Efficacy of Chondroprotective Food Supplements Based on Collagen Hydrolysate and Compounds Isolated from Marine Organisms.

Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

Asymmetry of P1 and vertebral arteries is not related to basilar tip aneurysm development or rupture.

OBJECTIVE: Lately, morphological parameters of the surrounding vasculature aside from aneurysm size, specific for the aneurysm location, e.g., posterior cerebral artery angle for basilar artery tip aneurysms, could be identified to correlate with the risk of rupture. We examined further image-based morphological parameters of the aneurysm surrounding vasculature that could correlate with the growth or the risk of rupture of basilar artery tip aneurysms. METHODS: Data from 83 patients with basilar tip aneurysms (27 not ruptured; 56 ruptured) and 100 control patients were assessed (50 without aneurysms and 50 with aneurysms of the anterior circle of Willis). Anatomical parameters of the aneurysms were assessed and analyzed, as well as of the surrounding vasculature, namely the asymmetry of P1 and the vertebral arteries. RESULTS: Patients with basilar tip aneurysm showed no significant increase in P1 or vertebral artery asymmetry compared with the control patients or patients with aneurysms of the anterior circulation, neither was there a significant difference in asymmetry between cases with ruptured and unruptured aneurysms. Furthermore, we observed no significant correlations between P1 asymmetry and the aneurysm size or number of lobuli in the aneurysms. CONCLUSION: We observed no significant difference in aneurysm size, rupture, or lobulation associated with P1 or vertebral artery (surrounding vasculature) asymmetry. Therefore, the asymmetry of the surrounding vessels does not seem to be a promising morphological parameter for the evaluation of probability of rupture and growth in basilar tip aneurysms in future studies.

The rupture of an anterior communicating artery aneurysm does not associate with an asymmetry in the A1 or A2 arteries: a retrospective study of radiological features.

BACKGROUND AND OBJECTIVES: Although the formation and rupture risk of an anterior communicating artery (ACoA) aneurysm has been the subject of many studies, no previous study has primarily searched for the relationship of the parent and daughter vessels and the impact of their size/diameter ratio on the potential rupture risk of an AcoA aneurysm. The objective of this study is to explore this link and to further analyse the surrounding vasculature of the anterior communicating artery aneurysm. MATERIALS AND METHODS: We conducted a retrospective analysis of 434 patients: 284 patients with an ACoA aneurysm (121 unruptured and 162 ruptured) and 150 control patients without an ΑCoA aneurysm. Radiological angiography investigations were used to assess the diameter ratios of the parent vessels in addition to ACoA aneurysm morphology parameters. RESULTS: When comparing the ruptured to the unruptured cases, we observed no significant difference in the parent or daughter vessel diameter ratios. Younger patient age (OR 0.96, p = 0.00) and a higher aneurysm size ratio (OR 1.10, p = 0.02) were of prognostic importance concerning the rupture risk of the aneurysm. The A1 diameter ratio and the A2 diameter were not statistically significant (OR 1.00, p = 0.99, and OR 3.38, p = 0.25 respectively). CONCLUSIONS: In our study, we focused on asymmetry in the parent and daughter vessels as well as traditional ACoA aneurysm morphological characteristics. We were able to label younger patient age and a greater size ratio as independent prognostic factors for ACoA aneurysm rupture. We were unable to label parent and daughter vessel asymmetry as prognostic factors. To validate our findings, parent and daughter vessel asymmetry should be subjected to future prospective studies.

Transcranial Doppler Ultrasound, Perfusion Computerized Tomography, and Cerebral Angiography Identify Different Pathological Entities and Supplement Each Other in the Diagnosis of Delayed Cerebral Ischemia.

