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Cerebrospinal fluid (CSF) metabolites are increasingly recognized as prognostic factors in aneurysmal subarachnoid hemorrhage (SAH). The CSF arginine/ornithine ratio (Arg/Orn) was shown to predict cerebral vasospasms and clinical outcome in SAH. The additive prognostic value of Arg/Orn over established prognostic scores has not been investigated. CSF Arg/Orn and the established prognostic scores SAH, FRESH, SAH-PDS, HAIR, Rosen–McDonald, Hunt and Hess, WFNS and modified Fisher scale were determined in a prospective cohort of patients with aneurysmal SAH. Logistic regression models to predict a favorable outcome, defined as a modified Rankin Scale score of 0–3 at 3 months follow-up, were constructed for each score, both with and without the addition of Arg/Orn. The impact of Arg/Orn was assessed comparing logistic regression models containing the respective score with and without Arg/Orn with the likelihood ratio chi-squared test. CSF Arg/Orn and clinical scores were determined in 38 SAH patients. Arg/Orn was an independent predictor of clinical outcome when added to established prognostic scores (p

BackgroundCommunity-acquired bacterial meningitis in adults is associated with significant morbidity and mortality; therefore, early prognostication is important to identify severe cases and possibly allocate more intensive treatment. We hypothesized that early intracranial hemorrhage portends a poor prognosis. The objective of this study was to evaluate the prognostic impact of early intracranial hemorrhage regardless of size and location on clinical outcome.MethodsRetrospective analysis of patients with community-acquired bacterial meningitis treated at a tertiary academic center between 2009 and 2019 about patient characteristics, cerebral imaging findings, and clinical outcome. Uni- and multivariable logistic regression analyses were performed to identify independent predictors of poor clinical outcomes defined as a modified Rankin scale score of 5 or 6 upon discharge.ResultsA total of 102 patients were included, of which 22.5% had poor clinical outcomes. Intracranial micro- or macrohemorrhages were present in 7.8% of cases and associated with poor clinical outcomes [odds ratio (OR) 55.75, 95% CI 3.08–1,008.48, p = 0.006] in multivariate analysis, further predictors included ischemic stroke (OR 15.06, 95% CI 1.32–172, p = 0.029), age (OR 2.56, 95% CI 1.4–4.67, p = 0.002), and reduced consciousness (OR 4.21, 95% CI 1.07–16.64, p = 0.04).ConclusionEarly cerebral hemorrhage (ECHO) is a potential prognostic marker for clinicians confronted with decision-making in patients who are critically ill with community-acquired bacterial meningitis.

Object: Inflammatory response is an important determinant of subsequent brain injury after deep-seated intracerebral hemorrhage (ICH). The ratio of red blood cell (RBC) distribution width to platelet count (RPR) has been established as a new index to reflect the severity of inflammation. To the best of our knowledge, no association between RPR and prognosis after spontaneous ICH has yet been reported.Methods: In all patients with deep-seated ICH treated at our Neurovascular Center from 2014 to 2020, initial laboratory values were obtained to determine RPR in addition to patient characteristics and known risk factors. Subsequent multivariate analysis was performed to identify independent risk factors for 90-day mortality after deep-seated ICH.Results: Hundred and two patients with deep-seated ICH were identified and further analyzed. Patients with an initial RPR < 0.06 exhibited significantly lower mortality rate after 90 days than those with an initial RPR ≥ 0.06 (27 vs. 57%; p = 0.003). Multivariate analysis identified “ICH score ≥ 3” (p = 0.001), “anemia on admission” (p = 0.01), and “elevated RPR ≥ 0.06” (p = 0.03) as independent predictors of 90-day mortality.Conclusions: The present study constitutes the first attempt to demonstrate that the ratio of RBC distribution width to platelets—as an independent inflammatory marker—might serve for prognostic assessment in deep-seated ICH.

ObjectIntra-tumoral hemorrhage is considered an imaging characteristic of advanced cancer disease. However, data on the influence of intra-tumoral hemorrhage in patients with brain metastases (BM) remains scarce. We aimed at investigating patients with BM who underwent neurosurgical resection of the metastatic lesion for a potential impact of preoperative hemorrhagic transformation on overall survival (OS).MethodsBetween 2013 and 2018, 357 patients with BM were surgically treated at the authors’ neuro-oncological center. Preoperative magnetic resonance imaging (MRI) examinations were assessed for the occurrence of malignant hemorrhagic transformation.Results122 of 375 patients (34%) with BM revealed preoperative intra-tumoral hemorrhage. Patients with hemorrhagic transformed BM exhibited a median OS of 5 months compared to 12 months for patients without intra-tumoral hemorrhage. Multivariate analysis revealed preoperative hemorrhagic transformation as an independent and significant predictor for worsened OS.ConclusionsThe present study identifies preoperative intra-tumoral hemorrhage as an indicator variable for poor prognosis in patients with BM undergoing neurosurgical treatment.

