Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma.

Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA.

The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra-spinal paraganglioma.

Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated 17 CEPs from 11 male and 6 female patients with a median age of 38 years (range 21-82), none with a family history of neuroendocrine neoplasia. Six of the 17 tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all 17 CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on 12 of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors.

Accuracy of the NSQIP risk calculator for predicting complications following adrenalectomy.

PURPOSE: Adrenalectomy is performed to treat functional pathology and remove tumors of malignant concern. The National Surgical Quality Improvement Program (NSQIP) risk calculator predicts 30-day complications and length of stay following index surgical procedures. We assess whether this tool accurately predicts complications following adrenalectomy procedures at a tertiary care academic medical center. METHODS: A retrospective review was performed for all adrenalectomies at a single institution from 2004 to 2016. 197 patients underwent adrenalectomy without concurrent resections. Predicted risk for NSQIP complications was calculated for each patient. The mean predicted and observed risks (%) at 30 days across all patients within each category were determined, and these were compared with two-sided one-sample t tests. RESULTS: Of 197 adrenalectomies, 180 were laparoscopic and 17 were open. For laparoscopic adrenalectomy, ten (5.5%) complications were observed including nine (5%) graded Clavien III or greater. All observed complication rates were significantly different than predicted (p values for all < 0.005). Mean observed length of stay was also significantly less than predicted (1.6 versus 2.1 days, p < 0.001). In the open adrenalectomy subgroup, there were no observed complications with observed mean length of stay equivalent to predicted (5.8 versus 5.3, p = 0.08) without a higher readmission rate (5.9 versus 6.0%). CONCLUSIONS: Statistical differences were noted between the actual complication rates of adrenalectomy versus those predicted by the NSQIP calculator. Certain observed differences may not necessarily have clinical significance. Urology procedure-specific calculators may better refine predictions for sub-specialty procedures with future work requisite to determine performance across all practice settings.

Computed Tomography Imaging Characteristics of Histologically Confirmed Papillary Renal Cell Carcinoma-Implications for Ancillary Imaging.

Low-attenuation renal lesions on non-contrast computed tomography (CT) are often considered to be benign cysts without need for further imaging. However, the papillary subtype of renal cell carcinoma (RCC) may have similar radiographic characteristics. A single-center retrospective review was therefore performed to identify extirpated papillary RCC (pRCC) specimens with correlation made to preoperative tumor imaging characteristics. A total of 108 pRCC specimens were identified of which 84 (27 type I, 17 type 2, 40 unspecified) had CT imaging available for review. Non-contrast CT was available for 73 tumors with 16 (22%) demonstrating Hounsfield units (HU) measurements fewer than 20 at baseline without differences between papillary subtypes. Mean attenuation following contrast administration was similar between papillary subtypes (45 HU for type 1 pRCC and 49 HU for type 2). This study highlights that pathologically proven pRCC is a heterogeneous entity in terms of density on preoperative CT imaging. A non-contrast CT scan with HU fewer than 20 may not be an adequate evaluation for incidental renal masses, as over 1 in 5 pRCCs demonstrate lower attenuation than this cutoff. Further study is needed to identify the appropriate role of ancillary imaging in the workup of seemingly benign-appearing renal lesions.

Postoperative Outcomes Associated With Neuraxial vs General Anesthesia Following Bilateral Total Knee Arthroplasty.

BACKGROUND: There is sparse evidence on the benefit of neuraxial (NA) vs general anesthesia (GA) as the primary anesthetic in postoperative outcomes following bilateral total knee arthroplasty. We sought to elucidate differences in outcomes in this surgical population using a national database. METHODS: We used data from the National Surgical Quality Improvement Program from 2007 to 2013 and compared rates of various postoperative outcomes in propensity-matched cohorts (NA vs GA). RESULTS: After exclusion, there were 1957 patients included in the final analysis, of which 26% received NA as the primary anesthetic. Propensity-matched cohorts were generated to ensure no differences in various comorbidities (including bleeding disorders or inadequate cessation of anticoagulation therapy), case duration, and patient demographics between both cohorts. Among the matched cohorts, there were no differences in preoperative platelet count, hematocrit, or international normalized ratio. NA was associated with decreased blood transfusion requirement and decreased total number of units of blood products transfused (P < .0001 for both outcomes). However, there were no differences in other outcomes, including hospital length of stay, pulmonary embolism, deep vein thrombosis, or urinary tract infections. CONCLUSION: Our study demonstrates that in matched cohorts, NA is associated with decreased blood transfusion requirements in patients undergoing bilateral total knee arthroplasty when compared to GA as the primary anesthetic.

High Incidence of Undiagnosed Cervical Myelopathy in Patients With Hip Fracture Compared With Controls.