INTRODUCTION: There is still controversial discussion of the value of transcranial Doppler (TCD) in predicting vasospasms in patients with aneurysmal SAH (aSAH). A newer method of predicting a delayed ischemic deficit (DCI) is CT perfusion (CTP), although it is not quite understood which kind of perfusion deficit is detected by this method since it seems to also identifying microcirculatory disturbances. We compared the TCD and CTP values with angiography and evaluated TCD and CTP changes before and after patients received intra-arterial spasmolytic therapy. MATERIAL AND METHODS: Retrospective analysis of TCD, CTP, and angiographies of N = 77 patients treated from 2013 to 2016. In 38 patients intra-arterial spasmolysis had been performed, and in these cases TCD and CTP data were compared before and after lysis. Thirty-nine patients had a pathological CTP but no angiographically seen vasospasm. RESULTS: There was no correlation between the known thresholds of mean transit time (MTT) in CTP and vasospasm or with mean velocities in TCD and vasospasm. After spasmolysis in patients with vasospasms, only the MTT showed significant improvement, whereas TCD velocities and Lindegaard index remained unaffected. CONCLUSION: TCD and CTP seem to identify different pathological entities of DCI and should be used supplementary in order to identify as many patients as possible with vasospasms after aSAH.

Meteorological factors for subarachnoid hemorrhage in the greater Düsseldorf area revisited: a machine learning approach to predict the probability of admission of patients with subarachnoid hemorrhage.

BACKGROUND: Reported data regarding the relation between the incidence of spontaneous subarachnoid hemorrhage (SAH) and weather conditions are conflicting and do so far not allow prognostic models. METHODS: Admissions for spontaneous SAH (ICD I60.*) 2009-2018 were retrieved form our hospital data base. Historical meteorological data for the nearest meteorological station, Düsseldorf Airport, was retrieved from the archive of the Deutsche Wetterdienst (DWD). Airport is in the center of our catchment area with a diameter of approximately 100 km. Pearson correlation matrix between mean daily meteorological variables and the daily admissions of one or more patients with subarachnoid hemorrhage was calculated and further analysis was done using deep learning algorithms. RESULTS: For the 10-year period from January 1, 2009 until December 31, 2018, a total of 1569 patients with SAH were admitted. No SAH was admitted on 2400 days (65.7%), 1 SAH on 979 days (26.7%), 2 cases on 233 days (6.4%), 3 SAH on 37 days (1.0%), 4 in 2 days (0.05%), and 5 cases on 1 day (0.03%). Pearson correlation matrix suggested a weak positive correlation of admissions for SAH with precipitation on the previous day and weak inverse relations with the actual mean daily temperature and the temperature change from the previous days, and weak inverse correlations with barometric pressure on the index day and the day before. Clustering with admission of multiple SAH on a given day followed a Poisson distribution and was therefore coincidental. The deep learning algorithms achieved an area under curve (AUC) score of approximately 52%. The small difference from 50% appears to reflect the size of the meteorological impact. CONCLUSION: Although in our data set a weak correlation of the probability to admit one or more cases of SAH with meteorological conditions was present during the analyzed time period, no helpful prognostic model could be deduced with current state machine learning methods. The meteorological influence on the admission of SAH appeared to be in the range of only a few percent compared with random or unknown factors.

Anatomical evaluation of intracranial aneurysm rupture risk in patients with multiple aneurysms.

