A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

Divergent Histopathological Networks of Frontotemporal Degeneration Proteinopathy Subytpes

Network analyses inform complex systems such as human brain connectivity, but this approach is seldom applied to gold-standard histopathology. Here, we use two complimentary computational approaches to model microscopic progression of the main subtypes of tauopathy versus TDP-43 proteinopathy in the human brain. Digital histopathology measures were obtained in up to 13 gray matter (GM) and adjacent white matter (WM) cortical brain regions sampled from 53 tauopathy and 66 TDP-43 proteinopathy autopsy patients. First, we constructed a weighted non-directed graph for each group, where nodes are defined as GM and WM regions sampled and edges in the graph are weighted using the group-level Pearson''s correlation coefficient for each pairwise node comparison. Additionally, we performed mediation analyses to test mediation effects of WM pathology between anterior frontotemporal and posterior parietal GM nodes. We find greater correlation (i.e., edges) between GM and WM node pairs in tauopathies compared with TDP-43 proteinopathies. Moreover, WM pathology strongly correlated with a graph metric of pathology spread (i.e., node-strength) in tauopathies (r = 0.60, p < 0.03) but not in TDP-43 proteinopathies (r = 0.03, p = 0.9). Finally, we found mediation effects for WM pathology on the association between anterior and posterior GM pathology in FTLD-Tau but not in FTLD-TDP. These data suggest distinct tau and TDP-43 proteinopathies may have divergent patterns of cellular propagation in GM and WM. More specifically, axonal spread may be more influential in FTLD-Tau progression. Network analyses of digital histopathological measurements can inform models of disease progression of cellular degeneration in the human brain.SIGNIFICANCE STATEMENT In this study, we uniquely perform two complimentary computational approaches to model and contrast microscopic disease progression between common frontotemporal lobar degeneration (FTLD) proteinopathy subtypes with similar clinical syndromes during life. Our models suggest white matter (WM) pathology influences cortical spread of disease in tauopathies that is less evident in TDP-43 proteinopathies. These data support the hypothesis that there are neuropathologic signatures of cellular degeneration within neurocognitive networks for specific protienopathies. These distinctive patterns of cellular pathology can guide future efforts to develop tissue-sensitive imaging and biological markers with diagnostic and prognostic utility for FTLD. Moreover, our novel computational approach can be used in future work to model various neurodegenerative disorders with mixed proteinopathy within the human brain connectome.     

Plasmacytoid variant urothelial bladder cancer: Is it time to update the treatment paradigm?

ObjectivesPlasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC.Materials and methodsA retrospective analysis of the Indiana University Bladder Cancer Database between January 2008 and June 2013 was performed comparing 30 patients with PCV UC at cystectomy to 278 patients with nonvariant (NV) UC at cystectomy who underwent surgery for muscle-invasive disease. Multivariable logistic regression was used to assess precystectomy variables associated with non–organ-confined disease at cystectomy and Cox regression analysis to assess variables associated with mortality.ResultsPatients with PCV UC who were diagnosed with a higher stage at cystectomy (73% pT3-4 vs. 40%, P = 0.001) were more likely to have lymph node involvement (70% vs. 25%, P<0.001), and positive surgical margins were found in 40% of patients with PCV UC vs. 10% of patients with NV UC (P<0.001). Median overall survival and disease-specific survival were 19 and 22 months for PCV, respectively. Median overall survival and disease-specific survival had not been reached for NV at 68 months (P<0.001). Presence of PCV UC on transurethral resection of bladder tumor was associated with non–organ-confined disease (odds ratio = 4.02; 95% CI: 1.06–15.22; P = 0.040), and PCV at cystectomy was associated with increased adjusted risk of mortality (hazard ratio = 2.1; 95% CI: 1.2–3.8; P = 0.016).ConclusionsPCV is an aggressive UC variant, predicting non–organ-confined disease and poor survival. Differentiating between non–muscle- and muscle-invasive disease in patients with PCV UC seems less important than the aggressive nature of this disease. Instead, any evidence of PCV on transurethral resection of bladder tumor may warrant aggressive therapy.     

