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OBJECTIVE WHO grade III meningiomas, also known as malignant meningiomas (MMs), are rare, and the heterogenous clinical course in patients with MM is not well described. To characterize the clinical course of patients with MM, granular clinical data were gathered from 51 patients treated at the Department of Neurosurgery and Radiation Oncology, Rigshospitalet, in Copenhagen, Denmark, between 2000 and 2020. METHODS The authors investigated outcome and timing in terms of 1) tumor progression and grade transformation in patients previously diagnosed with WHO grade I or II meningiomas (patients with a secondary MM [sMM]); 2) performance status and complications following surgery; and 3) transition to noncurative treatment and ultimately death. Complications, time between recurrences, and outcome (modified Rankin Scale [mRS] score) for every surgery were analyzed, both malignant and premalignant. RESULTS Of the 51 patients, 24 (47%) had an sMM. The time to WHO grade III transformation in the sMM group varied widely (median 5.5 years, range 0.5–22 years), but after transformation to a WHO grade III tumor, patients with an sMM and those with a primary MM (pMM) did not differ significantly in overall survival and cumulative risk of progression. Median overall survival for all 51 patients was 4.2 years (95% CI 2.6–7.2 years). Time from the decision to shift from curative to noncurative treatment until death was 3.8 months and the 30-day mortality rate following surgery was 11.8%. From a cumulative number of 151 surgeries, 10 surgeries were followed by improvement on the mRS, mRS score was unchanged in 70, and it worsened in 71. The MM was the underlying cause of death in 30 of 31 patients who had died at the end of follow-up. CONCLUSIONS Together, these findings clearly show a significant morbidity and mortality from the disease itself and from the treatment. These findings warrant studies of prognostic factors for earlier support and adjuvant measures in MM and identify a need for better palliative strategies in this patient group.

OBJECTIVE Meningioma is the most common primary intracranial neoplasm. Only 1%–3% of meningiomas are malignant according to the 2016 WHO criteria (WHO grade III). High-grade meningiomas present specific gene expression signatures indicating aggressive growth or recurrence. However, changes in gene expression and in neuroinflammatory gene expression signatures in WHO grade III meningiomas and during progression from WHO grade I or II to grade III are unknown. METHODS The authors used a NanoString targeted gene expression panel with focus on 787 genes relevant in meningioma pathology and neuroinflammatory pathways to investigate patients with grade III meningiomas treated at Rigshospitalet from 2000 to 2020 (n = 51). A temporal dimension was added to the investigation by including samples from patients’ earlier grade I and II meningiomas and grade III recurrences (n = 139 meningiomas). The authors investigated changes in neuroinflammatory gene expression signatures in 1) grade I meningiomas that later transformed into grade III meningiomas, and 2) grade III meningiomas compared with nonrecurrent grade I meningiomas. RESULTS The authors’ data indicate that FOXM1, TOP2A, BIRC5, and MYBL2 were enriched and the HOTAIR regulatory pathway was enriched in grade III meningiomas compared with nonrecurrent grade I meningiomas. They discovered a separation of malignant and benign meningiomas based only on genes involved in microglia regulation with enrichment of P2RY12 in grade I compared with grade III meningiomas. Interestingly, FOXM1 was upregulated in premalignant grade I meningioma years before the grade III transformation. CONCLUSIONS The authors found gene expression changes in low-grade meningiomas that predated histological transformation to grade III meningiomas. Neuroinflammation genes distinguished grade III from grade I meningiomas.

To investigate the association between fertility drugs and tumors of the central nervous system (CNS).This cohort study was based on The Danish Infertility Cohort and included 148,016 infertile women living in Denmark (1995-2017). The study cohort was linked to national registers to obtain information on use of specific fertility drugs, cancer diagnoses, covariates, emigration, and vital status. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all CNS tumors and separately for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS.During a median 11.3 years of follow-up, 328 women were diagnosed with CNS tumors. No marked associations were observed between use of the fertility drugs clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators and progesterone and CNS tumors. However, use of human chorionic gonadotropin was associated with a decreased rate of meningiomas (HR 0.49 95% CI 0.28-0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any of the fertility drugs.No associations between use of most types of fertility drugs and CNS tumors were observed. However, our findings only apply to premenopausal women and additional studies with longer follow-up time are necessary.

