Quality of life measurement in skin cancer patients:literature review and position paper of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes, Melanoma and Non-Melanoma Skin Cancer

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient Oriented Outcomes, Melanoma and Non‐Melanoma Skin Cancer (NMSC) present a review of the literature and position statement on health‐related (HR) QoL assessment in skin cancer patients. A literature search was carried out to identify publications since 1980 that included information about the impact of SC on QoL. Generic, dermatology‐specific, cancer‐specific, SC‐specific, facial SC‐specific, NMSC‐specific, basal cell carcinoma‐specific and melanoma‐specific QoL questionnaires have been used to assess HRQoL in SC patients. HRQoL was assessed in the context of creation and validation of the HRQoL instruments, clinical trials, comparison of QoL in SC and other cancers, other diseases or controls, HRQoL assessment after treatment, comorbidities, behaviour modification, predictors of QoL and survival, supportive care needs, coping strategies and fear of cancer recurrence. The most widely used instruments for HRQoL assessment in SC patients are the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ‐C30), the Functional Assessment of Cancer Therapy‐Melanoma (FACT‐M), Skin Cancer Index (SCI), Short Form 36 Item Health Survey (SF‐36) and the Dermatology Life Quality Index (DLQI). The TFs recommend the use of the cancer‐specific EORTC QLQ‐C30, especially in late stages of disease, and the melanoma‐specific FACT‐M and SC‐specific SCI questionnaires. These instruments have been well validated and used in several studies. Other HRQoL instruments, also with good basic validation, are not currently recommended because the experience of their use is too limited. Dermatology‐specific HRQoL instruments can be used to assess the impact of skin‐related problems in SC. The TFs encourage further studies to validate HRQoL instruments for use in different stages of SC, in order to allow more detailed practical recommendations on HRQoL assessment in SC

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old