Multiple Anatomical Locations Research Articles

Solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare tumor of mesenchymal origin that account for less than 2% of all soft tissue masses. Initially identified in the pleura, SFT has been identified in multiple anatomic locations and can arise anywhere in the body. The varying histologic features along with non-specific means of identification have led SFT to be associated with several different names. Over the last several decades, sustained advances through research and technology have led to more reliable methods for differentiating this distinct soft tissue tumor. Advances specifically in immunohistochemistry and molecular diagnostics have identified CD34 as the most consistent marker in SFT, however even this lacks specificity to conclusively narrow down the broad differential for exact identification. More recently the discovery of the NAB2-STAT6 fusion gene has led to more precise diagnosis of SFT. Like many other soft tissue tumors, surgical management is the mainstay of treatment for SFT with emphasis on obtaining tumor-negative margins. Radiation therapy and chemotherapy regimens have not demonstrated global effectiveness, and thus no standardized treatments have been identified. Given the rarity of SFT and current supportive evidence for therapies, management should be focused on tumor extirpation. Nonetheless, individualized therapy, determined within a multidisciplinary setting should be considered.

The association of epileptic focus estimated by magnetoencephalography with cognitive function in non-lesional epilepsy with continuous spikes and waves during slow wave sleep (ECSWS) children

ObjectiveEpilepsy with continuous spikes and waves during slow sleep (ECSWS) is associated with cognitive deficits. The underlying mechanism is thought to relate to disturbance of functions of the foci by the persistent epileptic activity. However, the relationship between epileptic foci and cognitive deficits remains largely unknown, except for in Landau–Kleffner syndrome. The aim of this study was to evaluate the relationship of epileptic foci estimated from magnetoencephalography (MEG) with cognitive functions at the period of diagnosis in non-lesional ECSWS children, excluding those with Landau–Kleffner syndrome. MethodsMEG data and the Wechsler intelligence scale for children-III scores at ECSWS diagnosis, and medical records, were reviewed. Multiple regression analysis was performed to examine the relationship of parameters of MEG spike dipole clusters, including anatomical location or laterality, with the Wechsler intelligence scale for children-III scores at ECSWS diagnosis. ResultsSixteen patients were included, all of whom were right-handed. Epilepsy onset (first unprovoked seizure) ranged from 31 to 110 months (mean, 68.5). The age at ECSWS diagnosis ranged from 72 to 156 months (mean, 108.9). The dipole clusters were estimated on the right Rolandic area (RA) in 4 patients (25%), right supramarginal gyrus (SMG) in 3 (19%), left RA in 2 (13%), left SMG in 2 (13%), bilateral RA in 3 (19%), multiple anatomical locations in 2 (13%). The age at epilepsy onset had the strongest prognostic effect, and full-scale intelligence quotient was relatively less-affected if the cluster was found on the SMG (β = 14.7, p = 0.031). Cases with only a right side cluster exhibited reduced impairment of perceptual organization compared with those with only a left side cluster or bilateral clusters (β = 17.48, p = 0.02). In 12 patients, long-term intellectual prognosis was evaluated, and was associated with intellectual level at the period of ECSWS diagnosis. ConclusionIn non-lesional ECSWS, the relationship between epileptic focus and cognitive deficits differs from that observed in adults. Rather, it is similar to epilepsies associated with congenital or early infantile brain insults, in that the left epileptic foci in right-handed patients were associated with lower non-verbal functions. Future studies are required to determine the role of plasticity of the immature brain in driving these differences.

Loss-of-function mutations in ATP6AP1 and ATP6AP2 in granular cell tumors

Granular cell tumors (GCTs) are rare tumors that can arise in multiple anatomical locations, and are characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs are currently unknown. Here, we apply whole-exome sequencing and targeted sequencing analysis to reveal mutually exclusive, clonal, inactivating somatic mutations in the endosomal pH regulators ATP6AP1 or ATP6AP2 in 72% of GCTs. Silencing of these genes in vitro results in impaired vesicle acidification, redistribution of endosomal compartments, and accumulation of intracytoplasmic granules, recapitulating the cardinal phenotypic characteristics of GCTs and providing a novel genotypic–phenotypic correlation. In addition, depletion of ATP6AP1 or ATP6AP2 results in the acquisition of oncogenic properties. Our results demonstrate that inactivating mutations of ATP6AP1 and ATP6AP2 are likely oncogenic drivers of GCTs and underpin the genesis of the intracytoplasmic granules that characterize them, providing a genetic link between endosomal pH regulation and tumorigenesis.

