Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam.

AIMS: To evaluate and compare the pharmacokinetics of IM and oral firocoxib, and IM meloxicam, and detect their effect on renal function and average daily gain (ADG) in lambs undergoing tail docking and castration. METHODS: Seventy-five male Romney lambs, aged 3-6 weeks, were randomised into five treatment groups (n = 15 per group): IM firocoxib (1 mg/kg); oral firocoxib (1 mg/kg); IM meloxicam (1 mg/kg); normal saline (approximately 2 mL, oral); or sham. Following the treatment administration, hot-iron tail docking and rubber ring castration were performed in all groups except the sham group, which did not undergo the procedures, but the animals were handled in the same manner as castrated and tail docked lambs. Blood samples were collected before and 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after treatment administration, and drug concentrations in plasma were quantified by liquid chromatography and mass spectrometry. Plasma urea and creatinine concentrations were determined at a commercial laboratory. Lamb body weights were recorded before and 2, 4 and 8 weeks after tail docking and castration. The pharmacokinetic analysis was carried out using a non-compartmental approach. Between-group and between-time-point differences were compared using mixed model analyses. RESULTS: There was no evidence for a difference in plasma elimination half-life between firocoxib given IM (LSM 18.6 (SE 1.4) hours), firocoxib given orally (LSM 18.2 (SE 1.4) hours), and meloxicam given IM (LSM 17. 0 (SE 1.4) hours). Firocoxib (IM) had a significantly greater volume of distribution (LSM 3.7 (SE 0.2) L/kg) than IM meloxicam (LSM 0.2 (SE 0.2) L/kg). Lambs in the meloxicam group had higher (p < 0.05) plasma urea and creatinine concentrations than those in the firocoxib, saline and sham groups. Lambs' ADG was decreased (p < 0.01) compared to the other treatment groups in the 0-2 week period following meloxicam administration. CONCLUSIONS AND CLINICAL RELEVANCE: Both formulations of firocoxib had a long plasma elimination half-life and large volume of distribution. There was a transient reduction in ADG in the meloxicam group, possibly due to mild renal toxicity. Comparative studies on dose-response effects of firocoxib and meloxicam in lambs following the procedures are required.Abbreviations: ADG: Average daily gain; Cmax: Maximum concentration; COX: Cyclooxygenase; LOD: Limit of detection; NSAID: Non-steroidal anti-inflammatory drugs; CL: Plasma clearance; T1/2el: Plasma elimination half-life; Tmax: Time to achieve Cmax; Vd: Volume of distribution.

Ulnar diaphyseal stress injuries: a case series.

AIM: To describe the demographics, clinical context, imaging findings, and management of a case series of ulnar diaphyseal stress injuries (UDSIs) and propose a unifying mechanism for these injuries based on the imaging findings. MATERIALS AND METHODS: Seven patients from University of Florida College of Medicine (seven total injuries; mean age: 19 ± 4.4 years; three females, four males) with available clinic and imaging data and without predisposing comorbidities were included in this retrospective study. The age, gender, laterality of injury with respect to the dominant hand, attributed inciting activity, imaging method, presence and location of stress injury findings, as well as the subsequent management were analysed. RESULTS: All patients were in the second or third decade of life and there was a slight male predominance to the case series (57%). All UDSIs in this series were unilateral. Fifty-seven percent of injuries involved the dominant ulna and all involved the ulnar diaphysis along the proximal-mid junction, mid diaphysis or mid-distal junction. All injuries involved portion of the ulnar origin of the flexor digitorum profundus (FDP). All patients were managed conservatively. CONCLUSION: UDSIs are uncommon and associated with a broad range of occupational or sports-related activities. All cases in this series involved the ulnar origin of the FDP suggesting an important role for the forces exerted by this muscular attachment on the underlying bone with regard to the development of UDSIs.

Is Pathological Exam for Disorders of the Appendix Testis Necessary?

