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Introduction: Tildrakizumab is a monoclonal antibody that targets the p19 subunit of IL-23, a crucial cytokine for Th17 cells. Tildrakizumab has been assessed in several Phase I, II, and III clinical trials and is approved for treatment of adults with moderate to severe plaque psoriasis who are indicated for systemic therapy. Areas covered: The available evidence on the efficacy, safety, and use of tildrakizumab in special populations was evaluated by 14 experts who critically reviewed the current literature. Expert opinion: Tildrakizumab has good efficacy that lasts for at least 5years in patients with moderate to severe psoriasis, and appears to be safe and well tolerated in the long-term with no apparent dose-related differences in adverse events, a low incidence of discontinuation due to adverse events, and no evidence of increased risk of malignancies. The safety and the efficacy of tildrakizumab has also been confirmed in special populations such as those with inflammatory bowel disease, cardiovascular disease, metabolic syndrome, and advanced age. Early intervention with IL-23-inhibitors, such as tildrakizumab, may help to control symptoms and change the long-term course of the disease in patients affected by plaque psoriasis, while improving the quality of life and potentially minimizing the risk of developing comorbidities.

Introduction: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations. Methods: On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement). Results: Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy. Conclusion: These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.

Psoriasis (PsO) has been associated with obesity, and its severity increases in obese subjects. The link between psoriatic condition and obesity is based on shared pathophysiological pathways where local and systemic inflammation promote each other; PsO is an inflammatory, immune-mediated disease, and the adipose tissue is the source of proinflammatory adipokines. Moreover, psoriatic arthritis (PsA) is an important comorbidity of PsO that reduces quality of life and makes difficult the patient’s management. Treatment of obese subjects with moderate to severe PsO, even more if PsA is present, is challenging because of reduced efficacy of several systemic drugs and increased risk of adverse events. Secukinumab, a monoclonal antibody that selectively binds to and neutralizes interleukin 17A, shows efficacy on PsO in all body weight groups, even in the highest, whose response has a slight downward trend. Clinical features of two obese subjects, affected by PsO and PsA, successfully treated with secukinumab, are described.

