Utilization of a highly adaptable murine air pouch model for minimally invasive testing of the inflammatory potential of biomaterials.

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days. Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells. Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.

Individually or as a Team-The Immunological Milieu in the Lung Caused by Migrating Single-Sex or Mixed-Sex Larvae of Schistosoma mansoni.

While the lung is considered an efficient site for stopping the larvae of the acute Schistosoma spp. infection phase from migrating through extensive inflammatory responses in the surrounding tissues, little is known about these processes. To date, the highest resistance to infection has been achieved in experimental studies with radiation-attenuated cercariae immunization, which elicits a strong Th1/Th2 response in the lung and results in up to 80% protection. Based on our own studies demonstrating a systemic, unpolarized Th1/Th2 response resulting from infection with male or female Schistosoma mansoni, we hypothesize that this atypical immune response is already detectable during the pulmonary passage of parasite larvae. Therefore, we examined the immune milieu in the lungs of mice caused by migrating schistosome larvae, either male or female (single-sex groups) or male + female (bisexual control), 4 and 16 days after infection in bronchoalveolar lavage and lung tissue by flow cytometry, qPCR, and multiplex analyzes. Our results show only minor differences in the inflammatory profile between the single-sex groups but significant differences compared with the bisexual control group. Both single-sex infected groups have increased expression of inflammatory markers in lung tissue, higher numbers of cytotoxic T cells (day 4 post-infection) and more T helper cells (day 16 post-infection), compared with the bisexual control group. A single-sex infection, regardless of whether it is an infection with male or female cercariae, causes an immune milieu in the lung that is clearly different from an infection with both sexes. In terms of identifying therapeutic targets to achieve resistance to re-infection, it is of great scientific interest to identify the differences in the inflammatory potential of male or female and male + female parasites.

Occurrence and Risk Factors of Relapse Activity after Vaccination against COVID-19 in People with Multiple Sclerosis: 1-Year Follow-Up Results from a Nationwide Longitudinal Observational Study.

Several studies reported post-SARS-CoV-2-vaccination (PV) symptoms. Even people with multiple sclerosis (PwMS) have concerns about disease activity following the SARS-CoV-2 vaccination. We aimed to determine the proportion of PwMS with PV relapses, the PV annualized relapse rate (ARR), the time from vaccination to subsequent relapses, and identify sociodemographic/clinical risk factors for PV relapses. PwMS were surveyed several times at baseline and four follow-ups as part of a longitudinal observational study regarding the safety and tolerability of the SARS-CoV-2 vaccination. The inclusion criteria for this analysis were age ≥18 years, ≥1 SARS-CoV-2 vaccination, and ≥1-year observation period since initial vaccination. Of 2466 PwMS, 13.8% reported PV relapses (mostly after second [N = 147] or booster vaccination [N = 145]) at a median of 8.0 (first/third quantile: 3.55/18.1) weeks PV, with the shortest period following initial vaccination (3.95 weeks). The ARR was 0.153 (95% confidence interval: 0.138-0.168), with a median observation period since initial vaccination of 1.2 years. Risk factors for PV relapses were younger age, female gender, moderate-severe disability levels, concurrent autoimmune diseases, relapsing-remitting MS courses, no DMT, and relapses within the year prior to the first vaccination. Patients' health conditions before/during initial vaccination may play a more important role in PV relapse occurrence than vaccination per se.

Frequency and Predictors of Relapses following SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis: Interim Results from a Longitudinal Observational Study.

Despite protection from severe COVID-19 courses through vaccinations, some people with multiple sclerosis (PwMS) are vaccination-hesitant due to fear of post-vaccination side effects/increased disease activity. The aim was to reveal the frequency and predictors of post-SARS-CoV-2-vaccination relapses in PwMS. This prospective, observational study was conducted as a longitudinal Germany-wide online survey (baseline survey and two follow-ups). Inclusion criteria were age ≥18 years, MS diagnosis, and ≥1 SARS-CoV-2 vaccination. Patient-reported data included socio-demographics, MS-related data, and post-vaccination phenomena. Annualized relapse rates (ARRs) of the study cohort and reference cohorts from the German MS Registry were compared pre- and post-vaccination. Post-vaccination relapses were reported by 9.3% PwMS (247/2661). The study cohort's post-vaccination ARR was 0.189 (95% CI: 0.167-0.213). The ARR of a matched unvaccinated reference group from 2020 was 0.147 (0.129-0.167). Another reference cohort of vaccinated PwMS showed no indication of increased post-vaccination relapse activity (0.116; 0.088-0.151) compared to pre-vaccination (0.109; 0.084-0.138). Predictors of post-vaccination relapses (study cohort) were missing immunotherapy (OR = 2.09; 1.55-2.79; p < 0.001) and shorter time from the last pre-vaccination relapse to the first vaccination (OR = 0.87; 0.83-0.91; p < 0.001). Data on disease activity of the study cohort in the temporal context are expected for the third follow-up.

Complications of influenza in 272 adult and pediatric patients in a German university hospital during the seasonal epidemic 2017-2018.

