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An accurate forecast of flare and coronal mass ejection (CME) initiation requires precise measurements of the magnetic energy buildup and release in the active regions of the solar atmosphere. We designed a new space weather mission that performs such measurements using new optical instruments based on the Hanle and Zeeman effects. The mission consists of two satellites, one orbiting the L1 Lagrangian point (Spacecraft Earth, SCE) and the second in heliocentric orbit at 1AU trailing the Earth by 80° (Spacecraft 80, SC80). Optical instruments measure the vector magnetic field in multiple layers of the solar atmosphere. The orbits of the spacecraft allow for a continuous imaging of nearly 73% of the total solar surface. In-situ plasma instruments detect solar wind conditions at 1AU and ahead of our planet. Earth-directed CMEs can be tracked using the stereoscopic view of the spacecraft and the strategic placement of the SC80 satellite. Forecasting of geoeffective space weather events is possible thanks to an accurate surveillance of the magnetic energy buildup in the Sun, an optical tracking through the interplanetary space, and in-situ measurements of the near-Earth environment.

A combined molecular and cultural method for the detection of the Mycobacterium tuberculosis complex (MTBC) and Mycobacterium avium subsp. paratuberculosis was developed and tested with artificially contaminated milk and dairy products. Results indicate that the method can be used for a reliable detection as a basis for first risk assessments. [ABSTRACT FROM AUTHOR]

A unique collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to two-centimeter safety margins. For a correct stage classification and treatment decision, a sentinel lymph node biopsy shall be offered in patients with tumor thickness ≥ 1.0 mm or ≥ 0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions should be primarily made by an interdisciplinary oncology team ("Tumor Board"). Adjuvant therapies can be proposed in completely resected stage IIB-IV. In stage II only PD-1 inhibitors are approved. In stage III anti-PD-1 therapy or dabrafenib plus trametinib for patients with BRAFV600 mutated melanoma can be discussed. In resected stage IV, nivolumab can be offered, as well as ipilimumab and nivolumab, in selected, high-risk patients. In patients with clinically detected macroscopic, resectable disease, neoadjuvant therapy with ipilimumab plus nivolumab followed complete surgical resection and adjuvant therapy according to pathological response and BRAF status can be offered. Neoadjuvant therapy with pembrolizumab followed by complete surgical resection and adjuvant pembrolizumab is also recommended. For patients with disease recurrence after (neo) adjuvant therapy, further treatment should consider the type of (neo) adjuvant therapy received as well as the time of recurrence, i.e., on or off therapy. In patients with irresectable stage III/IV disease systemic treatment is always indicated. For first line treatment PD-1 antibodies alone or in combination with CTLA-4 or LAG-3 antibodies shall be considered. In stage IV melanoma with a BRAFV600 mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy, in selected cases. In patients with primary resistance to immunotherapy and harboring a BRAFV600 mutation, this therapy shall be offered as second line. Other second line therapies include therapy with tumor infiltrating lymphocytes and combinations of immune checkpoint inhibitors not used in first line. This guideline is valid until the end of 2026., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amaral reports personal fees for advisory board membership from Delcath and Philogen; personal fees as an invited speaker from BMS, Neracare, Novartis and Pierre Fabre; personal fees for a writing engagement from CeCaVa and Medtrix; institutional fees as local principal investigator (PI) from Agenus Inc., AstraZeneca, BioNTech, BMS, HUYA Bioscience, Immunocore, IO Biotech, MSD, Pfizer, Philogen, Regeneron, Roche and University Hospital Essen; institutional fees as coordinating PI from Unicancer; institutional research grants from iFIT and Novartis; institutional funding from MNI - Naturwissenschaftliches und Medizinisches Institut, Neracare, Novartis, Pascoe, Sanofi and Skyline-Dx; non-remunerated membership of the American Society of Clinical Oncology (ASCO) and the Portuguese Society for Medical Oncology; and a role as clinical expert in the area of medical oncology for Infarmed. Dr. Arenberger reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, outside the submitted work. Dr Basset-Seguin has nothing to disclose. Dr. Bastholt reports personal fees for advisory boards from Bristol Myers-Squibb, Pierre Fabre, Merck MSD, Novartis and Roche, outside the submitted work. Dr. Bataille has nothing to disclose.Dr. Brochez has nothing to disclose.Dr. del Marmol reports grants and personal fees from BMS, grants and personal fees from SANOFI, personal fees from LEO Pharma, grants and personal fees from ALMIRALL, outside the submitted work.Dr. Dreno reports personal fees from MSD, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Fabre , outside the submitted work. Dr. Eggermont reports Consultant for: Agenus, Boehringer Ingelheim, BioInvent, BioNTech, Brenus, CatalYm, Eurobio, GenOway,IO Biotech, Imcheck, IQVIA, Merck&Co/MSD, Pfizer, QBiotics, Regeneron, Sairopa BV, ScanCell,Scorpion Therapeutics, Secarna, SkylineDx BV, Thermosome, Trained Immunity DiscoverySpeaker engagements: Merck/MSD, SkylineDx BVEquity: IO Biotech, Sairopa BV, SkylineDX BV. Dr. Fargnoli reports grants and personal fees from Almirall, personal fees from Leo Pharma, grants and personal fees from Janssen, personal fees from Novartis, personal fees from Lilly, personal fees from Sanofi, personal fees from UCB, personal fees from Abbvie, personal fees from AMGEN, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Sun Pharma, personal fees from BMS, personal fees from Kyowa Kyrin, personal fees from Pfizer, personal fees from MSD, outside the submitted work.Dr. Forsea has nothing to disclose.Dr. Garbe reports personal fees from CeCaVa, personal fees from MSD, personal fees from NeraCare, personal fees from Philogen, outside the submitted work.Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Highlight Therapeutics, personal fees from Iovance, personal fees from CureVac, personal fees from Xenthera, peronal fees from Agenus, personal fees from Almirall, and personal fees from Sun Pharma, outside the submitted work.Dr. Hoeller reports personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work.Dr. Kandolf reports personal fees for advisory boards from Bristol Myers-Squibb, MSD, Novartis Roche, Janssen, Abbvie, outside the submitted work.Dr. Kaufmann reports other from Abbvie, other from Almirall, other from Amgen, other from Astra Zeneca, other from Bionteck, other from BMS, other from Galderma, other from Incyte, other from Janssen , other from Leo, other from MSD, other from Novartis, other from Pfizer, other from Roche, other from Sanofi, outside the submitted work.Dr. Kelleners-Smeets reports personal fees from Sanofi, personal fees from Novartis, personal fees from MSD, personal fees from Sun Pharma, outside the submitted work.Dr. Lallas reports personal fees from Avene, personal fees from MSD, personal fees from Regeneron, personal fees from BMS, outside the submitted work.Dr. Lebbe reports personal fees from MSD, personal fees from Pierre Fabre, personal fees from BMS, personal fees from Sanofi, personal fees from immunocore, outside the submitted work.Dr. Leiter reports personal fees from Regeneron, Sanofi, personal fees from MSD, personal fees from Novartis, Almirall Hermal, personal fees from Sun Pharma, outside the submitted work.Dr. Longo has nothing to disclose.Dr. Lorigan reports grants and personal fees from Pierre Fabre, personal fees from MSD, grants and personal fees from BMS, personal fees from MLA diagnostics, outside the submitted work.Dr. Malvehy reports grants and personal fees from Almirall, personal fees from MSD, personal fees from Pierre Fabre, grants from Philogen, grants from Castle biosciences, grants from BMS, grants and personal fees from ISDIN, grants and personal fees from La Roche Posay, non-financial support and other from Vivascope, non-financial support and other from Damae medical, non-financial support and other from Canfield, non-financial support and other from Fotofinder, outside the submitted work.Dr. Mandala reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Regeneron, personal fees from Sun Pharma, outside the submitted work.Dr. Moreno-Ramírez has nothing to disclose.Dr. Nathan reports personal fees from Novartis, grants and personal fees from Immunocore, personal fees from BMS, personal fees from SunPharma, personal fees from MSD, outside the submitted work;Dr. Pellacani has nothing to disclose.Dr. Peris reports personal fees from Abbvie, personal fees from Lilly, personal fees from Leo Pharma, personal fees from Sanofi, personal fees from Almirall, personal fees from Novartis, personal fees from Boehringer, personal fees from Amgen, outside the submitted work.Dr. Saiag reports personal fees from Novartis, MSD, NeraCare, BMS, Pierre Fabre, Merck, personal fees and grants from Damae Medical, outside the submitted work.Dr. Stockfleth has nothing to disclose.Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work.Dr. van Akkooi reports grants and personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from MSD-Merck, grants and personal fees from Merck-Pfizer, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Sirius Medical, personal fees from 4SC, personal fees from Genmab, personal fees from Menarini Silicon Biosystems, from Skyline Dx, outside the submitted work.Dr. Vieira has nothing to disclose.Dr. Zalaudek reports personal fees from Philogen, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from La Roche Posay, personal fees from Sunpharma, personal fees from Biogena, personal fees from Cieffe Derma, outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

This guideline was developed in close collaboration with multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF) and the European Organization for Research and Treatment of Cancer (EORTC). Recommendations for the diagnosis and treatment of melanoma were developed on the basis of systematic literature research and consensus conferences. Cutaneous melanoma (CM) is the most dangerous form of skin tumor and accounts for 90 % of skin cancer mortality. The diagnosis of melanoma can be made clinically and must always be confirmed by dermoscopy. If melanoma is suspected, a histopathological examination is always required. Sequential digital dermoscopy and whole-body photography can be used in high-risk patients to improve the detection of early-stage melanoma. If available, confocal reflectance microscopy can also improve the clinical diagnosis in special cases. Melanoma is classified according to the 8th version of the American Joint Committee on Cancer classification. For thin melanomas up to a tumor thickness of 0.8 mm, no further diagnostic imaging is required. From stage IB, lymph node sonography is recommended, but no further imaging examinations. From stage IIB/C, whole-body examinations with computed tomography or positron emission tomography CT in combination with magnetic resonance imaging of the brain are recommended. From stage IIB/C and higher, a mutation test is recommended, especially for the BRAF V600 mutation. It is important to perform a structured follow-up to detect relapses and secondary primary melanomas as early as possible. A stage-based follow-up regimen is proposed, which in the experience of the guideline group covers the optimal requirements, although further studies may be considered. This guideline is valid until the end of 2026., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amaral reports personal fees for advisory board membership from Delcath and Philogen; personal fees as an invited speaker from BMS, Neracare, Novartis and Pierre Fabre; personal fees for a writing engagement from CeCaVa and Medtrix; institutional fees as local principal investigator (PI) from Agenus Inc., AstraZeneca, BioNTech, BMS, HUYA Bioscience, Immunocore, IO Biotech, MSD, Pfizer, Philogen, Regeneron, Roche and University Hospital Essen; institutional fees as coordinating PI from Unicancer; institutional