Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

How to diagnose axial spondyloarthritis early

Abstract: Background: Chronic low back pain (LBP), the leading symptom of ankylosing spondylitis (AS) and undifferentiated axial spondyloarthritis (SpA), precedes the development of radiographic sacroiliitis, sometimes by many years. Objective: To assign disease probabilities and to develop an algorithm to help in the early diagnosis of axial SpA. Methods: Axial SpA comprises AS and undifferentiated SpA with predominant axial involvement. Clinical features include inflammatory back pain (IBP), alternating buttock pain, enthesitis, arthritis, dactylitis, acute anterior uveitis, a positive family history, psoriasis, inflammatory bowel disease, and good response to NSAIDs. Associated laboratory findings include raised acute phase reactions, HLA-B27 association, and abnormalities on skeletal imaging. Sensitivities, specificities, and likelihood ratios (LRs) of these parameters were determined from published studies. A 5% prevalence of axial SpA among patients with chronic LBP was used. The probability of the presence of axial SpA, depending on the presence or absence of the above clinical features of SpA, was determined. A probability of ⩾90% was used to make a diagnosis of axial SpA. Results: The presence of inflammatory back pain features increased the probability of axial SpA from the background 5% prevalence to 14%. The presence of 2–3 SpA features was necessary to increase the probability of axial SpA to 90%. The highest LRs were obtained for HLA-B27 and MRI. Diagnostic algorithms to be used in daily practice were suggested. Conclusions: This approach can help clinicians to diagnose with a high degree of confidence axial SpA at an early stage in patients with IBP who lack radiographic sacroiliitis.

Assessing and grading congestion in acute heart failure: a scientific statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine

Abstract: Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present.

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients.

Abstract: 177Lutetium labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients. Methods: 145 patients (median age 73 years, range 43-88) with mCRPC were treated with 177Lu-PSMA-617 in 12 therapy centres between February 2014 and July 2015 with one to four therapy cycles and an activity range of 2 to 8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (CTCAE 4.0) based on serial blood tests and the attending physician’s report. Primary endpoint for efficacy was biochemical response as defined by a PSA decline ≥ 50% from baseline to at least two weeks after start of RLT. Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response were available in 99 patients and data for physician-reported/lab-based toxicity in 145/121 patients. The median follow-up was 16 weeks (range 2-30 weeks). Nineteen patients died during the observation period. Grade 3 to 4 hematotoxicity occurred in 18 patients: 10%, 4% and 3% of the patients experienced anemia, thrombocytopenia and leukopenia, respectively. Xerostomia occurred in 8%. Overall biochemical response rate was 45% following all therapy cycles, while 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. Conclusion: The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third line systemic therapies in mCRPC patients. Future Phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats

Abstract: Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.

A Controlled Trial of Erenumab for Episodic Migraine.

Abstract: BackgroundWe tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene–related peptide receptor, for the prevention of episodic migraine. MethodsWe randomly assigned patients to receive a subcutaneous injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly for 6 months. The primary end point was the change from baseline to months 4 through 6 in the mean number of migraine days per month. Secondary end points were a 50% or greater reduction in mean migraine days per month, change in the number of days of use of acute migraine–specific medication, and change in scores on the physical-impairment and everyday-activities domains of the Migraine Physical Function Impact Diary (scale transformed to 0 to 100, with higher scores representing greater migraine burden on functioning). ResultsA total of 955 patients underwent randomization: 317 were assigned to the 70-mg erenumab group, 319 to the 140-mg erenumab group, and 319 to the placebo group. The mean number of ...