Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial.

BACKGROUND: The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms. PATIENTS AND METHODS: Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed. RESULTS: The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen's κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen's κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis. CONCLUSIONS: Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation.

Ability of hydroxypropyl chitosan nail lacquer to protect against dermatophyte nail infection.

The development of a topical agent that would strengthen the nail, improve the natural barrier, and provide better drug penetration to the nail bed is needed. In this study, we examined the effects of a hydroxypropyl chitosan (HPCH)-based nail solution using a bovine hoof model. Following application of the nail solution, changes in the hardness of the hoof samples were measured using the Vickers method. Tensile and flexural strengths were tested by stretching or punching the samples, respectively. The ultrastructure was examined using scanning electron microscopy (SEM), and samples stained with periodic acid-Schiff (PAS) stain were used to determine the fungal penetration depth. The comparators included 40% urea and 70% isopropyl alcohol solutions. The HPCH nail solution increased hoof sample hardness in comparison to the untreated control sample (mean, 22.3 versus 19.4 Vickers pyramid number [HV]). Similarly, the HPCH solution increased the tensile strength (mean, 33.07 versus 28.42 MPa) and flexural strength (mean, 183.79 versus 181.20 MPa) compared to the untreated control. In contrast, the comparators had adverse effects on hardness and strength. SEM showed that the HPCH solution reduced the area of sample crumbling following abrasion compared to the untreated control (7,418 versus 17,843 pixels), and the PAS-stained images showed that the HPCH solution reduced penetration of the dermatophyte hyphae (e.g., penetration by Trichophyton mentagrophytes was <25 µm at day 9 versus 275 µm in the untreated control). Unlike chemicals normally used in cosmetic treatments, repeated application of the HPCH nail solution may help prevent the establishment of new or recurring fungal nail infection.

'Healthy skin': significance and results of an Italian study on healthy population with particular regard to 'sensitive' skin.

There is an increasing demand in general population regarding skin healthiness and improvement of aesthetical appearance, indicating that people require more information about how to treat healthy skin and to prevent skin disease. This study is the result of a campaign on healthy skin organized by the International Society of Plastic Dermatology. This campaign was at the same time an occasion to perform an epidemiological study on Italian population and was conducted during only one month (March 2004) throughout Italy. In total, 462 dermatologists all over Italy joined the project. Study protocol and diagnostic kits were provided to all adhering dermatologists. After signing an informed consent, subjects were assigned to undergo anamnesis, medical examination and stinging test with 10% lactic acid at the level of nasolabial fold. A total of 2101 duly compiled case record forms were sent back by the dermatologists. The analysis of the demographic features and lifestyle of the subjects who were attracted by the campaign allows us to draw the identikit of people interested in the maintenance of a healthy skin, i.e. mainly young women, who already lead a healthy life and took care of their skin. Sensitive skin was common in this healthy population.

Ptosis of submental skin: objective measurements and effect of age.

BACKGROUND/PURPOSE: Sagging of the face skin is a visible and unattractive characteristic of skin ageing. This phenomenon, due to both gravitational force and age-related alterations in the mechanical properties of skin, has never been quantitatively studied. The aim of this paper was, first, to define a method and a precise procedure allowing the objective measurement of this phenomenon and, second,to study how it is related to age. METHODS: We used an electronically controlled bed that allows the comparison of submental skin profiles in both the reclined and the upright positions. A parameter that characterises the sagging amplitude for an individual was defined and the reproducibility of measurement of this parameter was verified. RESULTS: Results, obtained from 66 female volunteers, demonstrated a statistically significant positive correlation between this new parameter and age, and also between this new parameter and the elastic recovery parameter of skin, as measured by torquemeter. CONCLUSION: Age-related changes of the skin's mechanical properties and of the various underlying skin tissues would explain this phenomenon. This new method and procedure should allow objective evaluation of the efficacy of any treatments (cosmetic, medical or surgical) proposed for rendering the appearance of people younger.

Irregularity skin index (ISI): a tool to evaluate skin surface texture.

BACKGROUND/AIMS: Irregularity of skin surface microtopography is difficult to evaluate in Euclidean geometry. Using a fast Fourier transform (FFT), it is possible to convert a space field into a frequency field and to obtain quantitative evaluation of this important feature of the skin. The aim of the present study was to test the applicability of a new parameter, derived from computer assisted FFT, to skin texture, in order to quantify its irregularity. This parameter has the additional advantage of being anisotropic. METHOD: The study was conducted on 50 female volunteers. Skin replicas were performed on a healthy area that was not chronically photo-exposed. A new parameter, called "irregularity skin index" (ISI), was identified from FFT. The correlation with volunteers' age was calculated. RESULTS: ISI was calculated by FFT in two different directions (referred to the x and y axis of the diagram of the FFT and named, respectively, ISIomegax and ISIomegay). The irregularity skin indexes increased with age of the subjects, showing a correlation with age of r=0.47 (ISIomegax) and r=0.51 (ISIomegay). CONCLUSION: By showing a relatively good correlation with age, ISI seems to be a promising parameter for the study of ageing skin.