Giuseppe Argenziano,1,* Paolo Amerio,2 Maria Grazia Aragone,3 Ginevra Baggini,4 Manuela Baldari,5 Gianpiero Castelli,6 Simmaco Coppola,7 Antonio Costanzo,8,9 Rocco De Pasquale,10 Maria Concetta Fargnoli,11 Caterina Foti,12 Claudia Giofrè,13 Serena Lembo,14 Claudia Leporati,15,16 Francesco Loconsole,17 Giovanna Malara,18 Ketty Peris,19,20 Antonio Giovanni Richetta,21 Paola Savoia,22 Rossana Tiberio,23 Massimo Travaglini,24 Maria Teresa Uzzauto,25 Luca Bianchi26,* 1Dermatology Unit, University of Campania, Naples, Italy; 2Department of Medicine and Aging Science and Dermatologic Clinic, University “G. d’Annunzio”, Chieti-Pescara, Chieti, Italy; 3ASL AL, Alessandria, Italy; 4Osp. Civile di Varzi, Pavia, Italy; 5ASL4 Liguria, Genova, Italy; 6UOSD of Dermatology, Ospedale Umberto I°, Siracusa, Italy; 7IQVIA, Rome, Italy; 8Department of Biomedical Sciences, Humanitas University, Milano, Italy; 9Skin Pathology Laboratory, Humanitas Research Hospital IRCCS, Milano, Italy; 10UOC Dermatologia, AOU Policlinico “G. Rodolico – San Marco”, Catania, Italy; 11Dermatology, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 12Department of Biomedical Science and Human Oncology, Dermatological Clinic, University of Bari, Bari, Italy; 13U.O.C. Dermatologia, A.O. Papardo, Messina, Italy; 14Dipartimento di Medicina, Chirurgia e Odontoiatria Scuola Medica Salernitana, University of Salerno, Fisciano, Italy; 15Dermatology Unit, ASL AL Casale Monferrato, Alessandria, Italy; 16Dermatology Unit, ASL TO4 Ivrea, Torino, Italy; 17Department of Dermatology, University of Bari, Bari, Italy; 18UOC of Dermatology, Grande Ospedale Metropolitano “BMM”, Reggio Calabria, Italy; 19Institute of Dermatology, Catholic University, Rome, Italy; 20Dermatology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 21Dipartimento di Scienze Cliniche Internistiche e Cardiovascolari Policlinico Umberto I University of Rome “La Sapienza”, Rome, Italy; 22Department of Health Science, Università del Piemonte Orientale, Novara, Italy; 23SCDU Dermatologia, AOU Maggiore della Carità, Novara, Italy; 24U.O.S.D. dermatologica - centro per la cura della psoriasi, Ospedale Perrino, Brindisi, Italy; 25U.O.C. Dermatologia, ASL Salerno, Ospedale “A:Tortora”-Pagani, Salerno, Italy; 26Dermatology Unit, Tor Vergata University Hospital, Rome, Italy*These authors contributed equally to this workCorrespondence: Giuseppe ArgenzianoDermatology Unit, University of Campania “Luigi Vanvitelli”, Via Pansini, 5, Naples, 80131, ItalyTel +39335415093Fax +39 069 762 5822Email g.argenziano@gmail.comLuca BianchiUniversity of Rome “Tor Vergata”, Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, ItalyTel +39 0620902739Fax +39 0620902742Email luca.bianchi@uniroma2.itPurpose: For patients with psoriasis, treatment adherence and persistence are fundamental if therapeutic goals are to be met. Patient Support Programs (PSPs) may be used as a support tool to assist patients and health care professionals optimize treatment and improve disease management.Patients and Methods: In Italy, the PSP PSOLife CARE, which began on the 9th of February 2017 and is ongoing, aimed to support patients with psoriasis under therapy with secukinumab (Cosentyx®). A team of medical professionals including Dermatologists, Psychologists, Nutritionists, and field Nurses provided outpatient treatment as well as remote support via phone calls. Patients had a standard duration in the Program of 6 months. This report analyzes the data of patients who benefited from the Program from February 2017 to August 2020, for a total observation of 42 months.Results: We provide here a descriptive report on the benefits of participation in the PSOLife CARE Program for patients with psoriasis and medical professionals involved in their care. Throughout their time in the PSOLife CARE Program, patient satisfaction remained consistently high with sustained improvements observed in all aspects of quality of life (ie emotional, social, physical, and economic). Despite exiting from the Program, most patients continued to adhere to secukinumab. Medical professionals also reported positive outcomes on their interactions with patients, with more than half of those surveyed rating the overall quality of the Program as “Outstanding”.Conclusion: By supporting treatment adherence, the PSOLife CARE Program may have empowered patients to better manage their psoriasis, increasing their satisfaction with treatment and quality of life.Keywords: dermatology, PSOLife CARE Program, quality of life, treatment adherence

Background and objectives: Psoriasis (Pso) is a common skin condition characterized by a strong psychosocial impact, and is nowadays accepted as a systemic immune-mediated inflammatory disease. Diagnostic&ndash, Therapeutic Care Pathways (DTCPs) represent a predefined sequence of diagnostic, therapeutic, and assistance activities that integrate the participation of several specialists to obtain, for each patient, the correct diagnosis and thus the most appropriate therapy. A DTCP was validated in our dermatology clinic (AOU Maggiore della Carit&agrave, Novara, Italy). The validation process included the detailed elaboration of a protocol of diagnosis, staging of care, therapies, and follow-up of the patient with Pso. The formalization and adaptation of our DTCP resulted in ISO 9001: 2015 certification in May 2019. Materials and methods: This process involved several stages, including analysis of context and the identification of (i) targets, (ii) indicators, and (iii) service providers. The evaluation was based on a cohort of over 200 patients affected by moderate to severe Pso, who were treated and followed-up at our institution from September 2017 to April 2019. Results: The ISO 9001:2015 quality certification process allowed us to identify our weaknesses, i.e., the long waiting times for the first visit and the reduced physician&ndash, patient ratio, but also our strengths, such as the commitment to clinical research, effective collaboration with other specialists, the efficient use of technological and human resources, and attention to ensuring patient follow-up. Conclusions: In qualifying for and achieving the ISO Quality Management System (QMS) certification we were heartened to realize that our basic methodology and approach were fit for purpose. The implementation of the ISO QMS helped us to reorganize our priorities by placing the patient at the center of the process and raising awareness that Pso is not just a skin disease.

