Arthralgia is frequent during PD1ab treatment. The clinical picture varies between synovitis of predominantly large joints, progressive osteoarthritis and arthralgia without evident joint damage. Vast majority of cases can be satisfactorily managed by NSAID and/or low-dose corticosteroids.

Results-Of 330 000 inhabitants, 755 suffered from cardiac arrest covered by the Heidelberg ALS services. In 512 patients, cardiopulmonary resuscitation had been initiated. Of 338 patients with cardiac aetiology, return of spontaneous circulation was achieved in 164 patients (49%), 48 (14%) were discharged alive, and 40 (12%) were alive one year later; most of these patients showed good neurological outcome. Thus, 4.85 patients with cardiac aetiology were saved by the ALS services and discharged alive per 100 000 inhabitants a year. Ventricular fibrillation or tachycardia was detected in 106 patients (31%), other cardiac rhythms in 40 (12%), and asystole in 192 (57%). Hospital discharge rates (and one year survival) in these subgroups were 34.0% (29.2%), 12.5% (7.5%), and 3.6% (3.1%), respectively. Discharge rates increased if cardiac arrest was witnessed (bystander, 20.0%; BLS/ALS personnel, 21.4%; nonwitnessed arrest, 3.3%; p < 0.01), and if the time period between the alarm and the arrival of the ALS unit was four minutes or less (< 4 minutes, 30.6%; 4-8 minutes, 10.4%; > 8 minutes, 8.1%; p < 0.001). In 69 patients with bystander witnessed cardiac arrest with ventricular fibrillation, the discharge rate was 37.7%; 21 patients were alive after one year. Conclusions-A two tier BLS and physician staVed ALS system is associated with good long term outcome of patients suVering from out-of-hospital cardiac arrest of cardiac aetiology in a midsized urban/suburban area. Further studies, however, are required to assess whether having a physician in the ALS unit is an independent determinant for improved long term outcome. (Heart 1999;82:674-679) Keywords: out-of-hospital cardiac arrest; emergency medical services; long term outcome; Utstein style Patient outcome after out-of-hospital cardiac arrest depends on individual, demographic, sociological, and logistic factors.

Endovascular treatment of penetrating aortic ulcers is associated with a relevant morbidity and mortality rate in frequently highly comorbid patients. Midterm results could prove a sustained treatment success regarding actuarial survival and aortic-related death. Emergencies show a significantly worse outcome, but treatment is still warranted in these symptomatic patients.

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Though a neglected disease with predominantly expert-opinion-based treatment strategies, cystic echinococcosis patients can greatly benefit from interdisciplinary management in cystic echinococcosis treatment centres and cyst-stage-based assignment of treatment modalities. Increased suspicion for cystic echinococcosis in migrants from endemic to non-endemic countries is urgently needed at the current level of global mobility.

Cancers acquire multiple somatic mutations that can lead to the generation of immunogenic mutation-induced neoantigens. These neoantigens can be recognized by the host's immune system. However, continuous stimulation of immune cells against tumor antigens can lead to immune cell exhaustion, which allows uncontrolled outgrowth of tumor cells. Recently, immune checkpoint inhibitors have emerged as a novel approach to overcome immune cell exhaustion and reactivate antitumor immune responses. In particular, antibodies blocking the exhaustion-mediating programmed death receptor (PD-1)/programmed death receptor ligand (PD-L1) pathway have shown clinical efficacy. The effects were particularly pronounced in tumors with DNA mismatch repair (MMR) deficiency and a high mutational load, which typically occur in the colon and endometrium. Here, we report on a 24-yr-old woman diagnosed with extrahepatic cholangiocarcinoma who showed strong and durable response to the immune checkpoint inhibitor pembrolizumab, although treatment was initiated at an advanced stage of disease. The patient's tumor displayed DNA MMR deficiency and microsatellite instability (MSI) but lacked other features commonly discussed as predictors of response toward checkpoint blockade, such as PD-L1 expression or dense infiltration with cytotoxic T cells. Notably, high levels of HLA class I and II antigen expression were detected in the tumor, suggesting a potential causal relation between functionality of the tumor's antigen presentation machinery and the success of immune checkpoint blockade. We suggest determining MSI status in combination with HLA class I and II antigen expression in tumors potentially eligible for immune checkpoint blockade even in the absence of conventional markers predictive for anti-PD-1/PD-L1 therapy and in entities not commonly linked to the MSI phenotype. Further studies are required to determine the value of these markers for predicting the success of immune checkpoint blockade.

Semiautomatic centerline analysis is beneficial for the assessment of aortic geometry and allows precise measurements of aortic diameters and lengths. It can be simple, fast, and reproducible, but it should be used with care considering its inherent limitations. Manually adjusted multiplanar reformations remain an essential tool for intuitive visualization of the vascular anatomy.

ObjectiveWe aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC).DesignLarge cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed.ResultsA roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microdeletion on chromosome 8q23.1 was detected as a new morphomolecular driver of β-catenin-activated HCA. RSPO2 fusion positive HCA displayed upregulation of RSPO2 protein, nuclear accumulation of β-catenin and transcriptional activation of β-catenin-target genes indicating activation of Wingless-Type MMTV Integration Site Family (WNT) signalling. Architectural and cytological atypia as well as interstitial invasion indicated malignant transformation in one of the RSPO2 rearranged b-HCAs. The RSPO2 gene rearrangement was also observed in three β-catenin-activated HCCs developing in context of chronic liver disease. Mutations of the human telomerase reverse transcriptase promoter—known to drive malignant transformation of CTNNB1-mutated HCA—seem to be dispensable for RSPO2 rearranged HCA and HCC.ConclusionThe RSPO2 gene rearrangement leads to oncogenic activation of the WNT signalling pathway in HCA and HCC, represents an alternative mechanism for the development of b-HCA and may drive malignant transformation without additional TERT promoter mutation.