Primary dermal melanoma in a patient with a history of multiple malignancies: a case report with molecular characterization

Introduction: Primary dermal melanoma (PDM) is a recently described clinical entity accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or subcutaneous tissue, and it shows no connections with the overlying epidermis. The differential diagnosis is principally made along with that of metastatic cutaneous melanoma. Case Report: A 72-year-old Caucasian woman with a history of multiple cancers (metachro-nous bilateral breast cancer, meningioma, clear cell renal cell carcinoma, uterine fibromatosis and intestinal adenomatous polyposis), came to our attention with a nodular lesion on her back. After removal of the lesion, the histology report indicated malignant PDM or metastatic malignant melanoma. The clinical and instrumental evaluation of the patient did not reveal any other primary tumour, suggesting the primitive nature of the lesion. The absence of an epithelial component argued for a histological diagnosis of PDM. Subsequently, the patient underwent a wide surgical excision with sentinel node biopsy, which was positive for metastatic melanoma. Finally, the mutational status was studied in the main genes that regulate proliferation, apoptosis and cellular senescence. No pathogenetic mutations in CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed. This suggests that alternative pathways and low-frequency alterations may be involved. Conclusions: The differential diagnosis between PDM and isolated metastatic melanoma depends on the negativity of imaging studies and clinical findings for other primary lesions. This distinction is important because 5-year survival rates in such cases are higher than in metastatic cases (80– 100 vs. 5–20%, respectively)

Thromboembolic Events in Patients with Influenza: A Scoping Review

Introduction: Influenza is an acute respiratory infection that usually causes a short-term and self-limiting illness. However, in high-risk populations, this can lead to several complications, with an increase in mortality. Aside from the well-known extrapulmonary complications, several studies have investigated the relationship between influenza and acute cardio and cerebrovascular events. Reviews of the thromboembolic complications associated with influenza are lacking. Objectives: the study aims to conduct a scoping review to analyze the epidemiological and clinical characteristics of patients suffering from influenza and thromboembolic complications. Materials and methods: A computerized search of historical published cases using PubMed and the terms "influenza" or "flu" and "thrombosis", "embolism", "thromboembolism", "stroke", or "infarct" for the last twenty-five years was conducted. Only articles reporting detailed data on patients with thromboembolic complications of laboratory-confirmed influenza were considered eligible for inclusion in the scoping review. Results: Fifty-eight cases with laboratory documented influenza A or B and a related intravascular thrombosis were retrieved. Their characteristics were analyzed along with those of a patient who motivated our search. The localizations of thromboembolic events were pulmonary embolism 21/58 (36.2%), DVT 12/58 (20.6%), DVT and pulmonary embolism 3/58 (5.1%), acute ischemic stroke 11/58 (18.9%), arterial thrombosis 4/58 (6.8%), and acute myocardial infarction 5/58 (8.6%). Discussion: Our findings are important in clarifying which thromboembolic complications are more frequent in adults and children with influenza. Symptoms of pulmonary embolism and influenza can be very similar, so a careful clinical evaluation is required for proper patient management, possible instrumental deepening, and appropriate pharmacological interventions, especially for patients with respiratory failure

A novel and inexpensive method for measuring volcanic plume water fluxes at high temporal resolution

© 2017 by the authors.Water vapour (H2O) is the dominant species in volcanic gas plumes. Therefore,measurements of H2O fluxes could provide valuable constraints on subsurface degassing and magmatic processes. However, due to the large and variable concentration of this species in the background atmosphere, little attention has been devoted to monitoring the emission rates of this species from volcanoes. Instead, the focus has been placed on remote measurements of SO2, which is present in far lower abundances in plumes, and therefore provides poorer single flux proxies for overall degassing conditions. Here, we present a new technique for the measurement of H2O emissions at degassing volcanoes at high temporal resolution (≈1 Hz), via remote sensing with low cost digital cameras. This approach is analogous to the use of dual band ultraviolet (UV) cameras for measurements of volcanic SO2 release, but is focused on near infrared absorption by H2O. We report on the field deployment of these devices on La Fossa crater, Vulcano Island, and the North East Crater of Mt. Etna, during which in-plume calibration was performed using a humidity sensor, resulting in estimated mean H2O fluxes of ≈15 kg·s-1 and ≈34 kg·s-1, respectively, in accordance with previously reported literature values. By combining the Etna data with parallel UV camera and Multi-GAS observations, we also derived, for the first time, a combined record of 1 Hz gas fluxes for the three most abundant volcanic gas species: H2O, CO2, and SO2. Spectral analysis of the Etna data revealed oscillations in the passive emissions of all three species, with periods spanning ≈40-175 s, and a strong degree of correlation between the periodicity manifested in the SO2 and H2O data, potentially related to the similar exsolution depths of these two gases. In contrast, there was a poorer linkage between oscillations in these species and those of CO2, possibly due to the deeper exsolution of carbon dioxide, giving rise to distinct periodic degassing behaviour

MicroRNAs as Molecular Switches in Macrophage Activation

The efficacy of macrophage- mediated inflammatory response relies on the coordinated expression of key factors, which expression is finely regulated at both transcriptional and post-transcriptional level. Several studies have provided compelling evidence that microRNAs play pivotal roles in modulating macrophage activation, polarization, tissue infiltration, and resolution of inflammation. In this review, we highlight the essential molecular mechanisms underlying the different phases of inflammation that are targeted by microRNAs to inhibit or accelerate restoration to tissue integrity and homeostasis. We further review the impact of microRNA-dependent regulation of tumor-associated macrophages and the relative implication for tumor biology

A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia

Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed

DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy

Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. In contrast to wild-type controls, Dusp5 null mice infused with ANG II developed PH and right ventricular (RV) hypertrophy. PH in Dusp5 null mice was associated with thickening of the medial layer of small PAs, suggesting an in vivo role for DUSP5 as a negative regulator of ANG II-dependent SMC proliferation. Consistent with this, overexpression of DUSP5 blocked ANG II-mediated proliferation of cultured human pulmonary artery SMCs (hPASMCs) derived from patients with idiopathic PH or from failed donor controls. Collectively, the data support a role for DUSP5 as a feedback inhibitor of ANG II-mediated ERK signaling and PASMC proliferation and suggest that disruption of this circuit leads to adverse cardiopulmonary remodeling. NEW & NOTEWORTHY Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism