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Introduction

Bladder cancer (BC) is diagnosed by cystoscopy, which is invasive, costly and causes considerable patient discomfort. MicroRNAs (miR) are dysregulated in BC and may serve as non-invasive urine markers for primary diagnostics and monitoring. The purpose of this study was to identify a urinary miR signature that predicts the presence of BC.

Methods

For the detection of potential urinary miR markers, expression of 384 different miRs was analyzed in 16 urine samples from BC patients and controls using a Taqman? Human MicroRNA Array (training set). The identified candidate gene signature was subsequently validated in an independent cohort of 202 urine samples of patients with BC and controls with microscopic hematuria. The final miR signature was developed from a multivariable logistic regression model.

Results

Analysis of the training set identified 14 candidate miRs for further analysis within the validation set. Using backward stepwise elimination, we identified a subset of 6 miRs (let-7c, miR-135a, miR-135b, miR-148a, miR-204, miR-345) that distinguished BC from controls with an area under the curve of 88.3%. The signature was most accurate in diagnosing high-grade non-muscle invasive BC (area under the curve?=?92.9%), but was capable to identify both low-grade and high-grade disease as well as non-muscle and muscle-invasive BC with high accuracies.

Conclusions

We identified a 6-gene miR signature that can accurately predict the presence of BC from urine samples, independent of stage and grade. This signature represents a simple urine assay that may help reducing costs and morbidity associated with invasive diagnostics.  相似文献   
33.

Background

We questioned whether there was a radiographic difference in hip geometry reconstruction and implant fixation between 3 different cementless stem design concepts in patients with primary end-stage hip osteoarthritis.

Methods

We retrospectively evaluated the preoperative and postoperative radiographs by 2 independent and blinded reviewers in a series of 264 consecutive patients who had received either a straight double-tapered stem with 3 offset options (group A), a straight double-tapered stem with 2 shape options and modular necks (group B), and a bone-preserving curved tapered stem with 4 offset options (group C). The following parameters were assessed: acetabular, femoral and hip offset (HO), center of rotation height, leg length difference (LLD), and the endosteal fit of stem in the proximal femur (canal fill index). Group comparisons were performed using a one-way analysis of variance and subsequent pairwise comparisons (t-test).

Results

Postoperatively, HO could be equally restored with all 3 stem designs (P = .079). The postoperative LLD was smaller in group C compared to group A (0.8 mm [standard deviation, 3.2] vs 2.6 mm [standard deviation, 4.5], P = .002). Best combined reconstruction of HO and LLD could be achieved with the short curved stem by junior and senior surgeons (HO: ?2.0 and ?2.1 mm; LLD: 1.9 and 0.7 mm, respectively). The proximal and mid-height canal fill indexes were higher in groups B and C compared to group A, indicating a better metaphyseal and diaphyseal fit in the proximal femur (both P < .001).

Conclusion

All 3 cementless stem designs allowed for good hip geometry reconstruction. Multiple shape and offset options allowed for a better metaphyseal stem fit and offered minor clinical advantages for leg length reconstruction. Modular necks did not provide reconstructive advantages in patients with primary hip osteoarthritis.  相似文献   
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Archivum Immunologiae et Therapiae Experimentalis - While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT) with allergen extracts is...  相似文献   
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Creatine (Cr) is a substrate for adenosine triphosphate synthesis, and it is the most used dietary supplement among professional and recreative athletes and sportsmen. Creatine supplementation may increase allergic airway response, but the cellular and molecular mechanisms are unknown. We used murine model of OVA‐induced chronic asthma and showed that Cr supplementation increased total proteins, ATP level, lymphocytes, macrophages, and IL‐5 levels in BALF, as well as IL‐5 in the supernatant of re‐stimulated mediastinal lymph nodes. IL‐5 and IL‐13 expression by epithelial cells and by peribronchial leukocytes were increased by Cr. Cr augmented the expression of P2 × 7 receptor by peribronchial leukocytes and by epithelial cells, and increased the accumulation of eosinophils in peribronchial space and of collagen fibers in airway wall. In human cells, while Cr induced a release of ATP, IL‐6, and IL‐8 from BEAS‐2B cells, whole blood cells, such as eosinophils, and CD4+ T cells, P2 × 7 receptor inhibitor (A740003) reduced such effects, as denoted by reduced levels of ATP, IL‐6, and IL‐8. Therefore, Cr supplementation worsened asthma pathology due to activation of airway epithelial cells and peribronchial leukocytes, involving purinergic signaling.  相似文献   
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Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available methods on bronchoalveolar lavage (BAL) and blood samples from 66 patients (age, 58 years [range, 45 to 64]; HSCT to ICU, 176 days [range, 85 to 407]) with ARF and pulmonary infiltrates were analyzed. In 47 patients (71%) a causative pathogen was identified (fungal, n?=?28; viral, n?=?26; bacterial, n?=?18). Polymicrobial findings involving several pathogen groups occurred in 20 patients (30%). Culture (12/16, 75%), galactomannan (13/15, 87%), and Aspergillus-PCR (8/9, 89%) from BAL but not serum galactomannan (6/14, 43%) helped to diagnose invasive aspergillosis (n?=?16, 24%). Aspergillus-PCR detected azole resistance in 2 cases. Mucorales was found in 7 patients (11%; BAL culture, n?=?6; Mucorales-PCR, n?=?1). Patients with identified pathogens had higher Simplified Acute Physiology Score II scores (P?=?.049) and inferior ICU survival (6% versus 37%, P?<?.01), which largely related to the presence of an invasive fungal infection. Eight patients (12%) had 1 or more viruses with uncertain lung pathogenicity as the sole microbiologic finding. A diagnostic microbiologic workup incorporating molecular- and biomarker-based assays identified pathogens in most HSCT recipients with ARF and pulmonary infiltrates admitted to the ICU. Implications of polymicrobial infection and pathogen patterns in these patients warrant further investigation.  相似文献   
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