RepoMed (Medizinische Hochschule Hannover)
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Combating COVID-19: MVA Vector Vaccines Applied to the Respiratory Tract as Promising Approach Toward Protective Immunity in the Lung
Get PDFThe lung is the vital target organ of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the majority of patients the most active virus replication seems to be found in the upper respiratory tract, severe cases however suffer from SARS-like disease associated with virus replication in lung tissues. Due to the current lack of suitable anti-viral drugs the induction of protective immunity such as neutralizing antibodies in the lung is the key aim of the only alternative approach-the development and application of SARS-CoV-2 vaccines. However, past experience from experimental animals, livestock, and humans showed that induction of immunity in the lung is limited following application of vaccines at peripheral sides such as skin or muscles. Based on several considerations we therefore propose here to consider the application of a Modified Vaccinia virus Ankara (MVA)-based vaccine to mucosal surfaces of the respiratory tract as a favorable approach to combat COVID-19
Die erhöhte Aktivität und Apoptose von eosinophilen Granulozyten in der Blasenflüssigkeit, Haut und dem peripherem Blut von Patienten mit bullösem Pemphigoid
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The Impact of Immunomodulatory Treatment on Kappa Free Light Chains as Biomarker in Neuroinflammation.
No full textBACKGROUND:Kappa free light chains (KFLC) are a promising new biomarker to detect neuroinflammation. Still, the impact of pre-analytical effects on KFLC concentrations was not investigated. METHODS:KFLC concentrations were measured in serum and cerebrospinal fluid (CSF) of patients with a newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) before (n = 42) or after therapy with high-dose methylprednisolone (n = 65). In prospective experiments, KFLC concentrations were analyzed in the same patients in serum before and after treatment with high-dose methylprednisolone (n = 16), plasma exchange (n = 12), immunoadsorption (n = 10), or intravenous immunoglobulins (n = 10). In addition, the influence of storage time, sample method, and contamination of CSF with blood were investigated. RESULTS:Patients diagnosed with MS/CIS and treated with methylprednisolone showed significantly lower KFLC concentrations in serum as untreated patients. Repeated longitudinal investigations revealed that serum KFLC concentrations continuously decreased after each application of methylprednisolone. In contrast, other immune therapies and further pre-analytical conditions did not influence KFLC concentrations. CONCLUSION:Our results show prominent effects of steroids on KFLC concentrations. In contrast, various other pre-analytical conditions did not influence KFLC concentrations, indicating the stability of this biomarker
Expression of Olig2, Nestin, NogoA and AQP4 have no impact on overall survival in IDH-wildtype glioblastoma.
No full textDespite many years of research efforts and clinical trials the prognosis of patients diagnosed with glioblastoma remains very poor. The oligodendrocyte transcription factor 2 (Olig2) was identified as a marker for glioma stem cells, which are believed to be responsible for glioma recurrence and therapy resistance. In this retrospective analysis we assessed the prognostic value of oligodendroglial and glioma stem cell markers in 113 IDH-wildtype glioblastomas. Immunohistochemical staining for Olig2, NogoA, AQP4 and Nestin was performed in combination with sequencing of IDH1 and IDH2 as well as promotor methylation analysis of the MGMT gene. Even though differences in overall survival according to Olig2 expression were observed, univariate and multivariate survival analysis did not reveal a firm significant prognostic impact of Olig2, NogoA, AQP4 or Nestin expression. Additionally, no differences in the expression of these markers depending on clinical status, age or gender were found. The established independent prognostic factors age = 70 and methylated MGMT gene promoter were significant in the multivariate analysis. In conclusion expression of oligodendroglial and glioma stem cell markers do not have an independent prognostic effect in IDH-wildtype glioblastoma
Toward a Computational Neuropsychology of Cognitive Flexibility.
