Objective The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic ...lymphohistiocytosis (HLH) in febrile children. Study design In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques. Results Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%. Conclusions The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.
Glioma is the most common type of malignant neoplasm in the central nervous system, with high incidence and mortality rate. MicroRNAs, as a class of small non-coding RNAs, play an important role in ...carcinogenesis and correlate with glioma diagnosis and prognosis. In this study, we investigated the microRNA-204 (miR-204) concentration in glioma tissues and its relation to the expression of ezrin and bcl-2 mRNA, as well as its potential predictive and prognostic values in glioma. The concentrations of miR-204 were significantly lower in glioma tissues than in non-tumor brain tissues and also were lower in high-grade than in low-grade gliomas (World Health Organization WHO grades III and IV vs grades I and II). The miR-204 concentration was inversely correlated with the ezrin and bcl-2 concentrations. The miR-204 concentration was classified as high or low according to the median value, and low miR-204 correlated with higher WHO grade, larger tumor, and worse Karnofsky performance score (KPS). Kaplan-Meier survival analysis demonstrated that patients with low miR-204 expression had shorter progression-free survival (PFS) and overall survival (OS) than patients with high miR-204 expression. In addition, univariate and multivariate analyses showed that miR-204 expression was an independent prognostic feature of OS and PFS. In conclusion, our study indicates that miR-204 is downregulated in glioma and may be a biomarker of poor prognosis in patients with this cancer.
Summary Background A new test ( care HPV; QIAGEN, Gaithersburg, MD, USA) has been developed to detect 14 high-risk types of carcinogenic human papillomavirus (HPV) in about 2·5 h, to screen women in ...developing regions for cervical intraepithelial neoplasia (CIN). We did a cross-sectional study to assess the clinical accuracy of care HPV as a rapid screening test in two county hospitals in rural China. Methods From May 10 to June 15, 2007, the care HPV test was done locally by use of self-obtained vaginal and provider-obtained cervical specimens from a screening population-based set of 2530 women aged 30 to 54 years in Shanxi province, China. All women were assessed by visual inspection with acetic acid (VIA), Digene High-Risk HPV HC2 DNA Test (HC2), liquid-based cytology, and colposcopy with directed biopsy and endocervical curettage as necessary. In 2388 women with complete data, 441 women with negative colposcopy, but unsatisfactory or abnormal cytology or who were positive on HC2 or the new care HPV test, were recalled for a second colposcopy, four-quadrant cervical biopsies, and endocervical curettage. An absence of independence between the tests was not adjusted for and the Bonferroni correction was used for multiple comparisons. Findings Complete data were available for 2388 (94·4%) women. 70 women had CIN2+ (moderate or severe CIN or cancer), of whom 23 had CIN3+. By use of CIN2+ as the reference standard and area-under-the-curve analysis with a two-sided alpha error level of 0·0083, the sensitivities and specificities of the care HPV test for a cut-off ratio cut-point of 0·5 relative light units, were 90·0% (95% CI 83·0–97·0) and 84·2% (82·7–85·7), respectively, on cervical specimens, and 81·4% (72·3–90·5) and 82·4% (80·8–83·9), respectively, on vaginal specimens (areas under the curve not significantly different, p=0·0596), compared with 41·4% (29·9–53·0) and 94·5% (93·6–95·4) for VIA (areas under the curve significantly different, p=0·0001 and p=0·0031, for cervical and vaginal-specimen comparisons for the care HPV test, respectively). The sensitivity and specificity of HC2 for cervical specimens were 97·1% (93·2–100) and 85·6% (84·2–87·1), respectively (areas under the curve not significantly different from the care HPV test on cervical specimens, p=0·0163). Interpretation The care HPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. Funding Bill & Melinda Gates Foundation.
Results of several studies have shown a possible beneficial effect of renin-angiotensin system (RAS) inhibitors on diabetic retinopathy, but the findings were contradictory. We did a systematic ...review and meta-analysis to assess the effect of RAS inhibitors on diabetic retinopathy.
We identified relevant publications in PubMed, Embase, Cochrane Library Central Register of Controlled Trials, and abstracts from main annual meetings. Only randomised controlled trials comparing angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) monotherapy with other antihypertensive drugs or placebo in type 1 or type 2 diabetes were eligible for inclusion in the analysis. The primary outcomes were progression and regression of diabetic retinopathy in all patients and several subgroups. Risk ratios (RRs) with corresponding 95% CIs were pooled. We also did a network meta-analysis to assess the effect of different antihypertensive drugs on diabetic retinopathy by ranking order. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42013004548.