research grants from iFIT and Novartis; institutional funding from MNI - Naturwissenschaftliches und Medizinisches Institut, Neracare, Novartis, Pascoe, Sanofi and Skyline-Dx; non-remunerated membership of the American Society of Clinical Oncology (ASCO) and the Portuguese Society for Medical Oncology; and a role as clinical expert in the area of medical oncology for Infarmed. Dr. Arenberger reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, outside the submitted work. Dr Basset-Seguin has nothing to disclose. Dr. Bastholt reports personal fees for advisory boards from Bristol Myers-Squibb, Pierre Fabre, Merck MSD, Novartis and Roche, outside the submitted work. Dr. Bataille has nothing to disclose. Dr. Brochez has nothing to disclose. Dr. del Marmol reports grants and personal fees from BMS, grants and personal fees from SANOFI, personal fees from LEO Pharma, grants and personal fees from ALMIRALL, outside the submitted work. Dr. Dreno reports personal fees from MSD, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Fabre, outside the submitted work. A. Eggermont Consultant for: Agenus, Boehringer Ingelheim, BioInvent, BioNTech, Brenus, CatalYm, Eurobio, GenOway, IO Biotech, Imcheck, IQVIA, Merck&Co/MSD, Pfizer, QBiotics, Regeneron, Sairopa BV, ScanCell, Scorpion Therapeutics, Secarna, SkylineDx BV, Thermosome, Trained Immunity Discovery Speaker engagements: Merck/MSD, SkylineDx BVEquity: IO Biotech, Sairopa BV, SkylineDX BV. Dr. Fargnoli reports grants and personal fees from Almirall, personal fees from Leo Pharma, grants and personal fees from Janssen, personal fees from Novartis, personal fees from Lilly, personal fees from Sanofi, personal fees from UCB, personal fees from Abbvie, personal fees from AMGEN, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Sun Pharma, personal fees from BMS, personal fees from Kyowa Kyrin, personal fees from Pfizer, personal fees from MSD, outside the submitted work. Dr. Forsea has nothing to disclose. Dr. Garbe reports personal fees from CeCaVa, personal fees from MSD, personal fees from NeraCare, personal fees from Philogen, outside the submitted work. Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Highlight Therapeutics, personal fees from Iovance, personal fees from CureVac, personal fees from Xenthera, peronal fees from Agenus, personal fees from Almirall, and personal fees from Sun Pharma, outside the submitted work. Dr. Hoeller reports personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work. Dr. Kandolf reports personal fees for advisory boards from Bristol Myers-Squibb, MSD, Novartis Roche, Janssen, Abbvie, outside the submitted work. Dr. Kaufmann reports other from Abbvie, other from Almirall, other from Amgen, other from Astra Zeneca, other from Bionteck, other from BMS, other from Galderma, other from Incyte, other from Janssen, other from Leo, other from MSD, other from Novartis, other from Pfizer, other from Roche, other from Sanofi, outside the submitted work. Dr. Kelleners-Smeets reports personal fees from Sanofi, personal fees from Novartis, personal fees from MSD, personal fees from Sun Pharma, outside the submitted work. Dr. Lallas reports personal fees from Avene, personal fees from MSD, personal fees from Regeneron, personal fees from BMS, outside the submitted work. Dr. Lebbe reports personal fees from MSD, personal fees from Pierre Fabre, personal fees from BMS, personal fees from Sanofi, personal fees from immunocore, outside the submitted work. Dr. Leiter reports personal fees from Regeneron, Sanofi, personal fees from MSD, personal fees from Novartis, Almirall Hermal, personal fees from Sun Pharma, outside the submitted work. Dr. Longo has nothing to disclose. Dr. Lorigan reports grants and personal fees from Pierre Fabre, personal fees from MSD, grants and personal fees from BMS, personal fees from MLA diagnostics, outside the submitted work. Dr. Malvehy reports grants and personal fees from Almirall, personal fees from MSD, personal fees from Pierre Fabre, grants from Philogen, grants from Castle biosciences, grants from BMS, grants and personal fees from ISDIN, grants and personal fees from La Roche Posay, non-financial support and other from Vivascope, non-financial support and other from Damae medical, non-financial support and other from Canfield, non-financial support and other from Fotofinder, outside the submitted work. Dr. Mandala reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Regeneron, personal fees from Sun Pharma, outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Nathan reports personal fees from Novartis, grants and personal fees from Immunocore, personal fees from BMS, personal fees from SunPharma, personal fees from MSD, outside the submitted work; Dr. Pellacani has nothing to disclose. Dr. Peris reports personal fees from Abbvie, personal fees from Lilly, personal fees from Leo Pharma, personal fees from Sanofi, personal fees from Almirall, personal fees from Novartis, personal fees from Boehringer, personal fees from Amgen, outside the submitted work. Dr. Saiag reports personal fees from Novartis, MSD, NeraCare, BMS, Pierre Fabre, Merck, personal fees and grants from Damae Medical, outside the submitted work. Dr. Stockfleth has nothing to disclose. Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work. Dr. van Akkooi reports grants and personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from MSD-Merck, grants and personal fees from Merck-Pfizer, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Sirius Medical, personal fees from 4SC, personal fees from Genmab, personal fees from Menarini Silicon Biosystems, from Skyline Dx, outside the submitted work. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports personal fees from Philogen, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from La Roche Posay, personal fees from Sunpharma, personal fees from Biogena, personal fees from Cieffe Derma, outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from European Association of Dermato-Oncology (EADO), European Dermatology Forum, European Society for Radiotherapy and Oncology (ESTRO), Union Européenne des Médecins Spécialistes, and the European Academy of Dermatology and Venereology developed updated recommendations on diagnosis and treatment of BCC. BCCs were categorised into 'easy-to-treat' (common) and 'difficult-to-treat' according to the new EADO clinical classification. Diagnosis is based on clinico-dermatoscopic features, although histopathological confirmation is mandatory in equivocal lesions. The first-line treatment of BCC is complete surgery. Micrographically controlled surgery shall be offered in high-risk and recurrent BCC, and BCC located on critical anatomical sites. Topical therapies and destructive approaches can be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial and low-risk nodular BCCs. Management of 'difficult-to-treat' BCCs should be discussed by a multidisciplinary tumour board. Hedgehog inhibitors (HHIs), vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCC. Immunotherapy with anti-PD1 antibodies (cemiplimab) is a second-line treatment in patients with a progression of disease, contraindication, or intolerance to HHI therapy. Radiotherapy represents a valid alternative in patients who are not candidates for or decline surgery, especially elderly patients. Electrochemotherapy may be offered when surgery or radiotherapy is contraindicated. In Gorlin patients, regular skin examinations are required to diagnose and treat BCCs at an early stage. Long-term follow-up is recommended in patients with high-risk BCC, multiple BCCs, and Gorlin syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland., Methods: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence., Results: In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD-1 therapies (n = 1003). Twelve-month RFS for anti PD-1 and BRAF + MEK inhibitor-treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335-2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD-1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443-0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p > 0.05). In both, anti PD-1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials., Conclusions: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024., Competing Interests: Conflict of interest statement Dr. Garbe reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from NeraCare, grants and personal fees from BMS, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. Dr. Amaral reports intitutional grants and personal fees from Novartis, institutional grants from NeraCare, personal fees from BMS, institutional grants from Sanofi, institutional grants from SkylineDx, personal fees from CeCaVa, personal fees from Pierre Fabre, outside the submitted work. Dr. Peris reports personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, personal fees from Lilly, personal fees from Leopharma, personal fees from Pierre Fabre, personal fees from Almirall, personal fees from Celgene, outside the submitted work. Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from Eisai, grants and personal fees from Immunocore, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Novartis Pharma, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, grants and personal fees from Replimune, grants and personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Seagen outside the submitted work. Dr. Arenberger reports personal fees from Amgen, personal fees from MSD, personal fees from Novartis, personal fees from BMS, grants and personal fees from Pfizer, personal fees from Sanofi, outside the submitted work. Dr Basset-Seguin has nothing to disclose. Dr. Bastholt reports personal fees for advisory boards from Bristol Myers-Squibb, Pierre Fabre, Merck MSD, Novartis and Roche, outside the submitted work. Dr. Bataille has nothing to disclose. Dr. del Marmol reports grants and personal fees from BMS, grants and personal fees from SANOFI, personal fees from Merck, grants and personal fees from almirall, personal fees from ABBVIE, personal fees from LEO pharma, personal fees from SUN Pharma, personal fees from Genzyme, outside the submitted work. Dr. Dréno reports grants and personal fees from BMS, personal fees from MSD, grants and personal fees from Roche, grants and personal fees from Fabre, grants and personal fees from Sanofi, outside the submitted work. Dr. Fargnoli reports grants, personal fees and non-financial support from Almirall, grants and personal fees from Leo Pharma, grants and personal fees from Janssen, grants, personal fees and non-financial support from Novartis, personal fees from Lilly, grants and personal fees from Sanofi, personal fees from UCB, personal fees from Abbvie, grants, personal fees and non-financial support from AMGEN, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Sun Pharma, personal fees from BMS, personal fees from Kyowa Kyrin, personal fees from Pfizer, personal fees from MSD, outside the submitted work. Dr. Forsea has nothing to disclose. Dr. Grob reports personal fees from Amgen, personal fees from MSD, personal fees from Novartis, grants and personal fees from Pierre Fabre, grants and personal fees from BMS, personal fees from Philogen, personal fees from Roche, personal fees from Sanofi, outside the submitted work. Dr. Hoeller reports personal fees from Amgen, personal fees from Almirall, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work. Dr. Kaufmann reports grants from Abbvie, grants from Almirall, grants from Amgen, grants from Astra Zeneca, grants from Biontech, grants from BMS, grants from BMS, grants from Celgene, grants from InflaRx, grants from Leo, grants from Lilly, grants from MSD, grants from Novartis, grants from Pfizer, grants from Pierre Fabre, grants from Regeneron, grants from Roche, grants from Sanofi, grants from UCB, outside the submitted work. Dr. Kelleners-Smeets has nothing to disclose. Dr. Lallas reports grants and personal fees from Sanofi, outside the submitted work. Dr. Lebbé reports grants and personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche, personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Lytvynenko has nothing to disclose. Dr. Malvehy reports grants and personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from BMS, grants and personal fees from Almirall, personal fees from Sunpharma, personal fees from Pierre Fabre, outside the submitted work. Dr. Moreno-Ramirez has nothing to disclose. Dr. Nathan reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, grants and personal fees from Immunocore, personal fees from 4SC, outside the submitted work. Dr. Pellacani reports personal fees from Novartis, personal fees from Sanofi, grants from Novartis, instruments from 3Gen, Vidix, Fotofinder and MAVIG GmbH, outside the submitted work. Dr. Saiag reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from NeraCare, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Sanofi, personal fees from Pierre Fabre/array, outside the submitted work. Dr. Stratigos reports personal fees from Sanofi, personal fees from Janssen CILAG, personal fees and non-financial support from Novartis, grants from Genesis Pharma, grants from Abbvie, grants and personal fees from BMS, personal fees from Regeneron, grants from Leo-Pharma, grants from Lilly, outside the submitted work. Dr. van Akkooi reports grants and personal fees from Amgen, personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from MSD-Merck, grants and personal fees from Merck-Pfizer, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Sirius Medical, personal fees from 4SC, outside the submitted work. Dr. Vieira reports personal fees from BMS, outside the submitted work. Dr. Zalaudek reports personal fees from Philogen, personal fees from MSD, personal fees from Novartis, personal fees from Sanofi, personal fees from La Roche Posay, personal fees from Sunpharma, personal fees from Biogena, personal fees from Cieffe Derma, outside the submitted work. Dr. Lorigan has nothing to disclose., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding and controlling the individual behavior of nanoscopic matter in liquids, the environment in which many such entities are functioning, is both inherently challenging and important to many natural and man-made applications. Here, we transport individual nano-objects, from an assembly in a biological ionic solution, through a nanochannel network and confine them in electrokinetic nanovalves, created by the collaborative effect of an applied ac electric field and a rationally engineered nanotopography, locally amplifying this field. The motion of so-confined fluorescent nano-objects is tracked, and its kinetics provides important information, enabling the determination of their particle diffusion coefficient, hydrodynamic radius, and electrical conductivity, which are elucidated for artificial polystyrene nanospheres and subsequently for sub-100-nm conjugated polymer nanoparticles and adenoviruses. The on-chip, individual nano-object resolution method presented here is a powerful approach to aid research and development in broad application areas such as medicine, chemistry, and biology., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Purpose: To investigate the clinical value of the inflammation based prognostic scores for patients with radiosurgically treated brain metastases (BM) originating from non-pulmonary primary tumor (PT)., Methods: A retrospective analysis of 340 BM patients of different PT origin (melanoma, breast, gastrointestinal, or genitourinary cancer) was performed. Pre-radiosurgical laboratory prognostic scores, such as the Neutrophil-to-Lymphocyte Ratio (NLR), the Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), and the modified Glasgow Prognostic Score (mGPS), were investigated within 14 days before the first Gamma Knife radiosurgical treatment (GKRS1)., Results: In our study cohort, the estimated survival was significantly longer in patients with NLR < 5 (p < 0.001), LMR > 4 (p = 0.001) and in patients with a mGPS score of 0 (p < 0.001). Furthermore, univariate and multivariate Cox regression models revealed NLR ≥ 5, LMR < 4 and mGPS score ≥ 1 as independent prognostic factors for an increased risk of death even after adjusting for age, sex, KPS, extracranial metastases status, presence of neurological symptoms and treatment with immunotherapy (IT) or targeted therapy (TT)., Conclusions: Summarizing previously published and present data, pre-radiosurgical mGPS and NLR groups seem to be the most effective and simple independent prognostic factors to predict clinical outcome in radiosurgically treated BM patients., (© 2021. The Author(s).)

Primary diffuse leptomeningeal melanomatosis (PDLMM) is an extremely rare and aggressive cancer type for which best treatment strategies remain to be elucidated. Herein, we present current and prospective diagnostic strategies and treatment management of PDLMM. Against the background of an extensive literature review of published PDLMM cases and currently employed therapeutic strategies, we present an illustrative case of a pediatric patient suffering from PDLMM. We report the first case of a pediatric patient with PDLMM who received combination treatment including trametinib and everolimus, followed by intravenous nivolumab and ipilimumab with concomitant intensive intraventricular chemotherapy, resulting in temporary significant clinical improvement and overall survival of 7 months. Following this clinical experience, we performed a comprehensive literature review, identifying 26 additional cases. By these means, we provide insight into current knowledge on clinical and molecular characteristics of PDLMM. Analysis of these cases revealed that the unspecific clinical presentation, such as unrecognized increased intracranial pressure (present in 67%), is a frequent reason for the delay in diagnosis. Mortality remains substantial despite diverse therapeutic approaches with a median overall survival of 4 months from diagnosis. On the molecular level, to date, the only oncogenic driver reported so far is mutation of NRAS ( n = 3), underlining a close biological relation to malignant melanoma and neurocutaneous melanosis. We further show, for the first time, that this somatic mutation can be exploited for cerebrospinal fluid liquid biopsy detection, revealing a novel potential biomarker for diagnosis and monitoring of PDLMM. Last, we use a unique patient derived PDLMM cell model to provide first insights into in vitro drug sensitivities. In summary, we provide future diagnostic and therapeutic guidance for PDLMM and first insights into the use of liquid biopsy and in vitro models for this orphan cancer type.