ObjectIn the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM.MethodsBetween 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI).ResultsA total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p5 mg/l” (p=0.01) and “frailest patients (mFI ≥ 0.27)” (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM.ConclusionsIn this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.

Homodimerization is essential for plasma membrane sorting of the liver bile acid transporter NTCP and its function as Hepatitis B/D Virus (HBV/HDV) receptor. However, the protein domains involved in NTCP dimerization are unknown. NTCP bears two potential GXXXG/A dimerization motifs in its transmembrane domains (TMDs) 2 and 7. The present study aimed to analyze the role of these GXXXG/A motifs for the sorting, function, and dimerization of NTCP. The NTCP mutants G60LXXXA64L (TMD2), G233LXXXG237L (TMD7) and a double mutant were generated and analyzed for their interaction with wild-type NTCP using a membrane-based yeast-two hybrid system (MYTH) and co-immunoprecipitation (co-IP). In the MYTH system, the TMD2 and TMD7 mutants showed significantly lower interaction with the wild-type NTCP. In transfected HEK293 cells, membrane expression and bile acid transport activity were slightly reduced for the TMD2 mutant but were completely abolished for the TMD7 and the TMD2/7 mutants, while co-IP experiments still showed intact protein-protein interactions. Susceptibility for in vitro HBV infection in transfected HepG2 cells was reduced to 50% for the TMD2 mutant, while the TMD7 mutant was not susceptible for HBV infection at all. We conclude that the GXXXG/A motifs in TMD2 and even more pronounced in TMD7 are important for proper folding and sorting of NTCP, and so indirectly affect glycosylation, homodimerization, and bile acid transport of NTCP, as well as its HBV/HDV receptor function.

ObjectiveSurgical resection represents a common treatment modality in patients with brain metastasis (BM). Postoperative prolonged mechanical ventilation (PMV) might have an enormous impact on the overall survival (OS) of these patients suffering from advanced cancer disease. We therefore have analyzed our institutional database with regard to a potential impact of PMV on OS of patients who had undergone surgery for brain metastases.Methods360 patients with surgically treated brain metastases were included. The definition of PMV consisted of postoperative mechanical ventilation lasting for more than 48 hours. Analysis of survival incorporating established prognostic factors such as age, location of BM, and preoperative physical status was performed.Results14 of 360 patients with BM (4%) suffered from postoperative PMV after surgical treatment of BM. Patients with PMV presented in a significantly more impaired neurological condition preoperatively than patients without (p

Objective: The need for continuous renal replacement therapy (CRRT) in patients with deep-seated intracerebral hemorrhage (ICH) requires sustained intensive care and often postpones further rehabilitation therapy. Therefore, an early identification of patients at risk is essential.Methods: From 2014 to 2019, all patients with deep-seated ICH who were admitted to intensive care for >3 days were included in the further analysis and retrospectively reviewed for the need for CRRT. All patients underwent CRRT with regional citrate anticoagulation for continuous veno-venous hemodialysis (CVVHD). Outcome was evaluated after 3 months using the modified Rankin scale. A multivariate analysis was performed to identify potential predictors for CRRT in patients with deep-seated ICH.Results: After applying the inclusion criteria, a total of 87 patients with deep-seated spontaneous ICH were identified and further analyzed. During the first 48 h after admission, 21 of these patients developed early acute kidney injury (AKI; 24%). During treatment course, CRRT became necessary in nine patients suffering from deep-seated ICH (10%). The multivariate analysis revealed “development of AKI during the first 48 h” [p = 0.025, odds ratio (OR) 6.1, 95% confidence interval (CI) 1.3–29.8] and “admission procalcitonin (PCT) value >0.5 μg/l” (p = 0.02, OR 7.7, 95% CI 1.4–43.3) as independent and significant predictors for CRRT in patients with deep-seated ICH.Conclusions: Elevated serum levels of procalcitonin on admission as well as early development of acute renal injury are independent predictors of the need for renal replacement therapy in patients with deep-seated intracerebral bleeding. Therefore, further research is warranted to identify these vulnerable patients as early as possible to enable adequate treatment.

Objective: In light of the ongoing COVID-19 pandemic and the associated hospitalization of an overwhelming number of ventilator-dependent patients, medical and/or ethical patient triage paradigms have become essential. While guidelines on the allocation of scarce resources do exist, such work within the subdisciplines of intensive care (e.g., neurocritical care) remains limited.Methods: A 16-item questionnaire was developed that sought to explore/quantify the expert opinions of German neurointensivists with regard to triage decisions. The anonymous survey was conducted via a web-based platform and in total, 96 members of the Initiative of German Neurointensive Trial Engagement (IGNITE)-study group were contacted via e-mail. The IGNITE consortium consists of an interdisciplinary panel of specialists with expertise in neuro-critical care (i.e., anesthetists, neurologists and neurosurgeons).Results: Fifty members of the IGNITE consortium responded to the questionnaire; in total the respondents were in charge of more than 500 Neuro ICU beds throughout Germany. Common determinants reported which affected triage decisions included known patient wishes (98%), the state of health before admission (96%), SOFA-score (85%) and patient age (69%). Interestingly, other principles of allocation, such as a treatment of “youngest first” (61%) and members of the healthcare sector (50%) were also noted. While these were the most accepted parameters affecting the triage of patients, a “first-come, first-served” principle appeared to be more accepted than a lottery for the allocation of ICU beds which contradicts much of what has been reported within the literature. The respondents also felt that at least one neurointensivist should serve on any interdisciplinary triage team.Conclusions: The data gathered in the context of this survey reveal the estimation/perception of triage algorithms among neurointensive care specialists facing COVID-19. Further, it is apparent that German neurointensivists strongly feel that they should be involved in any triage decisions at an institutional level given the unique resources needed to treat patients within the Neuro ICU.

