Psoriasis is an inflammatory, immune-mediated disease that is frequently associated with psychological comorbidities such as depression. The stigma patients feel because of the appearance of their skin may contribute to the high psycho-social burden of psoriasis. However, there is emerging evidence that overlapping biological mechanisms are, to a substantial degree, responsible for the close interaction between psoriasis and depression. Increased proinflammatory mediators, such as C-reactive protein or interleukin-6, are present in both psoriasis and depression, indicating that inflammation may represent a pathophysiological link between the diseases. Anti-inflammatory biologic therapies treat the clinical manifestations of psoriasis, but might also play a significant role in reducing associated depressive symptoms in patients with psoriasis. Comparison between single studies focusing on the change in depressive symptoms in psoriasis is limited by inconsistency in the depression screening tools applied.
Background: Anti-PD1 monoclonal antibody nivolumab is an approved therapy option for the treatment of advanced squamous cell non-small cell lung cancer (SQ-NSCLC) patients. Data outside clinical trials about therapy efficacy and safety in later therapy line treatments have rarely been described until now. Methods: We performed a retrospective data analysis of patients who were enrolled into the nivolumab Compassionate Use Program (CUP) in Germany. Sufficient clinical data of 40 patients were available for efficacy and safety analysis. Results: Overall, 47.5% of all treated patients were not affected by any adverse events (AEs); 17.5% of patients suffered from severe AEs. The 1-year survival rate was 61.3%. Estimated median progression-free survival (PFS) was 5.3 months. Patients who received nivolumab as third or later therapy line treatment (77.5%) achieved similar median PFS and 12-month overall survival rate of 52%. Conclusion: Our findings of immunotherapy treatment outside clinical trials support the results of studies in the past and confirm the efficacy and favorable toxicity profile of nivolumab treatment in advanced SQ-NSCLC patients. In addition, we can present some rarely described information about nivolumab treatment of heavily pretreated patients, which provides some evidence that immunotherapy could also be useful in later therapy lines.
Zusammenfassung Hintergrund Patientenerwartungen in Bezug auf den Nutzen einer medizinischen Behandlung stellen eine wichtige Determinante für die Placeboantwort dar. Sie können Entwicklung und Verlauf von Erkrankungen sowie Wirksamkeit und Verträglichkeit von Therapien maßgeblich beeinflussen. Die Mechanismen, die diese Placebo- und Noceboeffekte vermitteln, wurden bislang am besten auf dem Gebiet der Placeboanalgesie beschrieben. Aber auch in der Dermatologie findet sich eine zunehmende Evidenz dafür, dass verschiedene Symptome wie Schmerzen an der Haut und Pruritus (Jucken) sowie verschiedene dermatologische Erkrankungen durch die Behandlungserwartungen von Patienten moduliert werden können. Ziel der Arbeit Das Ziel dieser Arbeit ist die Darstellung der aktuellen Datenlage in Bezug auf den Einfluss von Erwartungseffekten auf dermatologische Symptome wie Pruritus und Hautschmerzen sowie auf verschiedene dermatologische Erkrankungen. Schließlich soll die Bedeutung dieses Themas für Ärzte, die Patienten mit Hautsymptomen behandeln, vermittelt werden. Material und Methoden Es handelt sich um eine narrative Übersichtsarbeit. Ergebnisse und Diskussion Eine zunehmende Anzahl von Studien an gesunden Probanden und dermatologischen Patienten zeigt, dass Hautsymptome wie Pruritus und Schmerzen durch die Induktion positiver Erwartungen verringert und durch die Induktion negativer Erwartungen verstärkt werden können. Vorherige Behandlungserfahrungen der Patienten sowie die Qualität und Quantität der Arzt-Patienten-Kommunikation spielen für die Induktion der Behandlungserwartung eine zentrale Rolle. Schlussfolgerung Techniken, die darauf abzielen, positive Erwartungseffekte von Patienten mit Hautsymptomen zu maximieren und negative zu minimieren, sollten in die klinische Routine implementiert werden.
Introduction: Fixed-dose pembrolizumab (200 mg abs., d1, q3w) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared to 2 ndline chemotherapy. Due to lack of validated imaging response criteria, respondersubgroups with potential survival benefit have not yet been identified. Here, we administered highdose pembrolizumab (10 mg/kg, d1, q2w) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum.Methods: Data from 27 patients with baseline and follow-up 18 F-FDG PET/CT imaging were retrospectively analyzed. RECIST v1.1, mRECIST, PERCISTSULpeak and PERCISTMTV were used separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) of responders were compared to non-responders using Kaplan-Meier and log-rank analyses. Programmed Cell Death Protein 1 (PD-L1) expression status was assessed and its association with outcome was investigated.Results: 27 patients had 18 F-FDG-PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 months, respectively. Response rates were 7%, 7%, 30%, and 30% based on RECIST v1.1, mRECIST, PERCISTSULpeak, and PERCISTMTV response criteria, respectively. Response according to PERCISTMTV predicted prolonged OS or PFS (p < 0.01), whereas all other imaging criteria and PD-L1 expression did not. Conclusion: 18 F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials.