Background: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. Materials and Methods: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for >= 12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of >= 90, >= 75 and = 50 and

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is creating an unprecedented global public health emergency with the continuous growth of infected individuals worldwide. Italy was one of the first European country to face the first wave of infection outside mainland China. The first case of COVID-19 was confirmed in Lombardy on February 20th , 2020, and subsequently, a rapid increase in the number of detected cases was observed, spreading through Italy and the rest of Europe.3 As of April 22nd , confirmed COVID-19 cases in Italy were 183,957.

The long-term efficacy and safety of dupilumab has been demonstrated in clinical trials and only in few real-world studies. We conducted an extension analysis from a previous 16-week study on 109 adult patients affected by moderate-to-severe atopic dermatitis treated with dupilumab. Eczema-Area-and-Severity-Index (EASI), itch numerical-rating-score (itch-NRS), Dermatology-Life-Quality-Index (DLQI) scores, drug survival rate and occurrence of adverse events after 24 and 48 weeks of dupilumab treatment were retrospectively collected. Dupilumab demonstrated sustained improvement of disease severity, pruritus, and quality of life in our series with an increasing percentage of patients gaining EASI75 and EASI90 response during the study period. Few patients interrupted treatment resulting in a very high drug survival rate. We also confirmed the favorable safety profile of the drug with absence of serious adverse events and serious infections throughout the 48-week period. The prevalence of conjunctivitis was low and mainly occurred in the mid-term with resolution of the majority of cases at 48 weeks.

The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) is closely associated with the secretion of exotoxin mycolactone. The cytotoxicity of mycolactone has been linked to its apoptogenic activity. We explored if low mycolactone concentrations, which are not able to induce apoptosis, can influence other essential activities on two primary human keratinocyte populations, keratinocyte stem cells (KSC) and transit amplifying cells (TAC), and on a human keratinocyte line, HaCaT. We demonstrated that 0.01 and 0.1 ng/ml mycolactone A/B are not able to induce apoptosis in primary human keratinocytes, but interfere with KSC wound repair. Moreover, the same toxin concentrations reduce cell proliferation of KSC and TAC and their ability to adhere to type IV collagen. HaCaT cells are more resistant to the toxin; nevertheless, they show a delayed woud repair when treated with 1 and 10 ng/ml mycolactone A/B. Moreover, these sub-apoptotic concentrations affect their ability to proliferate and adhere to collagen IV. Wound healing is a complex mechanism, which occurs "in vivo" as the outcome of many co-ordinated events. Sub-apoptotic mycolactone concentrations can affect essential mechanisms, which are required to achieve wound repair, such as adhesion, migration and proliferation of human keratinocytes.

The authors present a surgical procedure to remove two contiguous cutaneous lesions using a single transposition flap and suture line without an evident scar. This method is useful when rhomboid surgical exeresis could not represent the best choice to obtain an optimum aesthetic result.

Basal cell carcinoma (BCC) is a common skin cancer worldwide. However, BCC of the nipple and areola complex is rare. Men are more affected than women. Most of the cases were treated with simple excision. We report a case of BCC of the right nipple-areola complex in a 75-year-old man, treated with Mohs surgery and simple mastectomy.