Melanoma brain metastases (MBM) are common and associated with a particularly poor prognosis; they directly cause death in 60-70% of melanoma patients. In the past, systemic treatments have shown response rates around 5%, whole brain radiation as standard of care has achieved a median overall survival of approximately three months. Recently, the combination of immune checkpoint inhibitors and combinations of MAP-kinase inhibitors both have shown very promising response rates of up to 55% and 58%, respectively, and improved survival. However, current clinical evidence is based on multi-cohort studies only, as prospectively randomized trials have been carried out rarely in MBM, independently whether investigating systemic therapy, radiotherapy or surgical techniques. Here, an interdisciplinary expert team reviewed the outcome of prospectively conducted clinical studies in MBM, identified evidence gaps and provided recommendations for the diagnosis, treatment, outcome evaluation and monitoring of MBM patients. The recommendations refer to four distinct scenarios: patients (i) with 'brain-only' disease, (ii) with oligometastatic asymptomatic intra- and extracranial disease, (iii) with multiple asymptomatic metastases, and (iv) with multiple symptomatic MBM or leptomeningeal disease. Changes in current management recommendations comprise the use of immunotherapy - preferably combined anti-CTLA-4/PD-1-immunotherapy - in asymptomatic MBM minus/plus stereotactic radiosurgery which remains the mainstay of local brain therapy being safe and effective. Adjuvant whole-brain radiotherapy provides no clinical benefit in oligometastatic MBM. Among the systemic therapies, combined MAPK-kinase inhibition provides, in BRAF V600 -mutated patients with rapidly progressing or/and symptomatic MBM, an alternative to combined immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare to have following potential conflicts of interest: RG reports personal fees and non-financial support from Amgen, Bristol-Myers Squibb, Merck Serono, Novartis, Pierre Fabre, Roche and Sanofi Regeneron; personal fees from 4SC, Almirall Hermal, MSD and SUN Pharma; grants from Johnson & Johnson;, grants and personal fees form Pfizer; and grants, personal fees and non-financial support from Novartis. DV reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Ferring, Lilly and Roche; grants, personal fees and non-financial support from Merck. JCH reports personal fees from Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Sanofi, SUN Pharma and grants from Bristol-Myers Squibb. DK reports personal fees from Bristol-Myers Squibb during the conduct of this project, and from Novocure. CW has nothing to disclose. DS reports personal fees and non-financial support from Amgen, Merck Serono and Roche/Genentech; personal fees from 4SC, Agenus, Array BioPharma; Immunocore, Incyte, Pierre Fabre, Nektar, Pfizer, Philogen; Sandoz, Sanofi/Regeneron and from Regeneron; non-financial support from Merck; grants, personal fees, and other from Bristol-Myers Squibb (also during the conduct of this project); grants, personal fees, non-financial support and other from Novartis. TS is an employee of Bristol-Myers Squibb GmbH & Co KGaA (Munich, Germany), and reports personal fees from Bristol Myers-Squibb. SR reports a radiosurgery study grant from Accuray Inc outside the submitted work. TP reports personal fees from Bristol-Myers Squibb (during and outside the conduct of this project), Boehringer Ingelheim, Celgene, Janssen, MSD, Novartis, Roche and Takeda. CH reports consultancy, advisory boards and/or lectures for Amgen, AstraZeneca, Bristol-Myers Squibb, Incyte, MSD, Novartis, Pierre Fabre and Roche. TKE reports personal fees from Bristol-Myers Squibb (during and outside the conduct of the project); personal fees from Leo Pharma, MSD, Novartis, Roche, Sanofi. FM reports travel support or/and speaker’s fees or/and advisor’s honoraria by Novartis, Roche, BMS, MSD and Pierre Fabre and research funding from Novartis and Roche., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Infections caused by vancomycin-resistant Enterococcus faecium (VREfm) represent a major public health concern due to limited treatment options. Among invasive isolates of VREfm, ST117, ST80 and ST78 represent the most frequently detected STs by MLST in Germany. In this study, we investigated the genetic diversity of isolates of VREfm recovered from different nosocomial outbreaks in Bavaria, Germany, by WGS., Methods: Between January 2018 and April 2019, 99 non-replicate isolates of VREfm originating from nosocomial outbreaks at eight different hospitals in Bavaria were investigated for genetic diversity by WGS. In detail, complex types (CTs) were identified by core-genome MLST. Furthermore, an SNP analysis was performed for all VREfm strains., Results: Most of the isolates of this study (76%) belonged to three major clonal groups, which occurred in at least three hospitals: ST80/CT1065 vanB (n = 45; six hospitals), ST117/CT71 vanB (n = 11; four hospitals) and ST78/CT894like vanA (n = 19; three hospitals). Moreover, isolates of the predominant lineage ST80/CT1065 vanB showed a maximum difference of 36 SNPs as revealed by SNP analysis., Conclusions: Whole-genome analysis of VREfm causing nosocomial outbreaks suggests the occurrence of few endemic clonal lineages in Bavarian hospital settings, namely ST80/CT1065 vanB, ST117/CT71 vanB and ST78/CT894like vanA. Further studies are needed for a better understanding of the factors affecting the successful spread of the above-mentioned lineages., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT., Methods: We evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era., Results: The median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7-1.2 years). Patients treated with anti-PD-1 or a combination of anti-CTLA-4/PD-1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti-PD-1, anti-CTLA-4, or a combination of anti-CTLA-4/PD-1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT., Conclusion: In MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed through dermatoscopy. If a melanoma is suspected, a histopathological examination is required. Sequential digital dermatoscopy and