In patients with aneurysmal subarachnoid hemorrhage (aSAH) and multiple aneurysms, there is a need to objectively identify the ruptured aneurysm. Additionally, studying the intra-individual rupture risk of multiple aneurysms eliminates extrinsic risk factors and allows a focus on anatomical factors, which could be extrapolated to patients with single aneurysms too. Retrospective bi-center study (Department of Neurosurgery of the University Hospital Duesseldorf and Bern) on patients with multiple aneurysms and subarachnoid hemorrhage caused by the rupture of one of them. Parameters investigated were height, width, neck, shape, inflow angle, diameter of the proximal and distal arteries, width/neck ratio, height/width ratio, height/neck ratio, and localization. Statistical analysis and logistic regressions were performed by the R program, version 3.4.3. N = 186 patients with aSAH and multiple aneurysms were treated in either department from 2008 to 2016 (Bern: 2008-2016, 725 patients and 100 multiple aneurysms, Duesseldorf: 2012-2016, 355 patients, 86 multiple aneurysms). The mean age was 57 years. N = 119 patients had 2 aneurysms, N = 52 patients had 3 aneurysms, N = 14 had 4 aneurysms and N = 1 had 5 aneurysms. Eighty-four percent of ruptured aneurysms were significantly larger than the largest unruptured. Multilobularity of ruptured aneurysms was significantly higher than in unruptured. Metric variables describing the geometry (height, width, etc.) and shape are the most predictive for rupture. One or two of them alone are already reliable predictors. Ratios are completely redundant in saccular aneurysms.

The Sialic Acid-Dependent Nematocyst Discharge Process in Relation to Its Physical-Chemical Properties Is A Role Model for Nanomedical Diagnostic and Therapeutic Tools.

Formulas derived from theoretical physics provide important insights about the nematocyst discharge process of Cnidaria (Hydra, jellyfishes, box-jellyfishes and sea-anemones). Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and tubule-walls of nematocysts including their polysialic acid (polySia) dependent target function. Since a number of tumor-cells, especially brain-tumor cells such as neuroblastoma tissues carry the polysaccharide chain polySia in similar concentration as fish eggs or fish skin, it makes sense to use these findings for new diagnostic and therapeutic approaches in the field of nanomedicine. Therefore, the nematocyst discharge process can be considered as a bionic blue-print for future nanomedical devices in cancer diagnostics and therapies. This approach is promising because the physical background of this process can be described in a sufficient way with formulas presented here. Additionally, we discuss biophysical and biochemical experiments which will allow us to define proper boundary conditions in order to support our theoretical model approach. PolySia glycans occur in a similar density on malignant tumor cells than on the cell surfaces of Cnidarian predators and preys. The knowledge of the polySia-dependent initiation of the nematocyst discharge process in an intact nematocyte is an essential prerequisite regarding the further development of target-directed nanomedical devices for diagnostic and therapeutic purposes. The theoretical description as well as the computationally and experimentally derived results about the biophysical and biochemical parameters can contribute to a proper design of anti-tumor drug ejecting vessels which use a stylet-tubule system. Especially, the role of nematogalectins is of interest because these bridging proteins contribute as well as special collagen fibers to the elastic band properties. The basic concepts of the nematocyst discharge process inside the tubule cell walls of nematocysts were studied in jellyfishes and in Hydra which are ideal model organisms. Hydra has already been chosen by Alan Turing in order to figure out how the chemical basis of morphogenesis can be described in a fundamental way. This encouraged us to discuss the action of nematocysts in relation to morphological aspects and material requirements. Using these insights, it is now possible to discuss natural and artificial nematocyst-like vessels with optimized properties for a diagnostic and therapeutic use, e.g., in neurooncology. We show here that crucial physical parameters such as pressure thresholds and elasticity properties during the nematocyst discharge process can be described in a consistent and satisfactory way with an impact on the construction of new nanomedical devices.

An introduction to the pathophysiology of aneurysmal subarachnoid hemorrhage.

Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH. Angiographic vasospasm is probably important. However, a unifying theory for the pathophysiological changes following SAH has yet not been described. Some of these changes may be causally connected or present themselves as an epiphenomenon of an associated process. A causal connection between DCI and early brain injury (EBI) would mean that future therapies should address EBI more specifically. If the mechanisms following SAH display no causal pathophysiological connection but are rather evoked by the subarachnoid blood and its degradation production, multiple treatment strategies addressing the different pathophysiological mechanisms are required. The discrepancy between experimental and clinical SAH could be one reason for unsuccessful translational results.

Increased mortality of patients with aneurysmatic subarachnoid hemorrhage caused by prolonged transport time to a high-volume neurosurgical unit.

