Citations

Objectives To determine if a re‐transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1‐high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS). Patients and methods In a large retrospective multicentre cohort of 2451 patients with T1‐HG/G3 initially treated with bacille Calmette–Guérin, 935 (38%) had a re‐TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re‐TUR), group 2 (no muscle, re‐TUR), group 3 (muscle, no re‐TUR) and group 4 (muscle, re‐TUR). Clinical outcomes were compared across the four groups. Results Re‐TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re‐TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re‐TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints. Conclusions Our retrospective analysis suggests that re‐TUR may not be necessary in patients with T1‐HG/G3, if muscle is present in the specimen of the primary TUR.

BackgroundThyroid fine‐needle aspiration (FNA) is used to assess appropriate management of nodular thyroid lesions safely, but Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) and category IV (follicular neoplasm/suspicious for follicular neoplasm) lesions are problematic. This study aimed to evaluate the Afirma Gene Expression Classifier (GEC) results for lesions in those categories.MethodsMedical records of patients with thyroid FNA and GEC results were obtained from archived material. Results were compared to thyroidectomy histologic diagnoses.ResultsAmong 66 patients with FNA results (47 women and 19 men aged 26–89 years [mean, 59.4 years]), surgical reports were available for 38. Afirma GEC results were “nondiagnostic” for 10 of 66 (15.2%), “benign” for 22 (33.3%), and “suspicious” for 34 (51.5%). Surgical diagnosis was available for 38 of 66 patients (57.6%); GEC results for 6 (15.8%) of these were “nondiagnostic,” 27 (71.0%) were “suspicious,” and 5 (13.2%) were “benign.” One of 6 (16.7%) samples with “nondiagnostic” results, 1 of 5 (20%) with “benign” results, and 15 of 27 (55.6%) with “suspicious” results were malignant on histology. Papillary carcinoma was the most common tumor type (15 of 38; 39.5%).ConclusionsAfirma GEC results minimize the number of unnecessary operations. Afirma GEC testing may be reserved for FNAs with a category III diagnosis on follow‐up cytologic examination. We recommend a conservative approach for “suspicious” Afirma GEC results if Hürthle cells are seen with FNA. Diagn. Cytopathol. 2015;43:966–970. © 2015 Wiley Periodicals, Inc.

We investigate the in vivo patterns of stem cell divisions in the human hematopoietic system throughout life. In particular, we analyze the shape of telomere length distributions underlying stem cell behavior within individuals. Our mathematical model shows that these distributions contain a fingerprint of the progressive telomere loss and the fraction of symmetric cell proliferations. Our predictions are tested against measured telomere length distributions in humans across all ages, collected from lymphocyte and granulocyte sorted telomere length data of 356 healthy individuals, including 47 cord blood and 28 bone marrow samples. We find an increasing stem cell pool during childhood and adolescence and an approximately maintained stem cell population in adults. Furthermore, our method is able to detect individual differences from a single tissue sample, i.e. a single snapshot. Prospectively, this allows us to compare cell proliferation between individuals and identify abnormal stem cell dynamics, which affects the risk of stem cell related diseases.

Abstract Aims The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF). Methods and results HF patients (n = 186) and HF-free controls (n = 21) underwent right heart catheterization, echocardiography, pulmonary function testing and chest radiography that was blindly scored for the presence and severity of lung oedema. Lung congestion correlated directly with pulmonary vascular resistance (PVR, P = 0.004) and inversely with pulmonary artery (PA) compliance (P < 0.001) and the diffusion limit for carbon monoxide (DLCO, P = 0.009). Compared with dry lung HF, wet lung HF patients (congestion score > median) had 25% lower PA compliance and 25–35% higher PVR, transpulmonary gradients and PA pressures (40 vs. 32 mmHg, P < 0.001) despite marginally higher PA wedge pressure (PAWP; 22 vs. 19 mmHg, P = 0.002). Wet lung HF patients displayed more right ventricular (RV) dilatation and dysfunction, more restrictive ventilation and greater reduction of DLCO. The strongest correlates of lung congestion were NT-proBNP, haemoglobin, albumin, and glomerular filtration, all surpassing PAWP. After a median of 333 days (interquartile range 80–875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P < 0.0001), even after adjusting for PAWP, NT-proBNP, anaemia, CAD and renal dysfunction. Conclusion Interstitial lung oedema is associated with pulmonary vascular disease, RV overload and dysfunction and increased mortality in HF. These data reinforce the importance of aggressive decongestion in HF and suggest that novel agents aimed at reducing lung water may help to deter progression of pulmonary vascular disease and biventricular HF.