Testicular appendages are remnants of embryologic structures commonly encountered during pediatric operations. The literature is vague on the management of incidentally discovered testicular appendages found intraoperatively. We performed a retrospective review of 93 pediatric patients who were found to have an incidental testicular appendage during inguinal hernia repair, cryptorchidism, or testicular torsion cases from December 2017 to June 2020. 100% of the incidental testicular appendage pathology results were benign. All of the specimens were 1.0 cm or less in their largest dimension. Removal of these specimens is considered the standard of care at our institution to help prevent torsion of the testicular appendage, which is one of the leading causes of acute scrotum in children. The authors of this study argue that pathological analysis is unnecessary and may result in excessive use of resources without proven benefit.

Clinician perspectives on having point of care tests made available to them during out of hours home visiting.

BACKGROUND: Little is known about clinicians' perspectives on the use of point of care (POC) tests in assessment of acute illness during primary care out of hours (OOH) care. During a service improvement project, POC tests (including creatinine, electrolytes, haemoglobin and lactate) were made available to clinicians undertaking OOH home visits, with the clinicians allowed absolute discretion about when and whether they used them. METHOD: To explore clinicians' perspectives on having POC tests available during OOH home visits, we undertook a qualitative study with clinicians working in Oxfordshire OOH home visiting teams. We conducted 19 Semi-structured interviews with clinicians working in OOH, including those who had and had not used the POC tests available to them. To explore evolving perspectives over time, including experience and exposure to POC tests, we offered clinicians the opportunity to be interviewed twice throughout the study period. Our sample included 7 GPs (4 interviewed once, 3 interviewed twice - earlier and later during the study), 6 emergency practitioners (EPs) including advanced nurse practitioners and paramedics, 1 Healthcare Assistant, and 2 ambulatory care physicians. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: The clinicians reflected on their decision-making to use (or not use) POC tests, including considering which clinical scenarios were "appropriate" and balancing the resources and time taken to do POC tests against what were perceived as likely benefits. The challenges of using the equipment in patients' homes was a potential barrier, though could become easier with familiarity and experience. Clinicians who had used POC tests described benefits, including planning onward care trajectories, and facilitating communication, both between professionals and with patients and their families. CONCLUSION: Clinicians described a discriminatory approach to using POC tests, considering carefully in which situations they were likely to add value to clinical decision-making.

Use of test accuracy study design labels in NICE's diagnostic guidance.

BACKGROUND: A variety of study designs are available to evaluate the accuracy of tests, but the terms used to describe these designs seem to lack clarity and standardization. We investigated if this was the case in the diagnostic guidance of the National Institute of Care and Health Excellence (NICE), an influential source of advice on the value of tests. OBJECTIVES: To describe the range of study design terms and labels used to distinguish study designs in NICE Diagnostic Guidance and the underlying evidence reports. METHODS: We carefully examined all NICE Diagnostic Guidance that has been developed from inception in 2011 until 2018 and the corresponding diagnostic assessment reports that summarized the evidence, focusing on guidance where tests were considered for diagnosis. We abstracted labels used to describe study designs and investigated what labels were used when studies were weighted differently because of their design (in terms of validity of evidence), in relevant sections. We made a descriptive analysis to assess the range of labels and also categorized labels by design features. RESULTS: From a total of 36 pieces of guidance, 20 (56%) were eligible and 17 (47%) were included in our analysis. We identified 53 unique design labels, of which 19 (36%) were specific to diagnostic test accuracy designs. These referred to a total of 12 study design features. Labels were used in assigning different weights to studies in seven of the reports (41%) but never in the guidance documents. CONCLUSION: Our study confirms a lack of clarity and standardization of test accuracy study design terms. There seems to be scope to reduce and harmonize the number of terms and still capture the design features that were deemed influential by those compiling the evidence reports. This should help decision makers in quickly identifying subgroups of included studies that should be weighted differently because their designs are more susceptible to bias.

Tulip Giant Aneurysm Amputation and "Shingle Clip Cut Clip" Technique for Microsurgical Reconstruction of a Giant Thrombosed Middle Cerebral Artery Aneurysm.