21 randomised clinical trials with 13,823 participants were included in the meta-analysis. RAS inhibitors were associated with reduced risk of progression (absolute risk difference -3%, 95% CI -5 to -1; pooled RR 0.87, 95% CI 0.80-0.95; p=0.002) and increased possibility of regression of diabetic retinopathy (8%, 1-16; RR 1.39, 95% CI 1.19-1.61; p=0.00002). In normotensive patients, RAS inhibitors decreased risk of diabetic retinopathy progression (0.81, 0.69-0.94; p=0.007) and increased possibility of regression (1.43, 1.14-1.79; p=0.002). In hypertensive patients, RAS inhibitors were not associated with difference in risk of progression of diabetic retinopathy (0.93, 0.79-1.10; p=0.42) or possibility of diabetic retinopathy regression (2.21, 0.92-5.31; p=0.08). ACE inhibitors were associated with reduced risk of diabetic retinopathy progression (0.84, 0.75-0.94; p=0.002) and higher possibility of disease regression (1.50, 1.20-1.86; p=0.0003). ARBs were associated with a higher possibility of diabetic retinopathy regression (1.32, 1.07-1.61; p=0.008), but had no effect on disease progression (0.92, 0.80-1.06; p=0.25). Network meta-analysis showed the association of antihypertensive drugs with risk of diabetic retinopathy progression was lowest for ACE inhibitors, followed by ARBs, β blockers, calcium channel blockers, and placebo in rank order. The association of antihypertensive drugs with possibility of diabetic retinopathy regression was highest for ACE inhibitors, followed by ARBs, placebo, and calcium channel blockers in rank order.
In patients with diabetes, RAS inhibitors reduce the risk of diabetic retinopathy, and increase the possibility of diabetic retinopathy regression. ACE inhibitors might be better than ARBs for treating diabetic retinopathy, and might exert the most beneficial effect on diabetic retinopathy of all widely used antihypertensive drug classes.
To describe the age- and gender-specific prevalence, characteristics, and severity of diabetic retinopathy (DR) in a rural population in northern China.
A population-based cross-sectional study.
A ...total of 6830 Han Chinese aged 30 years and older from 13 villages of Yongnian County, Handan City, Hebei Province, China.
All participants underwent a standardized interview, a comprehensive eye examination, and fasting blood glucose testing according to the American Diabetes Association diagnostic criteria (fasting plasma glucose >or=7.0 mmol/l). Retinal photographs obtained after pupil dilation were graded for the presence and severity of DR according to the modified Early Treatment Diabetic Retinopathy Study classification system.
Any DR, retinopathy grades, macular edema, or vision-threatening retinopathy.
Of the 6830 eligible individuals participating in the study, 5597 (81.9%) had fasting blood glucose results available. Of these, 387 participants (6.9%) were diagnosed with diabetes mellitus, including 247 subjects with new diabetes mellitus (NDM) and 140 subjects with known diabetes mellitus (KDM). For these, gradable photographs were available for 368 subjects (95.1%). The overall prevalence of DR was 43.1% (95% confidence interval, 38.1-48.4) and was higher in persons with KDM (65.2%) than NDM (33.5%). The prevalence of proliferative DR, macular edema, and vision-threatening retinopathy was 1.6%, 5.2%, and 6.3%, respectively, with 12.1% with KDM having untreated vision-threatening DR. No age- or gender-related differences were present. The prevalence of DR was strongly related to duration of disease.
Our study reports a high prevalence of DR among adults 30 years and older with diabetes in rural China. On the basis of estimates obtained from our study, we projected that in rural China, 21.1 million persons aged 30+ years have diabetes and 9.2 million have DR, including 1.3 million with vision-threatening DR. There is a pressing need for appropriate screening and management of diabetes and its complications in rural China.
Highlights ● We reviewed clinical and imaging data of six tentorial DAVF patients with pial arterial supply of 53 consecutive DAVF patients treated by Onyx embolization. ● Incidence of complications ...of DAVF patients with pial arterial supply was significantly higher compared to DAVF patients without pial arterial supply. ● Pial arterial supply may be a risk factor of intraoperative hemorrhage during the transarterial embolization of DAVF through dural feeders. ● Obliterating pial feeding arteries before fistula embolization may decrease the risk of hemorrhage.
