German guidelines on community-acquired acute bacterial meningitis in adults.

INTRODUCTION: The incidence of community-acquired acute bacterial meningitis has decreased during the last decades. However, outcome remains poor with a significant proportion of patients not surviving and up to 50% of survivors suffering from long-term sequelae. These guidelines were developed by the Deutsche Gesellschaft für Neurologie (DGN) under guidance of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) to guide physicians through diagnostics and treatment of adult patients with acute bacterial meningitis. RECOMMENDATIONS: The most important recommendations are: (i) In patients with suspected acute bacterial meningitis, we recommend that lumbar cerebrospinal fluid (with simultaneous collection of serum to determine the cerebrospinal fluid-serum glucose index and blood cultures) is obtained immediately after the clinical examination (in the absence of severely impaired consciousness, focal neurological deficits, and/or new epileptic seizures). (ii) Next, we recommend application of dexamethasone and empiric antibiotics intravenously. (iii) The recommended initial empiric antibiotic regimen consists of ampicillin and a group 3a cephalosporin (e.g., ceftriaxone). (iv) In patients with severely impaired consciousness, new onset focal neurological deficits (e.g. hemiparesis) and/or patients with newly occurring epileptic seizures, we recommend that dexamethasone and antibiotics are started immediately after the collection of blood; we further recommend that -if the imaging findings do not indicate otherwise -a lumbar CSF sample is taken directly after imaging. (v) Due to the frequent occurrence of intracranial and systemic complications, we suggest that patients with acute bacterial meningitis are treated at an intensive care unit in the initial phase of the disease. In the case of impaired consciousness, we suggest that this is done at an intensive care unit with experience in the treatment of patients with severe CNS diseases. CONCLUSIONS: The German S2k-guidelines give up to date recommendations for workup, diagnostics and treatment in adult patients with acute bacterial meningitis.

Endovascular stroke therapy outside core working hours in a nationwide stroke system.

BACKGROUND: Endovascular therapy (EVT) has been established as a major component in the acute treatment of large vessel occlusion stroke. However, it is unclear whether outcome and other treatment-related factors differ if patients are treated within or outside core working hours. METHODS: We analyzed data from the prospective nationwide Austrian Stroke Unit Registry capturing all consecutive stroke patients treated with EVT between 2016 and 2020. Patients were trichotomized according to the time of groin puncture into treatment within regular working hours (08:00-13:59), afternoon/evening (14:00-21:59) and night-time (22:00-07:59). Additionally, we analyzed 12 EVT treatment windows with equal patient numbers. Main outcome variables included favorable outcome (modified Rankin Scale scores of 0-2) 3 months post-stroke as well as procedural time metrics, recanalization status and complications. RESULTS: We analyzed 2916 patients (median age 74 years, 50.7% female) who underwent EVT. Patients treated within core working hours more frequently had a favorable outcome (42.6% vs 36.1% treated in the afternoon/evening vs 35.8% treated at night-time; p=0.007). Similar results were found when analyzing 12 treatment windows. All these differences remained significant in multivariable analysis adjusting for outcome-relevant co-factors. Onset-to-recanalization time was considerably longer outside core working hours, which was mainly explained by longer door-to-groin time (p<0.001). There was no difference in the number of passes, recanalization status, groin-to-recanalization time and EVT-related complications. CONCLUSIONS: The findings of delayed intrahospital EVT workflows and worse functional outcomes outside core working hours in this nationwide registry are relevant for optimization of stroke care, and might be applicable to other countries with similar settings.

Bifurcation analysis for axisymmetric capillary water waves with vorticity and swirl.

We study steady axisymmetric water waves with general vorticity and swirl, subject to the influence of surface tension. This can be formulated as an elliptic free boundary problem in terms of Stokes' stream function. A change of variables allows us to overcome the generic coordinate-induced singularities and to cast the problem in the form "identity plus compact," which is amenable to Rabinowitz's global bifurcation theorem, whereas no restrictions regarding the absence of stagnation points in the flow have to be made. Within the scope of this new formulation, local curves and global families of solutions, bifurcating from laminar flows with a flat surface, are constructed.

Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis.

