Early goal-directed management after out-of-hospital cardiac arrest: lessons from a certified cardiac Arrest centre.

BACKGROUND: Despite continuous advances in post-resuscitation management, outcome after out-of-hospital cardiac arrest (OHCA) is limited. To improve the outcome, interdisciplinary Cardiac Arrest Centers (CACs) have been established in recent years, but survival remains low and treatment strategies vary considerably in clinical and geographical aspects. Here we analyzed a strategy of in-hospital post-resuscitation management while evaluating the outcome. METHODS: A broad spectrum of pre- and in-hospital parameters of 545 resuscitated patients, admitted to the Cardiac Arrest Center of the University Hospital of Marburg (MCAC) between 01/2018 and 12/2022 were retrospectively analyzed. Inclusion criteria were ≥ 18 years, resuscitation by emergency medical services, and non-traumatic cause of OHCA. RESULTS: In the overall patient cohort, the survival rate to hospital discharge was 39.8% (n = 217/545), which is 50.7% higher than in the EuReCa-TWO registry. 77.2% of the survivors had CPC status 1 or 2 (favorable neurological outcome) before and after therapy. A standardized 'therapy bundle' for in-hospital post-resuscitation management was applied to 445 patients who survived the initial treatment in the emergency department. In addition to basic care (standardized antimicrobial therapy, adequate anticoagulation, targeted sedation, early enteral and parenteral nutrition), it includes early whole-body CT (n = 391; 87.9%), invasive coronary diagnostics (n = 322; 72.4%), targeted temperature management (n = 293; 65.8%) and if indicated, mechanical circulatory support (n = 145; 32.6%) and appropriate neurological diagnostics. CONCLUSIONS: Early goal-directed post-resuscitation management in a well-established and highly frequented CAC leads to significantly higher survival rates. However, our results underline the need for a broader standardization in post-resuscitation management to ultimately improve the outcome.

Dynamics in the Neurotrauma Catchment Area of a German University Hospital during the COVID-19 Pandemic.

Objective: At the beginning of 2020, the COVID-19 pandemic enforced a rapid reallocation of healthcare resources. Our neurosurgical department is located in the German county of Marburg−Biedenkopf, about 80 km from the nearest major city. We were able to maintain our previously established open-door policy after the emergence of COVID-19. Here, we report on dynamics in the catchment area for neurotrauma patients at our department during the pandemic. Methods: 763 consecutive neurotrauma cases admitted to our department between 1 January 2018 and 31 December 2021 were analyzed retrospectively. Patients' age, gender, origin, diagnoses, and outcomes were recorded. The number of patients hospitalized with a COVID-19 infection in Germany (PHCG) were retrieved from the Robert Koch Institute (RKI). We defined calendar weeks with >1000 PHCG as high COVID-19 caseload weeks (HCLW). Chi-square and Fisher's exact served as statistical tests. Results: In 2020 and 2021, we observed a significantly increased number of neurotrauma patients who, with primary residence outside of our district, were admitted to our hospital compared to 2018 and 2019 (p < 0.001), while there were no significant differences in in-house mortality. During HCLW, a significantly increased number of neurotrauma patients with primary residence in the densely populated southwestern margin (SWM) of the contiguous part of our catchment area were referred to us compared to the time prior to the pandemic and between HCLW (p = 0.003). In neurotrauma patients admitted from the SWM during HCLW, there was no tendency towards higher in-house mortality. Conclusion: An open-door policy may moderate the risk of involuntarily triaging neurotrauma patients during a pandemic.

