The use of hybrid operating rooms in neurosurgery, advantages, disadvantages, and future perspectives: a systematic review.

BACKGROUND: Hybrid operating rooms (hybrid-ORs) combine the functionalities of a conventional surgical theater with the advanced imaging technologies of a radiological suite. Hybrid-ORs are usually equipped with CBCT devices providing both 2D and 3D imaging capability that can be used for both interventional radiology and image guided surgical applications. Across all fields of surgery, the use of hybrid-ORs is gaining in traction, and neurosurgery is no exception. We hence aimed to comprehensively review the use of hybrid-ORs, the associated advantages, and disadvantages specific to the field of neurosurgery. MATERIALS AND METHODS: Electronic databases were searched for all studies on hybrid-ORs from inception to May 2022. Findings of matching studies were pooled to strengthen the current body of evidence. RESULTS: Seventy-four studies were included in this review. Hybrid-ORs were mainly used in endovascular surgery (n = 41) and spine surgery (n = 33). Navigation systems were the most common additional technology employed along with the CBCT systems in the hybrid-ORs. Reported advantages of hybrid-ORs included immediate assessment of outcomes, reduced surgical revision rate, and the ability to perform combined open and endovascular procedures, among others. Concerns about increased radiation exposure and procedural time were some of the limitations mentioned. CONCLUSION: In the field of neurosurgery, the use of hybrid-ORs for different applications is increasing. Hybrid-ORs provide preprocedure, intraprocedure, and end-of-procedure imaging capabilities, thereby increasing surgical precision, and reducing the need for postoperative imaging and correction surgeries. Despite these advantages, radiation exposure to patient and staff is an important concern.

Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalization: a European multinational economic evaluation.

AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS: The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within 1 year. CONCLUSIONS: This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment.

The impact of myocardial fibrosis biomarkers in a heart failure population with atrial fibrillation-The HARVEST-Malmö study.

Background: Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF. Materials and methods: Patients hospitalized for HF (n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (ST-2), galectin-3 (GAL-3), growth/differentiation factor-15 (GDF-15), and matrix metalloproteinase 2, 3, and 9 (MMP-3, MMP-3, and MMP-9, respectively)] were analyzed using a proximity extension assay. Proteins with significant Bonferroni-corrected associations with mortality and re-hospitalization risk were taken forward to multivariable Cox regression analyses. Further, Bonferroni-corrected multivariable logistic regression models were used to study associations between protein plasma levels, prevalent AF, and severely enlarged left atrial volume index (LAVI ≥ 48 ml/m2). Results: Prevalent AF was observed in 194 patients at the hospitalization of whom 178 (92%) were re-hospitalized and 111 (57%) died during the follow-up period. In multivariable logistic regression models, increased plasma levels of TIMP-4, GDF-15, and ST-2 were associated with the prevalence of AF, whereas none of the seven proteins showed any significant association with severely enlarged LAVI. Increased plasma levels of five proteins yielded significant associations with all-cause mortality in patients with co-existing AF; TIMP-4 (HR 1.33; CI95% 1.07-1.66; p = 0.010), GDF-15 (HR 1.30; CI95% 1.05-1.62; p = 0.017), GAL-3 (HR 1.29; CI95% 1.03-1.61; p = 0.029), ST-2 (HR 1.48; CI95% 1.18-1.85; p < 0.001), and MMP-3 (HR 1.33; CI95% 1.09-1.63; p = 0.006). None of the proteins showed any significant association with re-hospitalization risk. Conclusion: In this study, we were able to demonstrate that elevated levels of three plasma proteins previously linked to myocardial fibrosis are associated with prevalent AF in a HF population. Additionally, higher levels of five plasma proteins yielded an increased risk of mortality in the HF population with or without co-existing AF.

Natural history and management of spinal cord arteriovenous shunts in pregnancy: A monocentric series of 10 consecutive cases with emphasis on endovascular treatment.