Early intervention with high-efficacy disease-modifying therapy (HE DMT) may be the best strategy to delay irreversible neurological damage and progression of multiple sclerosis (MS). In European healthcare systems, however, patient access to HE DMTs in MS is often restricted to later stages of the disease due to restrictions in reimbursement despite broader regulatory labels. Although not every patient should be treated with HE DMTs at the initial stages of the disease, early and unrestricted access to HE DMTs with a positive benefit-risk profile and a reasonable value proposition will provide the freedom of choice for an appropriate treatment based on a shared decision between expert physicians and patients. This will further optimize outcomes and facilitate efficient resource allocation and sustainability in healthcare systems and society.

[Guideline S1: Long COVID: Diagnostics and treatment strategies]. / Leitlinie S1: Long COVID: Differenzialdiagnostik und Behandlungsstrategien.

This guideline comprises the state of science at the time of the editorial deadline. In view of the high turnover of knowledge the guideline is designed as a living guideline. The main objective was to provide a tool for the use in primary care, being considered well suited as a first point of entry and for the provision of care. The guideline gives recommendations on the differential diagnosis of symptoms following SARS-CoV­2 infection, on their therapeutic options, as well as for guidance and care of the patients concerned. It also offers advice concerning return to daily life and rehabilitation. Long COVID being a very variable condition, we chose an interdisciplinary approach.

Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings.

OBJECTIVE: To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings. METHODS: We retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry. RESULTS: Three patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. None of the patients had epileptic seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR immunoreactivity. CONCLUSION: AMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.

German guidelines on the diagnosis and treatment of neurosyphilis.

INTRODUCTION: In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline "Neurosyphilis" has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline. MAIN RECOMMENDATIONS: (a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood-CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against Treponema pallidum. (d) In neurosyphilis, treatment with intravenous penicillin or ceftriaxone for 14 days is recommended. (e) The following parameters can be used to assess a therapeutic effect: clinical findings, serum VDRL, and CSF cell count. CONCLUSION: The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Thearpie in der Neurologie 2020).

Can propensity score matching be applied to cross-sectional data to evaluate Community-Based Rehabilitation? Results of a survey implementing the WHO's Community-Based Rehabilitation indicators in Vietnam.

OBJECTIVES: Community-Based Rehabilitation (CBR) is a multi-sectoral approach working to equalise opportunities and include people with disabilities in all aspects of life. The complexity of CBR and often limited resources lead to challenges when attempting to quantify its effectiveness, with randomisation and longitudinal data rarely possible. Statistical methods, such as propensity score matching (PSM), offer an alternative approach to evaluate a treatment when randomisation is not feasible. The aim of this study is to examine whether PSM can be an effective method to facilitate evaluations of results in CBR when data are cross-sectional. DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS: Data were collected using the WHO's CBR Indicators in Vietnam, with treatment assignment (participating in CBR or not) determined by province of residence. 298 participants were selected through government records. RESULTS: PSM was conducted using one-to-one nearest neighbour method on 10 covariates. In the unmatched sample, significant differences between groups were found for six of the 10 covariates. PSM successfully adjusted for bias in all covariates in the matched sample (74 matched pairs). A paired t-test compared the outcome of 'community inclusion' (a score based on selected indicators) between CBR and non-CBR participants for both the matched and unmatched samples, with CBR participants found to have significantly worse community inclusion scores (mean=17.86, SD=6.30, 95% CI 16.45 to 19.32) than non-CBR participants (mean=20.93, SD=6.16, 95% CI 19.50 to 22.35); t(73)=3.068, p=0.001. This result did not differ between the matched and unmatched samples. CONCLUSION: PSM successfully reduced bias between groups, though its application did not affect the tested outcome. PSM should be considered when analysing cross-sectional CBR data, especially for international comparisons where differences between populations may be greater.

Surgical revision of radial head fractures: a multicenter retrospective analysis of 466 cases.

