Retrospective study of postoperative survival of keratinocyte-derived skin cancer patients at the end of life.

BACKGROUND AND OBJECTIVES: Basal and squamous cell carcinoma (BCC, SCC), collectively referred to as keratinocyte-derived skin cancer (KC), are the most common human cancers worldwide. Surgery is the treatment of choice, but may represent overtreatment in the very elderly. This study aims to address this issue by investigating the life expectancy of patients over 80 years after surgery. PATIENTS AND METHODS: A single-center, retrospective study was performed to include surgically treated KC patients at the Department of Dermatology and Venereology of the University Hospital in St. Pölten, Austria, between 01.01.2011 and 31.12.2017, who were 80 years or older. Data on individual survival (cut-off April 30, 2020), date and cause of death were retrieved from the Austrian national demographic database at Statistics Austria (Vienna). RESULTS: 940 patients (450 female, 490 male, 639 BCCs, 301 SCCs) were included with 307 being alive at the cut-off date. Median postoperative survival was 57 months (95% CI, 54-63 months). CONCLUSIONS: With a median postoperative survival of almost 5 years, surgery remains a valid treatment option for KC at the end of life. However, 77 of the treated patients died within a year after surgery and preoperative assessment might have helped to avoid overtreatment in some of these cases.

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023.

On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.

Mycosis fungoides and Sézary syndrome - Review and outlook.

Mycosis fungoides and Sézary syndrome are the most important representatives of the heterogeneous group of cutaneous T-cell lymphomas. The diseases are rare and the diagnosis, which always requires a clinical-pathological correlation, is often delayed, especially in early forms of mycosis fungoides. The prognosis of mycosis fungoides depends on its stage and is usually favorable in the early stages. Clinically relevant prognostic parameters are missing and their development is the subject of current clinical research. Sézary syndrome, characterized by initial erythroderma and blood involvement, is a disease with a high mortality rate, in which good responses can now be achieved in many cases with new treatment options. The pathogenesis and immunology of the diseases is heterogeneous, with recent results pointing primarily to changes in specific signal transduction pathways that may be suitable as future treatment targets. Current therapy for mycosis fungoides and Sézary syndrome is primarily palliative with topical and systemic options either used alone or in combination. Only with allogeneic stem cell transplantation durable remissions can be achieved in selected patients. Similar to other areas of oncology, the development of new therapies for cutaneous lymphomas is currently changing from relatively untargeted empiricism to disease-specific, targeted pharmacotherapy based on knowledge from experimental research.

The bacterial pathogen and resistance spectrum in a dermatological inpatient ward: a six-year, retrospective, epidemiological study.

Aim: Treatment of bacterial soft tissue infections is an essential part of clinical dermatology, and the choice of antibiotic therapy is often empirical. The aim of this longitudinal retrospective study was to evaluate bacterial epidemiology, resistance patterns and antibiotic consumption in a dermatological inpatient ward. Method: Bacterial isolates and antimicrobial susceptibility testing from a dermatological inpatient ward were recorded retrospectively from 2011 to 2016. The antibiotic consumption was evaluated and given as the assumed defined daily dose [DDD] per 100 days of covering per year. Results: A total of 4,800 bacterial isolates were included (skin, mucous membrane and wounds 87%, urine 9.5%, blood 1.7%, tissue and tissue fluids 1.6%). The proportion of Gram-positive bacteria was 58% (Staphy loc occus aureus 37.8%, coagulase-negative staphylococci 21.5%, Enterococcus spp. 16.7%). Pseudomonas aeruginosa (27.2%), Escherichia coli (17.5%) and Proteus spp. (13.1%) were the most common Gram-negative bacteria. The proportion of multi-resistant pathogens was 5.8% for methicillin-resistant S. aureus, 0.9%, 0.8% and 1.8% for multi-resis tant P. aeruginosa, ESBL-producing E. coli and ESBL-producing Klebsiella pneumoniae of all isolates. Beta-lactam antibiotics were the most used drugs (14.4, 10.8, and 9.6 DDD/100 for aminopenicillins, cefalexin, and penicillin G), followed by clindamycin (9.0 DDD/100 patient days). Conclusion: In view of the frequency of bacterial soft tissue infections and their need for inpatient treatment with mostly empirically chosen antibiotics, systematic microbiological surveillance should be recommended for dermatological inpatient wards.

Chlormethin-Gel zur Behandlung der Mycosis fungoides: Ein Expertenkonsens aus Deutschland, Österreich und der Schweiz (DACH-Region) zum Therapiemanagement.

