Sensitivity of clinician-assessed efficacy outcome measurement instruments in trials of topical therapies for atopic dermatitis: a systematic review and meta-analysis.

The rising prevalence of atopic dermatitis (AD) in developing countries and its substantial socioeconomic impact have furthered research over the last two decades giving way to advances in its aetiopathogenesis and treatment. Topical therapies targeting newly identified AD signalling pathways are being developed. Numerous clinician-assessed disease severity outcome measurement instruments (OMIs) are available to evaluate the efficacy of investigational treatments in proof-of-concept (POC) trials for AD. However, little is known about the comparative sensitivity of these efficacy OMIs. We performed a systematic review and meta-analysis to compare the sensitivity of different OMIs in controlled trials of topical therapies for AD published between January 1, 2000 and April 7, 2020. Treatment effect size of OMIs reported at Week 4 was calculated with 95% Confidence Interval (CI). The sensitivity of OMIs was compared by pooling the standardized difference between means (Cohen's d and Cohen's h) for any two OMI-parameter combinations that were reported in ≥3 studies identified in our systematic review. Assessed parameters were difference between active and vehicle at Week 4 and change from baseline [CFB] and percentage change from baseline [%CFB] at Week 4. We identified a total of 15 studies with 3313 subjects examining 14 different OMIs were included in this quantitative meta-analysis. Continuous OMIs had a significantly higher treatment effect size vs. dichotomous OMIs (P = 0.006). Comparisons of Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), body surface area (BSA) and SCORing Atopic Dermatitis (SCORAD) for available parameters were performed and generally had a similar sensitivity, with BSA showing smaller overall effect size estimates. In conclusion, continuous OMIs used in topical clinical trials for AD had significantly higher treatment effect sizes when compared to dichotomous OMIs. Continuous OMIs could provide more power for POC trials with a small sample size in atopic dermatitis with topical therapies.

Immunohistochemical and genetic exploration of incompatible A blood group antigen expression in invasive micropapillary breast carcinoma: A case report.

INTRODUCTION: Invasive Micropapillary Carcinoma (IMPC) of the breast is a relatively rare subtype of invasive ductal carcinoma and represents the most inherently aggressive form. Expression of incompatible blood group A antigen in cancer of type O patients has been reported in several types of cancer, however, the biosynthetic mechanism and the genetic basis remain unclear until today. The aim of the present case report study was to evaluate the expression of incompatible blood group A antigen and to identify the genetic basis of this expression in IMPC of the breast. MATERIAL AND METHODS: One patient blood group O with Invasive Micropapillary Carcinoma was screened at Pathology Department of University Hospital CHU Ibn Rochd, Casablanca. ABH antigens expression was assessed by immunohistochemistry. ABO genotyping was performed by allele specific primers PCR-ASP and Exon 6 of ABO gene was sequenced with Sanger method. RESULTS: H antigen was expressed in endothelial and epithelial cells of normal tissue. However, H antigen expression was lost in both invasive micropapillary carcinomas. A antigen was expressed in IMPC with approximately 80% of positive cells. Tumor DNA was genotyped as heterozygous A/O. In normal DNA, we identified a single frameshift deletion c.320delA p.(Glu107Glyfs*12), which is removed from tumor DNA. CONCLUSION: Our findings suggest that incompatible A antigen expression in IMPC is due to glycosyltransferase A encoded by an A allele which is derived from O allele with a deletion at the position 320.

Distinctive roles of PKC delta isozyme in platelet function.

Platelet activation is a complex balance of positive and negative signaling pathways. Several protein kinase C (PKC) isoforms are expressed in human platelets. They are a major regulator of platelet granule secretion, activation and aggregation activity. One of those isoforms is the PKCδ isozyme, it has a central yet complex role in platelets such as opposite signaling functions depending on the nature of the agonist, it concentration and pathway. In fact, it has been shown that PKCδ has an overall negative influence on platelet function in response to collagen, while, following PAR stimulation, PKCδ has a positive effect on platelet function. Understanding the crucial role of PKCδ in platelet functions is recently emerging in the literature, therefore, further investigations should shed light into its specific role in hemostasis. In this review, we focus on the different roles of PKCδ in platelet activation, aggregation and thrombus formation.

ABO blood groups in relation to breast carcinoma incidence and associated prognostic factors in Moroccan women.

The association between blood groups ABO and different types of diseases was established in several previous studies. Our aim was to seek the possible association between the ABO blood group and breast cancer-associated prognostic factors. The Chi-squared analytic test was used to compare phenotypic ABO distribution among Moroccan blood donors and 442 cases of women suffering from breast carcinoma with archived files in Maternity Ward of University Hospital C.H.U Ibn Rochd between 2008 and 2011. High incidence of breast carcinoma was observed in blood type B patients (p < 0.05). Blood type B was associated with breast carcinomas overexpressing human epidermal growth factor receptor HER2 (p < 0.05) and high risk of cancer at age over 70 years (p < 0.001). Blood type A was associated with high risk of cancer among women younger than 35 years old. Blood type A and AB were associated with high incidence of lymph node metastasis (p < 0.05). Multivariate analysis has shown correlation between O blood type and estrogen receptor-positive tumor. Patients with blood group A, B, and AB were more likely to develop aggressive breast carcinoma. Further follow-up studies are necessary to clarify the role of ABH antigens in the progression of breast carcinoma.

PKCs in thrombus formation.

The protein kinase C (PKC) family has been implicated in several physiological processes regulating platelet activation. Each isoform of PKC expressed on platelets, may have a positive and/or negative role depending on the nature and concentration of the agonist. Mice lacking PKCα show much reduced thrombus formation in vivo, while PKCθ(-/-) showed inhibition of aggregation in response to PAR4. On the other hand, PKCδ by associating with Fyn, inhibits platelet aggregation. In addition, PKCß by interacting with its receptor RACK1 has been implicated in the primary phases of signaling via the αIIbß3 and finally PKCɛ appears to be involved in platelet function downstream GPVI. The present review discusses the latest observations relevant to the role of individual PKC isoforms in platelet activation and thrombus formation.