full-body photography can be used in risk persons to detect the development of melanomas at an earlier stage. Where available, confocal reflectance microscopy can improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the AJCC classification. Thin melanomas up to 0.8 mm tumor thickness does not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC whole-body examinations with CT or PET-CT in combination with brain MRI are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to support the frequency and extent of examinations. A stage-based follow-up scheme is proposed, which, according to the experience of the guideline group, covers the minimum requirements; further studies may be considered. This guideline is valid until the end of 2021., Competing Interests: Conflict of interest statement Dr. Garbe reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from NeraCare, grants and personal fees from BMS, personal fees from Pierre Fabre, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. Dr. Amaral reports personal fees and other from BMS, grants, personal fees, and others from Novartis, personal fees from Pierre Fabre, grants from Neracare, grants from Sanofi, outside the submitted work. Dr. Peris reports personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, personal fees from Lilly, personal fees from Leopharma, personal fees from Pierre Fabre, personal fees from Almirall, personal fees from Celgene, outside the submitted work. Dr. Hauschild reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckSerono, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Provectus, grants and personal fees from Regeneron, grants and personal fees from Roche, personal fees from OncoSec, grants and personal fees from Sanofi-Genzyme, personal fees from Sun Pharma, grants and personal fees from Novartis Pharma outside the submitted work. Dr. Arenberger reports personal fees from Amgen, personal fees from MSD, personal fees from Novartis, personal fees from BMS, personal fees from Roche, outside the submitted work. Dr. Bastholt reports grants from BMS, during the conduct of the study; personal fees from BMS, personal fees from Novartis, personal fees from Merck MSD, personal fees from Roche, personal fees from Incyte, personal fees from Bayer, outside the submitted work. Dr. Bataille reports personal fees from Novartis, personal fees from Merck MSD, outside the submitted work. Dr. del Marmol reports personal fees from MSD, from BMS, personal fees from Sanofi, grants and personal fees from ABVIE, grants from Jansen, outside the submitted work. Dr. Dréno reports grants and personal fees from BMS, personal fees from MSD, grants and personal fees from Roche, grants and personal fees from Fabre, grants and personal fees from Sanofi, outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall, grants and personal fees from Leo Pharma, personal fees from Janssen, grants and personal fees from Novartis, personal fees from Lilly, grants and personal fees from Sanofi, personal fees from UCB, grants and personal fees from Abbvie, personal fees from Celgene, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche, personal fees from Sun Pharma, outside the submitted work. Dr. Grob reports personal fees from Amgen, personal fees from MSD, personal fees from Novartis, personal fees from BMS, personal fees from Roche, personal fees from Pierre fabre, personal fees from MercK/Pfizer, outside the submitted work. Dr. Hoeller reports personal fees from Amgen, personal fees from MSD, personal fees from Novartis, personal fees from Incyte, personal fees from BMS, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work. Dr. Kaufmann reports grants and personal fees from Novartis and Roche, and grants from AbbVie, Amgen, Bionteck, BMS, Celgene, Galderma, Janssen, Leo, Lilly, Merck, MSD, Pierre Fabre, Regeneron, and Wyeth, outside the submitted work. Dr. Lallas reports personal fees from Amgen, personal fees from Novartis, personal fees from BMS, grants and personal fees from Roche, personal fees from Sanofi, outside the submitted work. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche, personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Malvehy reports personal fees from Amgen, personal fees from MSD, grants from Novartis, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Almirall, personal fees from Sun Pharma, outside the submitted work. Dr. Middleton reports personal fees from Amgen, grants and personal fees from Roche, grants from Astrazeneca, grants and personal fees from GSK, personal fees and other from Novartis, other from Millennium, personal fees, non-financial support and other from Immunocore, personal fees and other from BMS, personal fees and other from Eisai, other from Pfizer, personal fees, non-financial support and other from Merck/MSD, personal fees and other from Rigontec (acquired by MSD), other from Regeneron, personal fees from BiolineRx, personal fees and other from Array Biopharma (now Pfizer), non-financial support and other from Replimune, outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Pellacani reports personal fees from Novartis, personal fees from Sanofi, grants from Novartis, instruments from 3 Gen, Vidix, Fotofinder and MAVIG GmbH, outside the submitted work. Dr. Saiag reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from NeraCare, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Sanofi, personal fees from Pierre Fabre/array, outside the submitted work. Dr. Stratigos reports personal fees and/or research support from Novartis, Roche, BMS, Abbvie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports personal fees from Difa Cooper, personal fees from MSD, personal fees from Novartis, grants and personal fees from Roche, personal fees from Sanofi, personal fees from Almirall Hermal, personal fees from Mylan, personal fees from Sunpharma, outside the submitted work. Dr. Eggermont reports personal fees from Biocad, Biovent, BMS, CatalYm, Ellipses, GSK, Incyte, IO Biotech, ISA Pharmaceuticals, Merck GmbH, MSD, Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SkylineDx, Stellas, other from RiverD, SkylineDx, Theranovir, all outside the submitted work., (Copyright © 2019. Published by Elsevier Ltd.)