Lessons Learned from Developing Digital Teaching Modules for Medical Student Education in Neurosurgery during the COVID-19 Pandemic.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic forced students and teachers to rapidly adopt digital education methods. Proper guidance for and refinement of such methods is continuously required. Here, we report on the educational experience students and academic staff at the neurosurgical department of a German university hospital made with digital teaching modules (DTMs) that were newly developed due to the transition to digital teaching during the first year of the COVID-19 pandemic and on the insights gained therefrom. METHODS: Nine newly created DTMs provided students the option to anonymously evaluate each module by assigning a score from 0 (worst value) to 5 (best value) to it. Access count, evaluation count, average evaluation, number of included (interactive) figures, number of presented cases, number of linked publications, and number of included multiple-choice questions for each DTM were recorded retrospectively. For each DTM, we aimed to correlate access count, evaluation count, and average evaluation with the number of included (interactive) figures, number of presented cases, number of linked publications, and number of included multiple-choice questions. E-mail responses from individual students as to the DTMs were collected. Among students, an anonymous, voluntary online survey regarding the DTMs was conducted. RESULTS: Number of figures and average evaluation per DTM were significantly positively correlated (Spearman's rho = 0.85; p = 0.0037). Number of figures and number of evaluations per DTM were also significantly positively correlated (Spearman's rho = 0.78; p = 0.0137). Responses from individual students indicated that illustrative cases and interactive figures might further increase DTM popularity. CONCLUSION: As a valuable adjunct in medical student education, DTMs should contain (interactive) figures, illustrative cases, a scoring option, and the option to give individual feedback towards the academic staff.

The Demand for Elective Neurosurgery at a German University Hospital during the First Wave of COVID-19.

BACKGROUND: Patients' fear of the coronavirus disease 2019 (COVID-19) may delay inevitable treatment, putting potential benefits at risk. This single-center retrospective study aims to analyze temporal relationships of the first wave of the COVID-19 pandemic in Germany with the number of patients who sought and received elective neurosurgical treatment at a German university hospital. METHODS: Daily outpatient numbers (ON) and elective procedures (EP) were recorded at our department between 1 January 2020 and 30 June 2020 (baseline: between 1 January 2019 and 30 June 2019). In patients who received EP, we recorded indication, outcome, and length of stay (LOS). Moving averages of ON (MAON) and of EP were calculated. Data on governmental action taken in response to the pandemic and on coronavirus-positive cases in Germany (CPCG) were superimposed. Exponential and arc tangent curves (ATC) were fitted to the absolute numbers of CPCG. Phase shifts were estimated, and Spearman's rank correlation coefficient, rho, was calculated between the 2020 MAON and the derivative function of the fitted ATC (DFATC). Wilcoxon rank sum served as statistical test. Significance was assumed with p values of less than 0.05. RESULTS: ON were significantly decreased in April 2020 as compared to April 2019 (p = 0.010). A phase shift between the German lockdown, the DFATC, and the decrease in MAON was not detected, while a phase shift of 10 days between the DFATC and the subsequent increase in MAON was detected. The DFATC was significantly negatively correlated (rho = -0.92, p < 0.0001) to the MAON until 31 March 2020, and, when shifted by 10 days, the DFATC was significantly negatively correlated (rho = -0.87, p < 0.0001) to the MAON from 01 April 2020. EP (p = 0.023), including the subset of non-oncological EP (p = 0.032), were significantly less performed in the first half of 2020 as compared to the first half of 2019. In March and April 2020, we conducted significantly more EP due to motor deficits (p = 0.0267, and less), visual disturbances (p = 0.0488), and spinal instability (p = 0.0012), and significantly less EP due to radicular pain (p = 0.0489), as compared to March and April 2019. LOS ranked significantly higher in patients who received cranial or spinal EP in March and April 2020 as compared to March and April 2019 (p = 0.0497). Significant differences in outcome were not observed. CONCLUSION: The beginning of the COVID-19 pandemic was correlated to an immediate and significant decrease in ON, and to a significant decrease in the number of EP performed. The subsequent increase in ON was delayed. Adequate measures to promote timely discharge of patients may become increasingly relevant as the pandemic proceeds. Although we observed a shift in the range of indications towards significantly more EP in patients with neurological deficiencies, care should be taken to avoid potentially deleterious delays of necessary elective treatment in future pandemic situations.

Outcome after Interdisciplinary Treatment for Aneurysmal Subarachnoid Hemorrhage-A Single Center Experience.