BACKGROUND: Radial head fractures lead to persisting disability in a considerable number of cases. This study aimed to investigate their most common revision causes and procedures. METHODS: This multicenter retrospective study reviewed the cases of 466 adult patients who had undergone surgical revision after operative or nonoperative treatment of a radial head fracture. The initial diagnosis was a Mason type I fracture in 13.0%, Mason type II fracture in 14.6%, Mason type III fracture in 22.8%, Mason type IV fracture in 20.9%, terrible-triad injury in 12.8%, Monteggia-like lesion in 13.1%, and Essex-Lopresti lesion in 2.0%. Initial treatment was nonoperative in 30.2%, open reduction and internal fixation (ORIF) in 44.9%, radial head arthroplasty in 16.6%, radial head resection in 3.7%, sole treatment of concomitant injuries in 2.6%, and fragment excision in 2.0%. Up to 3 revision causes and procedures were recorded per case. RESULTS: The most common complications were stiffness (67.4%), instability (36.5%), painful osteoarthritis (29.2%), ORIF related (14.8%), nonunion or necrosis (9.2%), radial head arthroplasty related (7.5%), ulnar neuropathy (6.0%), and infection (2.6%). Revision procedures frequently included arthrolysis (42.1%), arthroplasty (24.9%), implant removal (23.6%), ligament repair or reconstruction (23.0%), débridement (14.2%), repeated ORIF (8.2%), and/or radial head resection (7.7%). Mason type I or II fractures were primarily revised because of stiffness and painful osteoarthritis. Complications after Mason type III fractures were predominantly ORIF related. Fracture-dislocations showed a wide range of complications, with instability and stiffness comprising the most common causes of revision. CONCLUSIONS: The complications of radial head fractures are characteristic to their classification. Knowledge of these findings might guide surgeons in treating these injuries and may help counsel patients accordingly.

Comprehensive Characterization of Extended Defects in Semiconductor Materials by a Scanning Electron Microscope.

Extended defects such as dislocations and grain boundaries have a strong influence on the performance of microelectronic devices and on other applications of semiconductor materials. However, it is still under debate how the defect structure determines the band structure, and therefore, the recombination behavior of electron-hole pairs responsible for the optical and electrical properties of the extended defects. The present paper is a survey of procedures for the spatially resolved investigation of structural and of physical properties of extended defects in semiconductor materials with a scanning electron microscope (SEM). Representative examples are given for crystalline silicon. The luminescence behavior of extended defects can be investigated by cathodoluminescence (CL) measurements. They are particularly valuable because spectrally and spatially resolved information can be obtained simultaneously. For silicon, with an indirect electronic band structure, CL measurements should be carried out at low temperatures down to 5 K due to the low fraction of radiative recombination processes in comparison to non-radiative transitions at room temperature. For the study of the electrical properties of extended defects, the electron beam induced current (EBIC) technique can be applied. The EBIC image reflects the local distribution of defects due to the increased charge-carrier recombination in their vicinity. The procedure for EBIC investigations is described for measurements at room temperature and at low temperatures. Internal strain fields arising from extended defects can be determined quantitatively by cross-correlation electron backscatter diffraction (ccEBSD). This method is challenging because of the necessary preparation of the sample surface and because of the quality of the diffraction patterns which are recorded during the mapping of the sample. The spatial resolution of the three experimental techniques is compared.

Epidemiology of amyotrophic lateral sclerosis and effect of riluzole on disease course.

OBJECTIVES: To assess the epidemiology of ALS in Austria and to evaluate the long-term effect of riluzole treatment on survival. METHODS: Hospital discharge and riluzole prescription databases were used to identify ALS cases from January 2008 to June 2012. Using the capture-recapture method we evaluated the incidence and prevalence of ALS and patients' survival in dependence of age, gender and riluzole treatment. RESULTS: The corrected incidence and prevalence of ALS were 3.13/100,000 person-years (95% CI, 2.77 to 3.50) and 9.14/100,000 persons (95% CI, 8.53 to 9.79), respectively. Median survival from diagnosis was 676 days (95% CI, 591 to 761). A younger age at diagnosis was associated with a longer survival. Gender did not appear to affect survival time. Riluzole therapy was associated with a survival advantage only for the initial treatment period. The adjusted hazard ratio of mortality for using riluzole increased continually over time resulting in an apparent reversal of its beneficial effect after 6 months of therapy. CONCLUSIONS: We report incidence and prevalence estimates that are on the upper end of the wide range discussed in literature. Riluzole seems to exert a beneficial effect only in the first 6 months of therapy.

The "central vein sign": is there a place for susceptibility weighted imaging in possible multiple sclerosis?

