Background and Purpose-A low ankle-brachial blood pressure index (ABI) is an established risk marker for cardiovascular disease and mortality in the general population, but little is known about its prognostic value in individuals with acute ischemic stroke or transient ischemic attack (TIA). Methods-An inception cohort of 204 patients with acute ischemic stroke or TIA was followed up for a mean of 2.3 years.At baseline, patients underwent ABI measurement and were assessed for risk factors, cardiovascular comorbidities, and cervical or intracranial artery stenosis. The association between low ABI (Յ0.9) and the risk of the composite outcome of stroke, myocardial infarction, or death was examined by Kaplan-Meier and Cox regression analyses. Results-A low ABI was found in 63 patients (31%) and was associated with older age, current smoking, hypertension, peripheral arterial disease, and cervical or intracranial stenosis. During a total of 453.0 person-years of follow-up, 37 patients experienced outcome events (8.2% per person-year), with a higher outcome rate per person-year in patients with low ABI (12.8% vs 6.3%, Pϭ0.03). In survival analysis adjusted for age and stroke etiology, patients with a low ABI had a 2 times higher risk of stroke, myocardial infarction, or death than those with a normal ABI (hazard ratioϭ2.2; 95% CI, 1.1 to 4.5). Additional adjustment for risk factors and cardiovascular comorbidities did not attenuate the association. Conclusions-A low ABI independently predicted subsequent cardiovascular risk and mortality in patients with acute stroke or TIA. ABI measurement may help to identify high-risk patients for targeted secondary stroke prevention. (Stroke. 2009;40:3700-3705.)
Hepatitis D virus (HDV), termed delta hepatitis, is a satellite virus of Hepatitis B virus (HBV). 1 Synchronous infection mostly leads to viral clearance, while metachronous infection generally causes chronic HBV/HDV coinfection, which is associated with rapid progression to severe liver disease and hepatocellular carcinoma. 1 Estimations vary between 12 million 2 and about 70 million people worldwide living with HBV/HDV. 3 The coinfection poses a relevant public health challenge in numerous countries. 3 Effective drug therapy options for chronic hepatitis B/D virus infections are still needed. Until 2020, interferon-alpha was the only available therapy and only approved for the treatment of chronic HBV infection. With serious side effects, poor tolerability and a limited efficacy of about 30%, it remains an ineffective option for the majority of patients. 4 Thus, there is a high medical need for new therapeutic options in chronic hepatitis B/D, and several new concepts have been tested in the last years. The first drug that has been granted provisional approval so far is bulevirtide (trade name Hepcludex, former denomination Myrcludex B, company name Myr GmbH, Burgwedel, DE; since December 2020 Gilead). The drug blocks the sodium/bile salt cotransporter NTCP (Na+−taurocholate cotransporting polypeptide), which is also the entry receptor for Hepatitis B and D viruses. 5 In July 2020, bulevirtide (2 mg/day s.c.) was provisionally approved in the European Union for the treatment of chronic hepatitis B/D. In Germany, it received market approval in September 2020 for all HBV/HDV coinfected patients with compensated liver disease. An early access program allowed for a therapy start with bulevirtide around 6 weeks before market approval. Here, we describe the first real-life treatment experience with bulevirtide at a German tertiary referral center.
Background According to current guidelines, treatment of patients with hepatic oligometastasis in pancreatic cancer is not reflected and systemic chemotherapy is recommended in those patients. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from clinical trials addressing this particular patient group is not available. Methods In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. The clinical trial will focus on a well-defined patient collective with metastatic load limited to the liver as target organ with a maximum of five metastases. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (nal-IRI + OX+ 5-FU/FA, NAPOX) was chosen as neoadjuvant chemotherapy; the choice was based on an ongoing clinical study in which NAPOX appeared manageable, with promising anti-tumor activity in first-line treatment of patients with metastatic pancreatic adenocarcinoma. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. Discussion This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Trial registration numbers EudraCT 2019–002734-37; NCT04617457.
ImportanceAutoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting–chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome.ObjectiveTo test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement.Design, Setting, and ParticipantsThis case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity.ExposurePrior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion.Main Outcomes and MeasuresThe patient’s response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes.ResultsRapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient’s scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%).Conclusions and RelevanceCD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.
Eines der zahlreichen, sowohl im tierischen als auch im menschlichen Körper vorkommenden Eiweiße heißt PrP C ("prion protein cellular" = zelluläres Prion-Protein). Es findet sich vor allem im Nervensystem, speziell im Gehirn. PrP C kommt in erster Linie an der Zelloberfläche vor und schützt die Zellen u. a. vor zweiwertigen Kupferionen, H 2 O 2 und freien Radikalen [1]. Gerät dieses normale Eiweiß PrP C in Kontakt mit einem PrP Sc genannten Eiweiß ("prion protein scrapie"; pathogene Form des Prion-Proteins, das in dieser Form zuerst bei Tieren gefunden wurde, die an Scrapie erkrankten), nimmt PrP C die Form von PrP Sc an; es ändert also seine Konformation. Daraus entwickelt sich eine Kettenreaktion, in der immer mehr PrP C in PrP Sc umgewandelt wird. PrP Sc wird in den Zellen abgelagert und induziert einen neuronalen Untergang mit der Folge eines spongiformen Abbaus des Gehirns [2]. Die Prionenerkrankungen des Menschen kommen vor als [3]: █ sporadische Form (sporadische Creutzfeldt-JakobKrankheit, sporadische letale Insomnie, sporadische fatale Insomnie) █ genetische Form (familiäre Creutzfeldt-Jakob-Krankheit, fatale familiäre Insomnie, Gertmann-Sträussler-Scheinker-Syndrom) █ übertragene Form (iatrogen, CJK-Variante, Kuru) Epidemiologie und Klinik Sporadische Creutzfeldt-Jakob-Krankheit (sCJK) Epidemiologie. Die sporadische Form der CreutzfeldtJakob-Krankheit ist weltweit die häufigste Erkrankungsform mit einer Inzidenz von 1 -2 Fällen pro 1 Million Einwohner. Diese Erkrankung tritt im mittleren und höheren Alter auf, der Erkrankungsgipfel liegt zwischen dem 60. und 70. Lebensjahr. Klinisches Bild. Klinisch steht eine rasch fortschreitende Demenz im Vordergrund. Fokal-neurologisch fallen eine Ataxie, Myoklonien, Pyramidenbahnzeichen sowie extrapyramidal-motorische Störungen auf. Das Spätstadium der Erkrankung ist durch den akinetischen Mutismus gekennzeichnet [4]. Die sCJK ist eine
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