Citations

BACKGROUNDThe cytologic diagnosis of urothelial carcinoma (UC) of the upper urothelial tract (UT) is challenging. Using the UroVysion probe set adds diagnostic value for the detection of bladder cancer in voided urine. In instrumented UT specimens, the authors encountered positive UT cytology and fluorescence in situ hybridization (FISH) cases that did not demonstrate subsequent UT carcinoma.METHODSThe performance of cytology and FISH in the presence or absence of concomitant bladder cancer within 2 years was compared in 61 patients (112 samples) from 2003 through 2009. The mean follow‐up was 3.2 years. The authors also compared the performance of near‐tetrasomy versus hypertetrasomy. Biopsy confirmation of UTUC in 21 patients was considered the gold standard.RESULTSCytology alone was found to be poorly sensitive (38%) but highly specific (89%) for the detection of UTUC. FISH was found to increase the sensitivity of cytology and decrease specificity. Tetrasomy FISH resulted in many false‐positive cases. Other false‐positive FISH results were likely due to the presence of bladder cancer cells contaminating the UT specimen.CONCLUSIONSCaution should be used when evaluating instrumented urine specimens of the UT from patients with a previous history of bladder carcinoma, and tetrasomy FISH results should not be interpreted as abnormal because it significantly lowers the specificity of the test. The combination of cytology and FISH appears to have good specificity while maintaining good sensitivity in evaluating UTUC when using modified scoring criteria for the appropriate patient population. Cancer (Cancer Cytopathol) 2014;122:459–467. © 2014 American Cancer Society.

Objective This study explored posterior nasopharyngeal augmentation with an acellular dermal matrix sheeting. Design Evaluation of the persistence and safety of a submucosal implant of rolled acellular dermis over a 3-month period in a piglet model. Setting Institute Hills Facility, part of the Mayo Clinic Rochester health care facility. Participants Fifteen 5-week-old domestic piglets of unspecified gender. Interventions Twelve piglets were implanted at age 5 weeks with a rolled sheet of acellular dermal matrix (Strattice). Implants were inserted in a submucosal pocket in the soft palate. Three piglets underwent sham operations, with creation of submucosal pockets without implantation. After a 3-month observation period, the palates were harvested for evaluation. Results Grossly, persistence of bulk at the surgical site in 5 of the 12 implanted piglets was noted at 3 months. Histologically, no persistence of the dermal matrix could be observed. Incorporation and/or resorption of the dermal matrix occurred with minimal to no host inflammatory response. Conclusion This experiment demonstrated the safety of a rolled acellular dermal implant in a submucosal location in a pig model, without surgical complication, host inflammatory reaction, or rejection. Minimal, if any, bulk of the implant persisted in the implanted location after 3 months. Although acellular dermal matrix sheeting appears to be safe and well-tolerated, it does not offer a long-term treatment option for posterior pharyngeal augmentation.

Reducing the incidence and mortality rates for clear cell renal cell carcinoma (ccRCC) remains a significant clinical challenge with poor 5‐year survival rates. A unique tissue cohort was assembled of matched ccRCC and distal nontumor tissues (n = 20) associated with moderate risk of disease progression, half of these from individuals who progressed to metastatic disease and the other half who remained disease free. These tissues were used for MALDI imaging MS profiling of proteins in the 2–20 kDa range, resulting in a panel of 108 proteins that had potential disease‐specific expression patterns. Protein lysates from the same tissues were analyzed by MS/MS, resulting in identification of 56 proteins of less than 20 kDa molecular weight. The same tissues were also used for global lipid profiling analysis by MALDI‐FT‐ICR MS. From the cumulative protein and lipid expression profile data, a refined panel of 26 proteins and 39 lipid species was identified that could either distinguish tumor from nontumor tissues, or tissues from recurrent disease progressors from nonrecurrent disease individuals. This approach has the potential to not only improve prognostic assessment and enhance postoperative surveillance, but also to inform on the underlying biology of ccRCC progression.

Background The utility of longitudinal, circumferential, and radial strain and strain rate in determining prognosis in chronic heart failure is not well established. Methods and Results In 416 patients with chronic systolic heart failure, we performed speckle‐tracking analyses of left ventricular longitudinal, circumferential, and radial strain and strain rate on archived echocardiography images (30 frames per second). Cox regression models were used to determine the associations between strain and strain rate and risk of all‐cause mortality, cardiac transplantation, and ventricular‐assist device placement. The area under the time‐dependent ROC curve ( AUC ) was also calculated at 1 year and 5 years. Over a maximum follow‐up of 8.9 years, there were 138 events (33.2%). In unadjusted models, all strain and strain rate parameters were associated with adverse outcomes ( P <0.001). In multivariable models, all parameters with the exception of radial strain rate ( P =0.11) remained independently associated, with patients in the lowest tertile of strain or strain rate parameter having a ≈2‐fold increased risk of adverse outcomes compared with the reference group ( P <0.05). Addition of strain to ejection fraction ( EF ) led to a significantly improved AUC at 1 year (0.697 versus 0.633, P =0.032) and 5 years (0.700 versus 0.638, P =0.001). In contrast, strain rate did not provide incremental prognostic value to EF alone. Conclusions Longitudinal and circumferential strain and strain rate, and radial strain are associated with chronic heart failure prognosis. Strain provides incremental value to EF in the prediction of adverse outcomes, and with additional study may be a clinically relevant prognostic tool.

AbstractBackgroundMortality rates in patients with bullous pemphigoid (BP) are higher than those in age‐matched counterparts. However, the specific causes of death in BP subjects have not been evaluated systematically.ObjectivesWe sought to characterize the causes of death in patients with BP as recorded by death certificate and to compare these with death data for age‐ and location‐matched control subjects.MethodsThis was a retrospective cohort analysis conducted in a large tertiary referral center. Twenty‐seven participants who had a confirmed antemortem diagnosis of BP, were residents of Olmsted County, Minnesota, and had died between January 1, 1999, and January 1, 2009, were included in the study. Underlying cause of death and multiple causes of death data for the study population were compared with data sourced from the Centers for Disease Control and Prevention (CDC) for a control group matched by age and geographic location of origin by International Classification of Diseases, 10th Revision (ICD‐10) block, and specific ICD‐10 codes.ResultsComparisons of specific ICD‐10 codes revealed increased rates of sepsis (P = 0.031), dementia (P = 0.049), and major depressive disorder (P = 0.005) in the study group. The collective incidence of ICD‐10 codes for infections indicated that infections were more frequent contributors to death in the study group (P = 0.035).ConclusionsClinicians should be mindful of contributors to death in patients with BP and might consider screening for mental health issues, educating patients on the early symptoms of sepsis, and minimizing risk factors for infection.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing—of expertise and/or funding—has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.