Shear wave elastography imaging (SWEI) with ultrasound uses an applied acoustic radiation force to obtain quantitative images of liver, breast, prostate, and other soft tissues. In SWEI, shear velocity waveforms are collected along a line, and then, the shear speed is estimated either with a k-space or a correlation-based method. Although these yield effective estimates in elastic media, both methods consistently overestimate the shear speed in viscoelastic soft tissue because neither considers the shear viscosity. To address this problem, we have created a new shear speed estimation approach that also accounts for the effect of shear viscosity. The new approach is evaluated in a computational model that calculates the three-dimensional (3D) intensity field generated by a linear array transducer in FOCUS (http://www.egr.msu.edu/~fultras-web) and then simulates the shear wave velocities in a viscoelastic medium with a 3D finite difference model. In the viscoelastic shear wave simulation model, the shear speed constant is 1.5 m/s, and the shear viscosity is 1 Pa·s. Correlation-based shear speed estimates are compared to the viscosity-compensated estimates, and the results show that the viscosity-compensated approach consistently achieves improved shear speed estimates relative to the correlation-based method. [Work supported in part by NIH Grant Nos. R01EB012079 and R01DK092255.]

Many methods for characterization of the mechanical properties of soft tissues using propagating shear waves have been developed over the past two decades. Most of these methods assume that the shear wave is traveling in an elastic, isotropic tissue. However, many soft tissues are viscoelastic and have material properties that are directionally dependent or anisotropic. We have been developing methods to measure waves propagating in soft tissues to estimate the anisotropic viscoelastic material properties. To refine our measurement methods, we have also developed techniques and models for simulating the wave propagation in these types of materials. We have developed specialized finite element and pseudo-spectral models that can simulate viscoelastic transversely isotropic materials and compared our results with measurements in ex vivo porcine muscle. Additionally, we have developed a finite element model that simulates wave propagation in the myocardium by creating a model of layered transverse isotropic media oriented at different angles. We examined the effect of frequency of the waves for estimating of the angle of propagation. We compared these simulation results with experimental results from an ex vivo porcine left ventricular wall. These simulation methods provide insight for optimizing our measurement methods for in vivo characterization of material properties.

Speaker normalization, a process whereby the perceptual system of a listener recalibrates to accommodate individual speakers, is proposed to account for the ease with which we understand speech produced by multiple speakers with different sized and shaped vocal tracts. A variety of vowel-, formant-, and speaker-intrinsic or extrinsic transforms have been proposed to model speaker normalization of vowels produced by multiple speakers (e.g., Mel, Bark, and Lobanov methods). Suitability of such normalization procedures has been examined extensively in non-disordered speaker populations. Unknown at this point, however, is the appropriateness of normalization procedures for transforming spectrally distorted vowels produced by speakers with dysarthria. Thus, we examined the suitability of two transforms, Bark and Lobanov, for normalizing vowels produced by a heterogeneous cohort of 45 speakers with dysarthria. Non-normalized (Hertz) and Bark transformed vowel tokens were classified via discriminant function analysis (DFA) with 55% and 56% accuracy, respectively. Classification accuracy of vowel tokens normalized using Lobanov’s method was 65%. The results of the DFAs were compared to perceptual data, which revealed listeners identified vowel tokens with 71% accuracy. These results suggest vowel-extrinsic and formant- and speaker-intrinsic normalization methods (e.g., Lobanov) are better suited to model speaker normalization of dysarthric vowels.

The percutaneous Melody valve is occasionally used for the treatment of bioprosthetic valve dysfunction and is an attractive option for patients at high risk for repeat operation. Anticoagulation is not routinely recommended following Melody valve placement. We present the case of a young woman who developed subacute spontaneous thrombosis of her Melody valve 15 months after placement. Her clinical status was compromised by severe tricuspid prosthesis stenosis and right-to-left shunting across a small residual atrial septal defect. Surgical replacement was required. To our knowledge, this is the first reported case of spontaneous thrombosis of a Melody valve in the tricuspid position.

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.