Efficacy of recombinant human C1 esterase inhibitor across anatomic locations in acute hereditary angioedema attacks.

Hereditary angioedema (HAE) may occur at or spread to multiple anatomic locations during an acute attack. Recombinant human C1 esterase inhibitor (rhC1-INH) is approved for treating acute HAE attacks. To examine the time to the beginning of symptom relief with rhC1-INH by attack location. Data for patients ≥12 years of age with an acute HAE attack who received rhC1-INH 50 IU/kg or placebo were pooled from two double-blind clinical trials with open-label extensions. The time to the beginning of symptom relief was defined as the first time point that the visual analog scale severity score at an attack location decreased by ≥20 mm versus baseline, with persistence. Data were reported as median time values (95% confidence interval [CI]). For abdominal attacks, the median time to the beginning of symptom relief was 60.0 minutes (95% CI, 47.0-62.0 minutes; n = 194 attacks) with rhC1-INH versus 240.0 minutes (95% CI, 45.0-720.0 minutes; n = 15 attacks) with placebo. The median time to the beginning of symptom relief for peripheral attacks was 105.0 minutes (95% CI, 90.0-120.0 minutes; n = 169 attacks) with rhC1-INH versus 303.0 minutes (95% CI, 180.0-720.0 minutes; n = 17 attacks) with placebo. For oro-facial-pharyngeal-laryngeal attacks or urogenital attacks, the median time to the beginning of symptom relief with rhC1-INH was 64.5 minutes (95% CI, 60.0-120.0 minutes; n = 36 attacks) and 119.0 minutes (95% CI, 40.0-270.0 minutes; n = 13 attacks), respectively, versus 306.0 minutes (95% CI, 30.0-495.0 minutes; n = 6 attacks) and 320.0 minutes (n = 1 attack) with placebo. In shortening the median time to the beginning of symptom relief of acute HAE attacks, rhC1-INH 50 IU/kg was efficacious, regardless of attack location.

Normal pancreatic parenchymal thickness by CT in healthy children.

Chronic pancreatitis is increasingly recognized in the pediatric population. Atrophy is an important, but qualitative, finding of chronic pancreatitis. To transition to a quantitative measure that can specifically define atrophy requires knowledge of normal pancreatic parenchymal bulk in children. The purpose of this study was to define normal pancreatic thickness (linear measurements) at multiple anatomic locations in the pancreas of healthy children. This was an Institutional Review Board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study. Three reviewers measured the thickness of the pancreas at four locations (head, neck, body, tail) on computed tomography (CT) examinations performed with intravenous contrast in children without a history of pancreatic disease. Measurements were made on 140 examinations, evenly distributed among 7 age groups (3-16.99years) with 10 males and 10 females in each group. Agreement and bias between reviewers were assessed by intra-class correlation coefficients (ICC) and Bland-Altman analyses. Correlation with age, height and weight were assessed with Spearman's rho (ρ). The mean (for 3 readers) thicknesses of the head, neck, body and tail were 1.3-2cm, 0.7-1cm, 0.9-1.6cm and 1-1.6cm, respectively, depending on patient age. Measurement agreement between reviewers was fair to good (ICC: 0.52-0.7). Bias between reviewers ranged from 0 to 3mm. Pancreatic thickness was weakly to moderately correlated with age (ρ=0.39-0.52), height (ρ=0.44-0.61) and weight (ρ=0.51-0.64). We have defined normal ranges for thickness of the pancreas at four locations, and have shown that these measurements depend on patient age and size. These data may be useful to more objectively define pancreatic atrophy in children with suspected pancreatic disease.

Moving beyond “complete surgical resection” and “optimal”: Is low-volume residual disease another option for primary debulking surgery?