Surgical wounds resulting from the excision of cutaneous malignancies or benign neoplasms can be repaired in a number of ways. One alternative, which has been used extensively in our practice, is the purse-string suture. This method offers many advantages respect to the traditional closure. In this cases report we describe four illustrative cases. These cases represent almost all the advantages of the pursestrings suture.

Background Estrogens and phytoestrogens can hinder the aging process through mechanisms related to estrogen receptors (ERs), guanine nucleotide-binding protein-coupled receptor (GPER30), mitochondria function and nitric oxide (NO) release. Up to date, however, the above issues are a matter of debate. Objective To examine the effects elicited by 17 β-estradiol and genistein against peroxidation in human keratinocytes/fibroblasts and evaluate the role played by ERs, GPER30, mitochondria and NO. Methods Human fibroblasts/keratinocytes, either subjected to peroxidation or not, were exposed to 17 β-estradiol/genistein in the absence or presence of the NO synthase (NOS) inhibitor, the ERs and GPER30 blockers, fulvestrant and G15, the phosphatidyl-inositol-3-kinase (PI3K-Akt), the p38 mitogen-activated protein (MAP) kinase and the extracellular signal–regulated kinases (ERK) 1/2 inhibitors. Specific kits were used for cell viability, NO, ROS and glutathione (GSH) detection and mitochondrial membrane potential measurement. Western Blot analysis was performed for kinases expression/activation detection. Results In physiological and peroxidative conditions, 17 β-estradiol/genistein respectively increased and reduced NO release by fibroblasts/keratinocytes. Moreover, both agents prevented the ROS release and the fall of cell viability and mitochondrial membrane potential, while increasing GSH levels and the proliferation rate. Fulvestrant and G15 counteracted all above responses. Also, the NOS, and the kinases blockers reduced the protection exerted by 17 β-estradiol/genistein on cell viability/mitochondria function. The involvement of PI3K-Akt and p38-MAPK was confirmed by Western blot. Conclusion 17 β-estradiol/genistein protected fibroblasts/keratinocytes against peroxidation by modulating oxidant/antioxidant system and mitochondria membrane potential, through mechanisms related to ERs and GPER30 and kinases activation.

Cryptococcus neoformans is opportunistic encapsulated yeast that represents the most frequent cryptococcal species found in humans. It can cause three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and cutaneous cryptococcosis. Cutaneous cryptococcosis may represent the dissemination of a systemic infection (especially from nervous or pulmonary primary site of infection) or may be the only localization, due to a direct inoculation into the skin, because of a traumatic injury. Primary cutaneous cryptococcosis (PCC) is rare and mainly affects elderly patients, from rural areas, with history of cutaneous injuries and activities predisposing wounds or exposure to bird droppings. Immunosuppression may be a predisponing factor. The most utilized treatment is fluconazole, but often, especially for ulcers or deep wounds; surgery is required for complete tissues repair. Herein, we present a case of PCC in an immunosuppressed patient, with destroying ulcers involving deep tissues, completely resolved after fluconazole treatment, without surgical intervention.

