal immunochemical test in a population-based colorectal cancer screening program.
The recruited patients were randomized to receive either WhatsApp Reinforced Education (WRE) or No Reinforced Education (NRE) (1:1). Patients in WRE group received one-off reinforced education of bowel preparation in text and video formats via WhatsApp Messenger four days prior to colonoscopy sent by investigator while NRE group received standard-of-care only.
Primary outcome was the bowel preparation adequacy rate as evaluated by Aronchick Scale. Secondary outcomes included bowel preparation adequacy rate as evaluated by Boston Bowel Preparation Scale, adenoma detection rate and risk factors of bowel preparation inadequacy. Continuous variables were described as means with standard deviation (SD) and analyzed with Student's t-test. The Pearson Chi Square Test or Fisher Exact Test was used to assess categorical variables when appropriate. Risk factors were determined by logistic regression.
From July 2017 to April 2019, 685 eligible patients were randomized to WRE (n = 343) and NRE (n = 342) groups. Patients in WRE group had higher bowel preparation adequacy rate as evaluated by Aronchik Scale (83.4% vs 75.4%, p = 0.010) and Boston Bowel Preparation Scale (94.2% vs 88.9%, p = 0.013). Adenoma detection rate was higher in WRE group but without statistical significance (71.4% vs 67.5%, p = 0.27). In logistic regression, WhatsApp Reinforced Education reduced the inadequate bowel preparation risk (Adjusted odds ratio: 0.564; 95% confidence interval: 0.371–0.856, p = 0.007). Male gender (Adjusted odds ratio AOR: 1.638; 95% confidence interval CI: 1.054–2.546, p = 0.028) and diabetes (AOR: 2.062; 95% CI: 1.215–3.497, p = 0.007) were risk factors of bowel preparation inadequacy.
Nurse-led mobile messenger-initiated reinforced education improves both pre- and post-irrigation bowel preparation quality of screening colonoscopy following positive fecal immunochemical test. It is readily incorporable in clinical practice because of its low setup cost.
Registered on 4 July 2017 on https://clinicaltrials.gov/ (NCT03209739).
Background and purpose
Hemodialysis (HD) may increase the risk of acute subdural hematoma (SDH) with high fatality, but the extent of this disease in non‐western populations is unclear. The incidence ...of and fatality from SDH in patients with end‐stage renal disease (ESRD) on HD were examined for an Asian population.
Methods
A cohort of 4709 newly diagnosed ESRD patients on HD from 1998 to 2010 and a control cohort of 18 663 subjects without any kidney disease were identified from a universal insurance claims database in Taiwan. The incidence and hazard of SDH for the two cohorts and 30‐day mortality from SDH were measured by the end of 2010.
Results
The incidence of SDH was 4.47‐fold higher in the HD cohort than in the control cohort (56.3 vs. 12.6 per 10 000 person‐years) with an adjusted hazard ratio (HR) of 3.81 (95% CI 2.77–5.25). HD patients with SDH had a high odds of 30‐day mortality with an adjusted odds ratio of 6.34 (95% CI 2.37–16.9).
Conclusions
ESRD patients with HD were demonstrated to be at high risk of subsequent SDH and to have a high mortality risk from SDH. Proper care for HD patients is necessary to prevent the devastating disorder.
Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of ...CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.
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