Background and Objectives: To identify predictors of outcome after aneurysmal subarachnoid hemorrhage (aSAH) in our interdisciplinary setting. Materials and Methods: 176 patients who had been treated for aSAH by a team of neurosurgeons and neuroradiologists between 2009 and 2017 were analyzed retrospectively. Age, gender, clinical presentation according to the Hunt and Hess (H&H) grading on admission, overall clot burden, aneurysm localization, modality of aneurysm obliteration, early deterioration (ED), occurrence of vasospasm in transcranial Doppler ultrasonography, delayed cerebral ischemia (DCI), spasmolysis, decompressive craniectomy (DC), cerebrospinal fluid (CSF) shunt placement, deep vein thrombosis (DVT), pulmonary embolism (PE), severe cardiac events (SCE), mortality on Days 14, and 30 after admission, and outcome at one year after the hemorrhage according to the Glasgow Outcome Scale (GOS) were recorded. Chi square, Fisher's exact, Welch's t, and Wilcoxon rank sum served as statistical tests. Generalized linear models were fitted, and ordered logistic regression was performed. Results: SCE (p = 0.049) were a significant predictor of mortality at 14 days after aSAH, but not later during the first year after the hemorrhage. Clipping as opposed to coiling (p = 0.049) of ruptured aneurysms was a significant predictor of survival on Day 30 after aSAH, but not later during the first year after the hemorrhage, while coiling as opposed to clipping of ruptured aneurysms was significantly related to a lower frequency of DVT during hospitalization (p = 0.024). Aneurysms of the anterior circulation were significantly more often clipped, while aneurysms of the posterior circulation were significantly more often coiled (p < 0.001). Age over 70 years (p = 0.049), H&H grade on admission (p = 0.022), overall clot burden (p = 0.035), ED (p = 0.009), DCI (p = 0.013), DC (p = 0.0005), and CSF shunt placement (p = 0.038) proved to be predictive of long-term outcome after aSAH. Conclusion: Long-term results after clipping and coiling of ruptured aneurysms appear equal in an interdisciplinary setting that takes aneurysm localization, available staff, and equipment into account.

Combined effects of resveratrol and radiation in GH3 and TtT/GF pituitary adenoma cells.

OBJECTIVE: Resveratrol and radiation decrease viability in various tumor cells. This study aims to investigate combined effects of resveratrol and radiation on viability, induction of apoptosis and necrosis, and expression of apoptosis modulators in rodent GH3 and TtT/GF pituitary adenoma cells in vitro. METHODS: Cells were incubated with 10-100 µM resveratrol. Medium and medium with ethanol served as controls. After 2 h, cells were irradiated with 0-5 Gray (Gy) and further incubated for 48-72 h. Cell viability was quantified using a hemocytometer. Cell death was assessed with an enzyme-linked immunosorbent assay (ELISA) that detects free nucleosomes in cell lysates and free nucleosomes released to the culture medium. Expression of B-cell lymphoma-2 protein (BCL-2) and BCL-2 associated Xprotein (BAX) was measured using quantitative real time-polymerase chain reaction (qRT-PCR) to analyze changes in BAX/BCL-2 ratio. RESULTS: Resveratrol and irradiation with 4 Gy alone and in combination significantly decreased cell viability (p = 0.017 and less). In the ELISA, 10 µM resveratrol significantly induced apoptosis in TtT/GF cells at 0 Gy (p < 0.001), but not at 3 or 5 Gy. In the ELISA, 10 µM resveratrol significantly induced necrosis in GH3 cells at 0, 3 and 5 Gy (p < 0.001). While qRT-PCR did not demonstrate a significant effect of 10 µM resveratrol or radiation on expression of BAX or BCL-2, a significant increase in the BAX/BCL-2 ratio was found after irradiation with 5 Gy in GH3 cells (p = 0.0027). CONCLUSION: While moderate irradiation solely led to inhibited proliferation, resveratrol induced cell death in rodent pituitary adenoma cells.

Survival in granular cell astrocytomas.