Background Dermatofibrosarcoma Protuberans is a rare, low-grade mesenchymal skin tumour, characterized by slow infiltrative growth and common local recurrence, with infrequent distant metastases. Objective The aim of this study is to better clarify clinico-pathological characteristics of this tumour and to evaluate the cure rates of Mohs Tubingen technique (MTT) and wide local excision. Eventually, we perform a literature review to compare our experience with published data. Methods A retrospective review was conducted on 135 patients diagnosed, treated and followed-up between 1997 and 2014 at two different institutions. Sixty-two patients underwent to wide local excision and 73 to MTT. The primary end-points were: percentage of recurrences, time-to-progression and recurrence annual risk rate. Then, the PubMed database was searched for Dermatofibrosarcoma Protuberans case series treated with standard surgical resection, wide local excision, Mohs micrographic surgery and MTT. The annual risk rate of recurrence calculated and reported for the four separate procedures, was pooled to compare them. Results Five out the 62 patients with wide local excision (8.1%) experienced recurrences after a mean follow-up of 4.7 years; the percentage of recurred patients 9 years after MTT was 5.5%, and the annual recurrence risk rate of 0.6%. Pooling these data with those from literature, the recurrence rate varies from 26% to 60% for standard surgical resection, from 0 and 41% for wide local excision, from 0 and 8,3% for Mohs micrographic surgery and from 0 to 5.5%. for MTT. The lowest annual recurrence risk rate was found for MTT. Conclusion Significantly lower recurrence rates were recorded in patients treated with classic or Tubingen Mohs technique. To the best of our knowledge, our case series is the widest treated with MTT ever described in the literature; these data may be useful to guide clinicians in the choice of the gold standard treatment for Dermatofibrosarcoma Protuberans. This article is protected by copyright. All rights reserved.

A new effective surgical procedure to repair chronic ulcers called minced micrografts technique has been recently reported. The technique consists in spreading a finely minced skin sample upon the wound bed. In this study, we investigate the in vitro release of cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1α, and granulocyte-colony stimulating factor), chemokines (monocyte chemoattractant protein-1 and growth-related oncogene-α), and growth factors (platelet-derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor) by minced (referred to as the minced sample) vs. not minced (referred to as the whole sample) human skin biopsy samples from the same donor. Factor release in the culture medium at different time points was detected using a multiplexed protein assay. The minced sample, which could behave like the skin fragments used in vivo in the autologous minced micrografts technique, expressed higher levels of tumor necrosis factor-α, interleukin-1α, platelet-derived growth factor, and basic fibroblast growth factor, and lower levels of interleukin-6, monocyte chemoattractant protein-1, growth related oncogene-α, and vascular endothelial growth factor compared with the whole sample. In conclusion, mincing of healthy skin may allow appropriate regulation of the inflammatory phase of wound healing and could induce overexpression of some growth factors, which facilitates the proliferative phase of healing.

Summary We describe two nonconsanguineous white patients with multiple pigmented basal cell carcinomas (BCCs) that were histopathologically confirmed. The first patient had calcification of the cerebral falx, multiple keratocysts in the jaw, and other malformations of the cranial and finger bones. The second patient presented with multiple dermoid cysts, calcification of the cerebral falx, keratocysts of the mandible, and agenesis of left kidney. Both patients had palmar pits. Both denied any family history of cutaneous tumours. On dermatoscopic examination of patient 1, multiple, bluish, confluent and large globules were seen. The second patient had blue ovoid globules, arborizing vessels, and areas shaped like maple leaves and spoke-wheels. Based on the clinical and radiological features we diagnosed both patients as having Gorlin syndrome (GS). To our knowledge, there are no previous reports of white patients with GS showing only pigmented BCCs. The dermatoscopic patterns were different in the two patients, and to our knowledge, this is the first report of a patient with GS showing a spoked-wheel dermatoscopic pattern.

The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) depends on cytotoxic effect of its exotoxin mycolactone. Since epidermis represents a barrier against infectious agents and balanced apoptosis is essential in epidermal homeostasis, we explored if mycolactone A/B induces apoptosis on two human keratinocyte populations, stem cells (KSC) and transit amplifying cells (TAC), and on human keratinocyte line, HaCaT. Treatment of TAC with 1 and 10 ng/ml mycolactone-induced 60 and 90% apoptosis. KSC were more resistant than TAC: 50 and 75% of cells underwent apoptosis after 10 and 100 ng/ml toxin-treatment. Higher doses (1000 ng/ml) induced about 30% apoptosis on HaCaT. In contrast, mycolactone A/B was devoid of toxicity neither on human hepatoma HuH7 nor on human embryonic kidney HEK 293 T cell lines. In conclusion, mycolactone induces apoptosis in human keratinocytes, thus contributing to Buruli ulcer lesions development.