PURPOSE: Intradural spinal cord arteriovenous shunts (IDSCAVS) are rare and constitute a challenging situation if symptoms occur during pregnancy. We present a series of ten such cases referred to our center: five cervical, four thoracic and one lumbar. METHODS: We retrospectively reviewed our global series of 215 IDSCAVSs between 2002 and March 2020 and found ten patients who had presented during pregnancy. Clinical, radiological and therapeutic data were studied. RESULTS: Seven shunts were AVM type niduses and three were micro AV-fistulae. All were associated with pial venous reflux and six hemorrhagic cases had pseudo aneurysms. Symptoms occurred mainly during the third trimester, 80% of patients presented with hemorrhage and spinal cord dysfunction. We embolized seven patients and proposed surgery in one, always after delivery: all recovered well. One woman declined treatment; one other was operated in emergency but did not improve. Mean follow-up was 3.9 years (0.5...19 years). CONCLUSIONS: Despite this small group of patients, our initial experience of IDSCAVSs diagnosed during pregnancy indicates that embolization is an effective management strategy if performed after delivery and a recovery period. Results indicate that IDSCAVSs seem to have a low risk of early rebleedings after the ictal event and may be closely followed up until delivery. The results obtained show good clinical outcome without long-term rebleeds. Women with known IDSCAVSs should not be discouraged from becoming pregnant, however it seems wise to embolize them before pregnancy in order to offer protection against risks during pregnancy.

Identifying clot composition using intravascular diffuse reflectance spectroscopy in a porcine model of endovascular thrombectomy.

BACKGROUND: Endovascular thrombectomy has revolutionized the management of acute ischemic stroke and proven superior to stand-alone intravenous thrombolysis for large vessel occlusions. However, failed or delayed revascularization may occur as a result of a mismatch between removal technique and clot composition. Determination of clot composition before thrombectomy provides the possibility to adapt the technique to improve clot removal efficacy. We evaluated the application of diffuse reflectance spectroscopy (DRS) for intravascular determination of clot composition in vivo. METHODS: Three clot types, enriched in red blood cells or fibrin or with a mixed content, were prepared from porcine blood and injected into the external carotids of a domestic pig. A guidewire-like DRS probe was used to investigate the optical spectra of clots, blood and vessel wall. Measurement positions were confirmed with angiography. Spectra were analyzed by fitting an optical model to derive physiological parameters. To evaluate the method's accuracy, photon scattering and blood and methemoglobin contents were included in a decision tree model and a random forest classification. RESULTS: DRS could differentiate between the three different clot types, blood and vessel wall in vivo (p<0.0001). The sensitivity and specificity for detection was 73.8% and 98.8% for red blood cell clots, 80.6% and 97.8% for fibrin clots, and 100% and 100% for mixed clots, respectively. CONCLUSION: Intravascular DRS applied via a custom guidewire can be used for reliable determination of clot composition in vivo. This novel approach has the potential to increase efficacy of thrombectomy procedures in ischemic stroke.

The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study.

AIMS: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. METHODS AND RESULTS: The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. CONCLUSION: In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.

BACKGROUND: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.

Risk prediction of future cardiac arrest by evaluation of a genetic risk score alone and in combination with traditional risk factors.

OBJECTIVES: Coronary heart disease (CHD) is a leading cause of death globally, commonly through sudden cardiac death. Cardiac arrest of cardiac origin (CA) is associated with a poor prognosis and there is a great need for risk assessment and intensified preventive actions. In this study we aim to assess if a genetic risk score for CHD, composed of 50 common CHD susceptibility variants (GRS), predicts CA and to evaluate a novel composite risk score including traditional risk factors as well as GRS. METHODS: The GRS score alone and in combination with traditional CHD risk factors were examined in relation to CA incidence among 23 000 middle aged subjects during 18.9 years of follow-up. The cohort excluded patients with a diagnosed history of CHD, heart failure or stroke. RESULTS: Two-hundred-fifty-two patients suffered a cardiac arrest during the follow up, of which 181 were CA. In a multivariate model with CHD risk factors, high versus low genetic risk predicted CA with a hazard ratio (HR) of 2.49 {(95% CI 1.50-4.12) (P < 0.001)}, surpassed only by higher estimates for male sex {HR = 2.91 (95% CI 2.09-4.06) (P < 0.001)}, ages 50-65 {HR = 2.74 (95% CI 1.42-5.25) (P = 0.003)} and ages 65-74 {HR = 5.10 (95% CI 2.56-10.16) (P < 0.001)}. Smoking, dyslipidemia, hypertension and diabetes mellitus also predicted CA but with lower HRs than GRS. A novel composite risk score including CHD risk factors as well as GRS predicted CA with a HR = 110.81 {(95% CI 15.43-795.63) (P < 0.001)} for the highest (5) versus the lowest quintile (1) of the risk score. CONCLUSIONS: Genetic risk of CHD is strongly associated with incident CA and when combined with traditional CHD risk factors may identify individuals who benefit from intensified preventive pharmacological treatment.

Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure.

AIMS: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. METHODS: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. CONCLUSION: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.

Vascular complications in pediatric craniopharyngioma patients: a case-based update.

PURPOSE: Craniopharyngiomas remain a challenging entity for neurosurgeons because of their deep-seated, midline location, and intimate relationship with critical neurovascular structures. With high long-term survival rates, patients with craniopharyngioma are likely to experience significant late morbidity related to both disease and therapy. METHOD AND RESULTS: In this paper, we present two cases of late vascular complications after multi-modal treatment of craniopharyngioma. CONCLUSION: Available data suggests that pediatric patients with craniopharyngioma represent a particularly vulnerable group.

Thrombectomy using the EmboTrap device: core laboratory-assessed results in 201 consecutive patients in a real-world setting.

BACKGROUND: We studied patients treated with the EmboTrap revascularization device in a prospective registry which is core laboratory evaluated by physicians from external centers. The goal was to determine how the EmboTrap would perform under the everyday conditions of a high-volume stroke center. METHODS: We examined all patients with acute stroke treated with the Embotrap device from October 2013 to March 2017 in our center. Imaging parameters and times were adjudicated by core laboratory personnel blinded to clinical information, treating physician, and clinical outcomes. Clinical evaluation was performed by independent neurologists and entered in a national registry. Evaluated endpoints were: successful revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS) 0-2). RESULTS: 201 consecutive patients with a median NIH Stroke Scale (NIHSS) score of 15 (range 2-30) were included. 170 patients (84.6%) achieved mTICI 2b-3 reperfusion. The median number of attempts was 2 (range 1-10) with 52.8% of the population achieving good functional outcomes (mRS 0-2) at 3 months. On univariate analysis, good functional outcome was associated with the number of attempts, puncture-to-reperfusion time, anterior circulation occlusion, and NIHSS score. On multivariate analysis, pre-treatment NIHSS (OR 0.845 per point, 95% CI 0.793 to 0.908, P<0.001) and puncture-to-reperfusion time (OR 0.9952 per min, 95% CI 0.9914 to 0.9975, P=0.023) were associated with good functional outcomes at 3 months. CONCLUSION: The Embotrap device has a high rate of successful reperfusion. Our core laboratory-audited single-center experience suggests the technical feasibility and safety of the Embotrap for first-line use in a real-world setting.

Midlife risk factor exposure and incidence of cardiac arrest depending on cardiac or non-cardiac origin.

OBJECTIVE: Little is known about midlife risk factors of future cardiac arrest. Our objective was to evaluate cardiovascular risk factors in midlife in relation to the risk of cardiac arrest (CA) of cardiac and non-cardiac origin later in life. METHODS: We cross-matched individuals of the population based Malmö Diet and Cancer study (n=30,447) with the local CA registry of the city of Malmö. Baseline exposures were related to incident CA. RESULTS: During a mean follow-up of 17.6±4.6years, 378 CA occurred, of whom 17.2% survived to discharge. Independent midlife risk factors for CA of cardiac origin included coronary artery disease {HR 2.84 (1.86-4.34) (p<0.001)}, diabetes mellitus {HR 2.37 (1.61-3.51) (p<0.001)} and smoking {HR 1.95 (1.49-2.55) (p<0.001)}. Dyslipidemia and history of stroke were also significantly associated with an elevated risk for CA of cardiac origin. Independent midlife risk factors for CA of non-cardiac origin included obesity (BMI>30kg/m2) {HR 2.37 (1.51-3.71) (p<0.001)}, smoking {HR 2.05 (1.33-3.15) (p<0.001)} and being on antihypertensive treatment {HR 2.25 (1.46-3.46) (p<0.001)}. CONCLUSION: Apart from smoking, which increases the risk of CA in general, the midlife risk factor pattern differs between CA of cardiac and non-cardiac origin. Whereas CA of cardiac origin is predicted by history of cardiovascular disease, dyslipidemia and diabetes mellitus, the main risk factors for CA of non-cardiac origin are obesity and hypertension. In addition to control of classical cardiovascular risk factors for prevention of CA, our results suggest that prevention of midlife obesity may reduce the risk of CA of non-cardiac origin.