Deep-seated intracerebral spontaneous haematomas (ICHs) pose a neurosurgical challenge in decision-making process as summarised in this review. No studies have been able to demonstrate a significant effect on surgical removal. The challenge to surgical removal is the damage the surgery causes to the healthy brain in connection with the surgical procedure. The application of minimally invasive techniques in the form of endoscopic removal of deep-seated ICHs, results in significantly less "trauma" to the healthy brain and hopefully a better prognosis for patients with deep-seated spontaneous ICHs.

Sodium fluorescein (fluorescein) crosses a disrupted blood-brain barrier similarly to gadolinium contrast in contrast-enhancing cerebral tumors. When exposed to light with 560 nm wavelength during surgery, fluorescein emits a yellow-green fluorescent light that can be visualized through an operating microscope equipped with an appropriate emission filter. The distribution of the fluorescence correlates with the contrast on a gadolinium contrast-enhanced MRI.The objective of this single-center retrospective study was to investigate if the use of fluorescein would increase the extent of resection and to examine if fluorescein guided resection influences postoperative neurological status.During the study period from August 2014 to August 2018, 117 patients were operated for cerebral metastases. Of these, 56 operations were guided by fluorescein and 61 by traditional white light. All patients had an early postoperative MRI within 72 h after surgery.The use of fluorescein increased the extent of resection in patients with cerebral metastases. The use of fluorescein was not associated with increased postoperative sequelae or neurological damage regardless of underlying primary cancer.Fluorescein is a helpful supplement in the neurosurgical treatment of cerebral metastases.

Mitochondrial dysfunction after transient cerebral ischemia can be monitored by cerebral microdialysis (CMD) using changes in the lactate and pyruvate concentrations and ratio. Other metabolites associated with mitochondrial (dys)function are, e.g., tricyclic acid (TCA) and purine metabolites. Ethyl pyruvate (EP) is a putative neuroprotectant, supposedly targeting mitochondrial energy metabolism, but its effect on cerebral energy metabolism has never been described using microdialysis. In this study we monitored the metabolic effects of EP in the endothelin-1 (ET-1) rat model using perfusion with 13C-succinate and analysis of endogenous and 13C-labeled metabolites in the dialysates by liquid chromatography-mass spectrometry (LC-MS). Adult Sprague Dawley rats (n = 27 of which n = 11 were included in the study) were subjected to the microdialysis experiments. Microdialysis probes were perfused with 13C-labeled succinate (1 mM), and striatal dialysates were collected at 30 min intervals before induction of the insult, during intracerebral application of ET-1, and during intravenous treatment with either EP (40 mg/kg) or placebo, which was administered immediately after the insult. The rats were subjected to transient cerebral ischemia by unilateral microinjection of ET-1 in the piriform cortex, causing vasoconstriction of the medial cerebral artery. Monitoring was continued for 5 h after reperfusion, and levels of endogenous and 13C-labeled energy metabolites before and after ischemia-reperfusion were compared in EP-treated and control groups. Infarct volumes were assessed after 24 h. In both the EP-treated and placebo groups, ET-1-induced vasoconstriction resulted in a transient depression of interstitial glucose and elevation of lactate in the ipsilateral striatum. In the reperfusion phase, the concentrations of labeled malate, isocitrate, and lactate as well as endogenous xanthine were significantly higher in the EP-group than in the placebo-group: (mean ± SEM) labeled malate: 39.5% ± 14.9, p = 0.008; labeled isocitrate: 134.8% ± 67.9, p = 0.047; labeled lactate: 61% ± 22.0, p = 0.007; and endogenous xanthine: 93.9% ± 28.3, p = 0.0009. In the placebo group, significantly elevated levels of uridine were observed (mean ± SEM) 32.5% ± 12.7, p = 0.01. Infarct volumes were not significantly different between EP-treated and placebo groups, p = 0.4679. CMD labeled with 13C-succinate enabled detection of ischemic induction and EP treatment effects in the ET-1 rat model of transient focal cerebral ischemia. EP administered as a single intravenous bolus in the reperfusion-phase after transient cerebral ischemia increased de novo synthesis of several key intermediate energy metabolites (13C-malate, 13C-isocitrate, and endogenous xanthine). In summary, mitochondria process 13C-succinate more effectively after EP treatment.