In this video, we present the case of a 61-year-old female who was brought to the emergency department after she had partial complex seizures. Computed tomography and magnetic resonance imaging of the brain revealed a right temporal lobe mass, which was initially thought to be a tumor. The patient was therefore referred to us for further management. The round nature of the lesion raised suspicion for an aneurysm. Computed tomography angiography was performed, followed by a diagnostic conventional cerebral angiogram, and confirmed the presence of a giant thrombosed aneurysm. Giant aneurysms represent 3%-5% of all cerebral aneurysms.1 They are more common in females with a ratio of 2:1 to 3:1.1 They have a high risk of rupture up to 50% in the posterior circulation and 40% in the anterior circulation over 5 years according to the International Study of Unruptured Intracranial Aneurysms Investigators.2,3 Their treatment can be complex and treacherous. Treatment options vary widely from parent artery sacrifice in select cases to clip reconstruction to an array of endovascular approaches such as flow diversion. In some cases a combination of both open and endovascular approaches might be necessary.4-8 In our case, we opted for an open surgical clip reconstruction. A superior temporal artery-middle cerebral artery bypass was attempted to allow for trapping of the aneurysm without risking ischemic complication distal to it. Unfortunately, the patient's vessels were too atherosclerotic to maintain patency. A strategy was then devised, which consisted of cutting the dome of the aneurysm and clearing the distal two thirds of the clot ("tulip technique") and then completing thrombus resection under temporary occlusion. Once clot removal was completed, the aneurysm was clipped using the "shingle clip cut clip" technique (Video 1). The patient's postoperative course was uneventful, and the patient remained seizure free.

Untargeted metabolic profiling of dogs with a suspected toxic mitochondrial myopathy using liquid chromatography-mass spectrometry.

'Go Slow myopathy' (GSM) is a suspected toxic myopathy in dogs that primarily occurs in the North Island of New Zealand, and affected dogs usually have a history of consuming meat, offal or bones from wild pigs (including previously frozen and/or cooked meat). Previous epidemiological and pathological studies on GSM have demonstrated that changes in mitochondrial structure and function are most likely caused by an environmental toxin that dogs are exposed to through the ingestion of wild pig. The disease has clinical, histological and biochemical similarities to poisoning in people and animals from the plant Ageratina altissima (white snakeroot). Aqueous and lipid extracts were prepared from liver samples of 24 clinically normal dogs and 15 dogs with GSM for untargeted liquid chromatography-mass spectrometry. Group-wise comparisons of mass spectral data revealed 38 features that were significantly different (FDR<0.05) between normal dogs and those with GSM in aqueous extracts, and 316 significantly different features in lipid extracts. No definitive cause of the myopathy was identified, but alkaloids derived from several plant species were among the possible identities of features that were more abundant in liver samples from affected dogs compared to normal dogs. Mass spectral data also revealed that dogs with GSM have reduced hepatic phospholipid and sphingolipid concentrations relative to normal dogs. In addition, affected dogs had changes in the abundance of kynurenic acid, various dicarboxylic acids and N-acetylated branch chain amino acids, suggestive of mitochondrial dysfunction.

Objective Pupillometry as an Adjunct to Prediction and Assessment for Oculomotor Nerve Injury and Recovery: Potential for Practical Applications.

BACKGROUND: Pupillary light reflex examinations are intrinsic to any good neurological examination. Consistent evidence has shown that automated pupillometry assessments provide superior accuracy and interrater correlation compared with bedside eye examinations. Pupillary indexes such as the neurological pupil index (NPI) can also provide several hours of warning before the advent of herniation syndromes or third nerve palsy. METHODS: We determined the unique temporal relationship between NPI changes and third nerve palsy occurrence and recovery in an initially neurologically intact hospitalized patient. A 53-year-old woman presented with aneurysmal subarachnoid hemorrhage and headaches. Her aneurysm was treated surgically without complications. After lumbar drainage for hydrocephalus, she developed isolated left third nerve palsy that slowly recovered over the following weeks. Pupilometer data were obtained throughout her hospital stay. RESULTS: A total of 121 pupillary measurement sets were obtained. The NPI had decreased to an abnormal level (<3) 12 hours before she became symptomatic. The NPI also started improving 24 hours before improvement in her clinical examination. The patient did not display signs of neurological dysfunction related to vasospasm during her stay. CONCLUSION: The NPI seems to reliably correlate with third nerve function and appears to possess predictive temporal properties that could allow practitioners to anticipate neurological injury and recovery. These findings could affect the fields of neurosciences, trauma, military medicine, critical care, and ophthalmology.

