Wound antisepsis has undergone a renaissance due to the introduction of highly effective wound-compatible antimicrobial agents and the spread of multidrug-resistant organisms (MDROs). However, a strict indication must be set for the application of these agents. An infected or critically colonized wound must be treated antiseptically. In addition, systemic antibiotic therapy is required in case the infection spreads. If applied preventively, the Wounds-at-Risk Score allows an assessment of the risk for infection and thus appropriateness of the indication. The content of this updated consensus recommendation still largely consists of discussing properties of octenidine dihydrochloride (OCT), polihexanide, and iodophores. The evaluations of hypochlorite, taurolidine, and silver ions have been updated. For critically colonized and infected chronic wounds as well as for burns, polihexanide is classified as the active agent of choice. The combination 0.1% OCT/phenoxyethanol (PE) solution is suitable for acute, contaminated, and traumatic wounds, including MRSA-colonized wounds due to its deep action. For chronic wounds, preparations with 0.05% OCT are preferable. For bite, stab/puncture, and gunshot wounds, polyvinylpyrrolidone (PVP)-iodine is the first choice, while polihexanide and hypochlorite are superior to PVP-iodine for the treatment of contaminated acute and chronic wounds. For the decolonization of wounds colonized or infected with MDROs, the combination of OCT/PE is preferred. For peritoneal rinsing or rinsing of other cavities with a lack of drainage potential as well as the risk of central nervous system exposure, hypochlorite is the superior active agent. Silver-sulfadiazine is classified as dispensable, while dyes, organic mercury compounds, and hydrogen peroxide alone are classified as obsolete. As promising prospects, acetic acid, the combination of negative pressure wound therapy with the instillation of antiseptics (NPWTi), and cold atmospheric plasma are also subjects of this assessment.

The risk of venous and arterial thromboembolism (VTE/ATE) associated with immune checkpoint inhibitors is currently unclear, and clinical trials evaluating these agents in patients with cancer did not provide information. Our aim was to quantify risk of VTE/ATE in a cohort of patients treated with immune checkpoint inhibitors, explore clinical impact, and investigate potential clinical risk factors. Patients treated with an immune checkpoint inhibitor at the Medical University of Vienna from 2015-2018 were identified using the in-house pharmacy records (n=672; most frequent entities: 30.4% melanoma, 24.1% non-small-cell lung cancer; 86% stage-IV-disease). A retrospective chart-review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were analysed within a competing-risk framework. Multi-state modelling was applied to study the impact of VTE/ATE on mortality. Over a median follow-up of 8.5 months, 47 VTE and 9 ATE were observed. Cumulative incidences of VTE and ATE were 12.9% [95% confidence interval (CI): 8.2-18.5)] and 1.8% [95%CI: 0.7-3.6]. Occurrence of VTE was associated with increased mortality (transition hazard-ratio (THR): 3.09 [95%CI: 2.07-4.60]. History of VTE predicted VTE occurrence (subdistribution hazard ratio (SHR): 3.69 [2.00-6.81]) and distant metastasis was non-significantly associated with VTE risk (SHR: 1.71 [95%CI: 0.62-4.73]). No association of VTE with ECOG performance-status, Charlson-Comorbidity-Index or the Khorana-score was observed, and rates of VTE were comparable among subgroups of tumour types and checkpoint-inhibitory agents. In conclusion, patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Furthermore, VTE occurrence was associated with increased risk of mortality.

Background: PD1 inhibitors as well as PD1/CTLA4 combinations have shown remarkable efficacy in the first-line treatment of metastatic melanoma. The impact of many concomitant medications on the clinical outcomes from PD1 based therapies remains elusive. Methods: We retrospectively analyzed 140 patients included in the Checkmate 069 phase II clinical trial as a discovery cohort, comparing ipilimumab monotherapy with ipilimumab combined with nivolumab. We compared response rates, progression-free survival and overall survival of patients treated or not with 11 different classes of comedications at immune therapy initiation. Disease stage, LDH levels, BRAF status, sex, age, and body mass index were also compared. Furthermore, a protein array was performed for 440 analytes in a subset of 135 patients for whom pretreatment serum was available. We validated the impact of proton pump inhibitors in an independent cohort of 68 PD1 monotherapy (pembrolizumab or nivolumab) treated patients. Results: In univariate analysis, baseline proton pump inhibitor treatment almost halved the objective response rates, reduced progression-free and overall survival of patients treated with ipilimumab and nivolumab but not with ipilimumab alone. This effect was maintained when accounted for multiple comparisons and in a multivariate analysis. Pretreatment serum protein analysis showed increased NCAM1 and CSF3R levels in PPI users. We found increased baseline blood leukocyte and neutrophil levels in correlation with PPI use. The results were confirmed in an independent cohort of 68, first-line melanoma patients. Conclusions: Our analysis shows that proton pump inhibitors could negatively impact on the benefit from PD1 based therapies both for monotherapy and also for ipilimumab and nivolumab combination therapy. PPIs might establish a unique inflammatory immune status, prior to immune therapy initiation that interferes with treatment efficacy. These results suggest that if possible PPIs should be avoided in patients who are destined for PD1-based immunetherapies. Also, the results will have important implication for design of future clinical trials.

Objective: The influence of different irrigation solutions, in conjunction with wet-to-moist cleansing, on the reduction of sessile, non-planktonic bacteria which colonise wounds, has not been investigated. In this study, the antibacterial effect of different irrigation solutions, during a 20-minute wet-to-moist cleansing, has been evaluated in chronic wounds. Methods: This study was designed as a prospective cohort study with 12 study arms and was conducted between June 2011 and April 2016. Patients with chronic wounds present for more than three months, irrespective of previous treatments, were recruited into this study. Quantitative wound swabs were obtained before and after a 20-minute, wet-to-moist cleansing, using different wound irrigation solutions. Sterile 0.9% saline served as a control. Results: We recruited 308 patients, of which 260 patients with 299 chronic wounds were eligible for analysis. Staphylococcus aureus was the most common recovered (25.5%) microorganism, of which 8% were meticillin-resistant Staphylococcus aureus (MRSA) strains. Although 0.9% saline supported cleansing of the wound bed, it did not significantly reduce the bacterial burden. The highest reduction of bacterial burden was achieved with an aqueous solution containing betaine, zinc and polyhexamethylene biguanide (polihexanide; ln RF=3.72), followed by a 3% saline solution containing 0.2% sodium hypochlorite (ln RF=3.40). The most statistically significant reduction of bacterial burden, although not the highest, was achieved with povidone-iodine (ln RF=2.98; p=0.001) and an irrigation solution containing sea salt 1.2% and NaOCl 0.04% (ln RF=2.51; p=0.002). Conclusion: If a reduction of bacterial burden is warranted, wound irrigation solutions containing a combination of hypochlorite/hypochlorous acid, or antiseptics such as polihexanide, octenidine or povidone-iodine, ought to be considered.

SummaryTalimogene laherparepvec (T‐VEC) is a intralesional oncolytic virotherapy, licensed in the European Union for locoregional advanced melanoma of American Joint Committee on Cancer stages IIIB, IIIC and IVM1a. Organ transplant recipients are currently excluded from all clinical trials dealing with immunotherapies due to the risk of transplant rejection. A 58‐year‐old white man with a history of heart and kidney transplantation in 2014 was diagnosed with melanoma (Breslow thickness 1·6 mm, stage pT2a) on the left arm in September 2015. In March 2016 he developed in transit metastases, and local therapy with a combination of topical imiquimod (5%) and cryotherapy of individual lesions was initiated. However, in November 2016 therapy was stopped following local progression of the metastases. An interdisciplinary decision to treat the patient with T‐VEC was taken. After 11 cycles of T‐VEC, the patient showed a complete response. As of June 2018, 11 months after the last treatment cycle of T‐VEC, the patient continues to be tumour free. The patient tolerated the therapy well with only mild adverse events and did not show any sign of graft rejection or loss of function of the transplanted organs. We conclude that T‐VEC can be a potentially effective and safe treatment in patients with a history of organ transplantation. Nevertheless, due to this special situation, the risks and benefits should always be discussed with an interdisciplinary tumour board.

q3w with an incidence ratio of 1.13 (0.19 e 4.70). Both groups had a high proportion of patients with low grade toxicity (fatigue, pruritus, rash; q6w 46%, q3w 42%). Table: 1821P Group characteristics (median, range) q6w q3w Age (yr) 72 (33-90) 72 (42-91) Follow-up time (months) 6.2 (0.1-11) 13.2 (2.5-44) Treatment cycles given 4 (1-10) 14 (3-57) Total treatment duration (patient-months) 391 1175.Conclusions: To our knowledge, this is the first analysis of toxicity data for a q6w Pembrolizumab regime. Incidence of CSirAEs is low. Low grade toxicity was common and over the course of treatment could impact quality of life. Despite limited number of events, the q6w schedule does not appear to lead to significantly higher toxicity and should be used in view of the reduced visit burden to patients and health services.Legal entity responsible for the study: the authors.

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DEL-1 (developmental endothelial locus-1) induces integrin signaling and recognizes phosphatidylserine exposed on apoptotic cells. We show that DEL-1, which is thought to be a secreted molecule, is not found in melanoma cell culture supernatants but is exported by an endosomal pathway and released via small extracellular vesicles (sEV). Proteomics of DEL-1 positive sEV, but not of DEL-1 negative sEV contain proteins associated with poor survival in cancer. To determine whether DEL-1 is suitable to predict treatment responses, we isolated sEV from plasma of melanoma patients before and 90 days of treatment with checkpoint inhibitors. Although we could not detect DEL-1 in plasma sEV even in patients with progressive disease (most likely due to the very low protein yield from sEV isolated from 1ml plasma), the principal component analysis allowed a clear differentiation between controls and patients as well as between patients before and after treatment. Interestingly, in one patient with complete regression, in the post treatment sample, the protein expression profile remained in the pre-treatment cluster. The low protein yield of patient sEV and the low patient number are clear limitations of this study, but results demonstrate that this method could have the potential to predict treatment responses.