ObjectivesTo examine the relationship between volume of residual disease and oncologic outcomes among patients with advanced-stage epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing primary debulking surgery (PDS). For patients that did not undergo a complete surgical resection (CSR), a surrogate for volume of residual disease was used to assess oncologic outcomes. MethodsMedical records of patients with FIGO stage IIIC and IV epithelial ovarian/fallopian tube/primary peritoneal carcinoma undergoing PDS between January 2010 and November 2014 were reviewed. Patient demographics, operative characteristics, residual disease, anatomic site of residual disease and outcome data were collected. Among patients who did not undergo CSR, but had ≤1 cm of residual disease, the number of anatomic sites (single location vs. multiple locations) with residual disease was utilized as a surrogate for volume of residual disease. The effect of residual disease volume on progression-free survival (PFS) and overall survival (OS) was evaluated. ResultsOf 240 patients undergoing PDS, 94 (39.2%) had CSR, 41 (17.1%) had ≤1 cm of residual disease confined to a single anatomic location (≤1 cm-SL), 67 (27.9%) had ≤1 cm of residual disease in multiple anatomic locations (≤1 cm-ML) and 38 (15.8%) were sub-optimally (SO) debulked. Median PFS for CSR, ≤1 cm-SL, ≤1 cm-ML and SO-debulked were: 23, 19, 13 and 10 months, respectively (p < 0.001). Median OS for CSR, ≤1 cm-SL, ≤1 cm-ML and SO-debulked were: Not yet reached, 64, 50 and 49 months, respectively (p = 0.001). ConclusionsFollowing PDS, CSR and ≤ 1 cm-SL patients have the best prognosis. In contrast, despite being considered “optimally debulked”, ≤1 cm-ML patients have survival similar to those SO-debulked.

The Ability to Reproducibly Record Cardiac Action Potentials From Multiple Anatomic Locations: Endocardially and Epicardially, In Situ and In Vitro.

For cardiac arrhythmia mapping and ablation procedures, the ability to record focal cardiac action potentials could aid in precisely identifying lesions, scarred tissue, and/or arrhythmic foci. Our study objective was to validate the electrophysiologic properties of a routinely employed large mammalian in vitro working heart model. Monophasic action potentials (MAPs) were recorded from 18 swine hearts during viable hemodynamic function both in situ (postmedian sternotomy) and in vitro (using Visible Heart methodologies). We placed specially designed mapping catheters in epicardial and endocardial locations. High-quality MAP signals were recorded for up to 2h, and MATLAB was utilized to evaluate relative duration and temporal/regional changes in waveform morphology. MAPs were reproducibly recorded from both epicardial and endocardial locations in situ and in vitro. No significant differences were noted in right atrial endocardial, right ventricular endocardial, right ventricular epicardial, or left atrial epicardial waveforms, when baseline recordings were compared to all other in situ and in vitro time points. Furthermore, MAP duration between right ventricular endocardial and epicardial waveforms was not significantly different, in situ or in vitro. The use of in vitro models like the Visible Heart is considered invaluable for the study of cardiac arrhythmias, the development of novel therapies, and/or preclinical testing of future cardiac mapping catheters and systems. Preclinical studies assessing in situ and/or in vitro recorded cardiac monophasic action potentials could be critical for the future development and validation of cardiac devices.

A foldable electrode array for 3D recording of deep-seated abnormal brain cavities

Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

Pulmonary artery imaging under free-breathing using golden-angle radial bSSFP MRI: a proof of concept.

To evaluate the feasibility of an improved motion and flow robust methodology for imaging the pulmonary vasculature using non-contrast-enhanced, free-breathing, golden-angle radial MRI. Healthy volunteers (n = 10, age 46 ± 11 years, 50% female) and patients (n = 2, ages 27 and 84, both female) were imaged at 1.5 T using a Cartesian and golden-angle radial 2D balanced SSFP pulse sequence. The acquisitions were made under free breathing without contrast agent enhancement. The radial acquisitions were reconstructed at 3 temporal footprints. All series were scored from 1 to 5 for perceived diagnostic quality, artifact level, and vessel sharpness in multiple anatomical locations. In addition, vessel sharpness and blood-to-blood clot contrast were measured. Quantitative measurements showed higher vessel sharpness for golden-angle radial (n = 76, 0.79 ± 0.11 versus 0.71 ± 0.16, p < .05). Blood-to-blood clot contrast was found to be 23% higher in golden-angle radial in the 2 patients. At comparable temporal footprints, golden-angle radial was scored higher for diagnostic quality (mean ± SD, 2.3 ± 0.7 versus 2.2 ± 0.6, p < .01) and vessel sharpness (2.2 ± 0.8 versus 2.1 ± 0.5, p < .01), whereas the artifact level did not differ (3.0 ± 0.9 versus 3.0 ± 1.0, p = .80). The ability to retrospectively choose a temporal resolution and perform sliding-window reconstructions was demonstrated in patients. In pulmonary artery imaging, the motion and flow robustness of a radial trajectory does both improve image quality over Cartesian trajectory in healthy volunteers, and allows for flexible selection of temporal footprints and the ability to perform real-time sliding window reconstructions, which could potentially provide further diagnostic insight.

Insights into the Impact of CD8+ Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression.

A thorough understanding of the role of human immunodeficiency virus (HIV) intrahost evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8+ lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to clinical manifestations similar to those for HIV-1 infection and AIDS progression, as well as a characteristic rapid disease onset. Comparison of this model with SIV-infected non-CD8+ lymphocyte-depleted macaques also provides a unique opportunity to investigate the role of CD8+ cells in viral evolution and population dynamics throughout the duration of infection. Using several different phylogenetic methods, we analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from SIVmac251-infected macaques with or without CD8+ lymphocyte depletion. SIV evolutionary and selection patterns in non-CD8+ lymphocyte-depleted animals were characterized by sequential population turnover and continual viral adaptation, a scenario readily comparable to intrahost evolutionary patterns during human HIV infection in the absence of antiretroviral therapy. Alternatively, animals that were depleted of CD8+ lymphocytes exhibited greater variation in population dynamics among tissues and cell populations over the course of infection. Our findings highlight the major role for CD8+ lymphocytes in prolonging disease progression through continual control of SIV subpopulations from various anatomical compartments and the potential for greater independent viral evolutionary behavior among these compartments in response to immune modulation.IMPORTANCE Although developments in combined antiretroviral therapy (cART) strategies have successfully prolonged the time to AIDS onset in HIV-1-infected individuals, a functional cure has yet to be found. Improvement of drug interventions for a virus that is able to infect a wide range of tissues and cell types requires a thorough understanding of viral adaptation and infection dynamics within this target milieu. Although it is difficult to accomplish in the human host, longitudinal sampling of multiple anatomical locations is readily accessible in the SIV-infected macaque models of neuro-AIDS. The significance of our research is in identifying the impact of immune modulation, through differing immune selective pressures, on viral evolutionary behavior in a multitude of anatomical compartments. The results provide evidence encouraging the development of a more sophisticated model that considers a network of individual viral subpopulations within the host, with differing infection and transmission dynamics, which is necessary for more effective treatment strategies.

Urine test for EGFR analysis in patients with non-small cell lung cancer.

Precision medicine approaches in oncology are reliant on the accurate genomic characterization of tumors. While tissue remains the mainstay specimen for molecular testing, tumor biopsies are riddled with challenges and limitations due to their invasive and site-specific nature. Tumor inaccessibility and intratumoral heterogeneity, in particular, represent significant obstacles to the identification of actionable genetic alterations and hence effective mono- and combination therapy strategies. Proof-of-concept studies indicate that circulating tumor DNA (ctDNA) released from multiple tumor regions and anatomical locations is more reflective of intra- and intertumoral heterogeneity. Non-invasive liquid biopsy approaches that allow for the analysis of ctDNA are thus being increasingly implemented in routine patient care for the detection and monitoring of cancer-associated mutations. Indeed, the use of plasma testing to screen for epidermal growth factor receptor (EGFR) T790M mutant positive non-small cell lung cancer (NSCLC) patients eligible for treatment with third-generation EGFR inhibitors was recently approved by the U.S. Food and Drug Administration and is incorporated into the most recent version of the National Comprehensive Cancer Center guidelines as an alternative to tissue biopsy. Urine represents another liquid biopsy specimen that is distinguished by its ease of collection, option for home collection, and lack of temporal and volumetric collection restrictions. Importantly, there is an accumulating body of evidence supporting the clinical validity of urinary EGFR mutant testing for the identification and stratification of patients likely to benefit from EGFR-directed therapies and as a means to assess patient response, the presence of residual disease, and emergence of resistant tumor cell populations.