An epidemiological investigation of an idiopathic myopathy in hunting dogs in New Zealand.

AIM: To conduct an epidemiological investigation of an idiopathic myopathy, known as "Go Slow" (GSM), which was initially recognised in dogs used for pig hunting. A secondary aim was to describe the hunting activities, diet and health of dogs used for pig hunting in New Zealand. METHODS: A retrospective cohort study was conducted between June 2014-June 2017. Cases of GSM in dogs were diagnosed by veterinarians using a combination of clinical history, physical examination findings, serum biochemistry and/or skeletal muscle histology. A telephone interview was conducted with the owner or primary veterinarian to provide information regarding the dog's diet and exercise over the 7 days preceding the onset of clinical signs. In August 2015, a separate online survey of owners of dogs used for pig hunting was conducted to characterise the normal hunting activities, diet and health of these dogs. RESULTS: A total of 86 cases of GSM were recruited, of which 58 (67%) were pig hunting dogs, 16 (19%) pet dogs and 12 (14%) working farm dogs. Cases were most commonly reported in the upper North Island, and 65 (76 (95% CI=67-85)%) were from the Northland region. Processed commercial dog food had been fed to 93 (95% CI=88-98)% of affected dogs. Ingestion of raw, frozen or cooked wild pig in the preceding week was reported for 76 (88 (95% CI=82-95)%) dogs with the myopathy. In the survey of owners of healthy pig hunting dogs, 203 eligible responses were received; pig hunting was reported to most commonly occur in Northland (20.2%), Waikato (22.3%) and Bay of Plenty (23.2%) regions. Commercial dog food was fed to 172 (85 (95% CI=80-90)%) of the dogs included in this survey, and 55 (27 (95% CI=20-33)%) had eaten wild pig in the preceding week. The most common reported health problem in pig hunting dogs was traumatic wounds. CONCLUSIONS: Cases of GSM were most commonly recognised in dogs used for pig hunting, but also occurred in pet and working farm dogs. The disease was most frequently reported in the upper North Island of New Zealand and ingestion of wild pig was a consistent feature in cases of this myopathy. CLINICAL RELEVANCE: To minimise the risk of dogs developing this myopathy, it would seem prudent to avoid feeding any tissues from wild pigs to dogs in areas where the disease is known to occur.

Transcavernous Approach to the Basilar Apex: A Cadaveric Prosection.

The transcavernous approach to the basilar artery, as initially described by Dolenc, is one of the most common and elegant approaches to the region. It affords a generous working and viewing angle, but it can be technically challenging and requires attention to detail at each step. We investigate this approach in this report via a cadaveric prosection with a focus on the value of each of the component steps in improving surgical view and exposure. The transcavernous approach steps are divided into extradural stages: orbitozygomatic osteotomy (a modern adjunct to Dolenc's original description), drilling of the lesser sphenoid wing, and anterior clinoidectomy; and intradural stages: wide splitting of the Sylvian fissure, unroofing of the oculomotor and trochlear nerves, and posterior clinoidectomy. The surgical windows afforded by each step in the approach are illustrated using microscopic images taken during the cadaveric prosection of a donor who happened to harbor a basilar apex aneurysm. An illustrative case and artist illustrations are used to emphasize the relative value of each step of the transcavernous exposure.

Plasma NT-proBNP and Cell-Free DNA Concentrations after Prolonged Strenuous Exercise in Working Farm Dogs.