BACKGROUND: Granular cell astrocytomas (GCAs) are rarely encountered aggressive glial neoplasms. Treatment options comprise surgery, radiotherapy, and chemotherapy. Due to the small number of cases, a standard therapeutic regimen for GCA does not exist. MATERIAL AND METHODS: We report on the case of a 64-year-old woman with GCA subjected to tumor biopsy followed by radiochemotherapy with temozolomide. We provide clinical, histopathologic, and magnetic resonance imaging findings as well as a complete follow-up. To assess the relation of age, gender, time of publication, and different treatment options with survival we performed log-rank tests and calculated Cox regression models and hazard ratios in data from all available reports on GCA. RESULTS: A significant difference in survival rates in favor of adjuvant therapy (radiotherapy or radiochemotherapy) at 12 months was found. Age > 70 years at the time of diagnosis had a significantly unfavorable impact on survival at 12 months. Although not statistically significant, a tendency toward higher probability of survival at 12 months was found in cases reported after 2002. In surgically treated patients, we could not find a significant impact of extent of resection on survival. A significant impact of gender on survival was not found. CONCLUSION: Adjuvant therapy is significantly related to a higher probability of survival at 12 months and may therefore be recommended for patients with a GCA. Further analysis of these rare neoplasms is warranted.

Resveratrol decreases B-cell lymphoma-2 expression and viability in GH3 pituitary adenoma cells of the rat.

OBJECTIVE: Resveratrol is a phytoestrogen with various antiproliferative and proapoptotic effects. This in vitro study aimed to analyze the effect of resveratrol on the viability and expression of modulators of apoptosis in GH3 pituitary adenoma cells of the rat. METHODS: GH3 cells were incubated with resveratrol concentrations from 20 to 100 µM for 48-72 hours. Cell viability was quantified using a hemocytometer. We assessed the ability of resveratrol to kill GH3 cells by an enzyme-linked immunosorbent assay (ELISA) of nucleosome liberation and by DNA degradation (unidimensional gel electrophoresis). Relative messenger RNA (mRNA) expression of survivin, B-cell lymphoma-2 protein (BCL-2) and BCL-2-associated X protein (BAX) normalized to ß2 microglobulin was measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: GH3 cell survival significantly decreased with increasing concentrations of resveratrol. In GH3 cells treated with 100 µM resveratrol, ELISA demonstrated a significant rise of nucleosome liberation, which typically occurs during apoptosis. In parallel, gel electrophoresis showed degradation of DNA into random fragments, pointing to a necrotic mode of cell death in most GH3 cells. In GH3 cells treated with 100 µM resveratrol, qRT-PCR detected a significant decrease of BCL-2 mRNA expression and a decrease of survivin mRNA expression, whereas a change of BAX mRNA expression could not be found. The BAX/BCL-2 ratio was significantly increased in GH3 cells after resveratrol treatment. CONCLUSIONS: Resveratrol reduces GH3 cell viability in a dose-dependent manner by inducing nonapoptotic cell death and apoptosis. Apoptosis in GH3 cells is probably mediated by resveratrol-dependent downregulation of apoptosis inhibitors, namely BCL-2 and possibly survivin. Further investigation of the potential effects of resveratrol on pituitary adenoma cells is warranted.

Embryonic and adult stem cells promote raphespinal axon outgrowth and improve functional outcome following spinal hemisection in mice.

Spinal cord injury (SCI) often results in permanent neurological deficits below the injury site. Serotonergic raphespinal projections promote functional recovery after SCI, but spontaneous regeneration of most severed axons is limited by the glial cyst and scar that form at the lesion site. Stem cell (SC) transplantation offers a promising approach for inducing regeneration through the damaged area. Here we compare the effects of transplantation of embryonic neural precursors (NPs) or adult mesenchymal SCs, both of which are potential candidates for SC therapy. The spinal cord was hemisected at the L2 neuromer in adult mice. Two weeks post-injury, we transplanted neural precursors or mesenchymal SCs into the cord, caudal to the hemisection. Injured mice without a graft served as controls. Mice were tested for functional recovery on a battery of motor tasks, then killed and analysed for survival of grafted cells, for effects of engraftment on the local cellular environment and for the sprouting of serotonergic axons. Both types of SCs survived and were integrated into the host tissue, but only the NPs expressed neuronal markers. All transplanted animals displayed an increased number of serotonin-positive fibres caudal to the hemisection, compared with untreated mice. And both cell types led to improved motor performance. These results point to a therapeutic potential for such cell grafting.