Practical handling of allergic reactions to COVID-19 vaccines: A position paper from German and Austrian Allergy Societies AeDA, DGAKI, GPA and ÖGAI.

Background: For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ.

Evidence for disseminated tumor cells in lymphatic vessels afferent to sentinel lymph nodes in patients diagnosed with cervical cancer.

Background: In patients diagnosed with cervical cancer, the purpose of lymphadenectomy is the removal of lymph nodes for diagnosis and potential treatment of metastasized tumor cells. It is unclear if afferent lymphatic vessels harbor tumor cells and, thus, may pose additional risk for recurrence or progression if not removed.

Aim: In this feasibility study, we analyzed the lymphatic vessels afferent to sentinel lymph node (SLN) using a highly sensitive and specific molecular marker for cervical cancer cells.

Pediatric ependymoma: A single-center experience from a developing country.

Background: Ependymomas are the third most common pediatric central nervous system (CNS) tumors, accounting for 6-12% of brain tumors in children. Management of these tumors remains challenging and recurrence occurs in over 50% of cases, mainly when complete resection is not achieved before radiotherapy. The 5-year overall survival (OS) ranges from 39 to 64%, with a 5-year progression-free survival (PFS) rate of 23-45%.

Transcatheter Aortic Valve Replacement in Young Low-Risk Patients With Severe Aortic Stenosis: A Review.

In the last decades, transcatheter aortic valve replacement (TAVR) revolutionized the treatment of symptomatic severe aortic stenosis. The efficacy and safety of TAVR were first proven in inoperable and high-risk patients. Then, subsequent randomized clinical trials showed non-inferiority of TAVR as compared to surgical aortic valve replacement also in intermediate- and low-risk populations.

Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US.

Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017.

TNFR2 is required for RIP1-dependent cell death in human leukemia.

Despite major advances in the treatment of patients with acute lymphoblastic leukemia in the last decades, refractory and/or relapsed disease remains a clinical challenge, and relapsed leukemia patients have an exceedingly dismal prognosis. Dysregulation of apoptotic cell death pathways is a leading cause of drug resistance; thus, alternative cell death mechanisms, such as necroptosis, represent an appealing target for the treatment of high-risk malignancies. We and other investigators have shown that activation of receptor interacting protein kinase 1 (RIP1)-dependent apoptosis and necroptosis by second mitochondria derived activator of caspase mimetics (SMs) is an attractive antileukemic strategy not currently exploited by standard chemotherapy.

Analysis of βAR-G and βAR-G complex formation by NMR spectroscopy.

The β-adrenergic receptor (βAR) is a prototypical G protein-coupled receptor (GPCR) that preferentially couples to the stimulatory G protein G and stimulates cAMP formation. Functional studies have shown that the βAR also couples to inhibitory G protein G, activation of which inhibits cAMP formation [R. P.

Transcatheter therapies for severe tricuspid regurgitation. Quo vadis?

Moderate-to-severe tricuspid regurgitation (TR) is common and is associated with a poor prognosis. To date, most patients are undertreated; therefore, transcatheter options could be clinically impactful in those who are denied surgery. Several transcatheter solutions have been developed that address the problem via leaflet enhancement, annuloplasty, or heterotopic implantation of self-expandable or balloon-expandable valves in the caval veins.

What clinicians and patients want: The past, the presence, and the future of the botulinum toxins.

Botulinum toxin (BoNT) is well established in clinical practice for more than 30 years. During this time the area of applications was broaden beyond the ophtalmologic and neurologic indications. Despite of decades of BoNT application with a huge increase of expertise and supporting methods for utilization as well, both patients and physicians claim about boundaries and limits in their daily treatment practice.

Loss of Piccolo Function in Rats Induces Cerebellar Network Dysfunction and Pontocerebellar Hypoplasia Type 3-like Phenotypes.

Piccolo, a presynaptic active zone protein, is best known for its role in the regulated assembly and function of vertebrate synapses. Genetic studies suggest a further link to several psychiatric disorders as well as Pontocerebellar Hypoplasia type 3 (PCH3). We have characterized recently generated Piccolo KO ( ) rats.

Entrustable Professional Activities in final year undergraduate medical training - advancement of the final year training logbook in Germany.

Training in the final year (FY) of undergraduate medical training currently does not adequately prepare students for the independent performance of medical professional activities after graduation. The concept of Entrustable Professional Activities (EPA) offers the opportunity for a competency-based FY training with the focus on medical professional activities. In regular meetings, the FY sub-working group of the German Medical Faculty Association (MFT), which includes representatives with clinical and didactic expertise of the Associations of Internal Medicine, Surgery and General Medicine, developed a concept for the competecy-orientated, EPA-based, FY model logbook 2.

Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans.

Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date.

Hemispheric asymmetries in resting-state EEG and fMRI are related to approach and avoidance behaviour, but not to eating behaviour or BMI.

