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Background and purpose: Venous thromboembolism (VTE) is a cause of increased morbidity and risk of death. Studies report VTE in up to 30% of glioma patients but the results vary. The VTE risk is relevant when evaluating prophylaxis to avoid unnecessary bleeding or overdiagnosis. This study examines the VTE incidence in patients with glioma WHO grade 2–4, and when VTE occurred, risk factors, and overall survival (OS) for patients with WHO grade 4. Materials and methods: In total 3,630 patients with WHO grade 2 (n = 230), grade 3 (n = 317), and grade 4 (n = 3,083) gliomas from 2010 to 2018 were identified using the Danish Neuro-Oncology Registry. VTE diagnoses and time of death were obtained from Statistics Denmark. Results and interpretation: The VTE incidence was 5.2, 6.3, and 6.8% in patients with WHO grade 2, 3, and 4 gliomas, respectively. The VTE incidence rate was highest during the first 3 months after the diagnosis with 53 events. Increasing age (HR 1.03, 95%CI 1.01–1.04), male sex (HR 1.47, 95%CI 1.09–1.99), poor performance status (HR 1.57, 95%CI 1.10–2.25), and post-operative long-course radiochemotherapy (HR 2.10, 95%CI 1.19–3.72) were predictors of VTE in patients with glioma WHO grade 4. There was no difference in OS comparing patients having VTE to those without (p = 0.068). In conclusion, patients with glioma WHO grade 2–4 were at high risk of VTE, especially the first 3 months after diagnosis. Increasing age, male sex, poor performance status, and long-course radiochemotherapy were associated with increased risk of VTE in patients with glioma WHO grade 4.

Background: There are no generally accepted criteria for selecting patients with recurrent glioblastoma for surgery. This retrospective study in a Danish population-based cohort aimed to identify prognostic factors affecting postoperative survival after repeated surgery for recurrent glioblastoma and to test if the preoperative New Scale for Recurrent Glioblastoma Surgery (NSGS) developed by Park CK et al could assist in the selection of patients for repeat glioblastoma surgery. Methods: Clinical data from 66 patients with recurrent glioblastoma and repeated surgery were analyzed. Kaplan–Meier plots were produced to illustrate survival in each of the three NSGS prognostic groups, and Cox proportional hazard regression was used to identify prognostic variables. Multivariable analysis was used to identify differences in survival in the three prognostic groups. Results: Six variables significantly affected postoperative survival: preoperative Karnofsky Performance Status (KPS)

Context About 30% of patients with active acromegaly experience paradoxically increased growth hormone (GH) secretion during the diagnostic oral glucose tolerance test (OGTT). Endogenous glucose-dependent insulinotropic polypeptide (GIP) is implicated in this paradoxical secretion. Objective We used the GIP receptor (GIPR) antagonist GIP(3-30)NH2 to test the hypothesis that GIP mediates this paradoxical response when GIPR is abundantly expressed in somatotropinomas. Methods A total of 25 treatment-naive patients with acromegaly were enrolled. Each patient underwent one OGTT during simultaneous placebo infusion and one OGTT during a GIP(3-30)NH2 infusion. Blood samples were drawn at baseline and regularly after infusions to measure GH. We assessed pituitary adenoma size by magnetic resonance imaging and GIPR expression by immunohistochemistry on resected somatotropinomas. For mechanistic confirmation, we applied in vitro and ex vivo approaches. The main outcome measure was the effect of GIP(3-30)NH2 on paradoxical GH secretion during OGTT as a measure of GIP involvement. Results In 4 of 7 patients with paradoxical GH secretion, GIP(3-30)NH2 infusion completely abolished the paradoxical response (P =.0003). Somatotrophs were available from 3 of 4 of these patients, all showing abundant GIPR expression. Adenoma size did not differ between patients with and without paradoxical GH secretion. Conclusion Of 25 patients with acromegaly, 7 had paradoxical GH secretion during OGTT, and pharmaceutical GIPR blockade abolished this secretion in 4. Corresponding somatotroph adenomas abundantly expressed GIPR, suggesting a therapeutic target in this subpopulation of patients. In vitro and ex vivo analyses confirmed the role of GIP and the effects of the antagonist. [ABSTRACT FROM AUTHOR]