Australasian general surgical training and emergency medical teams: a review

Emergency medical teams (EMTs) have provided surgical care in sudden‐onset disasters in low‐ and middle‐income countries. General surgeons have been heavily involved in many EMTs due to their traditional broad set of surgical skills and experience. With the increased subspecialization of general surgical training in many high‐income countries, including Australia and New Zealand, finding general surgeons with adequately broad experience is becoming more challenging. Furthermore, it is now considered standard for EMTs deploying to a sudden‐onset disaster to have undergone credentialing, demonstrating sufficient training of their deployed members. The purpose of this review was to highlight the challenges and potential solutions facing those involved in training and recruiting general surgeons for EMTs in Australasia.     

Radical Resection of Giant Congenital Melanocytic Nevus and Reconstruction With Meek-Graft Covered Integra Dermal Template

BACKGROUND: Giant congenital melanocytic nevi represent a surgical challenge, particularly in cases in which the size of the nevus exceeds certain extend and malignant transformations have to be considered. OBJECTIVE: To discuss through case report considerable surgical options when extensive giant congenital melanocytic nevi with malignant transformation are encountered. METHODS: We present an unusual case of a giant congenital melanocytic nevi of the entire back of a 44-year-old patient. To achieve radical resection with direct appropriate wound closure and acceptable outcome, the integument of the entire back was excised and covered with Integra, followed by split-thickness skin grafting after stable integration of the matrix. RESULTS: The approach resulted in a complete excision of the tumor and acceptable cosmetic and excellent biomechanical outcome. CONCLUSION: The introduced practice demonstrates a useful alternative to established methods, particularly if tumor excision in large areas and subsequent wound closure might be achieved in one procedure.     

Sexual satisfaction of women partners of circumcised men in a randomized trial of male circumcision in Rakai,Uganda

OBJECTIVE

To investigate the effect of adult medical male circumcision on female sexual satisfaction.

SUBJECTS AND METHODS

We investigated self‐reported sexual satisfaction among 455 women partners of men circumcised in a randomized trial of male circumcision for the prevention of human immunodeficiency virus in Rakai, Uganda. Women aged 15–49 years were interviewed about their sexual satisfaction before and after their partners were circumcised. We analysed female‐reported changes in sexual satisfaction using chi‐square or Fisher’s exact tests.

RESULTS

Only 2.9% (13/455) of women reported less sexual satisfaction after their partners were circumcised; 57.3% (255/455) reported no change in sexual satisfaction and 39.8% (177/455) reported an improvement in sexual satisfaction after their partner’s circumcision. There were no statistically significant differences in sexual satisfaction before and after partner’s circumcision by age, religion and education status.

CONCLUSION

The overwhelming majority of women (97.1%) report either no change or improved sexual satisfaction after their male partner was circumcised. These findings suggest that male circumcision has no deleterious effect on female sexual satisfaction.     

How long should you wait for a chest radiograph after placing a chest tube on water seal? A prospective study

OBJECTIVE: The purpose of this study was to determine the optimal time interval for identifying a pneumothorax (PTX) on chest radiograph (CXR) after placing a chest tube on water seal. METHODS: One hundred nineteen chest tubes were placed on water seal according to a prospective, observational study protocol. After water seal, both an early (3.1 +/- 2.1 hours) and a late (17.6 +/- 8.0 hours) CXR was obtained. RESULTS: Thirty-one patients had a PTX on follow-up CXRs. There were 22 early and 9 late PTXs identified. Three patients in the early group had a clinically significant PTX or an increase in the size of PTX on follow-up CXR. None of the patients in the late group had a clinically significant PTX (any worsening of their PTX) or required further intervention. CONCLUSION: A normal chest radiograph obtained 3 hours after placing a chest tube on water seal effectively excludes development of a clinically significant pneumothorax.