BACKGROUND: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration is increased in dogs with myocardial dysfunction, and cell-free DNA (cfDNA) increases in numerous disease states. In humans, both of these biomarkers can be altered after endurance exercise. OBJECTIVE: To investigate the effect of prolonged strenuous exercise on circulating NT-proBNP and cfDNA concentrations in working farm dogs. ANIMALS: Six healthy, privately owned working farm dogs (4 Huntaways and 2 heading dogs) from the same hill country farm in New Zealand. METHODS: Prospective, nonrandomised cohort study. Venous blood samples were collected before and after the dogs worked over 4 days. Plasma NT-proBNP concentrations were measured by a commercially available ELISA assay and cfDNA concentrations were determined by fluorometry without prior DNA extraction. RESULTS: The baseline (before work, Day 1) median plasma NT-proBNP concentration was 664 pmol/L. A linear mixed-effects model showed that work increased plasma NT-proBNP concentrations by 101 ± 9% (P < 0.001), but with each consecutive day of work, NT-proBNP concentrations declined by 16 ± 4% (P < 0.001). The baseline median plasma cfDNA concentration was 653 ng/mL, and plasma cfDNA concentrations increased by 138 ± 45 ng/mL after work (P = 0.004). CONCLUSIONS AND CLINICAL IMPORTANCE: The plasma concentration of NT-proBNP in healthy Huntaways and heading dogs after work can exceed the upper limit of the reference range. Results in dogs sampled on the day of prolonged strenuous exercise should be interpreted with caution. Plasma concentrations of cfDNA also increase with exercise, but further studies are needed to establish reference ranges in healthy dogs.

First report and histological features of Chlamydia pecorum encephalitis in calves in New Zealand.

CASE HISTORY: Between September and October 2013, 40 of 150 crossbred Friesian dairy calves on a farm in the Manawatu region of New Zealand developed neurological signs when between 1 and 3 months of age. Calves were grazed in multiple mobs and calves from each mob were affected. A variable response was observed to initial treatment with thiamine, fluoroquinolone antibiotics and non-steroidal anti-inflammatory drugs. CLINICAL AND PATHOLOGICAL FINDINGS: Affected calves exhibited a range of neurological signs that included generalised depression, hind limb ataxia with a stiff gait, and knuckling of the fetlocks. In advanced cases, calves became recumbent with opisthotonous. Over a 4-week period, 13 calves died or were subject to euthanasia and a thorough necropsy was performed on three of these calves. Necropsy findings included fibrinous peritonitis, pleuritis and pericarditis, with no gross abnormalities visible in the brain or joints. Histology of the brain was possible in seven of the affected calves, with lesions ranging from lymphocytic and histiocytic vasculitis and meningoencephalitis, to extensive thrombosis and neutrophilic inflammation. Immunohistochemistry using an anti-chlamydial lipopolysaccharide antibody revealed positive immuno-staining in all seven cases, with no brain samples exhibiting immunostaining for Histophilus somni. DNA was extracted from a sample of fresh brain from one case and chlamydial DNA sequences were amplified by PCR and found to be identical to Chlamydia pecorum. PCR was also performed on formalin-fixed brain tissue from three of the other cases, but no chlamydial DNA was amplified. DIAGNOSIS: Chlamydia pecorum meningoencephalomyelitis (sporadic bovine encephalomyelitis). CLINICAL RELEVANCE: This is the first time that C. pecorum has been confirmed as a cause of clinical disease in New Zealand. Practitioners should be aware of this disease as a differential in calves with neurological signs, and submit samples of formalin-fixed brain as well as fresh brain to enable confirmation of suspected cases using PCR analysis. Furthermore, these cases illustrate that the histological lesions in the brains of calves with C. pecorum are more variable than previously reported, and pathologists should be aware that histological features may overlap with those traditionally ascribed to other organisms, such as H. somni.

Use of the Atlantic nut clam (Nucula proxima) and catworm (Nephtys incisa) in a sentinel species approach for monitoring the health of Bay of Fundy estuaries.