Adjuvant Stereotactic Radiosurgery Reduces Need for Retreatments in Patients with Meningioma Residuals.

BACKGROUND: Radical surgical resection of cerebral meningiomas involving the dura mater of venous sinuses is challenging, and tumor residuals are frequently left after surgery. This study sought to evaluate the effect of adjuvant stereotactic radiosurgery (aSRS) on the time to significant growth of meningioma residuals requiring retreatment. METHODS: A total of 119 consecutive patients (2004-2013) receiving primary surgical treatment for a meningioma in proximity to a venous structure were included. The patients were assessed retrospectively, with a focus on retreatments and mortality. Radicality of initial tumor surgery was scored using postoperative magnetic resonance imaging. Three subgroups were identified: 1) radical total resection (RTR); 2) near-total resection (NTR), followed by aSRS (NTR + aSRS); and 3) NTR but no aSRS (NTR - aSRS). In the NTR - aSRS group, intervention was initiated after radiologic (magnetic resonance imaging) findings verified growth of residual tumor, in contrast to the NTR + aSRS group, which received aSRS before regrowth. Time to first retreatment, progression-free survival (PFS), and overall survival were analyzed with the log-rank test and multiple-events Cox regression. RESULTS: RTR was associated with the best prognosis. The patients in the NTR + aSRS group had significantly longer time to first retreatment compared with NTR - aSRS patients (P < 0.001). There was also a significant difference in mortality (P < 0.05) and a tendency to prolonged PFS (P = 0.07) in the NTR + aSRS group. The Cox regressions confirmed the positive effects of NTR + aSRS on time to retreatment (hazard ratio, 7.3; P < 0.01) and PFS (hazard ratio, 3.69; P = 0.055). CONCLUSIONS: aSRS of meningioma residuals had a positive effect on tumor control and should be considered in patients with meningioma residuals.

Brilliant blue G treatment facilitates regeneration after optic nerve injury in the adult rat.

Injuries to the adult mammalian visual system often lead to functional deficits with little or no chance of spontaneous recovery. Previous studies in rats have demonstrated beneficial effects of inhibition of the P2X7 receptor with brilliant blue G (BBG) after spinal cord injury; however, little is known about BBG as a potential treatment strategy for optic nerve injuries. Adult Sprague-Dawley rats were subjected to a controlled optic nerve crush lesion and randomized to treatment with BBG (50 mg/kg body weight intravenously) or vehicle for 2 days after injury. The temporal pattern of axonal breakdown and regeneration, as well as formation of the glial scar and microglia/macrophage activation, was studied at 7, 14, and 28 days after lesion induction by immunohistochemical analysis. Results show reduced glial scar formation, less macrophage activation, and signs indicative of axonal regeneration beyond the glial scar in treated animals. No significant side effects from the treatment were observed. Effects on axonal breakdown, regeneration, and glial scar formation are discussed in relation to the proposed beneficial effects of BBG treatment. The present study demonstrates positive effects of BBG treatment on neural repair after traumatic optic nerve injury, and also shows its feasibility as a proposed future clinical treatment strategy.

Evaluation of pre-arrest morbidity score and prognosis after resuscitation score and other clinical variables associated with in-hospital cardiac arrest in southern Sweden.