Much of our behaviour is driven by two motivational dimensions-approach and avoidance. These have been related to frontal hemispheric asymmetries in clinical and resting-state EEG studies: Approach was linked to higher activity of the left relative to the right hemisphere, while avoidance was related to the opposite pattern. Increased approach behaviour, specifically towards unhealthy foods, is also observed in obesity and has been linked to asymmetry in the framework of the right-brain hypothesis of obesity.

Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension.

Objective: Evaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE).

Methods: During the 48-week OLE, patients received sarilumab 200 mg subcutaneously once every 2 weeks. Safety (March 2017 cut-off) and efficacy, including patient-reported outcomes, were evaluated.

Incidence and Pattern of Spread of Lymph Node Metastasis in Patients With Low-grade Serous Ovarian Cancer.

Background/aim: Involvement of lymph nodes (LNs) and their surgical resection in low-grade ovarian cancer remains a field of discussion. The aim of this study was to determine the incidence and pattern of distribution of lymph node metastases in patients with low-grade serous ovarian cancer.

Patients And Methods: A retrospective analysis was carried out in patients with primary low-grade serous ovarian cancer who underwent primary surgery including systematic lymphadenectomy.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Age >69 Years with Acute Myelogenous Leukemia: On Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Reduced-intensity conditioning (RIC) allows for the use of allogeneic hematopoietic stem cell transplantation (HSCT) in older patients with acute myelogenous leukemia (AML). We compared outcomes between 713 patients age ≥70 years and 16,161 patients age 50 to 69 years who underwent HSCT between 2004 and 2014. A higher proportion of the older patients were male and had secondary AML, active disease, a peripheral blood stem cell graft, a matched unrelated donor, an RIC regimen, and a lower Karnofsky Performance Status (KPS) score (P< .

Structural Insights into the Process of GPCR-G Protein Complex Formation.

The crystal structure of the β2-adrenergic receptor (β2AR) bound to the G protein adenylyl cyclase stimulatory G protein (Gs) captured the complex in a nucleotide-free state (β2AR-Gs). Unfortunately, the β2AR-Gs complex does not provide a clear explanation for G protein coupling specificity. Evidence from several sources suggests the existence of a transient complex between the β2AR and GDP-bound Gs protein (β2AR-Gs) that may represent an intermediate on the way to the formation of β2AR-Gs and may contribute to coupling specificity.

Pre-existing malignancies in renal transplant candidates-time to reconsider waiting times.

Current proposals for waiting times for a renal transplant after malignant disease may not be appropriate. New data on malignancies in end-stage renal disease and recent diagnostic and therapeutic options should lead us to reconsider our current practice.

Exploring the precision of femtosecond laser-assisted descemetorhexis in Descemet membrane endothelial keratoplasty.

Objective: Descemet membrane endothelial keratoplasty (DMEK) remains a challenging technique. We compare the precision of femtosecond laser-assisted DMEK to manual DMEK.

Methods And Analysis: A manual descemetorhexis (DR) of 8 mm diameter was compared with a femtosecond laser-assisted DR of the same diameter (femto-DR) in 22 pseudophakic patients requiring DMEK.

Standard work-up of the low-risk kidney transplant candidate: a European expert survey of the ERA-EDTA Developing Education Science and Care for Renal Transplantation in European States Working Group.

Background: Existing guidelines on the evaluation and preparation of recipients for kidney transplantation target the entire spectrum of patients with end-stage renal disease. Within the ERA-EDTA Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) Working Group, it was proposed that in a subset of relatively young patients (<40 years) without significant comorbidities (such as diabetes or cardiovascular disease), the work-up for transplantation could be restricted to a small set of tests.

Methods: Aiming for agreement between transplant centres across Europe, we surveyed the opinion of 80 transplant professionals from 11 European states on the composition of a minimal work-up.

Seizure-induced microvascular injury is associated with impaired neurovascular coupling and blood-brain barrier dysfunction.

Objective: Blood-brain barrier (BBB) impairment, redistribution of pericytes, and disturbances in cerebral blood flow may contribute to the increased seizure propensity and neurological comorbidities associated with epilepsy. However, despite the growing evidence of postictal disturbances in microcirculation, it is not known how recurrent seizures influence pericytic membrane currents and subsequent vasodilation.

Methods: Here, we investigated successive changes in capillary neurovascular coupling and BBB integrity during recurrent seizures induced by 4-aminopyridine or low-Mg conditions.

Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA.

Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.

Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry.

The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts.

IgG3 is the IgG subclass with the strongest effector functions among all four IgG subclasses and the highest degree of allelic variability among all constant immunoglobulin genes. Due to its genetic position, IgG3 is often the first isotype an antibody switches to before IgG1 or IgG4. Compared with the other IgG subclasses, it has a reduced half-life which is probably connected to a decreased affinity to the neonatal Fc receptor (FcRn).