Pemphigus, an autoimmune blistering disease that affects the skin and mucous membranes, adversely impacts patients' quality of life (QOL). While there are various QOL measurement tools that can be used in this disease, few studies have assessed how a patient's change in disease severity can affect their QOL. This study aims to identify which disease severity index correlates best with the change in QOL. Fifty pemphigus patients completed QOL surveys with disease severity scored over two visits. QOL was assessed with the Autoimmune Bullous Disease Quality of Life (ABQOL), Dermatology Life Quality Index (DLQI), Skindex-29, and Short Form Survey 36 (SF-36). Disease severity was scored with the Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Correlations between the change in QOL scores and change in disease severity were analyzed using Spearman's coefficient (r). The change in PDAI showed a strong correlation (r = 0.60–0.79) with changes in the ABQOL, Skindex-29 symptoms (Skindex-S), and Skindex-29 functioning (Skindex-F) subscales for all patients (n = 50). For patients with mucosal disease (n = 24), the change in PDAI showed a strong correlation with changes in the ABQOL and Skindex-S subscale. For patients without mucosal disease, the change in PDAI showed a strong correlation with the Skindex-S. The change in ABSIS showed a strong correlation with Skindex-S for all patients and patients with no mucosal involvement, but showed no strong correlations for patients with mucosal involvement. The changes in PDAI always had a stronger correlation than the changes in ABSIS scores to changes in the ABQOL, DLQI, and Skindex-29 subscales, except where the PDAI and ABSIS scores were about the same for the Skindex-S subscale in patients with no mucosal involvement (r = 0.76 and r = 0.77, respectively). PDAI is superior to ABSIS in its correlation with validated QOL tools. The QOL tools that appear to be of most use in clinical trials and patient management are the Skindex-S and ABQOL.
The CRISPR/Cas9 system has recently emerged as a highly efficient modality in genetic engineering and has been widely considered for various therapeutic applications. However, since the effector protein, SpCas9, has a bacterial origin, its immunogenicity must be explored in further depth. Here, we found that the intact immune system, in wild-type C57BL/6J and BALB/cL mice, stimulates specific immune response against SpCas9, resulting in the rejection of SpCas9-expressing tumors. However, these tumors effectively grew in syngeneic C57BL/6J immunodeficient, T cell-depleted and Cas9-KI mice. Therefore, these observations suggest that this tumor rejection phenotype is T cell-dependent. The immunological clearance of SpCas9-expressing tumors in the immunocompetent group illustrates the possibility of misinterpreting the impact of CRISPR/Cas9-mediated gene editing on in vivo tumor biology and survival. Thus, these findings have important implications for the use of this exciting approach in in vivo studies, as well as to manipulate cancer cell biology for therapeutic applications.
ObjectiveThere is a need to identify concerns unique to patients with cutaneous lupus erythematosus (CLE), which may not be captured by current common-practice dermatological quality-of-life tools. This study formally characterises what bothers patients with CLE about their disease by conducting semistructured, qualitative interviews.MethodsSixteen patients with CLE were interviewed about how their cutaneous findings impact their daily life. Each interview was transcribed, coded and categorised for recurrent themes. Current CLE activity and damage were also assessed by the Cutaneous Lupus Activity and Severity Index tool.ResultsResponses were categorised into six themes, including Fear of Disease Progression, Unwanted Attention, Self-Consciousness, Physical Signs/Symptoms, Emotional Symptoms and Functional Decline. The most commonly reported themes were Self-Consciousness, mentioned by 13 of 16 (81.3%) patients, Physical Symptoms, mentioned by 12 of 16 (75%), and then Fear of Disease Progression, by 11 of 16 (68.8%). Frequently mentioned physical signs/symptoms included erythema, itch, dyspigmentation, scar and alopecia. The physical signs/symptoms were categorised as activity signs/symptoms, damage signs and other. For activity signs, erythema was mentioned most frequently (5 of 16), then scale (2 of 16). For activity symptoms, itch was mentioned most frequently (6 of 16), then pain (5 of 16). For damage signs, dyspigmentation was mentioned most frequently (4 of 16), followed by scarring (3 of 16). Patients less than 60 years old were more likely to report emotional symptoms than older patients (p<0.05), but there was no significant variation in frequency of reported themes between race, sex or subtype of CLE.ConclusionsThese patient experiences and resultant themes elucidated by this study are worth noting in future standardised estimations of the quality of life of patients with CLE. Additionally, the concerns shown by these interviews are important topics for providers to discuss when evaluating patient disease progression.
2796 selected patients who tested to five AG, including LG and DG, had positive reactions to at least one glucoside. 2 In our study, 1Á5% of consecutively tested patients were sensitized to DG and/or LG.Concomitant positive reactions between DG and LG were found in 37% of patients. This may be due to cross-sensitivity due to structural similarities, or concomitant sensitization as they are often present in the same products. A recent study suggested that both surfactants need to be tested to optimize detection of ACD. 4 We agree that the rate of concomitant reactions is not high enough to test only one screening glucoside in the baseline series. Other AG, such as coco, arachidyl or cetearyl glucoside, should be tested separately if ACD is suspected.Most patients were female, which could reflect their higher use of cosmetics. Most patients were atopic. In patients with atopic dermatitis, an impaired skin barrier may enhance penetration of allergens, or conversely may lead to overinterpretation of some irritant reactions, and these certainly appear to be irritant allergens at standard patch-test concentrations. 5 'Doubtful' reactions should be repeat tested, or the patient should undergo a repeat open-application test, to verify whether they represent true ACD.The ESCD recommended the addition of DG and LG to its baseline series in January 2019Á 6 Both have been recommended for inclusion in the updated BSCA facial series. 7 In this audit, each of DG and LG, when tested in an extended baseline series, had rates of positive reactions greater than 0Á5% in consecutive patients. We suggest that these allergens be included in the BSCA baseline series.
Immunotherapies have revolutionized cancer treatment. Immunotherapy is effective for the treatment of a wide range of cancer types and can mediate complete and durable tumor regression. Nonetheless, the field still faces many significant challenges, such as the need for personalized therapeutic strategies and better biomarkers, the difficulty of selecting the right combination therapy, and resistance to currently available immunotherapies. Both cancer and host immunity comprise significantly diverse and complex ecosystems, making immunogenomics an ideal field for functional genomics analysis. In this review, we describe the cancer-immunity cycle, how cancer cells manage to evade immune attack and the current hurdles in the path of cancer immunotherapy. Then, we discuss how functional genomics approaches can pave the way for more successful cancer immunotherapies.
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