OBJECTIVES: Susceptibility weighted imaging (SWI) may have the potential to depict the perivenous extent of white matter lesions (WMLs) in multiple sclerosis (MS). We aimed to assess the discriminatory value of the "central vein sign" (CVS). METHODS: In a 3-T magnetic resonance imaging (MRI) study, 28 WMLs in 14 patients with at least one circumscribed lesion >5 mm and not more than eight non-confluent lesions >3 mm were prospectively included. Only WMLs in FLAIR images with a maximum diameter of >5 mm were correlated to their SWI equivalent for CVS evaluation. RESULTS: Five patients fulfilled the revised McDonald criteria for MS and nine patients were given alternative diagnoses. Nineteen MS-WMLs and nine non-MS-WMLs >5 mm were detected. Consensus reading found a central vein in 16 out of 19 MS-WMLs (84 %) and in one out of nine non-MS-WMLs (11 %), respectively. The CVS proved to be a highly significant discriminator (P < 0.001) between MS-WMLs and non-MS-WMLs with a sensitivity, specificity, positive and negative predictive value and accuracy of 84 %, 89 %, 94 %, 73 % and 86 %, respectively. Inter-rater agreement was good (κ = 0.77). CONCLUSIONS: Even though the CVS is not exclusively found in MS-WMLs, SWI may be a useful adjunct in patients with possible MS. KEY POINTS: • MRI continues to yield further information concerning MS lesions. • SWI adds diagnostic information in patients with possible MS. • The "central vein sign" was predominantly seen in MS lesions. • The "central vein sign" helps discriminate between MS and non-MS lesions.

Cerebral infarction in bacterial meningitis: predictive factors and outcome.

In this study, we analysed the frequency, morphological patterns and clinical characteristics of cerebral ischaemia in bacterial meningitis. We sought to determine predictors for the development of vasculopathy and ischaemic infarction in patients with bacterial meningitis. Consecutive adult patients admitted between March 1998 and February 2009 to a neurological intensive care unit at a university hospital in Germany with the diagnosis of bacterial meningitis were included in the study. Standard criteria were used to define bacterial meningitis. From 68 patients with bacterial meningitis, six patients suffered from cerebral ischaemia (8.8%). In our cohort, reduced level of consciousness on admission (p = 0.01) and lower white blood cell (WBC) count in cerebrospinal fluid (CSF) (p = 0.012) were associated with development of ischaemic cerebrovascular complications. The short-term outcome of all patients was poor (median modified Rankin scale 4.5). In patients presenting with reduced level of consciousness on admission and/or low WBC count in CSF early cerebral imaging including MR angiography or CT angiography are warranted to detect impending cerebrovascular complications.

Photodamage to isolated mononucleotides--photodissociation spectra and fragment channels.

UV excitation of isolated singly-charged deprotonated mononucleotide anions in the gas phase can lead to their dissociation. We present mass spectrometry results, photodepletion and photofragment action spectra on the UV-photodissociation of deprotonated 2'-deoxyribonucleobase-5'-monophosphates with adenine, cytosine, guanine and thymine as nucleobases. We observe the same anionic fragments as in earlier experiments on collision-induced dissociation, although their relative intensities are quite different, especially with respect to the abundance of the deprotonated base anions. The fragment channels correspond to loss of genetic information by cleavage of the CN glycosidic bond and to strand breaking by severing the phosphate-sugar link. We compare the photodissociation spectra with UV absorption spectra of aqueous solutions of the same species and discuss the photodissociation behavior in the context of possible mechanisms and ergodic versus non-ergodic fragmentation.

When coughing can cause stroke--a case-based update on cerebral air embolism complicating biopsy of the lung.

Introducing gas to the circulation is a largely iatrogenic problem which can result in serious morbidity and even death. We report a case of CT-guided needle biopsy of a pulmonary lesion complicated by acute stroke. The English literature on cerebral air embolism is reviewed, including an update of current opinions on its pathomechanism, diagnostic findings, therapeutic strategies, and means of prevention.

Severe Guillain-Barré syndrome associated with chromosome 17p11.2-12 duplication.

We report a patient with Guillain-Barré syndrome (GBS), characterized by severe tetraparesis, bulbar syndrome, and ophthalmoparesis. The nadir was reached within 1 day, followed by respiratory insufficiency requiring mechanical ventilation. Molecular analysis revealed a duplication at chromosome 17p11.2-12, which is a known genetic cause of Charcot-Marie-Tooth disease type 1A (CMT1A). We suggest that this genotype may comprise a previously unrecognized genetic risk factor for GBS.

Purification and characterization of a new bioscouring pectate lyase from Bacillus pumilus BK2.

