Elastocapillary adhesion of a soft cap on a rigid sphere.

We study the capillary adhesion of a spherical elastic cap on a rigid sphere of a different radius. Caps of small area accommodate the combination of flexural and in-plane strains induced by the mismatch in curvature, and fully adhere to the sphere. Conversely, wider caps delaminate and exhibit only partial contact. We determine the maximum size of the cap enabling full adhesion and describe its dependence on experimental parameters through a balance of stretching and adhesion energies. Beyond the maximum size, complex adhesion patterns such as blisters, bubbles or star shapes are observed. We rationalize these different states in configuration diagrams where stretching, bending and adhesion energies are compared through two dimensionless parameters.

Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process.

BACKGROUND: Acne has long been understood as a multifactorial chronic inflammatory disease of the pilosebaceous follicle, where Cutibacterium acnes (subdivided into six main phylotypes) is a crucial factor. In parallel, the loss of microbial diversity among the skin commensal communities has recently been shown as often accompanied by inflammatory skin disorders. OBJECTIVE: This study investigated the association of C. acnes phylotype diversity loss and the impact on Innate Immune System (IIS) activation. METHODS: The IIS response of skin after incubation with phylotypes IA1, II or III individually and with the combination of IA1 + II + III phylotypes, was studied in an in vitro skin explant system. The inflammatory response was monitored by immunohistochemistry and ELISA assays, targeting a selection of Innate Immune Markers (IIMs) (IL-6, IL-8, IL-10, IL-17, TGF-ß). RESULTS: IIMs were significantly upregulated in skin when being incubated with phylotype IA1 alone compared with the combination IA1 + II + III. In parallel, ELISA assays confirmed these results in supernatants for IL-17, IL-8 and IL-10. CONCLUSION: We identify the loss of C. acnes phylotype diversity as a trigger for IIS activation, leading to cutaneous inflammation. These innovative data underline the possibility to set up new approaches to treat acne. Indeed, maintaining the balance between the different phylotypes of C. acnes may be an interesting target for the development of drugs.

TOXICAN: a guide for grading dermatological adverse events of cancer treatments.

PURPOSE: The dermatological toxicity of cancer treatments is frequent and sometimes debilitating. Its reference classification, the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), is sometimes difficult to use and does not include yet the newest toxicities. Our objective was to create a guide, TOXICAN, based on the CTCAE, which is easy to use in everyday practice and which facilitates the recognition and grading of these dermatological toxicities. METHODS: This guide was developed by a working group ("GESTIM") comprising oncodermatologists, allergists, pathologists, and researchers from Nantes University Hospital. It was based on the dermatological toxicities found in the CTCAE and adapted to daily practice. These toxicities were grouped into categories and associated with photographs of typical cases to aid recognition. A simplified grading scale derived from the CTCAE was also created. This booklet was validated by means of user evaluation, and then the Delphi consensus method. RESULTS: We selected 32 dermatological toxicities, including 12 created by our group, sorted into 7 categories: skin rash, dry skin/pruritus, hyperkeratotic papules, palmoplantar changes, hair and nail changes, mucosal changes, and others. Our simplified grading scale only differed from the CTCAE for one item, urticaria. Three items were modified after evaluation by the user group and 11 after application of the Delphi method. CONCLUSION: The objective of our practical guide is to facilitate the use of the CTCAE for recognizing and grading dermatological toxicity of cancer treatments in order to provide optimal guidance for therapeutic adaptations. Its impact on clinical practice remains to be evaluated.

Nursing wound care practices in Haiti: facilitators and barriers to quality care.

AIM: To describe the facilitators and barriers for nurses to perform quality wound care in three surgical wards of a hospital in Port-au-Prince, Haiti. BACKGROUND: Up to a quarter of patients in low- and middle-income countries may acquire at least one infection while hospitalized. There is a paucity of research investigating nursing wound care practices in low- and middle-income countries regarding the prevention of hospital-acquired infections. METHODS: The design was qualitative descriptive. We observed nursing staff on the general surgery, orthopaedics and maternity units while they performed routine dressing changes (n = 15). We interviewed nursing (n = 13) and medical residents (n = 3) and inquired about their perceptions of facilitators and barriers for nurses to perform quality wound care. FINDINGS: A number of wound care practices appeared well integrated including using gloves to remove dressings, applying sterile dressings, properly disposing of soiled materials, inspecting wounds for signs of infection and employing comfort and privacy measures. Areas that may need improvement included aseptic technique, hand hygiene, pain assessments, patient education and documentation. We identified four themes related to barriers and facilitators to perform quality wound care: (i) materials and resources; (ii) nurse-to-patient ratios, workload and support; (iii) roles and responsibilities of nurses; and (iv) knowledge and training of nurses. CONCLUSION: Nursing wound care practices may be optimized by improving nurses' professional status and working conditions. IMPLICATIONS FOR NURSING PRACTICE AND HEALTH POLICY: Greater financial investment in health care and (continuing) education, self-regulation and development of the nursing role, including more autonomy, are needed to elevate the professional status of nurses in Haiti. Institutional policies should promote best practices, clarify nursing roles and responsibilities and foster interdisciplinary collaboration in patient care.