350EMF Naltrexone as an Antidote to Prevent Delayed Neuropsychological Disabilities from Acute Poisoning With the Sarin Analogue Diisopropyl-fluorophosphate

To determine the mechanism of persistent neuropsychological disabilities seen in rats poisoned with the sarin analogue diisopropyl-fluorophosphate (DFP) and rescued with atropine and pralidoxime by identifying the biochemical targets and distribution of DFP in brain. A randomized controlled trial was conducted. Rats were randomized to receive DFP 5 mg/kg or vehicle by subcutaneous injection. Toxicity from DFP was treated with atropine and pralidoxime. Rats were then randomized to receive naltrexone or vehicle daily. Rats underwent behavioral testing using the Morris Water Maze and eye blink test. Brains were harvested and sectioned into multiple anatomical locations. Chromatography was performed to determine sites of naltrexone binding in the brains. The results of maze testing, eye blink determination, and chromatography was compared using T tests and ANOVA. IACUC approval was obtained. Toxicity from two prior experiments using DFP 5 mg/kg were not reproduced. Compared to prior experiments, one batch of DFP had inadequate potency while another was too toxic. The supplier admitted that they had no quality control for DFP and no chemical analysis. The protocol was amended to allow a dose ranging experiment for DFP. This problem delayed obtaining the results. We are now on track to have data to present at the 2017 ACEP Research Forum. The supplier cannot be counted on to supply DFP with consistent toxicity. Final conclusions are pending.

Human papillomavirus dysregulates the cellular apparatus controlling the methylation status of H3K27 in different human cancers to consistently alter gene expression regardless of tissue of origin.

High-risk human papillomaviruses (HPV) cause cancer at multiple distinct anatomical locations. Regardless of the tissue of origin, most HPV positive (HPV+) cancers show highly upregulated expression of the p16 product of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. Paradoxically, HPV+ tumor cells require continuous expression of this tumor suppressor for survival. Thus, restoration of normal p16 regulation has potential therapeutic value against HPV induced cancers. Normally, p16 transcription is tightly controlled at the epigenetic level via polycomb repressive complex-mediated tri-methylation of histone 3 lysine 27 (H3K27me3). Although a mechanism by which HPV induces p16 has been proposed based on tissue culture models, it has not been extensively validated in human tumors. In this study, we used data from over 800 human cervical and head and neck tumors from The Cancer Genome Atlas (TCGA) to test this model. We determined the impact of HPV status on expression from the CDKN2A locus, the adjacent CDKN2B locus, and transcript levels of key epigenetic regulators of these loci. As expected, HPV+ tumors from both anatomical sites exhibited high levels of p16. Furthermore, HPV+ tumors expressed higher levels of KDM6A, which demethylates H3K27me3. CpG methylation of the CDKN2A locus was also consistently altered in HPV+ tumors. This data validates previous tissue culture studies and identifies remarkable similarities between the effects of HPV on gene expression and DNA methylation in both cervical and oral tumors in large human cohorts. Furthermore, these results support a model whereby HPV-mediated dysregulation of CDKN2A transcription requires KDM6A, a potentially druggable target.

Inflammatory myofibroblastic tumor of the lumbar spinal canal

Rationale:Inflammatory myofibroblastic tumor (IMT) is a rare type of mesenchymal tumor. IMT can arise in multiple anatomic locations. IMT of the lumbar spinal canal is exceptionally rare.Patient concerns:Here, we report the case of a 56-year-old male patient with an IMT who was in good health until 1 year prior to admission, when he began experiencing pain in both lower extremities and the lower back.Interventions:A space-occupying lesion in the lumbar canal was identified by magnetic resonance imaging and then surgically resected.Diagnoses:Histopathological analysis of the lesion revealed a composition of mucous edema, inflammatory cells, collagenous fibers, and spindle cells that were diffuse and positive for smooth muscle actin and CD68; focal positive for vimentin and desmin; and negative for CD34 (marker of vascular endothelial cells), CD21, CD23, CD35, S-100, Epstein–Barr virus infection, Ki-67, and anaplastic lymphoma kinase. Thus, the diagnosis was an IMT of the lumbar canal.Outcomes:In the spinal canal, IMT should be considered in the evaluation of tumors although it is a very rare diagnosis. It is a benign lesion, but it has potential for invasion and recurrence.Lessons:There are no characteristic imaging features of these tumors, but they can be addressed by complete surgical excision. Patients with these lesions should undergo frequent long-term follow-up to detect and address recurrence.