HINTERGRUND: Chlormethin-Gel ist in Europa zur Therapie von Patienten mit Mycosis fungoides in allen Krankheitsstadien zugelassen. Die optimalen Behandlungsregime hinsichtlich Frequenz, Dosierung, Kombinations- oder Erhaltungstherapien sind noch nicht vollständig etabliert. METHODIK: Zehn in der Erforschung und Behandlung kutaner T-Zell-Lymphome erfahrene Experten aus Deutschland, Österreich und der Schweiz (DACH-Region) wurden schriftlich zu Indikation, Anwendungsfrequenz, Beurteilung des Therapieerfolgs, Begleittherapie, Nebenwirkungen, Kombinationstherapien in späteren Krankheitsstadien, Erhaltungstherapie und Adhärenz im Rahmen der Therapie der Mycosis fungoides mit Chlormethin-Gel befragt. Die strukturiert aufbereiteten Ergebnisse der Umfrage wurden in einer Konsensuskonferenz diskutiert und Empfehlungen zum Management der Therapie mit Chlormethin-Gel entwickelt. ERGEBNISSE: Wesentlich für die Therapie mit Chlormethin-Gel ist ein individuelles, symptomorientiertes Therapiemanagement. Systemische Nebenwirkungen des Wirkstoffs sind wegen der fehlenden systemischen Verfügbarkeit bei topischer Anwendung unwahrscheinlich. Die häufig auftretende allergische oder irritativ-toxische Kontaktdermatitis kann durch eine Anpassung des Therapieregimes, Therapiepausen sowie nebenwirkungsspezifische und unterstützende Maßnahmen häufig beherrscht werden. Ein einschleichender Therapiebeginn mit Anwendung von Chlormethin-Gel jeden zweiten Tag kann die Tolerabilität wesentlich verbessern, insbesondere wenn die Therapie alternierend mit topischen Kortikosteroiden erfolgt. SCHLUSSFOLGERUNGEN: Die Anwendung von Chlormethin-Gel bei Mycosis fungoides wird durch die begleitende Kontaktdermatitis häufig eingeschränkt. Mit einem geeigneten Therapie- und Nebenwirkungsmanagement können vermeidbare Therapieabbrüche verhindert werden und mehr Patienten von der Therapie profitieren.

The optimal use of chlormethine gel for mycosis fungoides: An expert consensus from Germany, Austria and Switzerland (DACH region).

BACKGROUND: In Europe chlormethine gel is licensed for the management of patients with mycosis fungoides of all stages. However, the optimal regimen regarding frequency and dosing as well as combination and maintenance therapy is not well established. METHODS: Ten experts experienced in research and management of cutaneous T-cell lymphomas from Germany, Austria, and Switzerland (DACH region) were asked in written form to report on indication for chlormethine gel, frequency of use, monitoring, concomitant therapies, adverse effects, combination therapies in later stages of the disease, maintenance therapy, and adherence to this therapy for mycosis fungoides. The structured answers were discussed in a consensus conference and recommendations were developed. RESULTS: Essential for therapy with chlormethine gel is an individualized and symptom-oriented management. Because of the lack of systemic resorption of topically administered chlormethine gel, systemic adverse events are unlikely. An allergic or irritative-toxic contact dermatitis is common but manageable with adaptation of the regimen, interruption of administration, and symptom-specific supportive measurements. A step-up initial approach with application of chlormethine gel every other day is associated with a better tolerability, especially if it is alternated with topical corticosteroids. CONCLUSIONS: The use of chlormethine gel in the management of mycosis fungoides is often limited by a concomitant contact dermatitis. An adequate therapeutic regimen and the management of adverse effects can preclude an unnecessary withdrawal of therapy so that more patients can benefit from this treatment option.

Proteome analysis of NRF2 inhibition in melanoma reveals CD44 up-regulation and increased apoptosis resistance upon vemurafenib treatment.