ObjectiveAlthough the treatment of glioblastoma patients is well established in neuro-oncological surgery, precious scarce data is available on patients with glioblastoma requiring postoperative prolonged mechanical ventilation (PMV). Therefore, the aim of the present study was to determine the influence of PMV on overall survival (OS) in patients with glioblastoma.MethodsPatients with newly diagnosed glioblastoma who had undergone surgical therapy and complete subsequent neuro-oncological treatment at the authors’ neuro-oncological center from January 2013 to December 2018 were selected and included in the further analysis. PMV was defined as mechanical ventilation for more than 24 h after surgery. Survival analyses were performed, including established prognostic factors such as age, Karnofsky performance score, MGMT-promoter methylation status and extent of resection.ResultsA total of 240 patients with newly diagnosed glioblastoma and subsequent surgical treatment were identified. 13 patients (5%) suffered from PMV during the treatment course of glioblastoma. All but one patient were successfully weaned from mechanical ventilation. Patients suffering from PMV achieved significantly less often favorable functional outcome after 3, 6, 9, and 12 months compared to patients without PMV. Multivariate analysis revealed PMV to constitute a significant prognostic factor for OS, independent of other prognostic factors (p

Lakes represent a considerable natural source of methane to the atmosphere compared to their small global surface area. Methanotrophs in sediments and in the water column largely control methane fluxes from these systems, yet the diversity, electron accepting capacity and nutrient requirements of these microorganisms have only been partially identified. Here we investigated the role of electron acceptors alternative to oxygen and sulfate in microbial methane oxidation at the oxycline and in anoxic waters of the ferruginous meromictic Lake La Cruz, Spain. Active methane turnover in a zone extending well below the oxycline was evidenced by stable carbon isotope-based rate measurements. We observed a strong methane oxidation potential throughout the anoxic water column, which did not vary substantially from that at the oxic/anoxic interface. Both in the redox-transition and anoxic zones, only aerobic methane-oxidizing bacteria were detected by fluorescence in situ hybridization and sequencing techniques, suggesting a close coupling of cryptic photosynthetic oxygen production and aerobic methane turnover. Additions of nitrate, nitrite and to a lesser degree iron and manganese oxides also stimulated bacterial methane consumption. We could not confirm a direct link between the reduction of these compounds and methane oxidation and we cannot exclude the contribution of unknown anaerobic methanotrophs. Nevertheless, our findings from Lake La Cruz support recent laboratory evidence that aerobic methanotrophs may be able to utilize alternative terminal electron acceptors under oxygen limitation.

The stable nitrogen (N) and oxygen (O) isotope ratios (15N/14N and 18O/16O, respectively) of nitrate (NO3-) were measured during incubations of freshly collected seawater to investigate the effect of light intensity on the isotope fractionation associated with nitrate assimilation and possible co-occurring regeneration and nitrification by in situ plankton communities. Surface seawater was collected off the coast of Vancouver, Canada, in late fall and in late summer and was incubated under different laboratory light conditions for 10 and 30 days, respectively. In the late summer experiments, parallel incubations were supplemented with 15NH4+ and H218O tracers to monitor co-occurring nitrification. Differences in irradiance in the fall incubations resulted in reduced nitrate consumption at low light, but had no distinguishable impact on the N-isotope isotope effect (15ε) associated with NO3- assimilation, which ranged between 5 and 8‰. The late-summer community incubations, in contrast, showed reduced growth rates at low light and more elevated 15ε of 11.9 ± 0.4‰, compared to 8.4 ± 0.3‰ at high-light conditions. The seasonal differences could reflect physiological adaptations of the fall plankton community to reduced irradiance, such that their incubation at low light did not elicit the increase in proportional cellular nitrate efflux required to raise the isotope effect. In both the fall and summer incubations, the ratio of the coincident rises in the δ15N and δ18O of NO3- was comparable to previous monoculture phytoplankton experiments, with a ∆δ18O:∆δ15N of ~1, regardless of light level. A decoupling of ∆δ18O:∆δ15N is expected if nitrification occurs concomitantly with nitrate assimilation. The lack of such decoupling is best explained by the absence of significant nitrification in any of our study’s treatments, an interpretation supported by our inability to identify any tracer 15N and 18O uptake into the NO3- pool in the late-summer community incubations.