BACKGROUND: Time has shown to be a relevant factor in the prognosis for a multitude of clinical conditions. The current analysis aimed to establish whether delayed admission to specialized care is a risk factor for increased mortality in case of high-grade aneurysmal subarachnoid hemorrhage. MATERIAL AND METHODS: Consecutive patients with aneurysmal subarachnoid hemorrhage were enrolled retrospectively if they had a World Federation of Neurological Surgeons Grading System grade of 5. Predictor variables for in-hospital mortality reflecting demographic, spatial, temporal treatment, and neurological factors were recorded from hospital medical records and emergency physicians' reports. We performed statistical analysis on the influence between the predictor variables and in-hospital mortality. RESULTS: The study included 61 patients with an average age of 58 years. The overall in-hospital mortality rate was 28% (17/61 patients). A delayed transport to specialized neurosurgical care was associated with increased in-hospital mortality. Transportation time was mainly prolonged in cases where an alternative diagnosis was made by the emergency physician. Mortality was highest in patients with cardiovascular complications of subarachnoid hemorrhage. CONCLUSION: Delayed admission to specialized care is associated with a higher mortality rate in patients with high-grade aneurysmal subarachnoid hemorrhage. Accompanying non-neurosurgical, mainly cardiac complications might be a significant factor leading to delayed admission. The emergency physician should be aware that cardiovascular abnormalities are a relevant complication and sometimes the first identified clinical feature of high-grade subarachnoid hemorrhage.

Life-threatening posterior reversible encephalopathy syndrome in the cerebellum treated by posterior fossa decompression.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome associated with various clinical conditions, such as headache, encephalopathy, and seizures. It is reversible if a prompt diagnosis is made and treatment undertaken. We report a 52-year-old male with hypertensive crisis. Progressing somnolence and an unresponsive left pupil occurred. MRI revealed an intra-axial hyperintensity of the cerebellum and brainstem and occlusive hydrocephalus suggestive of encephalitis or a tumor. Because of the life-threatening clinical picture, posterior fossa decompression was performed. Histopathology failed to identify any pathology. After decompression, the edema improved immediately. Under life-threatening conditions, a decompressive craniectomy in PRES seems to achieve the same results as supportive treatment.

Demographic distribution of hospital admissions for brain arteriovenous malformations in Germany--estimation of the natural course with the big-data approach.

BACKGROUND: Estimation of the natural history of arteriovenous malformations based on short-term observation is potentially biased by multiple factors. Retrieval of demographic information of all AVM patients of national data pools and comparison with the national demographic profile might be another way to approach the natural history. MATERIALS AND METHODS: Upon request, the German Federal Statistical Office provided the numbers of patients admitted in Germany from 2009 through 2013 with ICD Q28.2 (brain AVM) as primary discharge diagnosis, and the corresponding age distribution. Age-related admission rates of AVM were calculated by comparison with the German demographic distribution. RESULTS: A total of 6527 patients were hospitalized from 2009-2013 with brain AVM (Q28.2) as the principal diagnosis. Age-specific admission rate during the first year of life was high with 19.0/100,000 during the 5-year study period, corresponding to a yearly admission rate of 3.8 per 100,000 babies. Apart from the high admission rate during the first year of life, the admission rate was low, but steadily increasing during first decades of life reaching a plateau with 11.1/100,000 in the age group 30-34 years, corresponding to an annual admission rate of 2.2/100,000. After the age of 30-34 years, admission rates decreased continuously, reaching 0 in the age group 90-95 years. The lifetime risk of admission in terms of admission per 100,000 age-matched people was calculated by retrograde integration of the admission rates. At the age of 1 year, the cumulative number of future admissions for AVM during lifetime amounted to 131.3/100,000 children. For the older age groups, the chance of future admission for AVM decreased as expected, reaching 43.8/100,000 by the age of 50 and 0 by the age of 90. CONCLUSIONS: Despite some open issues, the current data suggests that achieving old age with an untreated brain AVM is unlikely. Furthermore, the data support the concept that most brain AVMs are not necessarily a congenital entity but develop during the first decades of life.