Background Dermatofibrosarcoma protuberans is a rare cutaneous sarcoma that progresses slowly. Although it exhibits pronounced local aggressiveness, it rarely metastasises. The condition is difficult to treat on account of asymmetric and unpredictable growth as well as the frequency of relapse. Treatment is primarily surgical. Patients and methods We report 31 cases of dermatofibrosarcoma protuberans operated at the Dermatology Clinic of Novara between 1997 and 2004 using the Tubingen technique. An immunohistochimical study was performed and screening was carried out for possible extension of the neoplasm into muscle. Results Muscular involvement was seen in 4 cases. No relapses were seen over a median survival period of 3 years and no patients were lost to follow-up. Discussion The Mohs technique is the surgical method of reference and allows tumour eradication with sparing of healthy tissue. The Tubingen method constitutes an alternative approach requiring fewer histological sections. The results obtained in our series were good and no relapses were seen over a median survival period of 3 years.

Resume Introduction Les chordomes sont des tumeurs osseuses extradurales rares, qui derivent des residus de la notochorde, une structure embryonnaire formant l’axe originel de la colonne vertebrale. Ils representent 0,1 p. 100 de toutes les tumeurs intracrâniennes. Le chordome est un cancer a malignite locale, avec une tendance a l’envahissement des tissus environnants. La localisation cutanee est exceptionnelle. Observation Chez un homme âge de 56 ans, apparaissait une lesion nodulaire vegetante du sillon nasogenien gauche de la taille d’une noisette. Cette lesion survenait quelques mois apres une intervention chirurgicale pour une recidive fronto-glabellaire d’un chordome qui s’etait manifeste 6 ans auparavant a la base du crâne. Discussion Nous rapportons ce cas en raison de la rarete des localisations cutanees et des conditions particulieres de survenue de cette localisation faciale. Celle-ci pourrait etre due a un ensemencement tumoral per operatoire lors des interventions chirurgicales anterieures.

Pachyonychia congenita (PC, OMIM #615726) is a rare autosomal-dominant genodermatosis divided into two subtypes: PC-1 (Jadassohn-Lewandowski type, OMIM#167200) and PC-2 (Jackson-Lawler type, OMIM#167210). Both subtypes manifest with hypertrophic onychodystrophy and a variable degree of focal palmoplantar keratoderma (PPK), angular cheilitis and follicular keratoses of elbows, knees and hips. PC-1 usually shows most prominent leukokeratosis and is associated with K6a and K16 mutations. PC-2 shows [...]

A new effective surgical procedure to repair chronic ulcers called minced micrografts technique has been recently reported. The technique consists in spreading a finely minced skin sample upon the wound bed. In this study, we investigate the in vitro release of cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1α, and granulocyte-colony stimulating factor), chemokines (monocyte chemoattractant protein-1 and growth-related oncogene-α), and growth factors (platelet-derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor) by minced (referred to as the minced sample) vs. not minced (referred to as the whole sample) human skin biopsy samples from the same donor. Factor release in the culture medium at different time points was detected using a multiplexed protein assay. The minced sample, which could behave like the skin fragments used in vivo in the autologous minced micrografts technique, expressed higher levels of tumor necrosis factor-α, interleukin-1α, platelet-derived growth factor, and basic fibroblast growth factor, and lower levels of interleukin-6, monocyte chemoattractant protein-1, growth related oncogene-α, and vascular endothelial growth factor compared with the whole sample. In conclusion, mincing of healthy skin may allow appropriate regulation of the inflammatory phase of wound healing and could induce overexpression of some growth factors, which facilitates the proliferative phase of healing.