Designing an effective environmental monitoring system for population responses requires knowledge of the biology of appropriate sentinel species and baseline information on the area's physical and chemical characteristics. This study collected information in Saint John Harbor, NB, Canada, for two abundant marine benthic invertebrates, the Atlantic nut clam (Nucula proxima) and the catworm (Nephtys incisa) to characterize their seasonal and spatial variability, determine the ideal sampling time and methods, and develop baseline data for future studies. We also evaluated whether contamination is impacting invertebrates by comparing sediment metal concentrations to responses of benthic infauna. Metals were generally below sediment quality guidelines except for nickel and arsenic. Clam densities were variable between sites but not seasons, whereas catworm densities were not significantly different between sites or seasons. Overall, these species show potential for environmental monitoring, although investigation at more contaminated sites is warranted to assess their sensitivity.

A novel combined glucocorticoid-mineralocorticoid receptor selective modulator markedly prevents weight gain and fat mass expansion in mice fed a high-fat diet.

BACKGROUND: We have previously shown that antagonism of the mineralocorticoid receptor (MR) results in a potent antiadipogenic activity, in vitro and in vivo. Excessive glucocorticoid exposure is associated with obesity and related disorders in humans and mice. METHODS: In this study, responses to a novel combined glucocorticoid receptor (GR)/MR antagonist were investigated in a model of diet-induced obesity. Female 10-week-old C57BL/6J mice were fed with normal chow or a high-fat diet (HFD) for 9 weeks. Mice fed a HFD were concomitantly treated for 9 weeks with the GR antagonist mifepristone (80 mg kg(-1) per day) or the novel combined GR/MR antagonist CORT118335 (80 mg kg(-1) per day). Male, juvenile 6-week-old C57BL/6J mice fed HFD were treated with CORT118335 for 4 weeks. RESULTS: Mice fed a HFD showed a significant increase in total body weight and white fat mass, with impaired glucose tolerance and increased fat infiltration in livers. Interestingly, only CORT118335 completely prevented the HFD-induced weight gain and white fat deposition, whereas mifepristone showed no effect on body weight and modestly increased subcutaneous fat mass. Importantly, food intake was not affected by either treatment, and CORT118335 dramatically increased PGC-1α protein expression in adipose tissue, without any effect on UCP1. Both CORT118335 and mifepristone produced metabolic benefit, improving glucose tolerance, increasing adiponectin plasma levels, decreasing leptin and reducing mean adipocyte size. When tested in vitro, CORT118335 markedly reduced 3T3-L1 differentiation and reversed MR-mediated pro-adipogenic effects of aldosterone; differently, GR-mediated effects of dexamethasone were not antagonized by CORT118335, suggesting that it mostly acts as an antagonist of MR in cultured preadipocytes. CONCLUSIONS: Combined GR/MR pharmacological antagonism markedly reduced HFD-driven weight gain and fat mass expansion in mice through the increase in adipose PGC-1α, suggesting that both receptors represent strategic therapeutic targets to fight obesity. The effects of CORT118335 in adipocytes seem predominantly mediated by MR antagonism.

Use of a harvested radial artery graft with preservation of the vena comitantes to reduce spasm risk and improve graft patency for extracranial to intracranial bypass: Technical note.

BACKGROUND AND SIGNIFICANCE: The vessels of choice for cerebrovascular high-flow direct bypass procedures are the radial artery and the saphenous vein. Radial artery grafts have become favored over saphenous vein grafts because of higher patency rates and better size matching to appropriate recipient vessels. Radial grafts are prone to spasm however, and this may be seen in 4-10% of cases and can be associated with ischemic sequelae. The standard technique for radial artery harvest calls for complete separation of the artery from its adventitial attachments and associated venous network. There is reason to believe that this could contribute to spasm risk and possibly even thrombosis. Radial graft outcomes appear to be improved when the vena comitantes is preserved in cardiac and peripheral applications. We report the novel use of a harvested radial artery graft with preservation of its venae comitantes for extracranial to intracranial bypass. CLINICAL PRESENTATION: The patient is a 59-year-old male who had a blunt head trauma with associated loss of consciousness and who was led to the incidental discovery of a large fusiform middle cerebral artery (MCA) aneurysm. CONCLUSION: Preservation of the vena comitantes when harvesting a radial arterial graft for bypass, along with dual (arterial and venous) anastomoses, and concomitant use of intra-operative vaso-dilatory maneuvers to prevent spasm, may improve overall graft patency and patient outcome.