Identification of antigen-specific, lung resident memory B cells after influenza infection

Abstract B cells display phenotypic and functional heterogeneity in multiple anatomical locations following vaccination or infection. Influenza-specific memory B cells (Flu+BMEM cells) are found in both lymphoid tissues and lung. It is unclear whether these cells represent circulating or resident memory B cell (BRM) populations. We hypothesized that a portion of the Flu+BMEM cell population in the lung would be non-circulating, BRMs. To determine whether Flu+BMEM cells in the lung are circulating or resident, we parabiotically joined previously-infected, congenically-mismatched mice for 2 weeks and marked those cells currently in circulation by infusing anti-B220 and identified those that have trafficked between the partners by their expression of the CD45 congenic marker. The lungs of these mice had large populations of hemagglutinin and nucleoprotein -specific BMEM cells that did not attain equilibrium within 2 weeks of parabiosis, suggesting that they are non-circulating. The Flu+ BRMs in the lungs consisted of 56% IgM+ and 43.9% isotype-switched BRMs. They were established as early as 15 days after infection and maintained for at least 60 days. The formation of Flu+ BRMs required the germinal center (GC), as blocking CD40L with MR1 antibody, during the primary infection abrogated BRM. However, MR1-treatment of mice with established BRM did not affect BRMs in the lung, even though Flu+ GC B cells could be detected in the LN for up to 90 days. These data suggest that GC-dependent lung-BRMs are established early after infection and maintained independently of GCs. These findings are important in the development of vaccines that elicit BRMs and they will provide mechanistic information into the function of Ag+BMEM cells residing in the mucosa.

Non-ossifying fibromas: Case series, including in uncommon upper extremity sites.

AIMTo investigate non-ossifying fibromas (NOFs) common fibrous bone lesions in children that occur in bones of the lower extremities.METHODSWe analyzed 44 cases of NOF including 47 lesions, which were referred with a working diagnosis of neoplastic lesions. Lesions were located in the upper extremities (1 proximal humerus, 1 distal radius) and the lower extremities (25 distal femurs, 12 proximal and 4 distal tibias, and 4 proximal fibulas).RESULTSThree cases had NOFs in multiple anatomical locations (femur and fibula in 1 case, femur and tibia in 2 cases). Overall, larger lesions > 4 cm and lesion expansion at the cortex were seen in 21% and 32% of cases, respectively. Multiple lesions with bilateral symmetry in the lower extremities suggest that these NOFs were developmental bone defects. Two patients suffered from fracture and were treated without surgery, one in the radius and one in the femur. Lesions in the upper extremities (i.e., humerus of a 4-year-old female and radius of a 9-year-old male) expanded at the cortex and lesion size increased with slow ossification.CONCLUSIONNOFs in the lower extremity had fewer clinical problems, regardless of their size and expansiveness. In these two upper extremity cases, the NOFs had aggressive biological features. It seems that there is a site specific difference, especially between the upper extremity and the lower extremity. Furthermore, NOFs in the radius are predisposed to fracture because of the slender structure of the radius and the susceptibility to stress.

Characteristics and outcome of recurrence in molecularly defined adult-type ovarian granulosa cell tumors