A unique collaboration of multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with 1- to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumour thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team ("Tumor Board"). Adjuvant therapies in stage III/IV patients are primarily anti-PD-1, independent of mutational status, or dabrafenib plus trametinib for BRAF-mutant patients. In distant metastasis, either resected or not, systemic treatment is indicated. For first-line treatment, particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In particular scenarios for patients with stage IV melanoma and a BRAF-V600 E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harbouring a BRAF-V600 E/K mutation, this therapy shall be offered in second-line. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future., Competing Interests: Conflict of interest statement C.G. reports receiving personal fees from Amgen, Pierre Fabre, Philogen and MSD; and reports receiving grants and personal fees from Novartis, NeraCare, BMS, Roche and Sanofi, outside the submitted work. T.A. reports receiving personal fees and other grants from BMS, Novartis, Pierre Fabre, Neracare and Sanofi, outside the submitted work. K.P. reports receiving personal fees from Novartis, Roche, Sanofi, Lilly, Leopharma, Pierre Fabre, Almirall and Celgene, outside the submitted work. A.H. reports receiving grants and personal fees from Amgen, BMS, MerckSerono, MSD / Merck, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme, and Novartis Pharma; receiving personal fees from OncoSec and Sun Pharma, outside the submitted work. P.A. reports receiving personal fees from Amgen, MSD, Novartis, BMS and Roche, outside the submitted work. L.B. reports receiving grants from BMS, during the conduct of the study; personal fees from BMS, Novartis, MerckMSD, Roche, Incyte, Bayer, outside the submitted work. V.B. reports receiving personal fees from Novartis and MerckMSD, outside the submitted work. V.d.M. reports receiving personal fees from MSD, BMS and Sanofi; grants and personal fees from ABVIE; grants from Jansen, outside the submitted work. B.M. reports grants and personal fees from BMS, Roche, Fabre and Sanofi; personal fees from MSD, outside the submitted work. M.C.F. reports receiving grants and personal fees from Almirall, Leo Pharma, Novartis, Sanofi, Abbvie and Galderma; personal fees from Janssen, Lilly, UCB, Celgene, Pierre Fabre, Mylan, Medac Pharma, Roche, Sun Pharma, outside the submitted work. J.J.G. reports receiving personal fees from Amgen, MSD, Novartis, BMS, Roche, Pierre fabre, MercK / Pfizer, outside the submitted work. C.H. reports receiving personal fees from Amgen, MSD, Novartis, Incyte, BMS, Pierre Fabre, Roche, Sanofi, outside the submitted work. R.K. reports receiving grants and personal fees from Novartis and Roche; and grants from AbbVie, Amgen, Bionteck, BMS, Celgene, Galderma, Janssen, Leo, Lilly, Merck, MSD, Pierre Fabre, Regeneron and Wyeth, outside the submitted work. A.L. reports personal fees from Amgen, Novartis, BMS and ,Sanofi grants and personal fees from Roche, outside the submitted work. C.L. reports receiving grants and personal fees from Bristol-Myers Squibb and Roche; personal fees from MSD, Novartis, Amgen, Avantis Medical Systems, Pierre Fabre, Pfizer, Incyte, outside the submitted work. J.M. reports personal fees from Amgen, personal fees from MSD, grants from Novartis, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Almirall, personal fees from Sun Pharma, outside the submitted work. M.M. reports receiving personal fees from Amgen and BiolineRx; grants and personal fees from Roche and GSK; grants from Astrazeneca; personal fees and other from Novartis, Eisai, Array Biopharma (now Pfizer), Rigontec (acquired by MSD), and BMS; other from Millennium, RegeneronPfizer; personal fees, non-financial support and other from Immunocore, Replimun and Merck / MSD, outside the submitted work. D.M-.R. has nothing to disclose. G.P. reports receiving personal fees from Novartis, personal fees from Sanofi, grants from Novartis, instruments from 3Gen, Vidix, Fotofinder and MAVIG GmbH, outside the submitted work. P.S. reports receiving personal fees from Amgen, MSD and Pierre Fabre / array; grants and personal fees from Novartis, NeraCare, BMS, Roche, and Sanofi, outside the submitted work. A.J.S. reports personal fees and/or research support from Novartis, Roche, BMS, Abbvie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. Dr. Vieira has nothing to disclose. I.Z. reports receiving personal fees from Difa Cooper, MSD, Sanofi, Almirall Hermal, Novartis, Mylan and Sunpharma; grants and personal fees from Roche, outside the submitted work. A.M.M.E. reports receiving personal fees from Biocad, Biovent, BMS, CatalYm, Ellipses, GSK, Incyte, IO Biotech, ISA Pharmaceuticals, MerckGmbH, MSD, Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SkylineDx, Stellas; other from RiverD, SkylineDx, Theranovir, all outside the submitted work., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate whether a microelectromechanical system (MEMS) inertial sensor module is as accurate as fiber-optic gyroscopes when classifying subjects as normal for clinical stance and gait balance tasks., Methods: Data of ten healthy subjects were recorded simultaneously with a fiber-optic gyroscope (FOG) system of SwayStar™ and a MEMS sensor system incorporated in the Valedo® system. Data from a sequence of clinical balance tasks with different angle and angular velocity ranges were assessed. Paired t -tests were performed to determine significant differences between measurement systems. Cohen's kappa test was used to determine the classification of normal balance control between the two sensor systems when comparing the results to a reference database recorded with the FOG system. Potential cross-talk errors in roll and pitch angles when neglecting yaw axis rotations were evaluated by comparing 2D FOG and 3D MEMS recordings., Results: Statistically significant ( α =0.05) differences were found in some balance tasks, for example, "walking eight tandem steps" and various angular measures ( p < 0.03). However, these differences were within a few percent (<2.7%) of the reference values. Tasks with high dynamic velocity ranges showed significant differences ( p =0.002) between 2D FOG and 3D MEMS roll angles but no difference between 2D FOG and 2D MEMS roll angles. An almost perfect agreement could be obtained for both 2D FOG and 2D MEMS ( κ =0.97) and 2D FOG and 3D MEMS measures ( κ =0.87) when comparing measurements of all subjects and tasks., Conclusion: MEMS motion sensors can be used for assessing balance during clinical stance and gait tasks. MEMS provides measurements comparable to values obtained with a highly accurate FOG. When assessing pitch and roll trunk sway measures without accounting for the effect of yaw, it is recommended to use angle and angular velocity measures for stance, and only angular velocity measures for gait because roll and pitch velocity measurements are not influenced by yaw rotations, and angle errors are low for stance., Competing Interests: D. Roetenberg and C. Höller are employees of Hocoma AG producing the Valedo inertial sensors used in this study. J. H. J. Allum is a consultant for the company Balance International Innovation GmbH producing the SwayStar equipment used in this study., (Copyright © 2019 Daniel Roetenberg et al.)