Microsurgical and histological identification and definition of an interdural incision zone in the dorsolateral cavernous sinus.

OBJECTIVES: The anatomy of the cavernous sinus is described controversially in a number of publications. In the present cadaveric study, the architecture of the dorsolateral wall of the cavernous sinus is studied microsurgically and histologically. MATERIALS AND METHODS: Twenty cadaveric skulls have been dissected through a classical surgical frontotemporal approach. The temporal skull base was flattened and anatomical landmarks like the meningo-orbital band, superior orbital fissure, foramina rotundum, ovale, and spinosum were identified. Lateral of the trigeminal foramina, the dura was cut and the periosteal dural layer was separated from the meningeal layer, identifying an interdural zone. The length and the extent of this zone were evaluated. The dural architecture of the interdural incision zone was examined histologically. RESULTS: In all specimens, two dural layers lateral of the trigeminal foramina could be separated. The identified interdural incision zone extended in a length of 3.8-6.4 cm in the antero-posterior direction. The zone could be followed medially to the superior orbital fissure for 5.3 mm and lateral of the foramen spinosum for 6.4 mm. The separation of the dural layers allowed the approach to the superior border of the cavernous sinus through this interdural incision zone. The histological analysis of the interdural incision zone showed clearly the existence of two dural layers. CONCLUSIONS: The architecture of the temporal-fossa-dura allows the microsurgical separation of two meningeal dural layers through a length of 5-6 cm next to the trigeminal foramina. Opening this interdural incision zone allowed exploring the superior border of the cavernous sinus.

The transmaxillary endoscopic approach to the orbit.

OBJECTIVE: In this surgical-anatomical cadaveric study we investigate the feasibility of the transmaxillary endoscopic approach to the intraorbital space. Anatomical landmarks are defined, the endoscopic view in the orbital space is studied and complications that can occur are discussed. METHODS: Nine formalin-fixed heads were used to study the transmaxillary endoscopic approach to the orbit. The approach was used twice on each head (once for each maxilla). Therefore, we report our results on 18 transmaxillary intraorbital approaches. For better differentiation of anatomical structures, the veins and arteries were injected with blue and red plastic respectively in six cadaveric heads. RESULTS: The transmaxillary approach enables viewing the inferior intraconal structures without endangering the infraorbital nerve and its artery and without diversion of the inferior rectus muscle. The optic nerve was visualised more easily through the approach medial to the inferior rectus muscle instead of lateral to the muscle since the ciliary nerves are in the way in the lateral approach. The combination of the approaches medial and lateral to the inferior rectus muscle allows very good identification of all important anatomical structures in the inferior intraconal space. CONCLUSION: The transmaxillary endoscopic approach to the orbit is a useful new approach in the surgical armamentarium for orbital lesions. The overview of the inferior part of the orbit is excellent, and the lateral part of the optic nerve can be visualised. Careful anatomical dissection allows visualisation of important anatomical structures in the orbit without damaging nerves or arteries.

Estimated low risk of rupture of small-sized unruptured intracranial aneurysms (UIAs) in relation to intracranial aneurysms in patients with subarachnoid haemorrhage.