Get PDFCognitive inflexibility is a well-documented, yet non-specific corollary of many neurological diseases. Computational modeling of covert cognitive processes supporting cognitive flexibility may provide progress toward nosologically specific aspects of cognitive inflexibility. We review computational models of the Wisconsin Card Sorting Test (WCST), which represents a gold standard for the clinical assessment of cognitive flexibility. A parallel reinforcement-learning (RL) model provides the best conceptualization of individual trial-by-trial WCST responses among all models considered. Clinical applications of the parallel RL model suggest that patients with Parkinson's disease (PD) and patients with amyotrophic lateral sclerosis (ALS) share a non-specific covert cognitive symptom: bradyphrenia. Impaired stimulus-response learning appears to occur specifically in patients with PD, whereas haphazard responding seems to occur specifically in patients with ALS. Computational modeling hence possesses the potential to reveal nosologically specific profiles of covert cognitive symptoms, which remain undetectable by traditionally applied behavioral methods. The present review exemplifies how computational neuropsychology may advance the assessment of cognitive flexibility. We discuss implications for neuropsychological assessment and directions for future research
Diagnosis and Differential Diagnosis of Neurological Adverse Events during Immune Checkpoint Inhibitor Therapy.
Get PDFTherapy with immune checkpoint inhibitors (ICIs) has improved overall survival and cancer-related morbidity of cancer treatment even in cancer entities with poor prognosis. Since the approval of the first ICI, ipilimumab, for treatment of advanced melanoma by the Food and Drug Administration (FDA) in 2011, the spectrum of indications and approved ICIs has grown, rapidly. Up to now, seven different ICIs for more than 20 indications are available. However, their mechanisms of action can lead to immune-related adverse events (irAEs). In particular, neurological irAEs are clinically relevant. Although they are rare, an early and accurate diagnosis is challenging and neurological disease course and sequelae are potentially fatal. Between 08/2017 and 03/2020, 31 patients received ICI treatment at Hannover Medical School and presented with neurological adverse events (N-irAEs). Treated malignancies were metastatic melanoma, bronchial carcinoma, and urothelial cell carcinoma. All patients received comprehensive neurological diagnostics including clinical examination and magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) analysis was obtained in 21 patients and electroneurography was performed in 22 patients. Although N-irAEs were suspected in all 31 patients, 11 patients had other conditions leading to neurological symptoms including tumor metastases in seven patients and hemorrhagic or ischemic stroke in four patients. In the following, these patients are referred to as the differential diagnosis (DD) group. Patients with N-irAEs suffered from immune mediated neuropathy (9/20), myositis and/or myasthenic syndrome (6/20), or encephalitis/cerebellitis (5/20). Except for cell count, CSF results did not differ between the N-irAEs and the DD group. Symptoms related to N-irAEs are rather unspecific potentially mimicking other tumor-related symptoms such as metastases. Patients with malignancy are predominantly not treated by neurologists. Because of the complexity of neurological symptoms, detailed neurological investigations in specialized institutions are necessary in patients with new neurological symptoms and need to be critically discussed with treating oncologists
Role of wearable rhythm recordings in clinical decision making-The wEHRAbles project.
Get PDFBACKGROUND:Multiple wearable devices for rhythm analysis have been developed using either photoplethysmography (PPG) or handheld ECG. HYPOTHESIS:The aim of this survey was to assess impact of these technologies on physicians' clinical decision-making regarding initiation of diagnostic steps, drug therapy, and invasive strategies. METHODS:The online survey included 10 questions on types of devices, advantages, and disadvantages of wearable devices as well as case scenarios for patients with supraventricular arrhythmias and atrial fibrillation (AF). RESULTS:A total of 417 physicians (median age 37 [IQR 32-43] years) from 42 countries world-wide completed the survey. When presented a tracing of a regular tachycardia by a symptomatic patient, most participants would trigger further diagnostic steps (90% for single-lead ECG vs 83% for PPG, P < .001), while a single-lead ECG would be sufficient to perform an invasive EP study in approximately half of participants (51% vs 22% for PPG, P < .001). When presented with a single-lead ECG tracing suggesting AF, most participants (90%) would trigger further diagnostic steps. A symptomatic AF patient would trigger anticoagulation treatment to a higher extent as an asymptomatic patient (59% vs 21%, P < .001). PPG tracings would only rarely lead to therapeutic steps regardless of symptoms. Most participants would like scientific society recommendations on the use of wearable devices (62%). CONCLUSIONS:Tracings from wearable rhythm devices suggestive of arrhythmias are most likely to trigger further diagnostic steps, and in the case of PPG recordings rarely therapeutic interventions. A majority of participants expect these devices to facilitate diagnostics and arrhythmia screening but fear data overload and expect scientific society recommendations on the use of wearables
