3687. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial.
作者: Akimichi Morita.;Bruce Strober.;A David Burden.;Siew Eng Choon.;Milan J Anadkat.;Slaheddine Marrakchi.;Tsen-Fang Tsai.;Kenneth B Gordon.;Diamant Thaçi.;Min Zheng.;Na Hu.;Thomas Haeufel.;Christian Thoma.;Mark G Lebwohl.
来源: Lancet. 2023年402卷10412期1541-1551页
Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare prevention.
3689. Primary brain tumours in adults.
作者: Martin J van den Bent.;Marjolein Geurts.;Pim J French.;Marion Smits.;David Capper.;Jacoline E C Bromberg.;Susan M Chang.
来源: Lancet. 2023年402卷10412期1564-1579页
The most frequent adult-type primary CNS tumours are diffuse gliomas, but a large variety of rarer CNS tumour types exists. The classification of these tumours is increasingly based on molecular diagnostics, which is reflected in the extensive molecular foundation of the recent WHO 2021 classification of CNS tumours. Resection as extensive as is safely possible is the cornerstone of treatment in most gliomas, and is now also recommended early in the treatment of patients with radiological evidence of histologically low-grade tumours. For the adult-type diffuse glioma, standard of care is a combination of radiotherapy and chemotherapy. Although treatment with curative intent is not available, combined modality treatment has resulted in long-term survival (>10-20 years) for some patients with isocitrate dehydrogenase (IDH) mutant tumours. Other rarer tumours require tailored approaches, best delivered in specialised centres. Targeted treatments based on molecular alterations still only play a minor role in the treatment landscape of adult-type diffuse glioma, and today are mainly limited to patients with tumours with BRAFV600E (ie, Val600Glu) mutations. Immunotherapy for CNS tumours is still in its infancy, and so far, trials with checkpoint inhibitors and vaccination studies have not shown improvement in patient outcomes in glioblastoma. Current research is focused on improving our understanding of the immunosuppressive tumour environment, the molecular heterogeneity of tumours, and the role of tumour microtube network connections between cells in the tumour microenvironment. These factors all appear to play a role in treatment resistance, and indicate that novel approaches are needed to further improve outcomes of patients with CNS tumours.
3698. Role of preoperative in-hospital delay on appendiceal perforation while awaiting appendicectomy (PERFECT): a Nordic, pragmatic, open-label, multicentre, non-inferiority, randomised controlled trial.
作者: Karoliina Jalava.;Ville Sallinen.;Hanna Lampela.;Hanna Malmi.;Ingeborg Steinholt.;Knut Magne Augestad.;Ari Leppäniemi.;Panu Mentula.
来源: Lancet. 2023年402卷10412期1552-1561页
Appendicectomy remains the standard treatment for appendicitis. No international consensus exists on the surgical urgency for acute uncomplicated appendicitis, and recommendations vary from surgery without delay to surgery within 24 h. Longer in-hospital delay has been thought to increase the risk of perforation and further morbidity. Therefore, we aimed to compare the rate of appendiceal perforation in patients undergoing appendicectomy scheduled to two different urgencies (<8 h vs <24 h).
3700. Dilated cardiomyopathy: causes, mechanisms, and current and future treatment approaches.
作者: Stephane Heymans.;Neal K Lakdawala.;Carsten Tschöpe.;Karin Klingel.
来源: Lancet. 2023年402卷10406期998-1011页
Dilated cardiomyopathy is conventionally defined as the presence of left ventricular or biventricular dilatation or systolic dysfunction in the absence of abnormal loading conditions (eg, primary valve disease) or significant coronary artery disease sufficient to cause ventricular remodelling. This definition has been recognised as overly restrictive, as left ventricular hypokinesis without dilation could be the initial presentation of dilated cardiomyopathy. The causes of dilated cardiomyopathy comprise genetic (primary dilated cardiomyopathy) or acquired factors (secondary dilated cardiomyopathy). Acquired factors include infections, toxins, cancer treatment, endocrinopathies, pregnancy, tachyarrhythmias, and immune-mediated diseases. 5-15% of patients with acquired dilated cardiomyopathy harbour a likely pathogenic or pathogenic gene variant (ie, gene mutation). Therefore, the diagnostic tests and therapeutic approach should always consider both genetic and acquired factors. This Seminar will focus on the current multidimensional diagnostic and therapeutic approach and discuss the underlying pathophysiology that could drive future treatments aiming to repair or replace the existing gene mutation, or target the specific inflammatory, metabolic, or pro-fibrotic drivers of genetic or acquired dilated cardiomyopathy.
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