Malignant melanoma is the deadliest form of skin cancer and NRF2 has been proposed as a main regulator of tumor cell malignancy. Still the mechanisms how NRF2 is contributing to melanoma progression are incompletely understood. Here we analyzed the effects of either NRF2 induction or depletion, and we also quantified changes on the whole cell proteome level. Our results showed that inhibition of NRF2 leads to a loss of reactive oxygen species protection, but at the same time to an induction of an epithelial mesenchymal transition (EMT) phenotype and an up-regulation of the stem cell marker CD44. Additionally, cells devoid of NRF2 showed increased cell viability after treatment with a MYC and a BRAF inhibitor. Importantly, survival upon vemurafenib treatment was dependent on CD44 expression. Finally, analysis of archival melanoma patient samples confirmed a vice versa relationship of NRF2 and CD44 expression. In summary, we recorded changes in the proteome after NRF2 modulation in melanoma cells. Surprisingly, we identified that NRF2 inhibition lead to induction of an EMT phenotype and an increase in survival of cells after apoptosis induction. Therefore, we propose that it is important for future therapies targeting NRF2 to consider blocking EMT promoting pathways in order to achieve efficient tumor therapy.

Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer-study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II.

BACKGROUND: Diabetes and its sequelae such as diabetic foot ulcer are rising health hazards not only in western countries but all over the world. Effective, yet safe treatments are desperately sought for by physicians, healthcare providers, and of course patients. METHODS/DESIGN: APOSEC, a novel, innovative drug, is tested in the phase I/II study MARSYAS II, where its efficacy to promote healing of diabetic foot ulcers will be determined. To this end, the cell-free secretome of peripheral blood mononuclear cells (APOSEC) blended with a hydrogel will be applied topically three times weekly for 4 weeks. APOSEC is predominantly effective in hypoxia-induced tissue damages by modulating the immune system and enhancing angiogenesis, whereby its anti-microbial ability and neuro-regenerative capacity will exert further positive effects. In total, 132 patients will be enrolled in the multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-ranging phase I/II study and treated with APOSEC at three dose levels or placebo for 4 weeks, followed by an 8-week follow-up period to evaluate safety and efficacy of the drug. Wound area reduction after 4 weeks of treatment will serve as the primary endpoint. CONCLUSION: We consider our study protocol to be suitable to test topically administered APOSEC in patients suffering from diabetic foot ulcers in a clinical phase I/II trial. TRIAL REGISTRATION: EudraCT 2018-001653-27 . Registered on 30 July 2019. ClinicalTrials.gov NCT04277598 . Registered on 20 February 2020. TITLE: "A randomized, placebo-controlled, double-blind study to evaluate safety and dose-dependent clinical efficacy of APO-2 at three different doses in patients with diabetic foot ulcer (MARSYAS II)".

Microarray-Based Detection of Allergen-Reactive IgE in Patients with Mastocytosis.

BACKGROUND: Because of a high risk to develop fatal anaphylaxis, early detection of immunoglobulin E (IgE)-dependent allergy is of particular importance in patients with mastocytosis. OBJECTIVE: We examined whether microarray-based screening for allergen-reactive IgE (allergen-chip) is a sensitive and robust approach to detect specific IgE in patients with mastocytosis. METHODS: Sera for 42 patients were analyzed, including 4 with cutaneous mastocytosis, 2 with mastocytosis in the skin, and 36 with systemic mastocytosis. In addition, sera from an age- and sex-matched control cohort (n = 42) were analyzed. RESULTS: In 15 of 42 patients with mastocytosis (35.7%), specific IgE was detected by allergen-chip profiling. Ves v 5 and Bet v 1 were the most frequently detected allergens (Ves v 5: 16.7% of patients; Bet v 1: 11.9% of patients). Allergen reactivity was confirmed by demonstrating upregulation of CD203c on blood basophils upon exposure to the respective allergen(s) in these patients. Specific IgE was identified by chip studies in 11 of 26 patients with mastocytosis with mediator-related symptoms (42.3%) and in 4 of 14 patients with mastocytosis without symptoms (28.6%). In the cohort with known allergy, 9 of 9 patients (100%) had a positive allergen-chip result. In patients with mastocytosis without a known allergy (n = 31), the chip identified 6 positive cases (19.5%). The prevalence of chip-positive patients was slightly lower in the mastocytosis group (35.7%) compared with age- and sex-matched controls (40.5%). CONCLUSIONS: Although specific IgE may not be detectable in all sensitized patients with mastocytosis, allergy chip-profiling is a reliable screening approach for the identification of patients with mastocytosis suffering from IgE-dependent allergies.

Hemiarthroplasty in a patient with femoral neck fracture and pyoderma gangrenosum: a case report and review of the literature.

