Successful full clinical remission of bullous pemphigoid with intravenous pulse methylprednisolone and cyclophosphamide: a case report

We report a case of a 73 year old man with generalized bullous pemphigoid (BP). Oral steroid therapy was contr-indicated due to his personal medical history. The patient was treated with intravenous methylprednisolone pulse therapy (I.M.P.T.) followed by oral cyclophosphamide with satisfactory results. The therapeutic challenges of BP are being discussed with emphasis given on intravenous methylprednisolone pulse therap

Psoriasis and Skin Comorbidities

Psoriasis is a heterogeneous skin disease with many clinical presentations in patients with different medical backgrounds. Medical specialties such as rheumatology, pathology, and cardiology focus lately on the systemic inflammation nature of the psoriatic disease. From the Dermatologist’s point of view, the revolution of therapeutic spectrum in many autoimmune skin diseases, as well as the progression noted in physiopathological mechanism, the skin comorbidities became an important issue regarding therapeutic choice

Structured Expert Consensus on Actinic Keratosis:Treatment Algorithm Focusing on Daylight PDT

BACKGROUND: A practical and up-to-date consensus among experts is paramount to further improve patient care in actinic keratosis (AK). OBJECTIVES: To develop a structured consensus statement on the diagnosis, classification, and practical management of AK based on up-to-date information. METHODS: A systematic review of AK clinical guidelines was conducted. This informed the preparation of a 3-round Delphi procedure followed by a consensus meeting, which combined the opinions of 16 clinical experts from 13 countries, to construct a structured consensus statement and a treatment algorithm positioning daylight photodynamic therapy (dl-PDT) among other AK treatment options. RESULTS: The systematic review found deficiencies in current guidelines with respect to new AK treatments such as ingenol mebutate and dl-PDT. The Delphi panel established consensus statements across definition, diagnosis, classification, and management of AK. While the diagnosis of AK essentially rests on the nature of lesions, treatment decisions are based on several clinical and nonclinical patient factors and diverse environmental attributes. Participants agreed on ranked treatment preferences for the management of AK and on classifying AK in 3 clinical situations: isolated AK lesions requiring lesion-directed treatment, multiple lesions within a small field, and multiple lesions within a large field, both requiring specific treatment approaches. Different AK treatment options were discussed for each clinical situation. CONCLUSIONS: The results provide practical recommendations for the treatment of AK, which are readily transferable to clinical practice, and incorporate the physician's clinical judgement. The structured consensus statement positioned dl-PDT as a valuable option for patients with multiple AKs in small or large fields

Dermoscopic hemorrhagic dots: an early predictor of response of psoriasis to biologic agents

17siBACKGROUND: Biologic agents are routinely used in the treatment of severe psoriasis. The evaluation of treatment response is mainly based on the physician's global clinical assessment. OBJECTIVE: To investigate whether dermoscopy might enhance the assessment of response of psoriasis to treatment with biologic agents. METHODS: Patients with severe psoriasis scheduled to receive a biologic agent were enrolled in the study. A target lesion from each patient was clinically and dermoscopically documented at baseline and after one, two and six months. The clinical response was evaluated by the recruiting clinicians at all visits, while dermoscopic images were evaluated by two independent investigators, blinded to the clinical information. Chi Square test was used for cross-tabulation comparisons, while odds ratios, 95% confidence intervals and p values were calculated using univariate logistic regression. RESULTS: Overall, there was a significant correlation between clinical response and vessel distribution at all time points: a regular vessel distribution correlated with no response, a clustered distribution with partial response, and the dermoscopic absence of vessels with complete response. The presence of dermoscopic hemorrhagic dots was a potent predictor of favorable clinical response at the subsequent visit at all time points. Among lesions initially clinically responding and later recurring, 87.5% displayed dermoscopic dotted vessels despite the macroscopic remission. CONCLUSION: Dermoscopy might be a useful additional tool for evaluating the response of psoriatic patients to biologic agents. Hemorrhagic dots represent an early predictor of clinical response, while the persistence or reappearance of dotted vessels might predict clinical persistence or recurrence, respectively.openopenLallas, Aimilios; Argenziano, Giuseppe; Zalaudek, Iris; Apalla, Zoe; Ardigo, Marco; Chellini, Patricia; Cordeiro, Natalia; Guimaraes, Mariana; Kyrgidis, Athanassios; Lazaridou, Elizabeth; Longo, Caterina; Moscarella, Elvira; Papadimitriou, Ilias; Pellacani, Giovanni; Sotiriou, Elena; Vakirlis, Efstratios; Ioannides, DimitriosLallas, Aimilios; Argenziano, Giuseppe; Zalaudek, Iris; Apalla, Zoe; Ardigo, Marco; Chellini, Patricia; Cordeiro, Natalia; Guimaraes, Mariana; Kyrgidis, Athanassios; Lazaridou, Elizabeth; Longo, Caterina; Moscarella, Elvira; Papadimitriou, Ilias; Pellacani, Giovanni; Sotiriou, Elena; Vakirlis, Efstratios; Ioannides, Dimitrio

International study on inter-reader variability for circulating tumor cells in breast cancer

Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement.Methods: CellSearch® images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (κ) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test.Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median κ of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and ≥3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median κ of 0.74 (range 0.25 to 0.90).Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required

Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Mutational analysis of the <it>KRAS </it>gene has recently been established as a complementary <it>in vitro </it>diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of <it>KRAS </it>might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although <it>KRAS </it>is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of <it>KRAS </it>in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.</p> <p>Methods</p> <p>Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. <it>KRAS </it>mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type <it>KRAS </it>or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.</p> <p>Results</p> <p>We found no evidence of <it>KRAS </it>oncogenic mutations in all analyzed tumors.</p> <p>Conclusions</p> <p>This study indicates that <it>KRAS </it>mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.</p

Processed pseudogenes acquired somatically during cancer development

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5′ truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context

The tale of TILs in breast cancer : a report from the International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed deathligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.The National Health and Medical Research Council of Australia; the Cure; the Royal Australasian College of Physicians; the NIH/NCI ; the National Breast Cancer Foundation of Australia Endowed Chair; the Breast Cancer Research Foundation, New York and the Breast Cancer Research Foundation (BCRF).www.nature.com/npjbcanceram2022Immunolog

Black holes, gravitational waves and fundamental physics: a roadmap

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'