BackgroundThe rate of seroconversion after COVID-19 vaccination in patients with moderate to severe psoriasis requiring systemic treatment is poorly understood.ObjectivesThe aim of this prospective single-center cohort study performed between May 2020 and October 2021 was to determine the rate of seroconversion after COVID-19 vaccination in patients under active systemic treatment for moderate to severe psoriasis.MethodsInclusion criteria were systemic treatment for moderate to severe psoriasis, known COVID-19 vaccination status, and repetitive anti-SARS-CoV-2-S IgG serum quantification. The primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination.Results77 patients with a median age of 55.9 years undergoing systemic treatment for moderate to severe psoriasis were included. The majority of patients received interleukin- (n=50, 64.9%) or tumor necrosis factor (TNF)-α inhibitors (n=16, 20.8%) as systemic treatment for psoriasis; nine patients (11.7%) were treated with methotrexate (MTX) monotherapy, and one patient each received dimethyl fumarate (1.3%), respectively apremilast (1.3%). All included patients completed COVID-19 vaccination with two doses over the course of the study. Serum testing revealed that 74 patients (96.1%) showed an anti-SARS-CoV-2-S IgG seroconversion. While all patients on IL-17A, -12 or -12/23 inhibitors (n=50) achieved seroconversion, three of 16 patients (18.8%) receiving MTX and/or a TNF-α inhibitor as main anti-psoriatic treatment did not. At follow-up, none of the patients had developed symptomatic COVID-19 or died from COVID-19.ConclusionsAnti-SARS-CoV-2-S IgG seroconversion rates following COVID-19 vaccination in psoriasis patients under systemic treatment were high. An impaired serological response, however, was observed in patients receiving MTX and/or TNF-α inhibitors, in particular infliximab.
Psoriasis is a chronic inflammatory disease causing erythematous, scaly skin patches that are often itchy and painful. With a prevalence of around 2% in Western populations, it is among the most widespread skin conditions. 1,2 The pathological mechanisms are relatively well understood and effective systemic treatments to reduce skin symptoms have been developed. 3,4 However, a huge portion of psoriasis patients suffer from psychological comorbidities, foremost depressive symptoms. 5,6 Several factors are thought to underlie this connection between psoriasis and depression. On the one hand, the disabling symptoms have a significant impact on patients' quality of life and the easily visible plaques may lead to stigmatization and social withdrawal. 7 On the other hand, there is growing evidence that the peripheral systemic inflammation associated with psoriasis may facilitate the development of depression as well. 8
(1) Background: Melanoma has the highest mortality of all cutaneous tumors, despite recent treatment advances. Many relevant genetic events have been identified in the last decade, including recurrent ARID1A mutations, which in various tumors have been associated with improved outcomes to immunotherapy. (2) Methods: Retrospective analysis of 116 melanoma samples harboring ARID1A mutations. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome applying Kaplan–Meier (log-rank test), Fisher’s exact and Chi-squared tests. (3) Results: The majority of ARID1A mutations were in cutaneous and occult melanoma. ARID1A mutated samples had a higher number of mutations than ARID1A wild-type samples and harbored UV-mutations. A male predominance was observed. Many samples also harbored NF1 mutations. No apparent differences were noted between samples harboring genetically inactivating (frame-shift or nonsense) mutations and samples with other mutations. No differences in survival or response to immunotherapy of patients with ARID1A mutant melanoma were observed. (4) Conclusions: ARID1A mutations primarily occur in cutaneous melanomas with a higher mutation burden. In contrast to findings in other tumors, our data does not support ARID1A mutations being a biomarker of favorable response to immunotherapies in melanoma. Larger prospective studies would still be warranted.
Zusammenfassung Hintergrund Psoriasisplaques an den Unterschenkeln zeigen sich oftmals besonders therapierefraktär. Eine Kompressionstherapie könnte an dieser Lokalisation möglicherweise eine sinnvolle ergänzende Therapiemaßnahme darstellen. Jedoch bestehen oft Bedenken, dass ein Köbner-Phänomen zu einer Verschlechterung des Hautbefundes führen könnte. Daher sollten in dieser Studie die Effekte einer Kompressionstherapie auf Psoriasisplaques bei gleichzeitig bestehenden Ödemen an den Unterschenkeln untersucht werden. Patienten und Methoden Es erfolgte ein Halbseitenversuch bei dem zusätzlich zum „standard of care“ eine 4‑wöchige Kompressionstherapie durchgeführt wurde. Der primäre Endpunkt war das klinische Ansprechen der Psoriasis-Plaques an den Unterschenkeln im Seitenvergleich gemessen mittels Lesion Severity Score (LSS) und der lokal betroffenen Körperoberfläche in Woche 4 im Vergleich zum Ausgangsbefund. Sekundäre Endpunkte bezogen sich auf „patient-reported outcomes“. Ergebnisse In die finale Analyse gingen die Daten von 30 Patienten ein. Die mittleren LSS-Befunde sowie die subjektiven Schmerzen der Patienten zeigten in der rein deskriptiven Auswertung eine geringgradig stärkere Verbesserung im Bereich des komprimierten im Vergleich zum nicht komprimierten Unterschenkel. Es ergaben sich keine Hinweise auf ein Köbner-Phänomen. Diskussion Es handelt sich um die erste klinische Studie, die systematisch den Einfluss einer Kompressionstherapie auf Psoriasisplaques untersuchte. Im Untersuchungszeitraum von 4 Wochen ergaben sich zwar keine signifikanten Besserungen der Psoriasisplaques, allerdings auch keine Hinweise für eine Verschlechterung des Hautbefundes. Folglich kann eine antiödematöse Kompressionstherapie bei Patienten mit Psoriasis unter Beachtung der grundlegenden Kontraindikationen ohne Komplikationen durchgeführt werden.
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