OBJECTIVE: To evaluate pre-arrest morbidity score (PAM), prognosis after resuscitation score (PAR) and to identify additional clinical variables associated with survival after in-hospital cardiac arrest (IHCA) treated with cardiopulmonary resuscitation (CPR). METHODS: A retrospective observational study involving all cases of IHCA at Skåne University Hospital Malmö 2007-2010. RESULTS: Two-hundred-eighty-seven cases of IHCA were identified (61.3% male; mean age 70 years) of whom 20.2% survived until discharge. The odds ratio (95% confidence interval) for death prior to discharge was 6.49 (1.50-28.19) (p=0.013) for PAM>6 and 3.88 (1.95-7.73) (p<0.001) for PAR>4. At PAM- and PAR-scores >5, specificity exceeded 90%, while sensitivity was only 20-30%. The odds ratio for in-hospital mortality was 0.38 (0.20-0.72) (p=0.003) for patients with cardiac monitoring, 9.86 (5.08-19.12) (p<0.001) for non-shockable vs shockable rhythm, 0.32 (0.15-0.69) (p=0.004) for presence of ST-elevation myocardial infarction (STEMI), 0.27 (0.09-0.78) (p=0.016) for patients with independent Activities of Daily Life (ADL) and 13.86 (1.86-103.46) (p=0.010) for patients with malignancies. Heart rate (HR) on admission (per bpm) [1.024 (1.009-1.040) (p=0.002)] and sodium plasma concentration on admission (per mmoll(-1)) [0.92 (0.85-0.99) (p=0.023)] were significantly associated with in-hospital mortality. CONCLUSION: PAM- and PAR-scores do not sufficiently discriminate between in-hospital death and survival after IHCA to be used as clinical tools guiding CPR decisions. We confirm that malignancy is associated with increased in-hospital mortality, and cardiac monitoring, shockable rhythm, STEMI and independent ADL, with decreased in-hospital mortality. Interestingly, our results suggest that HR and plasma sodium concentration upon admission may represent new tools for risk stratification.

Increased survival using delayed gamma knife radiosurgery for recurrent high-grade glioma: a feasibility study.

OBJECTIVE: The current study retrospectively assessed delayed gamma knife radiosurgery (GKRS) in the management of high-grade glioma recurrences. METHODS: A total of 55 consecutive patients with high-grade glioma comprising 68 World Health Organization (WHO) III and WHO IV were treated with GKRS for local recurrences between 2001 and 2007. All patients had undergone microsurgery and radiochemotherapy, considered as standard therapy for high-grade glioma. Complete follow-up was available in all patients; median follow-up was 17.2 months (2.5-114.2 months). Median tumor volume was 5.2 mL, prescription dose was 20 Gy (14-22 Gy), and median max dose was 45 Gy (30-77.3 Gy). RESULTS: The patients with WHO III tumors showed a median survival of 49.6 months with and a 2-year survival of 90%. After GKRS of the recurrences, these patients showed a median survival of 24.2 months and a 2-year survival of 50%. The patients with WHO IV tumors had a median survival of 24.5 months with a 2-year survival of 51.4%. After the recurrence was treated with GKRS, the median survival was 11.3 months and a 2-year survival: 22.9% for the WHO IV patients. CONCLUSION: The current study shows a survival benefit for high-grade glioma recurrences when GKRS was administered after standard therapy. This is a relevant improvement compared with earlier studies that had had not been able to provide a beneficial effect timing radiosurgery in close vicinity to EBRT.

Glial reactions in a rodent cauda equina injury and repair model.

In the adult rat, an avulsion injury of lumbosacral ventral roots results in a progressive and pronounced loss of the axotomized motoneurons. A subsequent acute implantation of an avulsed ventral root into the spinal cord has neuroprotective effects. However, it has not been known whether a surgical implantation of an avulsed ventral root into the spinal cord for neural repair purposes affects intramedullary glial and microglial reactions. Here, adult female Sprague-Dawley rats underwent a unilateral L5-S2 ventral root avulsion injury with or without acute implantation of the L6 ventral root into the spinal cord. At 4 weeks postoperatively, immunohistochemistry using primary antibodies to GFAP (astrocytes), Ox-42 (microglia), and ED-1 (macrophages) was performed at the L6 spinal cord segment, and quantified using densitometry. Our results show that a lumbosacral ventral root avulsion injury induces an activation of astrocytes, microglia, and macrophages in the ventral horn. Interestingly, an acute implantation of an avulsed root into the white matter does not significantly affect the activation of glial cells or macrophages in the ventral horn. We speculate that neuroprotective and axonal growth promoting benefits of the combined glial and microglial/ macrophage responses may outweigh their potential negative effects, as previous studies have shown that implantation of avulsed roots is a successful strategy in promoting reinnervation of peripheral targets.