Background Anticoagulation therapy has been recommended by major guidelines to reduce the risk of recurrent stroke in patients with atrial fibrillation-associated ischemic stroke (AFAIS). However, in ...real-world clinical practice, oral anticoagulants with either vitamin K antagonists or nonvitamin K antagonists are often underused for these patients. Here, we sought to investigate the current status of oral anticoagulant use in patients with AFAIS in northwestern China. Methods We reviewed medical records of consecutive patients with AFAIS discharged from 14 hospitals in northwestern China between January 2012 and May 2015. Results A total of 1014 cases were included in this study. The mean age of the patients was 70.3 ± 10.8 years. Fifty-four percent were female. Among all participants, only 20.0% received anticoagulants (19.4% warfarin and .6% nonvitamin K antagonist oral anticoagulants), whereas 57.5% took antiplatelet drugs and 22.5% received neither anticoagulant nor antiplatelet treatment. Anticoagulant use decreased with increasing age and CHA2DS2-VASc scores. The proportions of anticoagulant use at discharge in patients younger than 65 years, 65-74 years, and 75 years or older were 28.5%, 20.7%, and 13.9%, respectively. Nonvalvular atrial fibrillation patients with CHA2DS2-VASc scores of 2, 3, 4, 5, 6, and 7 had anticoagulant use rates at discharge of 19.2%, 24.8%, 20.3%, 13.7%, 8.1%, and 8.0%, respectively. Conclusions In northwestern China, oral anticoagulants are substantially underutilized in patients with AFAIS, especially in patients at higher risk of stroke, suggesting a large treatment gap in the secondary prevention management in patients with AFAIS.
Abstract Background Both low tube voltage and sinogram-affirmed iterative reconstruction (IR) techniques hold promise to decrease radiation dose at coronary CT angiography (CCTA). The increased ...iodine contrast at low tube voltage allows for minimizing iodine load. Objective To assess the effect of reduced x-ray tube voltage, low iodine concentration contrast medium and IR on image quality and radiation dose at CCTA. Methods Two hundred thirty-one consecutive patients with suspected coronary artery disease were enrolled in this prospective, multicenter trial and randomized to 1 of 2 dual-source CCTA protocols: 120-kVp with 370 mgI/mL iopromide or iopamidol (n = 116; 44 women; 55.3 ± 9.8 years) or 100 kVp with 270 mgI/mL iodixanol (n = 115; 48 women; 54.2 ± 10.4 years). Reconstruction was performed with filtered back projection and IR. Attenuation, image noise, signal-to-noise ratio, and contrast-to-noise ratio were measured and image quality scored. Size-specific dose estimates and effective doses were calculated. Results There were no significant differences in mean arterial attenuation (406.6 ± 76.7 vs 409.7 ± 65.2 Hounsfield units; P = .739), image noise (18.7 ± 3.8 vs 17.9 ± 3.4 Hounsfield units; P = .138), signal-to-noise ratio (22.5 ± 5.4 vs 23.7 ± 6.1; P = .126), contrast-to-noise ratio (17.5 ± 5.5 vs 18.3 ± 6.1; P = .286), or image quality scores (4.1 ± 0.9 vs 4.0 ± 0.9; P > .05) between 120-kVp filtered back projection–reconstructed and 100-kVp IR-reconstructed series. Mean iodine dose was 26.5% lower (18.3 ± 0.5 vs 24.9 ± 0.9 g; P < .0001), mean size-specific dose estimate was 35.1% lower (17.9 ± 6.6 vs 27.5 ± 8.2 mGy; P < .0001), and effective dose was 34.9% lower (2.3 ± 1.0 vs 3.5 ± 1.1 mSv; P < .0001) with the 100 kVp compared with the 120-kVp protocol, respectively. Conclusion Using low x-ray tube voltage and IR allows for decreasing the iodine load and effective radiation dose at CCTA while maintaining image quality.
Purkinje cells (PCs) have a steeper rate dependence of repolarization and are more susceptible to arrhythmic activity than do ventricular myocytes (VMs). Late sodium current (I
) is rate dependent ...and contributes to rate dependence of repolarization.
This study sought to test our hypothesis that PCs have a larger rate dependence of I
, contributing to their steeper rate dependence of repolarization and higher susceptibility to arrhythmic activity, than do VMs.
I
was recorded in isolated rabbit PCs and VMs with the whole-cell patch clamp technique. Action potential was examined using the microelectrode technique.
Compared with VMs, PCs exhibited a significantly larger rate dependence of I
with a larger I
to basic cycle length (BCL) slope. Moreover, PCs had a larger rate dependence of I
decay and slower recovery kinetics. Interestingly, the larger rate dependence of I
matched to a steeper rate dependence of action potential duration (APD) in PCs. The I
blocker tetrodotoxin significantly blunted, while the I
enhancer anemone toxin (ATX-II) significantly increased, the rate dependence of I
and APD in PCs and VMs. In the presence of ATX-II, the rate dependence of I
in PCs was markedly larger than that in VMs, causing a much steeper rate dependence of APD in PCs. Accordingly, PCs exhibited greater rate-dependent electrical instability and were more prone to ATX-II-induced early afterdepolarizations, which were completely inhibited by the I
inhibitor ranolazine.
PCs have a significantly larger rate dependence of I
than do VMs because of distinctive I
decay and recovery kinetics, which contributes to their larger rate adaptation, and simultaneously predisposes them to a higher risk of arrhythmogenesis.