OBJECTIVES: To identify the incidence of undiagnosed cervical myelopathy in patients who fall and develop hip fractures compared with age-matched controls. DESIGN: Prospective, case-control study. SETTING: University level 1 Trauma Center. PATIENTS/PARTICIPANTS: Consecutive patients who presented with hip fractures after a fall. A total of 159 patients were screened; 66 patients (38 arthroplasty, 28 fracture) were eligible for enrollment in the study. Exclusion criteria included cognitive impairment, known diagnosis of cervical myelopathy, previous cervical spine surgery, inability to comply with examination, or refusal to participate. The control group was age-matched elderly patients who underwent total hip arthroplasty (THA). INTERVENTION: Patient interview and physical examination for cervical myelopathy. MAIN OUTCOME MEASUREMENTS: Myelopathy was diagnosed by clinical history elements (Japanese Orthopaedic Association score ≤15) and pathologic reflexes. Comparison of the incidence of myelopathy in the study population with the control population was performed using Fisher exact test. RESULTS: There were no statistically significant differences between the fracture and THA groups in mean patient age or male/female ratio. There was a statistically significant increased incidence of myelopathy in hip fracture patients (18%) compared with the THA group (0%, P = 0.01). CONCLUSIONS: Hip fracture is a complex multifactorial process, and most patients (60%) were excluded due to known cognitive impairment. However, 18% of previously undiagnosed patients who were cognitively intact manifested clinical findings consistent with cervical spondylotic myelopathy. Consideration should be given to screening for undiagnosed myelopathy among patients with hip fracture to reduce the risk of subsequent fractures. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The influence of semantic processing on odor identification ability in schizophrenia.

Despite the well-documented observation of odor identification deficits in schizophrenia, less is known about where the disruption in the process of correctly identifying an odor occurs. This study aimed to determine the potential moderating effects of semantic processing on the observed olfactory dysfunction in schizophrenia. Schizophrenia patients and healthy comparison subjects completed two versions of the University of Pennsylvania Smell Identification Test (UPSIT): an uncued free-response version and the standard multiple-choice paradigm, as well as three semantic measures: The Boston Naming Test, Animal Naming, and Pyramids and Palm Tree Test. Schizophrenia patients yielded significantly lower scores than the comparison group on the standard UPSIT and on semantic measures. No relationship was observed between olfactory and semantic task performance in patients. These data suggest that odor identification deficits may not be primarily due to semantic processing deficits in schizophrenia.

Facial emotion perception in schizophrenia: a meta-analytic review.

OBJECTIVES: A considerable body of literature has reported on emotion perception deficits and the relevance to clinical symptoms and social functioning in schizophrenia. Studies published between 1970-2007 were examined regarding emotion perception abilities between patient and control groups and potential methodological, demographic, and clinical moderators. DATA SOURCES AND REVIEW: Eighty-six studies were identified through a computerized literature search of the MEDLINE, PsychINFO, and PubMed databases. A quality of reporting of meta-analysis standard was followed in the extraction of relevant studies and data. Data on emotion perception, methodology, demographic and clinical characteristics, and antipsychotic medication status were compiled and analyzed using Comprehensive Meta-analysis Version 2.0 (Borenstein M, Hedges L, Higgins J and Rothstein H. Comprehensive Meta-analysis. 2. Englewood, NJ: Biostat; 2005). RESULTS: The meta-analysis revealed a large deficit in emotion perception in schizophrenia, irrespective of task type, and several factors that moderated the observed impairment. Illness-related factors included current hospitalization and--in part--clinical symptoms and antipsychotic treatment. Demographic factors included patient age and gender in controls but not race. CONCLUSION: Emotion perception impairment in schizophrenia represents a robust finding in schizophrenia that appears to be moderated by certain clinical and demographic factors. Future directions for research on emotion perception are discussed.

Plasmodium vivax-associated acute respiratory distress syndrome after extended travel in Afghanistan.

A 21-year-old soldier developed anorexia, vomiting, diarrhea and fever 10 days after returning to the United States from an 8-month deployment in Afghanistan. His symptoms persisted over the next 5 days until he presented in respiratory failure with a partial pressure oxygen: concentration of inspired oxygen (PaO(2):FiO(2)) ratio of 63, requiring urgent intubation and ventilator support. Chest roentgenogram revealed diffuse bilateral alveolar opacities consistent with acute respiratory distress syndrome. Although sputum and blood cultures did not reveal a causative agent, Giemsa-stained blood smears were positive for Plasmodium vivax alone, which was later confirmed by small subunit ribosomal RNA polymerase chain reaction amplification. After a tenuous course marked by splenic rupture and prolonged requirement for ventilator support, the patient ultimately recovered. Although generally considered benign, this and other recent reports of vivax malaria-associated lung injury emphasize the need for persistent pursuit of the diagnosis in febrile travelers returning from vivax endemic locations as well as aggressive monitoring for and management of life-threatening complications.