Methylprednisolone treatment does not influence axonal regeneration or degeneration following optic nerve injury in the adult rat.

BACKGROUND: Methylprednisolone (MP) is often used to treat optic nerve injury. However, its effects in experimental crush injury have not been extensively evaluated. METHODS: Adult Sprague-Dawley rats were subjected to a standardized optic nerve crush injury. Animals were treated either with 30 mg/kg MP intravenous bolus followed by subcutaneous injections every 6 hours for 48 hours, or with a drug vehicle alone. RESULTS: The injury resulted in a partial loss of neuronal nuclei-labeled retinal neurons and a corresponding degeneration of axons distal to the injury. EDI-labeled macrophages accumulated at the site of lesion, phagocyting FJ-labeled axonal debris. Regenerative fibers expressing growth associated protein-43 were seen proximal to the lesion, but did not traverse the glial scar. Analysis of optic nerve function using visual evoked potentials showed typical signals in intact animals, which were abolished after injury in MP-treated and untreated animals. CONCLUSIONS: We did not detect any effects of MP on retinal cell survival, macrophage activity at the site of injury, axonal degeneration/regeneration, or visual function. These experimental results provide a physiologic underpinning for the lack of efficacy demonstrated in a large trial of MP treatment of clinical optic nerve injury.

A temporal study of axonal degeneration and glial scar formation following a standardized crush injury of the optic nerve in the adult rat.

PURPOSE: In this methodological study, we describe a standardized optic nerve injury model in adult rats. The temporal pattern of the glial response is mapped in relation to axonal regeneration and degeneration. METHODS: A standardized optic nerve crush injury was made in adult rats, using a fine pair of forceps with a preset pressure of 0.6 N during 10 seconds. RESULTS: This crush injury resulted in a pronounced astroglial and microglial proliferation 2-7 dpi. Degenerative axons distal to the lesion presented a gradual decrease in neurofilament immunoreactivity. In contrast, Fluoro-Jade staining was gradually increased in these degenerative axons from 2-7 dpi. Regeneration was observed proximal to the lesion in sprouts double labeled with the tracer Fluoro-Gold and anti-GAP43. CONCLUSION: The standardized optic nerve crush injury model used in the present study resulted in a reproducible degenerative pattern including a pronounced astroglial and microglial proliferation. The gradual decrease in Neurofilament immunoreactivity in degenerative axons, and a gradual increase in Fluoro-Jade staining was paralleled with a spontaneous regeneration proximal to the lesion, shown with tracing and GAP43-immunoreactivity. The combination of these markers and this experimental setup thus allows analysis of the entire degenerative/regenerative process in a standardized CNS axotomy model.

Macrophage stimulation using a group B-streptococcus exotoxin (CM101) leads to axonal regrowth in the injured optic nerve.

PURPOSE: A group B-streptococcus exotoxin (CM101) was administered following optic nerve injury in adult rats in order to analyze putative effects on macrophages, glial scar formation and regrowth of axons in the lesioned optic nerve. METHODS: After a standardized intraorbital optic nerve crush, animals were randomized to treatment with CM101 (30 microm/kg body weight, iv, repeated every other day) or vehicle alone. Morphology (semithin sections) and immunohistochemistry directed towards macrophages (ED1), neurofilament (NF), astrocytes (GFAP) and regenerative sprouts (GAP43) were employed at different time-points up to 28 dpi. RESULTS: A significant increase of ED1-positive macrophages (p < 0.05) was observed at 7, 14 and 28 dpi in treated animals compared to untreated, indicative of macrophage stimulation. Less degenerative structures were found in sections distal to the injury in treated animals, seemingly due to a pro-phagocytic effect. Reactive gliosis was significantly (p < 0.05) less pronounced in CM101-treated animals. The presence of GAP43-positive sprouts and neurofilament-positive neurites distal to the lesion in treated animals indicate regrowth of axons crossing the glial scar. CONCLUSION: Treatment with group B-streptococcus exotoxin leads to macrophage stimulation, increased phagocytosis of inhibitory debris, and a less dense reactive gliosis, which in turn allows for regrowth of axons through the glial scar.