BACKGROUND: Pyoderma gangrenosum is a rare ulcerating skin disease of unknown etiology, making its coincidence with orthopedic trauma a rare challenge. Patients are at risk of progression of the existing lesions and development of new lesions upon skin injury when surgical procedures are performed. To our knowledge, this is the first report in the literature of disease unrelated surgery during active pyoderma gangrenosum. CASE PRESENTATION: We present a case of femoral neck fracture in a Caucasian patient with concurrent pyoderma gangrenosum localized in the axilla. Hemiarthroplasty was safely performed after disease activity was reduced with systemic corticosteroids. Tissue-protective wound closure was used together with perioperative corticosteroids and antibiotics. No signs of pyoderma gangrenosum developed at the surgical wound site, and the axillary lesions showed constant improvement until healing with scar tissue. CONCLUSIONS: In our patient, the preoperative steroid treatment, perioperative antibiotics, and soft tissue protective surgical technique led to successful management of this rare coincidence.

Phototherapy of cutaneous T-cell lymphomas.

Cutaneous T-cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas arising in the skin. Mycosis fungoides (MF), the most common variant, is characterised by clonal proliferation of skin residing malignant T-cells. Initially appearing with erythematous patches and plaques it follows a chronic course with progression to cutaneous tumours and extracutaneous involvement in some patients. Phototherapy with ultraviolet A radiation combined with 8-methoxypsoralen (PUVA) and with narrow-band ultraviolet B radiation (NB-UVB) are among the first line options for the treatment of MF and can induce remission in most patients. Sézary syndrome (SS) is a rare and more aggressive CTCL variant with generalized skin involvement. Patients with SS and with erythroderma from MF can benefit from treatment with extracorporeal photochemotherapy (ECP) where peripheral blood is exposed to PUVA. Phototherapy can be safely combined with systemic agents, most notably interferon-alpha and retinoids. Another photoresponsive CTCL variant is lymphomatoid papulosis (LP), a CD30+ lymphoproliferative disease characterised by chronically recurring papules. The disease responds favourably to PUVA but low dose methotrexate might be preferred for long term disease control. Recently updated treatment guidelines have been published to provide evidence-based algorithms for the stage-oriented treatment of MF, SS and LP. Areas of uncertainty are treatment schedules that are currently not optimised for CTCL, the use of phototherapy for maintenance, and the value of ultraviolet A1 radiation, excimer lasers, and photodynamic therapy.

Lebensqualität und Behandlungsziele bei Psoriasis aus Patientensicht: Ergebnisse eines österreichweiten Querschnitt-Survey.

HINTERGRUND: Patienten mit Psoriasis sind mit einer krankheitsbedingten Einschränkung ihrer Lebensqualität konfrontiert, weshalb einer hochqualitativen dermatologischen Versorgung ein besonderer Stellenwert zukommt. PATIENTEN UND METHODIK: Wir führten einen bundesweiten Querschnitt-Survey in Österreich (BQSAustria Psoriasis 2014/2015) mit dem Schwerpunkt auf Lebensqualität und Therapiezufriedenheit bei Patienten mit Psoriasis in dermatologischer Behandlung vorwiegend an Zentren mit überwiegend tertiären Versorgungsaufgaben durch. ERGEBNISSE: 70,2 % der 1184 befragten Patienten berichtete über eine eingeschränkte Lebensqualität (DLQI 2-5: 29,4 %; 6-10: 19,3 %; 11-15: 11,5 %; 16-20: 5,2 % und > 20: 4,9 %) trotz Behandlung innerhalb der letzten vier Wochen (mit lokaler Therapie in 88,2 % und/oder systemischer Therapie in 38,7 % der Fälle). Mit den verabreichten Therapien konnte im Durchschnitt kein einziges von 25 definierten subjektiven Behandlungszielen im gewünschten Ausmaß erreicht werden. So litten 82,2 % der Patienten trotz Behandlung weiter unter Juckreiz, wobei statistisch hochsignifikante Assoziationen mit einem schlechten Gesundheitszustand in der letzten Woche (Spear-man-Rangkorrelation; p = 1.1e-45), dem Ausmaß des psoriatischen Körperoberflächenbefalls (p = 3.2e-11) und Kopfhautbefalls (p = 3.2e-11) sowie Schmerzen (p = 2.3e-22) vorlagen. Die Behandlung mit einem Biologikum war mit einer signifikant höheren Patientenzufriedenheit verbunden (Wilcoxon-Test, p = 2.0e-16). SCHLUSSFOLGERUNGEN: Die Lebensqualität der meisten österreichischen Patienten mit Psoriasis in dermatologischer Versorgung ist krankheitsbedingt beeinträchtigt, und es besteht ein Verbesserungspotenzial bei der Umsetzung von Behandlungszielen.