Snapshot MR technique to measure OEF using rapid frequency mapping.

Magnetic resonance (MR)-based oxygen extraction fraction (OEF) measurement techniques that use blood oxygen level-dependent (BOLD)-based approaches require the measurement of the R2' decay rate and deoxygenated blood volume to derive the local oxygen saturation in vivo. We describe here a novel approach to measure OEF using rapid local frequency mapping. By modeling the MR decay process in the static dephasing regime as two separate dissipative and oscillatory effects, we calculate the OEF from local frequencies measured across the brain by assuming that the biophysical mechanisms causing OEF-related frequency changes can be determined from the oscillatory effects. The Parameter Assessment by Retrieval from Signal Encoding (PARSE) technique was used to acquire the local frequency change maps. The PARSE images were taken on 11 normal volunteers, and 1 patient exhibiting hemodynamic stress. The mean MR-OEF in 11 normal subjects was 36.66±7.82%, in agreement with positron emission tomography (PET) literature. In regions of hemodynamic stress induced by vascular steal, OEF exhibits the predicted focal increases. These preliminary results show that it is possible to measure OEF using a rapid frequency mapping technique. Such a technique has numerous advantages including speed of acquisition, is noninvasive, and has sufficient spatial and temporal resolution.

Measuring and monitoring ICP in Neurocritical Care: results from a national practice survey.

INTRODUCTION: The use of intracranial pressure (ICP) monitors is nearly synonymous with Neurocritical Care. Recent studies in nursing literature have report high levels of practice variance associated with ICP monitoring and treatment. There are no recent practice surveys to describe how critical care physicians and nurses who are familiar with ICP management provide care to their patients. METHODS: A short survey was developed and disseminated electronically to the members of the Neurocritical Care Society. RESULTS: The summary from 241 professionals provides evidence that there is significant practice variation associated with ICP monitoring and management. CONCLUSION: The results highlight the need to develop standardized approaches to measuring, monitoring, recording, and treating ICP.

A didactic and hands-on module enhances resident microsurgical knowledge and technical skill.

BACKGROUND: Simulation has been adopted as a powerful training tool in many areas of health care. However, it has not yet been systematically embraced in neurosurgery because of the absence of validated tools, assessment scales, and curricula. OBJECTIVE: To use our validated microanastomosis module and scale to evaluate the effects of an educational intervention on the performance of neurosurgery residents at the 2012 Congress of Neurological Surgeons Annual Meeting. METHODS: The module consisted of an end-to-end microanastomosis of a 3-mm vessel and was divided into 3 phases: (1) a cognitive and microsuture prelecture testing phase, (2) a didactic lecture, and (3) a cognitive and microsuture postlecture testing phase. We compared resident knowledge and technical proficiency from the pretesting and posttesting phases. RESULTS: One neurosurgeon and 7 neurosurgery residents participated in the study. None had previous experience in microsurgery. The average score on the microsuture prelecture and postlecture tests, as measured by our assessment scale, was 32.50 and 39.75, respectively (P = .001). The number of completed sutures at the end of each procedure was higher for 75% of participants in the postlecture testing phase (P = .03). The average score on the cognitive postlecture test (12.75) was significantly better than that of the cognitive prelecture test (8.38; P = .001). CONCLUSION: Simulation has the potential to enhance resident education and to elevate proficiency levels. Our data suggest that a focused microsurgical module that incorporates a didactic component and a technical component can enhance resident knowledge and technical proficiency in microsurgical anastomosis.

Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas.

Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79). Mutations in IDH1 or IDH2 were associated with longer overall survival (P=0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (P=0.021). IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors.