Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall ...survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman's rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0-35.4) months, the rwPFS was 3.9 months (95%CI 3.5-4.9), the rwTtNT was 10.7 months (95%CI 9.0-12.9), and the rwToT was 6.2 months (95%CI 5.1-6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been ...associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of
were more susceptible (OR = 1.79,
= 0.0038), whereas those with
(OR = 0.57,
= 0.0011) and homozygotes for
(OR = 0.39,
= 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4
T lymphocytes, using RNAseq. In these cells, we found a higher expression of
,
and
and lower expression of
and
in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
BackgroundImmune checkpoint inhibition (ICI) is an essential treatment option in melanoma. Its outcome may be improved by a preceding radiation of metastases. This study aimed to investigate the ...impact of a preceding radiotherapy on the clinical outcome of ICI treatment.MethodsThis multicenter retrospective cohort study included patients who received anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or anti-programmed cell death protein 1 (PD-1) ICI with or without preceding radiotherapy for unresectable metastatic melanoma. ICI therapy outcome was measured as best overall response (BOR), progression-free (PFS) and overall survival (OS). Response and survival analyses were adjusted for confounders identified by directed acyclic graphs. Adjusted survival curves were calculated using inverse probability treatment weighting.Results835 patients who received ICI (anti-CTLA-4, n=596; anti-PD-1, n=239) at 16 centers were analyzed, whereof 235 received a preceding radiotherapy of metastatic lesions in stage IV disease. The most frequent organ sites irradiated prior to ICI therapy were brain (51.1%), lymph nodes (17.9%) and bone (17.9%). After multivariable adjustment for confounders, no relevant differences in ICI therapy outcome were observed between cohorts with and without preceding radiotherapy. BOR was 8.7% vs 13.0% for anti-CTLA-4 (adjusted relative risk (RR)=1.47; 95% CI=0.81 to 2.65; p=0.20), and 16.5% vs 25.3% for anti-PD-1 (RR=0.93; 95% CI=0.49 to 1.77; p=0.82). Survival probabilities were similar for cohorts with and without preceding radiotherapy, for anti-CTLA-4 (PFS, adjusted HR=1.02, 95% CI=0.86 to 1.25, p=0.74; OS, HR=1.08, 95% CI=0.81 to 1.44, p=0.61) and for anti-PD-1 (PFS, HR=0.84, 95% CI=0.57 to 1.26, p=0.41; OS, HR=0.73, 95% CI=0.43 to 1.25, p=0.26). Patients who received radiation last before ICI (n=137) revealed no better survival than those who had one or more treatment lines between radiation and start of ICI (n=86). In 223 patients with brain metastases, we found no relevant survival differences on ICI with and without preceding radiotherapy.ConclusionsThis study detected no evidence for a relevant favorable impact of a preceding radiotherapy on anti-CTLA-4 or anti-PD-1 ICI treatment outcome in metastatic melanoma.
Zusammenfassung
Die Methoden zur Behandlung akuter und chronischer Wunden unterliegen einer steten Weiterentwicklung, Reevaluierung und Anwendung innovativer Therapieformen. Die Vakuumtherapie zur ...Wundbehandlung gehört zu den etablierten Behandlungsmodalitäten. Ein innovatives Verfahren kombiniert die Vakuumtherapie mit der automatisierten, kontrollierten Zufuhr und Drainage wirkstoffhaltiger Lösungen zur topischen Wundbehandlung im Wundbett und auch wirkstofffrei durch Instillation physiologischer Kochsalzlösung (Unterdruck‐Instillationstherapie). Hierdurch können die Effekte der konventionellen Vakuumtherapie mit denen der lokalen Antisepsis kombiniert werden. Hierdurch kommt es zu einer Reduktion der Wundfläche, einer Induktion von Granulationsgewebe sowie einer Reduktion der Keimbesiedelung der Wunden. Bisher publizierte Studien konzentrieren sich auf die Anwendung dieses Therapieverfahrens zur Behandlung orthopädisch‐chirurgischer Krankheiten. Die Datenlage bezüglich der Vakuum‐Instillationstherapie in der Dermatochirurgie beschränkt sich derzeit auf Fallberichte und Einzelfallerfahrungen. Randomisierte, prospektive Studien zum Vergleich der Vakuum‐Instillationstherapie zur Behandlung dermatologischer Krankheitsbilder existieren bislang nicht. Ziele des vorliegenden Artikels sind die Vorstellung der Vakuumtherapie mit Instillation einschließlich ihres Wirkprinzips, deren mögliche Komplikationen, die Diskussion erdenklicher Kontraindikationen sowie eine Übersicht über die aktuell verfügbare Datenlage. Zusammenfassend scheint sich die Evidenz zu verdichten, dass mittels Unterdruck‐Instillationstherapie sowohl einfache als auch komplizierte Wunden effizient behandelt werden können, was sich in einer deutlichen Beschleunigung der Wundgranulation mit konsekutiv früher möglichem Defektverschluss äußert.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Within the group of classical reticulate pigment disorders of the skin, Galli-Galli disease (GGD), Dowling-Degos disease (DDD), Kitamura's disease (RPK), Haber's syndrome (HS), and reticulate ...acropigmentation of Dohi (RAD) are included and distinguished clinically and histopathologically. The clinical appearance of the reticulate pigment disorders of the skin is similar, with slight differences in age of onset and associated disorders. The histopathologic features of reticulate pigment disorders of the skin are comparable, with the exception of the unique hallmark of suprabasal acantholysis, which can be observed exclusively in GGD. Based on a critical discussion, we recommend using major and minor defining criteria for diagnosing skin lesions compatible with the reticulate pigment dermatoses of the skin. Herein we discuss a unifying nosological concept to provide straightforward diagnoses of the reticulate pigment disorders of the skin with a therapeutic impact.
Pre‐ and perioperative aspects of dermatosurgery Müller, Cornelia S. L.; Hubner, Wakiko; Thieme‐Ruffing, Sigrid ...
Journal der Deutschen Dermatologischen Gesellschaft,
February 2017, 2017-Feb, 2017-02-00, 20170201, Volume:
15, Issue:
2
Journal Article
Peer reviewed
Open access
Summary
Dermatosurgery occupies an exceptional position among all surgical disciplines. Above all, this includes the fact that, with very few exceptions, the vast majority of surgical interventions ...can be performed under local or regional anesthesia, usually in smaller procedure rooms that are spatially separated from larger operating suites. Thus, peri‐ and postinterventional patient monitoring is the responsibility of the dermatosurgeon and his team. Though inherently smaller, this team still has to observe numerous perioperative requirements that – in larger surgical specialties – would be attended to by a host of various specialists working in concert. Said requirements include hygienic aspects, knowledge concerning pre‐ and intraoperative patient monitoring, managing surgical site infections, adequate postsurgical pain management, as well as detailed pharmacological knowledge with respect to common local anesthetics and the toxic and allergic reactions associated therewith. Not only does this require interdisciplinary collaboration and shared responsibility for the patient. It also necessitates the development and implementation of quality‐oriented and evidence‐based guidelines that, in the dermatosurgical setting, usually extend far beyond the scope of the specialty per se. The objective of the present CME article is the condensed presentation of interdisciplinary aspects relating to the most important perioperative issues.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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