BACKGROUND: The influenza season 2017-2018 of the northern hemisphere was the highest since 2001 and was caused predominantly by influenza B virus. METHODS: We performed a retrospective analysis of all patients in a university hospital in northern Germany with laboratory-confirmed influenza during the winter season 2017-2018 and analyzed underlying conditions, complications, and outcome. RESULTS: A total of 272 cases of influenza were diagnosed: 70 influenza A (25.7%), 201 influenza B (73.9%), and 1 co-infection. Of 182 adults, 145 were hospitalized, 73 developed pneumonia, 11 developed myocardial infarction, two a transient ischemic attack, one a stroke, and one perimyocarditis. Eleven of the 145 hospitalized adult patients (7.6%) died, ten of them because of pneumonia. All of them had preexisting diseases. Pneumonia was associated with a mortality of 13.7%. Underlying cardiac insufficiency was correlated with higher mortality (7/51 with versus 4/126 patients without cardiac insufficiency; p < 0.05). Ninety cases of influenza were diagnosed in 89 children (30 A, 60 B), one child had first influenza B, then influenza A. Twenty-eight children (31%) were hospitalized, 15 children developed one or more complications (lower respiratory tract infections, meningeal irritations, febrile seizures, otitis media, myositis). No child died. Influenza vaccination status was known in 149 adult patients, pneumonia occurred more frequently in non-vaccinated individuals (43/90; 47.8%) than in vaccinated patients (18/59; 30.5%, p < 0.05). CONCLUSION: Patients with influenza should be monitored for secondary pneumonia and myocardial infarction, and vaccination should be enforced especially in patients with coronary heart disease and cardiac insufficiency.

Vaccination in multiple sclerosis patients treated with highly effective disease-modifying drugs: an overview with consideration of cladribine tablets.

Infectious diseases are an important consideration in autoimmune conditions such as multiple sclerosis. Infective episodes may trigger relapses and significantly deteriorate the course of the disease. Some immunotherapies may cause increased rates of infection-related adverse events. Thus, infection and vaccine-related issues should be included in the individualized patient-specific treatment strategy and counseling before starting therapy and regularly on treatment. Clinical and epidemiological studies as well as pharmacovigilance data repeatedly demonstrated the safety of the great majority of vaccines in multiple sclerosis patients. Moreover, studies have shown that vaccinations with killed/inactivated vaccines do not increase the short-term risk of relapse or deterioration in multiple sclerosis, whereas infections have been shown to provoke relapses. The available evidence indicates reduced humoral vaccination efficacy on treatment with MS drugs acting on the S1P receptor, natalizumab, and B-cell depleting therapies. Recent data for cladribine tablets suggest the potential of effective immunization in the interval of the two treatment courses and after completion of therapy. Regardless of treatment, vaccine efficacy may be optimized with proper timing of application. Multiple sclerosis patients receiving highly effective therapies should be vaccinated according to general recommendations for healthy adults. Immunization against COVID-19 is highly recommended for all multiple sclerosis patients regardless of age and comorbidities. Preliminary data show the potential of adequate responses in patients treated with cladribine tablets.

[The corona pandemic and multiple sclerosis: vaccinations and their implications for patients-Part 2: vaccine technologies]. / Die Corona-Pandemie und Multiple Sklerose: Impfungen und deren Implikationen für Patienten ­ Teil 2: Impfstofftechnologien.

Along with the challenges posed by the globally circulating COVID-19 pandemic, there have been some epochal advances in the field of vaccine technologies. In addition to the traditionally used dead, live and protein-based vaccines, vector-based and gene-based vaccines gained enormous attention in the course of this health crisis. The aim of this article is to provide an overview of multiple sclerosis (MS) and vaccination, recent advances in the SARS-CoV­2 vaccine landscape as well as a detailed discussion of the various vaccine technologies. Finally, clear recommendations in the context of disease-modifying treatment and vaccination in MS are highlighted.

[The corona pandemic and multiple sclerosis: vaccinations and their implications for patients-Part 1: recommendations]. / Die Corona-Pandemie und Multiple Sklerose: Impfungen und deren Implikationen für Patienten ­ Teil 1: Empfehlungen.

The ongoing COVID-19 pandemic is a global health crisis. New challenges are constantly emerging especially for the healthcare system, not least with the emergence of various viral mutations. Given the variety of immunomodulatory and immunosuppressive therapies for multiple sclerosis (MS) and the immense developments in vaccine production, there is a high need of information for people with MS. The aim of this article is therefore to provide an overview of MS and COVID-19 as well as to clarify the implications for patients with MS, especially regarding vaccination and to formulate appropriate recommendations.

[Screening of Mothers in a COVID-19 Low-Prevalence Region: Determination of SARS-CoV-2 Antibodies in 401 Mothers from Rostock by ELISA and Confirmation by Immunofluorescence]. / Mütter-Screening in einem COVID-19-Niedrig-Pandemiegebiet: Bestimmung SARS-CoV-2-spezifischer Antikörper bei 401 Rostocker Müttern mittels ELISA und Immunfluoreszenz-Bestätigungstest.