Background Chronic venous leg ulcers represent an urgent and increasing problem for public health. The use of skin autografts results in a greater therapeutic success in healing chronic ulcers. Objective A simple method of skin autografting that could permit a wider use of skin grafts in outpatients is needed. A new technique allowing skin autografting in a simple one-step process, without complex surgical procedures or expensive technical supplies, is presented. Methods A small, full-thickness skin specimen taken from the patient is finely minced and spread on his leg ulcer bed allowing to cover a surface many times wider than the sample itself. Results This method induces faster re-epithelization of chronic leg ulcers that failed to heal despite good conservative local therapy and give the possibility to repair very large ulcers with small fragments of skin. A clinical case is shown as an example out of 20 ulcers we recently treated. Conclusion Our preliminary report shows that this technique results in a greater therapeutic success (18 of 20 cases) in healing chronic leg ulcers, a common pathology that often affects outpatients treated for very long periods at home or in the Dermatologist's office. In our experience, this new and successful reparative possibility makes ‘mince grafting’ a recommendable procedure.

Cells require appropriate interaction with extracellular matrix proteins mediated by integrins to grow, differentiate and survive. Many cell types including nervous cells undergo anoikis, a substrate-dependent apoptosis, when adhesion is impaired. Resistance of tumors to cytotoxic drugs is probably due to disturbed apoptosis programs. The proteolytic enzymes caspases are the main executioners of apoptosis. It was reported that caspase-8 expression is deficient in some neuroblastoma cells. We demonstrated that human neuroblastoma cell line SK-B-BE, differentiated with retinoic acid, expressed caspases 3, 8 and 9. Caspases 8 and 3, but not caspase-9 were activated in SK-N-BE cells cultured in suspension or on aspecific adhesive substrate. Cell positive to caspase-8 were classified into four stages, by morphometric and densitometric parameters. The use of the specific caspase-8 inhibitor Z-IETD-FMK dramatically reduced apoptosis, demonstrating that caspase-8 is the upstream initiator caspase during SK-N-BE cells anoikis. Among matrix proteins, type I collagen is the most effective and fibronectin the least in delaying anoikis. The activation of caspases 8 and 3 by unligated integrins was dependent on the state of neuronal differentiation, since the most differentiated cell was the most vulnerable to anoikis. These data show that activation of caspase-8 is specifically required to promote anoikis in SK-N-BE neuroblastoma cells.

ejd.2011.1297 Auteur(s) : Ginevra PERTUSI1 giny.p@libero.it, Francesca GRAZIOLA1, Giordana ANNALI1, Christian GIANI1, Federica VERONESE1, Andrea GUALA2, Rossana TIBERIO1, Enrico COLOMBO1 1 Dermatological Clinic, University of Piemonte Orientale “A. Avogadro”, Via Solaroli 17, 28100 Novara, Italy 2 Pediatric Department, Castelli Hospital, Via Crocetta, 28921 Pallanza, Italy Congenital onychodyplasia of the index fingers (COIF), also known as Iso-Kikuchi Syndrome, is a rare disorder, characterized [...]

Epidermolytic PalmoPlantar keratoderma (EPPK) Vörner-type is an autosomal dominantly inherited skin disease, characterized by severe thickening of the palms and soles, caused by mutations in the keratin K9 (KRT9) gene. To date, a number of KRT9 mutations have been detected, most of which affect the highly conserved 1A region of the central alpha-helical domain, important for keratin heterodimerization. The most common mutation is the substitution of the arginine in position 163 with a tryptophan (R163W), which has been reported in North American, European, and Japanese populations. In a small number of cases, EPPK is associated with knuckle pad keratosis, but no correlation between this additional phenotype and a specific mutation has been found. Moreover, K9 is not normally expressed in knuckle skin, raising the question of the pathogenic mechanism leading to this additional phenotype. Here we show that in a family affected by EPPK and knuckle pad keratosis, carrying the R163W substitution, wild type (wt) and mutated K9 are strongly expressed in knuckle pads. These results suggest that the knuckle pad phenotype is due to ectopical expression of K9.