ObjectiveAdult-type ovarian granulosa cell tumors (AGCTs) have an unpredictable tendency to relapse. In a carefully validated patient cohort, we evaluated the prognostic factors related to AGCT recurrence. MethodsWe identified all patients diagnosed with AGCT during 1956–2014 in Helsinki University Hospital, with a minimum follow-up of one year (n=240). After a histological review supplemented with FOXL2 (402C-G) mutation status analysis, we analyzed the clinical data for association with relapse. ResultsThe final cohort included 164 (68%) molecularly defined AGCTs (MD-AGCTs). The majority of the women were postmenopausal (63%), and 92% of tumors were stage I. The median follow-up time was 15.5years. Fifty-two (32%) patients developed tumor recurrence, of whom 55% had successive recurrences. Multiple-site recurrences were common, and nearly half of the recurrences were asymptomatic. The median time to the first relapse was 7.4years, and 75% of relapses occurred within ten years after primary diagnosis. The median disease-free survival was 11.3years. Premenopausal status at initial diagnosis, FIGO stage Ic versus Ia, and tumor rupture associated with relapse. However, tumor rupture was the only independent predictive factor. Of the relapsed patients, 48% died of AGCT in a median time of 15.3years. ConclusionTumor rupture is the strongest predictive factor for recurrence, and these patients might benefit from a more aggressive initial treatment approach. AGCT requires active follow up for 10 to 15years after primary diagnosis, since recurrences may develop late, asymptomatically and in multiple anatomical locations.

The Operative Burden of General Surgical Disease and Non-Battle Injury in a Deployed Military Treatment Facility in Afghanistan.

Contemporary medical operations support a mobile, nonconventional force involved in nation building, counterinsurgency, and humanitarian operations. Prior reports have described surgical care for disease and nonbattle injuries (DNBI). The purpose of this report is to describe the prevalence and scope of DNBI managed by general surgeons in a contemporary, deployed medical facility. A 2-year retrospective review of the operative logbook from the U.K. Role 3 Multinational Hospital, Camp Bastion, Afghanistan, was performed to determine the prevalence and makeup of procedures performed for DNBI by general surgeons. Nontrauma general surgical procedures accounted for 7.7% (n = 279 of 3,607 cases) of cases; appendectomy (n = 146) was the most common, followed by drainage of soft tissue (n = 55) and oral abscesses (n = 5), scrotal exploration (n = 12), and hernia repair (n = 7). A total of 7.2% (n = 20 of 279) of cases fell outside the standard scope of practice of an urban, civilian general surgeon. Although the prevalence of operative procedures for DNBI was low, the spectrum of cases included those not typically managed in the civilian setting of the United Kingdom. With an evolving decline in case volume performed in multiple anatomic locations due to subspecialization during surgical training, this gap in expertise is likely to increase.

Characteristics of 1616 Consecutive Dog Bite Injuries at a Single Institution.

Dog bite injuries remain a common form of pediatric trauma. This single-institution study of 1616 consecutive dog bite injuries over 4 years revealed a much higher prevalence of dog bites as compared with other similar centers. Though inpatient admission was rare (9.8%), 58% of all patients required laceration repair, primarily in the emergency department. Infants were more than 4 times as likely to be bitten by the family dog and more than 6 times as likely to be bitten in the head/neck region. Children ≤5 years old were 62% more likely to require repair; and 5.5% of all patients required an operation. Pit bull bites were implicated in half of all surgeries performed and over 2.5 times as likely to bite in multiple anatomic locations as compared to other breeds. The relatively high regional prevalence and younger age of injured patients as compared with other centers is a topic of further study but should draw attention to interventions that can minimize child risk.

United States National Pain Strategy for Population Research: Concepts, Definitions, and Pilot Data

National Pain Strategy population research objectives include: estimating chronic pain prevalence, studying pain treatment with electronic health care data, and developing metrics to assess progress in reducing chronic pain impact. In this article, the National Pain Strategy Population Research Workgroup reviews concepts relevant to achieving these aims. High-impact chronic pain was defined as persistent pain with substantial restriction of life activities lasting 6months or more. In pilot work, we tested a brief assessment of high-impact chronic pain, and used electronic health records data to describe pain-related health care. A mail survey of adult health plan enrollees (N=770) reported that 14% had high-impact chronic pain. Relative to persons with lower-impact chronic pain, those with high-impact chronic pain were more often frequent users of health care for pain, reported lower quality of life, greater pain-related interference with activities, and more often reported pain at multiple anatomic locations. Analyses of health care data (N=289,464) reported that pain patients had higher health care costs compared with others and that pain services were typically delivered in primary care. These results support the feasibility of developing data on chronic pain through national health interview surveys and large electronic health care databases. Pilot analyses supported the feasibility of brief chronic pain assessments suitable for national health surveys and use of electronic health care databases to develop data regarding trends in the delivery of pain treatments, costs, and effectiveness. These methods are relevant to achieving the aims of the US National Pain Strategy.