Profile of vemurafenib-induced severe skin toxicities.

BACKGROUND: Vemurafenib, a BRAF inhibitor, is commonly associated with skin toxicity. The impact of severe forms is unknown. OBJECTIVE: To determine the rate of permanent vemurafenib discontinuation due to grade 3-4 skin toxicity, features of these toxicities, their recurrence rate after a switch to dabrafenib and their impact on overall survival. METHODS: Retrospective cohort study of 131 patients treated with vemurafenib for melanoma between November 2010 and December 2014. Data on skin toxicities, the need for vemurafenib adjustment and the impact of switching to dabrafenib were collected. Regarding survival analysis, a conditional landmark analysis was performed to correct lead-time bias. RESULTS: Among the 131 vemurafenib-treated patients, 26% developed grade 3-4 skin toxicity. Forty-four percent of them permanently discontinued their treatment, mainly due to rash and classic skin adverse reactions (Steven-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms). Conversely, photosensitivity and carcinomas rarely required treatment adjustment. Grade 3-4 rashes were associated with clinical or biological abnormalities in 94% of patients. Among the 10 patients who subsequently switched to dabrafenib, skin toxicity recurred only in one patient. Overall survival was significantly prolonged in case of severe skin toxicity emerging within the first 4 (P = 0.014) and 8 weeks (P = 0.038) on vemurafenib, with only a trend at 12 weeks (P = 0.052). Median overall survival was also prolonged in case of severe rash. CONCLUSION: In this study, vemurafenib was continued in 56% of patients with grade 3-4 skin toxicity, which was associated with prolonged overall survival when emerging within the first 4 and 8 weeks of treatment. While developing severe skin adverse reactions permanently contraindicates vemurafenib use, other rashes should lead to retreatment attempts with dose reduction. In case of recurrence, dabrafenib seems to be an interesting option. For other skin toxicities, including photosensitivity and cutaneous carcinoma, treatment adjustment is usually not needed.

Development of squamous cell carcinoma into basal cell carcinoma under treatment with Vismodegib.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in humans. Vismodegib, a Hedgehog pathway inhibitor, has proved its effectiveness in treating non-resectable advanced BCC. AIM: However, its action on squamous cell carcinoma (SCC) is unknown. We present three SCC cases developed into BCC in vismodegib-treated patients. MATERIAL AND METHODS: We have described three cases of patients developing SCC during treatment by vismodegib for BCC. RESULTS: Patient 1 was treated with vismodegib for five facial BCC. Due to the progression of one of the lesions at month 3 (M3), a biopsy was performed and showed SCC. Patient 2 was treated with vismodegib for a large facial BCC. A biopsy was performed at M2 on a BCC area not responding to treatment and showed SCC. Patient 3 was treated with vismodegib for a BCC on the nose. Due to vismodegib ineffectiveness, a biopsy was performed and showed SCC. DISCUSSION: Two similar cases have been described in the literature. This could be due to the appearance of the squamous contingent of a metatypical BCC or to the squamous differentiation of stem cells through inhibition of the hedgehog pathway. CONCLUSION: In practice, any dissociated response of a BCC to vismodegib should be biopsied.

Incidence and characteristics of melanoma brain metastases developing during treatment with vemurafenib.

Vemurafenib is indicated for the treatment of patients with BRAF (V600)-mutant metastatic melanoma. We studied for the first time the characteristics of brain metastases developed during treatment with vemurafenib in real-life conditions. We included all patients treated over 3 years with vemurafenib in our department for metastatic melanoma without initial brain involvement. Our primary endpoint was to assess the incidence of brain metastases in these patients. Our secondary endpoints were to identify the risk factors for metastases occurrence and their characteristics and course. In our retrospective cohort of 86 patients, 20% had developed brain metastases on average 5.3 months after vemurafenib initiation. The median follow-up was 9 months (1-26 months). Radiological examinations revealed multiple brain metastases in 41% of patients. The only risk factor for metastasis occurrence identified was a high number of metastatic sites when initiating vemurafenib (p = 0.045). Metastasis development was associated with a trend toward a decrease in overall survival from 12.8 to 8.5 months (p = 0.07) and a significant decrease in progression-free survival from 7 to 5 months (p = 0.04). Among the patients who developed brain metastases, 82% died, of whom 64% within 3 months, versus 58% of patients without brain metastases over the same period. The extra-cerebral disease was well controlled in 59% of patients during brain progression. In vemurafenib-treated melanoma patients, brain metastases are frequent and associated with a particularly poor prognosis. Because of their high frequency in patients with controlled extra-cerebral disease, brain explorations should be systematically performed during treatment.