BACKGROUND: In children, the infection with SARS-CoV-2, the cause of COVID-19, tends to be clinically inapparent more often or less severe than in adults. The spread of this infection from children poses a danger to vulnerable adults. Therefore, child care institutions and schools currently are widely closed. METHODS: Since the status of infection tends to be congruent in mothers and their children, we tested 401 mothers of children between 1 and 10 years in the city of Rostock (State of Mecklenburg-Westpomerania, northeast of Germany), for the presence of RNA of SARS-CoV-2 in throat swabs, and of antibodies against SARS-CoV-2 in serum. RESULTS: In none of the mothers tested, RNA of this virus was detected in the throat swab. In the ELISA test, IgG antibodies were positive in one serum sample, IgA antibodies were positive in 11, and borderline in 3 serum samples. All 401 sera were negative in the indirect immunofluorescence test (IIFT) with FITC-labeled IgG, IgA, und IgM antibodies. CONCLUSION: At the time of this study, neither SARS-CoV-2 RNA, nor specific antibodies against SARS-CoV-2 were detectable in the mothers tested in Rostock.

[Indications for varicella zoster and herpes zoster vaccination in multiple sclerosis: current situation]. / Varicella-zoster- und Herpes-zoster-Impfindikation bei Multipler Sklerose: aktuelle Situation.

In patients with multiple sclerosis (MS) primary varicella zoster virus (VZV) infections (chickenpox) or reactivation (shingles, herpes zoster) pose a particular challenge for neurologists and physicians in everyday clinical practice. On the one hand the various immunotherapeutic agents for treatment of MS have differently expressed risks for VZV-associated infections and on the other hand the currently available vaccination strategies (dead vs. live vaccines, single vs. combination vaccines) require an individualized approach. Moreover, in addition to the optimal timing of vaccination during the course of MS, the appropriate vaccine and, where indicated, the use of antiviral drugs should be determined.

Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany.

OBJECTIVES: The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline. METHODS: Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability. RESULTS: Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration. CONCLUSIONS: Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.

[Clostridium Difficile: Monoclonal Antibody Therapy and Vaccines]. / Clostridium difficile: Antikörpertherapie und Impfungen.

Hospital-acquired Clostridium difficile infections have become much more frequent in recent years. Besides treatment with antibiotics and fecal microbiota transplant, new preventive strategies are available now. Bezlotoxumab is an antibody against toxin B and may reduce the risk of relapse by roughly 10 %. Several vaccine candidates against toxins A and B and surface-associated antigens were immunogenic and are tested in clinical trials to investigate the efficacy and safety.

[Ascites and Renal Insufficiency in a 25 Year Old Woman]. / Aszites und erhöhte Nierenretentionsparameter bei einer 25-jährigen Frau.

CLINICAL CASE: We report of a 25 year old woman who presented with acute dysuria. She had a normal vaginal delivery three months earlier. She developed increasing ascites and laboratory findings were indicative for acute renal failure. DIAGNOSIS AND THERAPY: An explorative laparotomy revealed a tiny leak of the urinary bladder that was sutured. CONCLUSION: Spontaneous intraperitoneal bladder rupture is rare and clinically present as ascites and acute renal failure. The evaluation of the cause for atraumatic bladder ruptures may be challenging.

Tuberculosis-associated hemophagocytic lymphohistiocytosis with subsequent unmasking cryptococcal immune reconstitution inflammatory syndrome (IRIS) in an HIV-negative man.

A 22-year-old HIV-negative man from Ghana was diagnosed with severe hemophagocytic lymphohistiocytosis (HLH) induced by multiorgan tuberculosis with peritoneal, hepatic, pericardial, myocardial, pleural, pulmonary, and bone manifestation. His body mass index was 12.9 m2/kg. Bioptic material of a peritoneal biopsy grew M. tuberculosis, sensitive to all first-line antituberculous drugs. HLH resolved with antituberculous therapy, without additional anti-inflammatory therapy being given. The initial CT scan of his brain was normal. After 5 months of antituberculous treatment, he developed a paralysis of the left arm. A cerebral MRT showed ring-enhanced lesions. Blood cultures and lumbar puncture revealed Cryptococcus neoformans var. grubi. The HIV test was repeatedly negative. Antituberculous treatment was continued for a total of 9 months, and additional treatment with antifungal therapy was established. He recovered fully after 14 months of antifungal treatment.

Bilateral deafness two days following influenza vaccination: a case report.

OBJECTIVE: We report a case of deafness occurring in a temporal context of an influenza vaccination in a 79-year-old woman. METHODS: Case report and review of the literature on influenza causing deafness. RESULTS: A 79-year-old woman with normal hearing developed acute bilateral sensorineural hearing loss two days after a seasonal influenza vaccination, other obvious reasons for acute hearing loss were excluded. CONCLUSION: This patient appears to be the first reported case of bilateral deafness following a trivalent seasonal influenza vaccination.