Cerebral microdialysis allows for continuous sampling of brain metabolites. The approach is typically used to monitor glucose, lactate and pyruvate in neurointensive care patients with compromised blood flow (ischemia).Here we propose a microdialysis LC-MS approach with the aim of measuring the majority of TCA (tricarboxylic acid cycle)-centered metabolites along with incorporation of 13C from perfused 13C4 succinate to get additional important information related to the ischemic brain metabolism.The approach was evaluated using a rat model of transient cerebral ischemia, which was induced by local application of endothelin-1.

The primary objective of this retrospective study was to evaluate the diagnostic yield and morbidity/mortality associated with frameless stereotactic neuronavigated intracranial biopsies with and without the use of fluorescein.Patient cases from January 2007 to December 2017 were identified using the ICD-10 procedure code AAG00. Relevant clinical data, including histological diagnosis, were collected retrospectively from the electronic patient charts and independently reviewed by two authors.111 biopsies obtained from 103 patients were identified. Of these, 109 biopsies yielded a diagnosis and resulted in a diagnostic yield of 98.2%. Fluorescein was used in 13 biopsies (11.7%). Twelve patients (10.8%) experienced postoperative complications, and the mortality attributed to the surgery was 1.8%. In 12.6% of cases, the biopsies showed inflammation or nonspecific reactive changes. No statistically significant differences were observed in diagnostic yield or number and severity of complications according to whether intraoperative histological examination was used or not.Although direct comparisons between studies are difficult due to lack of consensus about the definition of diagnostic yield, the present study reports a similar diagnostic yield to other studies. Intraoperative histopathological analysis appeared to give little extra benefit.

Companies’ software ecosystem – composed of local applications and cloud computing services – is made up by the connection of integration platforms and applications. Run-time systems are arguably the most considerable components for integration platforms performance. Our literature review has identified that most integration run-time systems adopt a global pool as configuration for threads. However, it is possible to configure local thread pools to increase the performance of run-time systems. This article brings a comparison between two configurations of thread pools simulating the execution of a real integration problem. Results show that the execution performance through the local pool configuration exceeds the performance through the global pool in high workload scenarios. These results were reviewed by rigorous statistical analysis. info:eu-repo/semantics/acceptedVersion

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Greater trochanteric pain syndrome (GTPS) is a term used to describe disorders of the peritrochanteric region. This constellation of conditions includes greater trochanteric bursitis, gluteus medius (GM) tears, and external coxa saltans or snapping hip syndrome. Tears of the abductor mechanism, more specifically gluteus medius tears, have recently gained a considerable amount of interest in the orthopaedic literature. Abductor tears were first described by Bunker and Kagan in the late 1990s. They used the rotator cuff as an analogous structure to describe the pathological process associated with gluteus medius tears. Tears of the gluteus medius tendon can often be difficult to recognize. The clinical presentation is often attributed to trochanteric bursal inflammation, without any further workup. Provocative hip physical examination findings are an important key to proper diagnosis of abductor injuries. Depending on the size of the tear, patients with abductor tendon pathology may present with a Trendelenburg gait and reduced resisted abduction strength accompanied by pain. Initial noninvasive management of greater trochanteric pain syndrome includes oral or topical anti-inflammatory medication and activity modification. Physical therapy or other treatment modalities can be considered, with a focus on core strengthening, truncal alignment, and iliotibial band stretching. Gluteus medius tears have historically been repaired in an open fashion; however, the advent of new endoscopic surgery techniques has allowed for a less invasive approach. Access to the peritrochanteric space affords the surgeon with access to pathology associated with the greater trochanter, iliotibial band, trochanteric bursa, sciatic nerve, short external-rota tors, iliopsoas tendon, and the gluteus medius and minimus tendon attachments. Over the last decade, we have seen rapid technological advances in hip arthroscopy, improved diagnostic imaging and interpretation, and an improved understanding of intra-articular and peritrochanteric hip pathology. As the emphasis on hip arthroscopy in residency and fellowship training programs continues to increase, the learning curve for endoscopic management of peritrochanteric disorders will continue to improve.