OBJECTIVE: International guidelines for the management of unruptured intracranial aneurysms (UIAs) recommend observation in aneurysms <10 mm due to the estimated low risk of rupture. The aim of our study was analyse the data of recently treated patients with ruptured cerebral aneurysms with the special focus on size and configuration in view of the frequency scale in a daily routine setting. METHODS: We reviewed the data of all patients with aneurysmal subarachnoid haemorrhage (SAH) during the last 24 months at our institution. Configuration and size of the aneurysms were measured. Clinical data were collected using the following classifications for analysis: Hunt and Hess (H&H), modified Rankin Scale (mRS) and Fisher classification. RESULTS: Data of 135 patients with aneurysmal SAH (98 women, 37 men; ratio 2.6:1) were analysed. Analysis showed that 19 aneurysms (14 %) were >10 mm (mean size, 19.2 mm) and 116 aneurysms (85.9 %) <10 mm (mean size, 6.2 mm). In total, 112 were categorised as berry-like configured aneurysms (n = 113 <10 mm, n = 3 >10 mm), 18 as multi-lobar (n = 16 <10 mm, n = 2 >10 mm) and 5 as fusiform (n = 4 <10 mm, n = 1, >10 mm). CONCLUSION: Since the results of our study showed that the majority of the aneurysms are <10 mm (mean, 6.2 mm), it is justified to challenge the recommendations of the international guidelines in a daily routine setting. We believe that the published data are not convincing enough to play a guidance role in daily routine. Due to improving surgical and endovascular techniques with satisfying results and the high number of ruptured small aneurysms, we believe a change in attitude in management of small-sized aneurysms is needed. Further diagnostic models are needed to determine the risk of rupture of intracranial aneurysms properly to obtain adequate treatment for UIAs.

Interdisciplinary Therapeutic Approaches to Atypical and Malignant Meningiomas.

Meningiomas have the highest incidence among brain tumors. In contrast to benign tumors that constitute the majority of this tumor entity, the treatment of aggressive meningiomas (WHO Grade 2 and 3) is more challenging, requiring gross total removal of the tumor and the affected dura and adjuvant radiotherapy. Sometimes the location and/or the configuration of the tumor do not favor radical surgical resection without endangering the patient's clinical condition after surgery and pharmacological therapy has, until now, not been proven to be a reliable alternative. Discussion: In this narrative review, we discuss the current literature with respect to the management of meningiomas, discussing the importance of the grade of resection in the overall prognosis of the patient and in the planning of adjuvant therapy. Conclusions: According to the location and size of the tumor, radical resection should be taken into consideration. In patients with aggressive meningiomas, adjuvant radiotherapy should be performed after surgery. In cases of skull base meningiomas, a maximal, though safe, resection should take place before adjuvant therapy. An interdisciplinary approach is beneficial for patients with primary or recurrent meningioma.

Association of aneurysmatic subarachnoid hemorrhage rate with environmental changes or emotional bursts.

INTRODUCTION: In the present letter we share the results of an analysis of more than 140,000 non traumatic arterial subarachnoid hemorrhages whereas the majority of them is expected to be after aneurysm rupture, in which we investigate a possible correlation of climatic changes and emotional bursts as correlating factors for such a rupture. METHODS: We obtained the daily number of SAH from 2006 to 2018 for males and females from the German National statistics agency. The ICD codes provided to us were I60.1-I60.7, which are SAHs originating from intracranial arteries and excluding traumatic SAH and other not specified SAH. RESULTS: An increase of mean SAH per day could be seen in winter compared to summer and family events seemed to have a protective effect against aneurysmal SAH. Additionally 6.55 more women per day suffer an SAH compared to men. CONCLUSION: There is a statistical significant higher risk of aneurysm ruptures in winter and in females, and a statistical lower number in Mother's day.

Traumatic carotid cavernous fistulas. Rare and life threatening.

