Surrounding skin management in venous leg ulcers: A systematic review

Objectives: Chronic venous insufficiency may lead to the development of venous leg ulcers, the most common form of chronic wounds in the lower extremity. Key to venous leg ulcer care is the maintenance of healthy skin surrounding the ulcer, as failure to maintain skin integrity may influence the healing outcome. We thus reviewed the scientific literature looking for assessment and management instruments regarding this common but often neglected issue. Method: The search included all studies published between 2000 and May 2019. Keywords used were: “peri-wound skin care”, “surrounding skin venous ulcers”, “surrounding skin management leg ulcers”, and “peri-lesional skin management”. Results: Management of moisture-balance with the selection of appropriate dressings is the most important target in surrounding-wound skin care. Moreover, contact dermatitis related to products and the dressings themselves is a neglected problem in patients with chronic leg ulcers which clinicians increasingly have to manage. The literature search revealed that there is an increasing interest in the use of noninvasive assessment tools in the field of wound care, and focusing on the surrounding-wound skin plays a role in assessing the potential of wound healing. Transepidermal water loss measurement (TEWL) and ultrasonography are two of the measurement techniques available. Conclusion: The integrity of the surrounding skin is necessary for wound healing, and appropriate management is needed to address this aspect which is part of an overall approach to treating wounds

Atypical ulcers: Diagnosis and management

Atypical ulcers show atypical clinical features, histology, localization, and resistance to standard therapies. The persistence of a chronic ulcer despite treatment with standard therapies requires a more specific diagnostic investigation. Diagnosis involves obtaining the history and performing clinical examination and additional tests. A skin biopsy is frequently used to confirm unclear diagnosis. In difficult cases, microbiological and immunohistochem-ical examinations, laboratory blood tests, or instrumental tests should be evaluated. The treatment of atypical wounds is characterized by local systemic therapy and pain control. Our results highlight the need for early diagnosis, and standardized and targeted management by a multidisciplinary wound healing center

Lichen planus mimicking atypical melanocytic lesion in a man with dark skin

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Positive and negative aspects of GRI reporting as perceived by Brazilian organizations

This paper aims to identify the positive and negative aspects in the sustainability reporting framework proposed by the Global Reporting Initiative (GRI). The research was conducted through content analysis of 27 companies’ responses to three questions: “Why does the company where you work prepare a sustainability report?” “What are the positive aspects you identify in the framework for GRI reporting?” and “What are the negative aspects you identify in the framework for GRI reporting?” The questionnaire was sent to all Brazilian companies that published sustainability reports using the GRI guidelines between 2011 and 2013 related to the base year 2010. We found that respondents viewed the GRI guidelines and the reports they created as management tools for sustainability and that they assist in benchmarking sustainability performance and legitimizing the sustainability actions of the organization. Furthermore, some respondents indicated that the reports themselves are marketing tools. On the other hand, the respondents reported difficulties in understanding the proposed GRI guidelines. They considered the guidelines complex, ambiguous, and too flexible, which undermined both the standardization of the reports and the ability to compare reports. Based on these comments, it is recommended that the GRI develop a simpler and less flexible reporting methodology

PIK3CA-Related Overgrowth Spectrum From Diagnosis to Targeted Therapy: A Case of CLOVES Syndrome Treated With Alpelisib