Objective. Outcome measures for pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) are only partially validated. The aim of the present study was to establish an expert consensus regarding which outcome measures are most appropriate for clinical trials in PAH-SSc. Methods. Sixty-nine PAH-SSc experts (rheumatologists, cardiologists, pulmonologists) rated a list of disease domains and measurement tools in an Internet-based 3-stage Delphi consensus study. In stages 2 and 3, the medians of domains and measurement tools and frequency distributions of ratings, along with requests for re-ratings, were distributed to respondents to provide feedback. A final score of items was identified by means of cluster analysis. Results. The experts judged the following domains and tools as most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure and cardiac function both measured by right heart catheterization and echocardiography, exercise testing measured by 6-minute walking test and oxygen saturation at exercise, severity of dyspnea measured on a visual analog scale, discontinuation of treatment measured by (serious) adverse events, quality of life/activities of daily living measured by the Short Form 36 and Health Assessment Questionnaire disability index, and global state assessed by physician measured by survival. Conclusion. Among experts in PAH-SSc, a core set of outcome measures has been defined for clinical trials by Delphi consensus methods. Although these outcome measures are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present measures, as well as potential research measures, in further studies.

The primary goal in caring for the traumatized patient is to provide effective resuscitative interventions while minimizing the time from injury to definitive care. The emergency physician is often called on to provide the initial stabilization and resuscitation. This is done most effectively if one is well versed in trauma care and has an organized approach to the multiply injured patient. This article discusses several current controversies in the emergent care of the multiply injured patient. Most of the issues are currently under investigation, whereas others have been addressed only as opinion in the medical literature. A balanced view of these topics is presented so that the reader will be better informed on how to care for these patients.

A case of intraoral trauma leading to thrombosis of the internal carotid artery in a child is reported. Presentation, evaluation, and treatment of this entity are reviewed. Sequelae of this injury include delayed neurological deficits and death.

Study objective: To determine the efficacy and feasibility of adenosine for the treatment of paroxysmal supraventricular tachycardia (PSVT) in the prehospital setting. Design: Prospective case series. Setting: Large, urban, advanced life support emergency medical services system. Participants: One hundred twenty-nine adult patients with PSVT, as identified by paramedic personnel. Pregnant patients and those taking carbamazepine or dipyridamole were excluded. Interventions: Dose of 12 mg adenosine by rapid IV push followed by a 5-mL saline flush and a repeat dose of 12 mg adenosine IV push if the patient's rhythm remained unchanged. Measurements and main results: Six-second lead II rhythm strips and vital signs were documented before and 2 minutes after the administration of adenosine. Demographic information, past medical history, medications, number of adenosine doses given, and complications were recorded by the paramedic on a case-report form. One hundred six of 129 (82%) of the case-report forms included the rhythm strips from before and after adenosine administration. Actual initial rhythms were determined by a consensus panel. The initial rhythms were PSVT in 79% (84 of 106) of patients, atrial fibrillation in 12% (13 of 106), sinus tachycardia in 5% (five of 106), atrial flutter in 2% (two of 106), and ventricular tachycardia in 2% (two of 106). Eighty-five percent (71 of 84) of patients in PSVT were successfully converted to sinus rhythms; four (5.6%) of these patients required a second 12-mg dose. One patient in atrial fibrillation spontaneously converted to normal sinus rhythm and one patient in ventricular tachycardia converted after adenosine. All other patients not initially in PSVT remained in their initial rhythm. Complications occurred in 12 of 129 patients and included chest pain (five), flushing (three), shortness of breath (two), nausea (one), anxiety (one), dizziness (one), headache (one), and seizure (one). All complications were transient and required no treatment. Prior history of PSVT was the only variable associated with a higher rate of conversion ( P =.029). Conclusion: Paramedics are able to accurately identify PSVT using a single lead. Adenosine is safe and effective treatment for PSVT in the prehospital setting. This series is the largest prehospital study of adenosine use to date. [Gausche M, Persse DE, Sugarman T, Shea SR, Palmer GL, Lewis RJ, Brueske PJ, Mahadevan S, Melio FR, Kuwata JH, Niemann JT: Adenosine for the prehospital treatment of paroxysmal supraventricular tachycardia. Ann Emerg Med August 1994;24:183-189.]