An alkalophilic bacterium was isolated based on the potential of extra-cellular enzymes for bioscouring. The bacterium was identified as a new strain of Bacillus pumilus BK2 producing an extra-cellular endo-pectate lyase PL (EC 4.2.2.2). PL was purified to homogeneity in three steps and has a molecular mass of 37.3+/-4.8 kDa as determined by SDS-PAGE and an isoelectric point of pH 8.5. Peptide mass mapping by nano-LC-MS of PL revealed 15% homology with a pectate lyase from Bacillus sp. The pectate lyase exhibited optimum activity at pH 8.5 and around 70 degrees C in Tris/HCl buffer. It showed a half-life at 30 degrees C of more than 75 h. Stability decreased with increasing temperature, extremely over 60 degrees C. The enzyme did not require Ca2+ ions for activity, and was strongly inhibited by EDTA and Co2+. PL was active on polygalacturonic acid and esterified pectin, but the affinity showed a maximum for intermediate esterified pectins and decreased over a value of 50% of esterification. The best substrate was 29.5% methylated pectin. PL cleaved polygalacturonic acid via a beta-elimination mechanism as shown by NMR analysis. PL released unsaturated tetragalacturonic acid from citrus pectin and polygalacturonic acid, but did not show any side activities on other hemicelluloses. On polygalacturonic acid PL showed a Km of 0.24 gl(-1) and a vmax of 0.72 gl(-1)min(-1). The applicability of pectate lyase for the bioscouring process was tested on a cotton fabric. Removal of up to 80% of pectin was proven by means of ruthenium red dyeing and HPAEC (65%). Structural contact angle measurements clearly indicated the increased hydrophilicity of enzyme treated fabrics.

A photoactivated diazopyruvoyl cross-linking agent for bonding tissue containing type-I collagen.

On the basis of the earlier examples of diazopyruvoyl (DAP) groups reported by Lawton for covalent binding and cross-linking of proteins and oligopeptides and our recent demonstration that a coumaryl diazopyruvamide was used to label Type-I collagen, we have extended our investigations to the synthesis and cross-linking capabilities of a bis-DAP polyethylene glycol to cross-link Type-I collagen. The new photoactivated cross-linking agent, N,N'-bis(3-diazopyruvoyl)-2,2'-(ethylenedioxy)bis(ethylamine) (DPD, 2), has been designed and synthesized specifically to "weld" collagenous tissues by cross-linking Type-I collagen. A working model for the photochemical welding studies of collagenous tissues was developed using gelatin strips (gel strips) composed of denatured Type-I collagen. Gel strips are transparent to near-UV and visible light, uniform in thickness, and have reproducible composition. Furthermore, the availability of nucleophilic amine sites in gel strips was demonstrated by reaction with o-phthalaldehyde, producing a fluorescent derivative of the protein. Gel strips were coated with a solution of DPD in chloroform 7 irradiated at 320-390 nm, and the resulting bonded gel strips were tested for the strength of the weld. The welds were generally brittle and had average tensile strengths that exceeded 100 N/cm2. Welds were not formed in the absence of light or DPD. Scanning electron microscopy studies revealed a pockmarked surface from severed welds. Welds of rabbit Achilles tendon were also obtained using the tethered diazopyruvamide. These welds were much weaker, having an average tensile strength of 11.95 N/cm2 for DPD-2,2'-ethylenedioxy(bis)ethylamine comonomers in the cross-linking reaction. In both studies the welds obtained by this method were significantly stronger than the controls.

A new paraclinical CSF marker for hypoxia-like tissue damage in multiple sclerosis lesions.

Recent studies on the immunopathology of multiple sclerosis revealed a heterogeneity in the patterns of demyelination, suggesting interindividual differences in the mechanism responsible for myelin destruction. One of these patterns of demyelination, characterized by oligodendrocyte dystrophy and apoptosis, closely mimics myelin destruction in acute white matter ischaemia. In the course of a systematic screening for virus antigen expression in multiple sclerosis brains, we identified a monoclonal antibody against canine distemper virus, which detects a cross-reactive endogenous brain epitope, highly expressed in this specific subtype of actively demyelinating multiple sclerosis lesions with little or no immunoreactivity in other active multiple sclerosis cases. The respective epitope, which is a phosphorylation-dependent sequence of one or more proteins of 50, 70 and 115 kDa, is also expressed in a subset of active lesions of different virus-induced inflammatory brain diseases, but is present most prominently and consistently in acute lesions of white matter ischaemia. Its presence is significantly associated with nuclear expression of hypoxia-inducible factor-1 alpha within the lesions of both inflammatory and ischaemic brain diseases. The respective epitope is liberated into the CSF and, thus, may become a useful diagnostic tool to identify clinically a defined multiple sclerosis subtype.