Introduction: Occipital condyle fracture (OCF) is rare. It may, however, pose a serious threat to the patient due to destabilization of the craniocervical junction. Correct diagnosis and effective treatment are essential to prevent long-term complications. The aim of this study was to retrospectively investigate our current treatment program with focus on the functional outcome. Diagnosis and classification systems were evaluated for their usefulness in the clinical practice. Materials and Methods: We retrospectively reviewed all patients treated conservatively for an occipital condylar fracture from 2010 to 2015 at our department. Fracture classifications were performed according to three established systems. The patients were followed up with clinical examination and plain radiographs at weeks 2, 6, and 12 with the addition of a dynamic flexion-extension X-ray at week 14. Results: Totally 24 patients met the inclusion criteria. One was lost to follow-up and two ended treatment before completing the full treatment program due to a clinical decision. Fracture displacement was neither detected nor was any neurological deficits observed. Most patients were pain free after 6 weeks. After 14 weeks' treatment, two patients still had neck pain; the rest were pain free. Conclusions: Our data suggest that twelve weeks' conservative treatment is not necessary for unilateral OCFs without atlanto-occipital dissociation (AOD). We recommend 6 weeks of conservative treatment, with clinical control and flexion-extension radiographs before ending treatment. Plain radiography is of limited value in the clinical control of this fracture type. Anderson and Montesano and Tuli et al. classification systems fulfill an academic role. We found the classification system by Mueller et al. to be more helpful in everyday clinical practice.

Background and purpose: Venous thromboembolism (VTE) is a cause of increased morbidity and risk of death. Studies report VTE in up to 30% of glioma patients but the results vary. The VTE risk is relevant when evaluating prophylaxis to avoid unnecessary bleeding or overdiagnosis. This study examines the VTE incidence in patients with glioma WHO grade 2-4, and when VTE occurred, risk factors, and overall survival (OS) for patients with WHO grade 4. Materials and methods: In total 3,630 patients with WHO grade 2 (n = 230), grade 3 (n = 317), and grade 4 (n = 3,083) gliomas from 2010 to 2018 were identified using the Danish Neuro-Oncology Registry. VTE diagnoses and time of death were obtained from Statistics Denmark. Results and Interpretation: The VTE incidence was 5.2, 6.3, and 6.8% in patients with WHO grade 2, 3, and 4 gliomas, respectively. The VTE incidence rate was highest during the first 3 months after the diagnosis with 53 events. Increasing age (HR 1.03, 95%CI 1.01-1.04), male sex (HR 1.47, 95%CI 1.09-1.99), poor performance status (HR 1.57, 95%CI 1.10-2.25), and post-operative long-course radiochemotherapy (HR 2.10, 95%CI 1.19-3.72) were predictors of VTE in patients with glioma WHO grade 4. There was no difference in OS comparing patients having VTE to those without (p = 0.068). In conclusion, patients with glioma WHO grade 2-4 were at high risk of VTE, especially the first 3 months after diagnosis. Increasing age, male sex, poor performance status, and long-course radiochemotherapy were associated with increased risk of VTE in patients with glioma WHO grade 4. [ABSTRACT FROM AUTHOR]

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 micro-dialysis allows continuous sampling of extracellular metabolites, including glucose, lactate and pyruvate. Transient ischemic events cause a rapid drop in glucose and a rise in lactate levels. Following such events, the lactate/pyruvate (L/P) ratio may remain elevated for a prolonged period of time. In neurointensive care clinics, this ratio is considered a metabolic marker of ischemia and/or mitochondrial dysfunction. Here we propose a novel, sensitive microdialysis liquid chromatography-mass spectrometry (LC-MS) approach to monitor mitochondrial dysfunction in living brain using perfusion with 13C-labeled succinate and analysis of 13C-labeled tricarboxylic acid cycle (TCA) intermediates. This approach was evaluated in rat brain using malonate-perfusion (10−50 mM) and endothelin-1 (ET-1)-induced transient cerebral ischemia. In the malonate model, the expected changes upon inhibition of succinate dehydrogenase (SDH) were observed, i.e., an increase in endogenous succinate and decreases in fumaric acid and malic acid. The inhibition was further elaborated by incorporation of 13C into specific TCA intermediates from 13C-labeled succinate. In the ET-1 model, increases in non-labeled TCA metabolites (reflecting release of intracellular compounds) and decreases in 13C-labeled TCA metabolites (reflecting inhibition of de novo synthesis) were observed. The analysis of 13C incorporation provides further layers of information to identify metabolic disturbances in experimental models and neuro-intensive care patients.

Objective: To explore the feasibility of home monitoring of epilepsy patients with a novel subcutaneous electroencephalography (EEG) device, including clinical implications, safety, and compliance via the first real‐life test. Methods: We implanted a beta‐version of the 24/7 EEG SubQ (UNEEG Medical A/S, Denmark) subcutaneously in nine participants with temporal lobe epilepsy. Data on seizures, adverse events, compliance in using the device, and use of antiepileptic drugs (AEDs) were collected. EEG was recorded for up to 3 months, and all EEG data were reviewed visually to identify electrographic seizures. These were descriptively compared to seizure counts and AED changes reported in diaries from the same period. Results: Four hundred ninety days of EEG and 338 electrographic seizures were collected. Eight participants completed at least 9 weeks of home monitoring, while one cancelled participation after 4 weeks due to postimplantation soreness. In total, 13 cases of device‐related adverse events were registered, none of them serious. Recordings obtained from the device covered 73% of the time, on average (range 45%‐91%). Descriptively, electrographic seizure counts were substantially different from diary seizure counts. We uncovered several cases of underreporting and revealed important information on AED response. Electrographic seizure counts revealed circadian distributions of seizures not visible from seizure diaries. Significance: The study shows that home monitoring for up to 3 months with a subcutaneous EEG device is feasible and well tolerated. No serious adverse device‐related events were reported. An objective seizure count can be derived, which often differs substantially from self‐reported seizure counts. Larger clinical trials quantifying the benefits of objective seizure counting should be a priority for future research as well as development of algorithms for automated review of data. [ABSTRACT FROM AUTHOR]