Purpose: Carotid-cavernous fistulas (CCFs) are often underdiagnosed or misdiagnosed. In polytraumatized patients, the focus is primarily on treating potentially life-threatening conditions such as increased intracranial pressure and hemorrhages. This case report aims to identify common diagnostic mistakes in rare pathologies. Objective: We present a case of a young female patient who was admitted to the emergency room after a motorbike accident. The patient's vital parameters were successfully stabilized, and she spent approximately four weeks in the ICU and neurosurgical ward. The patient exhibited limited communication, ophthalmoplegia, and a swollen, red left eye. After four weeks, the patient's parents initiated admission to our department due to the suspicious red swollen eye. Angiography revealed a complete rupture of the internal carotid artery (ICA) into the cavernous sinus, and occlusion of the ICA showed significant improvement in the eye edema and the patient's mental state. Two days later, the patient was able to communicate with complex sentences. Three months after the occlusion, the patient showed positive progress, posting dancing videos on TikTok. Conclusion and Importance: A carotid-cavernous fistula presenting with a red swollen eye can be misdiagnosed as retrobulbar hematoma or conjunctivitis. Failure to recognize and treat it promptly can lead to severe morbidity.

Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms.

The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure-function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood-brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.

Profile and Prognosis of Spontaneous Lobar Intracerebral Hemorrhage: Comparison of 6-month Survival with STICH II and the MISTIE III Lobar Hemorrhage Subset.

BACKGROUND: Randomized trials on spontaneous lobar intracerebral hemorrhage (ICH) provided no convincing evidence of the superiority of surgical treatment. Since recruitment in the trials was under the premise of equipoise, a selection bias toward patients who did not need surgery or were in hopeless condition must be suspected. The aim of the actual analysis was to compare outcome and patient profile of an unselected hospital series with recent randomized trials and to develop a prognostic model. METHODS: Of 821 patients with spontaneous ICH managed at the neurosurgical department of the University Hospital Düsseldorf between 2013 and 2018, 159 had lobar bleedings. Patient characteristics, hematoma volume, treatment modality, and 6-month survival were compared with STICH II and the subset of lobar hemorrhage in the MISTIE III trial. In addition, a prognostic model for 6-month survival in our patients was developed using a random forest classifier. RESULTS: One hundred and seven patients were managed by surgical evacuation of the hematoma and 52 without surgical evacuation. Median hemorrhage volume in our surgical cohort was 66 and 42 mL in the conservative cohort, compared with 38 and 36 mL in the STICH II trial, and 46 and 47 mL in the surgical and conservative MISTIE III lobar hemorrhage subset. Median initial Glasgow Coma Scale (GCS) score was 12 in our surgical group and 11 in the conservative group, compared with 13 in the STICH II cohorts and 12 in the MISTIE III lobar hemorrhage subset. Median age in our surgical and conservative cohorts was 73 and 74 years, respectively, compared with 65 years in both STICH II cohorts and 68 years in the MISTIE II subsets. Twenty-nine percent of our surgical cohort and 55% of our conservatively managed patients deceased within the first 6 months, compared with 18 and 24%, respectively, in STICH II and 17 and 24% in the MISTIE III subset. Our prognostic model identified large hemorrhage volumes and low admission GCS score as main unfavorable prognostic factors for 6-month survival. The random forest classifier achieved a predictive accuracy of 78% and an area under curve (AUC)- value of 88% regarding survival at 6 months, on a test set independent of the training set. CONCLUSIONS: In comparison with our surgical group, the STICH II and MISTIE III cohorts, recruited under the premise of physician equipoise, underrepresented patients with large ICHs. The cohorts in the randomized trials were therefore biased toward patients with a favorable perspective under conservative management. Initial hematoma volume and admission GCS were the main prognostic factors in our patients.

A rare case of extradural lumbar nerve root cavernoma.

We present a very rare case of an extradural nerve root cavernoma of the lumbar spine. The patient had signs of radiculopathy for the last 3 years. Conservative treatment was unsuccessful. The MRI-image revealed a lesion mimicking neurinoma of the left L3 nerve root. Surgical removal of the lesion was performed by an extreme lateral transmuscular approach. Intraoperatively, the lesion showed signs of intratumoural bleeding. In the histological analysis, a cavernoma of the nerve root was established. Despite the benign nature of these very rare lesions, complete surgical removal should be performed since a spontaneous regression is not to be expected and surgery relieves the patients from their symptoms.