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term referring to various clinical entities, which share the same pathogenetic mechanism. These conditions are caused by somatic gain-of-function mutations in PIK3CA, which encodes the 110-kD catalytic α subunit of PI3K (p110α). These PIK3CA mutations occur as post-zygotic events and lead to a gain of function of PI3K, with consequent constitutional activation of the downstream cascades (e.g., AKT/mTOR pathway), involved in cellular proliferation, survival and growth, as well as in vascular development in the embryonic stage. PIK3CA-related cancers and PROS share almost the same PIK3CA mutational profile, with about 80% of mutations occurring at three hotspots, E542, E545, and H1047. These hotspot mutations show the most potent effect on enzymatic activation of PI3K and consequent downstream biological responses. If present at the germinal level, these gain-of-function mutations would be lethal to the embryo, therefore we only see them in the mosaic state. The common clinical denominator of PROS disorders is that they are sporadic conditions, presenting with congenital or early childhood onset overgrowth with a typical mosaic distribution. However, the severity of PROS is highly variable, ranging from localized and apparently isolate overgrowth to progressive and extensive lipomatous overgrowth associated with life-threatening vascular malformations, as seen in CLOVES syndrome. Traditional therapeutic approaches, such as sclerotherapy and surgical debulking, are often not curative in PROS patients, leading to a recrudescence of the overgrowth in the treated area. Specific attention has been recently paid to molecules that are used and studied in the oncogenic setting and that are targeted on specific alterations of the pathway PI3K/AKT/mTOR. In June 2018, Venot et al. showed the effect of Alpelisib (BYL719), a specific inhibitor for the p110α subunit of PI3K, in patients with PROS disorders who had severe or life-threatening complications and were not sensitive to any other treatment. In these cases, dramatic anatomical and functional improvements occurred in all patients across many types of affected organ. Molecular testing in PROS patients is a crucial step in providing the conclusive diagnosis and then the opportunity for tailored therapy. The somatic nature of this group of diseases makes challenging to reach a molecular diagnosis, requiring deep sequencing methods that have to be performed on DNA extracted from affected tissue. Moreover, even analyzing the DNA extracted from affected tissue there is no guarantee to succeed in detection of the casual somatic mutation, since the affected tissue itself is highly heterogeneous and biopsy approaches can be burdened by incorrect sampling or inadequate tissue sample. We present an 8-year-old girl with CLOVES syndrome, born with a large cystic lymphangioma involving the left hemithorax and flank, multiple lipomas, and hypertrophy of the left foot and leg. She developed severe scoliosis. Many therapeutic approaches have been attempted, including Sildenafil treatment, scleroembolization, laser therapy, and multiple debulking surgeries, but none of these were of benefit to our patient's clinical status. She then started treatment with Rapamycin from May 2019, without significant improvement in both vascular malformation and leg hypertrophy. A high-coverage Whole Exome Sequencing analysis performed on DNA extracted from a skin sample showed a mosaic gain-of-function variant in the PIK3CA gene (p.H1047R, 11% of variant allele frequency). Once molecular confirmation of our clinical suspicion was obtained, after a multidisciplinary evaluation, we decided to discontinue Sirolimus and start targeted therapy with Alpelisib (50 mg/day). We noticed a decrease in fibroadipose overgrowth at the dorsal level, an improvement in in posture and excellent tolerability. The treatment is still ongoing

Prognostic Indicators of Wound Healing in Atypical Wounds: A Case Series

Healing rate is the most accurate method to predict healing; however, there are no data in atypical ulcers. We retrospectively analyzed clinical features, associated comorbidities, and therapies of 159 patients with atypical ulcers. In a subgroup of 59 patients, we analyzed the areas, perimeters, and the healing rate (mm/d) as prognostic indicators of wound healing. Atypical ulcers were more frequent among women (n = 98) with an average age of 76 years. Confirmed by biopsy, the etiologies were as follows: inflammatory diseases (38%), neoplastic ulcers (29%), vasculitis (21%), drug-induced ulcers (7%), and infectious ulcers (4%). Systemic therapies were applied based on the different etiologies. Wound bed preparation principles guided the local treatment. The average reduction of the area during the observation interval was 36%, while the average reduction in the perimeter was 41%. Overall, 51 ulcers showed a reduction in wound size and 8 ulcers showed an increase. Neoplastic ulcers were the group with the fastest healing rate, with an average speed of 0.24 mm/d. The slowest healing occurred in the inflammatory group with an average healing rate of 0.032 mm/d. The initial area and perimeters influenced wound healing; however, ulcer etiology and comorbidities significantly altered the healing rate