Background: Compromised cerebral energy metabolism is common in patients with bacterial meningitis. In this study, simultaneous measurements of cerebral oxygen tension and lactate/pyruvate ratio were compared to explore whether disturbed energy metabolism was usually caused by insufficient tissue oxygenation or compromised oxidative metabolism of pyruvate indicating mitochondrial dysfunction.Subject and Methods: Ten consecutive patients with severe streptococcus meningitis were included in this prospective cohort study. Intracranial pressure, brain tissue oxygen tension (PbtO2 ), and energy metabolism (intracerebral microdialysis) were continuously monitored in nine patients. A cerebral lactate/pyruvate (LP) ratio <30 was considered indicating normal oxidative metabolism, LP ratio >30 simultaneously with pyruvate below lower normal level (70 µmol/L) was interpreted as biochemical indication of ischemia, and LP ratio >30 simultaneously with a normal or increased level of pyruvate was interpreted as mitochondrial dysfunction. The biochemical variables were compared with PbtO2 simultaneously monitored within the same cerebral region.Results: In two cases, the LP ratio was normal during the whole study period and the simultaneously monitored PbtO2 was 18 ± 6 mm Hg. In six cases, interpreted as mitochondrial dysfunction, the simultaneously monitored PbtO2 was 20 ± 6 mm Hg and without correlation with the LP ratio. In one patient, exhibiting a pattern interpreted as ischemia, PbtO2 decreased below 10 mm Hg and a correlation between LP and PbtO2 was observed.Conclusion: This study demonstrated that compromised cerebral energy metabolism, evidenced by increased LP ratio, was common in patients with severe bacterial meningitis while not related to insufficient tissue oxygenation. [ABSTRACT FROM AUTHOR]

Introduction: Occipital condyle fracture (OCF) is rare. It may, however, pose a serious threat to the patient due to destabilization of the craniocervical junction. Correct diagnosis and effective treatment are essential to prevent long-term complications. The aim of this study was to retrospectively investigate our current treatment program with focus on the functional outcome. Diagnosis and classification systems were evaluated for their usefulness in the clinical practice. Materials and Methods: We retrospectively reviewed all patients treated conservatively for an occipital condylar fracture from 2010 to 2015 at our department. Fracture classifications were performed according to three established systems. The patients were followed up with clinical examination and plain radiographs at weeks 2, 6, and 12 with the addition of a dynamic flexion-extension X-ray at week 14. Results: Totally 24 patients met the inclusion criteria. One was lost to follow-up and two ended treatment before completing the full treatment program due to a clinical decision. Fracture displacement was neither detected nor was any neurological deficits observed. Most patients were pain free after 6 weeks. After 14 weeks' treatment, two patients still had neck pain; the rest were pain free. Conclusions: Our data suggest that twelve weeks' conservative treatment is not necessary for unilateral OCFs without atlanto-occipital dissociation (AOD). We recommend 6 weeks of conservative treatment, with clinical control and flexion-extension radiographs before ending treatment. Plain radiography is of limited value in the clinical control of this fracture type. Anderson and Montesano and Tuli et al. classification systems fulfill an academic role. We found the classification system by Mueller et al. to be more helpful in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Background:The aim of this study was to evaluate the clinical outcome of patients with severe bacterial meningitis where intracranial pressure (ICP) monitoring has been performed. Methods:A retrospective observational study including patients admitted 1st.January 2005 to 31st.December 2014. Thirty nine patients age 18–89 years were included. All the patients received intensive care with mechanical ventilation, ICP monitoring, sedation, antibiotics and corticosteroids according to current guidelines. Clinical outcome was defined as death during hospitalization or survival at hospital discharge. Results:The most common pathogen wasStreptococcus pneumoniae(26; 67%). Thirteen patients died (33%) and neurologic impairment was noted in twenty two (84.6%) surviving patients. InS. pneumoniaecases patients with adverse outcome were significantly older (p = 0.0024) and immunosuppressed (p = 0.034). Lower mean-cerebral perfusion pressure (CPP) was found to correlate with adverse outcome (p = 0.005). Cerebrospinal fluid (CSF) was drained in fourteen patients. Increased ICP (>20 mmHg) was observed in twenty four patients. No significant correlation was found between measured ICP and head CT scans with signs of elevated ICP. Conclusions:Patients with severe meningitis should be admitted to intensive care units and evaluated for ICP monitoring regardless of head CT findings. [ABSTRACT FROM PUBLISHER]