Reduction of inflammatory slan (6‐sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept

Dermal dendritic cells (DCs) play a central role in the immunopathology of psoriasis. We previously identified slanDCs as pro‐inflammatory TNF‐α, IL‐23‐ and IL‐12‐producing DCs in human blood and as prominent inflammatory dermal TNF‐α secreting and CD11c‐positive DC subset in psoriasis. Here, we ask for the effects of TNF‐α‐inhibition on inflammatory slanDCs in skin and blood of 10 patients with psoriasis during 24 weeks of treatment with etanercept. Treatment with etanercept reduced the frequency of dermal slanDCs but did not induce apoptosis as determined by lack of increased active caspase‐3‐expression. In parallel, we found increased frequencies of slanDCs in blood which expressed lower levels of HLA‐DR. Stimulating slanDCs isolated from the blood of healthy donors in vitro induced a strong production of IL‐1β, IL‐6, IL‐23 and IL‐12p70. This capacity was efficiently reduced in the presence of etanercept, thereby indicating that TNF‐α is an autocrine stimulus for maturation and pro‐inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment with etanercept did reduce the number of dermal slanDCs in parallel to the overall expression of TNF‐α and IL‐23p19. However, successful treatment did not down‐regulated the percentage of dermal slanDCs that stained positive for TNF‐α and IL‐23p19 indicating that remaining slanDCs kept their pro‐inflammatory capacity. This study provides novel insights into the immune regulatory properties of etanercept at the level of inflammatory slanDCs in vivo in skin and blood as well as in vitro.     

Quantity and Quality Relationships in Cardiovascular Medicine

Hospital volume and often also operator volume have documented impacts on the quality of care for aortic and aortocoronary bypass surgery, for percutaneous angioplasty and for radiofrequency ablation for arrhythmias, whereas data are less consistent for treatment of acute myocardial infarction. A review of this research is given. In the Nordic countries hospitals are small, and often the plateau of the learning curve cannot be reached. To discourage low-volume centers from embarking upon too complicated interventional or surgical procedures, the author suggests that a minimal number should be set for certain major procedures, both for hospitals and for physicians.     

Change in quality of life of medically hospitalized patients – A one-year follow-up study

Objectives: To examine changes in quality of life (QOL) among elderly medically hospitalized patients one year after hospitalization, and to explore factors associated with the changes.

Methods: A one-year follow-up study included 363 (175 men) medical inpatients with age range 65–98 (mean 80.2, SD 7.5) years. Information was collected at baseline and follow-up using the WHOQOL-BREF questionnaire assessing the physical, psychological, social and environment domain of QOL as the dependent variable, and the Mini-Mental State Examination, Lawton and Brody's scales for physical self-maintenance and instrumental activities of daily living, the Hospital Anxiety and Depression scale and assistance in living as the independent variables.

Results: The mean score of the physical domain of QOL had increased (mean change 0.6, SD 2.5; p?p? Conclusion: Good cognitive, physical and emotional health at baseline and follow-up were associated with improved QOL in previously hospitalized elderly patients independent of their need for assistance in living.     

Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.