The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone (SVZ) cells reach the olfactory bulb (OB) in rodents. This migration has been well studied in vivo, but an organotypic in vitro model would facilitate more experimental investigations. Here we introduce a slice culture preparation of the rat forebrain including en suite the rostral part of the lateral ventricle, the RMS and the OB. The preparation was validated with regard to endogenous cell proliferation and migration by tracking bromodeoxyuridine (BrdU)-labelled cells in newly established and 3 and 6 week old cultures. For testing the migratory abilities of exogenous precursor cells, rat SVZ neurospheres and human neural (HNS1 cells) and mesenchymal (hMSC-TERT) stem cell lines were micrografted to the rostral SVZ of 1 and 7 day old cultures. Two weeks later graft derivatives were identified by immunohistochemical staining for human nuclei (HNS1/hMSC-TERT cells) and BrdU (HNS1 cells/neurospheres). Numerous HNS1 cells and BrdU-positive neurosphere cells were found in the RMS. Having reached the OB, subpopulations of the cells expressed the astroglial markers glial fibrillary acidic protein/hAM and the neuronal markers NeuN/tyrosine hydroxylase. Interestingly, the hMSC-TERT cells remained at the implantation site, demonstrating a diversity in migratory capability of different precursor cells. In conclusion, the RMS in rat forebrain slice cultures retains its ability to support migration of endogenous and exogenous neural precursors, making the cultures highly feasible for studies of conditions and factors regulating cell migration., This research was supported by the Danish MRC (J. No. 22-02-0150/22-02-0008), the Danish Centre for Stem Cell Research (J. No. 2052-01-0045) and as part of the European Science Foundation EUROCORES Programme EuroSTELLS, by funds from the European Commission Sixth Framework Programme (contract no. ERAS-CT-2003-980409). Work at the AMS group was supported by grants from the European Union (QLK3-CT-2001-02120), and Spanish Ministry of Science and Technology (MCYT SAF2001-1038-C02-02).

Study purpose: To evaluate the efficacy of adenosine in the treatment of emergency department patients with unstable paroxysmal supraventricular tachycardia (PSVT). Design: A retrospective chart review conducted over two years. Setting: A university-affiliated hospital ED. Participants: Patients with unstable PSVT (systolic blood pressure of less than 90 mm Hg, chest pain, pulmonary edema, and/or altered mental status) who were treated with adenosine. Interventions: Patients' preadenosine and postadenosine heart rates, symptoms, and blood pressure were recorded, as were complications and recurrence of PSVT. PSVT was diagnosed by surface ECG. Results: Twelve patients were identified (three men and nine women with a mean age of 47.6 years). Nine patients presented with hypotension (mean systolic blood pressure, 79 mm Hg), ten with chest pain, and six with both chest pain and hypotension. There were no patients with altered mental status or pulmonary edema. Eight patients converted to sinus rhythm with a single 6-mg bolus of adenosine; the remaining four required an additional 12-mg bolus. In all cases, chest pain and hypotension resolved within minutes of conversion to sinus rhythm. There were no clinically significant adverse effects or recurrence of PSVT during ED observation (mean, 1.8 hours). All patients responded to adenosine; none required electrical cardioversion. Conclusion: In the unstable patient with PSVT, adenosine appears to be a safe and effective alternative to current advanced cardiac life support-recommended immediate electrical cardioversion.

The report describes an interface between an IBM 1800 computer and a DEC PDP-7 computer. It has the following features: (1) it allows the transfer of blocks of data directly from the memory of one computer to the memory of the other, at up to 125,000 words per second, in parallel with program execution; (2) it allows a program running on one machine to interact asynchronously with one running on the other through a system of 'attention interrupts'; (3) it is relatively simple to control, being symmetric to both computers; (4) it compensates automatically, in either of two modes, for the difference in word length between the PDP-7 and the 1800.

The background that led to the development ofthe first catalytic and enantioselective carbon-fluorine bond-forming reaction is presented. Two different approaches, i.e. the use of nucleophilic and electrophilic fluorinating agents, respectively, have been pursued. Well-defined RU(II) 16-electron systems of the type [RuF(PP)2]+ (where PP is a chelating diphosphine), as well as analogous complexes containing tetradentate PNNP ligands, were found to catalyze the halogen exchange reaction of activated alkyl chlorides, bromides, and iodides in the presence of TIF as the fluorine source. Isolable crystalline [TiCl2 (TADDOLato)] complexes are efficient catalysts in the enantioselective fluorination of 2-substituted 1,3-dicarbonyl compounds with Selectfluor® (also called F-TEDA; 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis{tetrafluoroborate}). Levels of enantioselectivity up to 90% ee were obtained.