Effect of awake prone position on diaphragmatic thickening fraction in patients assisted by noninvasive ventilation for hypoxemic acute respiratory failure related to novel coronavirus disease

Background: Awake prone position is an emerging rescue therapy applied in patients undergoing noninvasive ventilation (NIV) for acute hypoxemic respiratory failure (ARF) related to novel coronavirus disease (COVID-19). Although applied to stabilize respiratory status, in awake patients, the application of prone position may reduce comfort with a consequent increase in the workload imposed on respiratory muscles. Thus, we primarily ascertained the effect of awake prone position on diaphragmatic thickening fraction, assessed through ultrasound, in COVID-19 patients undergoing NIV. Methods: We enrolled all COVID-19 adult critically ill patients, admitted to intensive care unit (ICU) for hypoxemic ARF and undergoing NIV, deserving of awake prone positioning as a rescue therapy. Exclusion criteria were pregnancy and any contraindication to awake prone position and NIV. On ICU admission, after NIV onset, in supine position, and at 1\ua0h following awake prone position application, diaphragmatic thickening fraction was obtained on the right side. Across all the study phases, NIV was maintained with the same setting present at study entry. Vital signs were monitored throughout the entire study period. Comfort was assessed through numerical rating scale (0 the worst comfort and 10 the highest comfort level). Data were presented in median and 25th\u201375th percentile range. Results: From February to May 2021, 20 patients were enrolled and finally analyzed. Despite peripheral oxygen saturation improvement [96 (94\u201397)% supine vs 98 (96\u201399)% prone, p = 0.008], turning to prone position induced a worsening in comfort score from 7.0 (6.0\u20138.0) to 6.0 (5.0\u20137.0) (p = 0.012) and an increase in diaphragmatic thickening fraction from 33.3 (25.7\u201340.5)% to 41.5 (29.8\u201350.0)% (p = 0.025). Conclusions: In our COVID-19 patients assisted by NIV in ICU, the application of awake prone position improved the oxygenation at the expense of a greater diaphragmatic thickening fraction compared to supine position. Trial registration ClinicalTrials.gov, number NCT04904731. Registered on 05/25/2021, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04904731

Metastatic eccrine porocarcinoma: report of a case and review of the literature

Eccrine porocarcinoma (EPC) is a rare type of skin cancer arising from the intraepidermal portion of eccrine sweat glands or acrosyringium, representing 0.005-0.01% of all cutaneous tumors. About 20% of EPC will recur and about 20% will metastasize to regional lymph nodes. There is a mortality rate of 67% in patients with lymph node metastases. Although rare, the occurrence of distant metastases has been reported

Peripheral T-cell Lymphoma with Cyclin D1 overexpression: a case report.

Abstract Peripheral T-cell lymphomas not otherwise specified are generally considered aggressive non-Hodgkin lymphomas, because of poor natural outcome and response to therapy. They show a complex karyotype without any specific genetic hallmark. We report a case of peripheral T-cell lymphoma not otherwise specified with heterogeneous nuclear Cyclin D1 immunohistochemical overexpression, due to gene copy gain, a phenomenon similar to that observed in Mantle Cell Lymphoma characterized by t(11;14)(q13;q32). In this case report we underline the diagnostic pitfall rapresented by Cyclin D1 immunoistochemical overexpression in a T-cell lymphoma. Several pitfalls could lead to misinterpretation of diagnosis, therefore, we underlined the need to integrate the classical histology and immunohistochemistry with molecular tests as clonality or Fluorescence in situ hybridization. Virtual slide The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1117747619703769</p

Increased HOX C13 expression in metastatic melanoma progression.

Abstract Background The process of malignant transformation, progression and metastasis of melanoma is not completely understood. Recently, the microarray technology has been used to survey transcriptional differences that might provide insight into the metastatic process, but the validation of changing gene expression during metastatic transition period is poorly investigated. A large body of literature has been produced on the role of the HOX genes network in tumour evolution, suggesting the involvement of HOX genes in several types of human cancers. Deregulated paralogous group 13 HOX genes expression has been detected in melanoma, cervical cancer and odonthogenic tumors. Among these, Hox C13 is also involved in the expression control of the human keratin genes hHa5 and hHa2, and recently it was identified as a member of human DNA replication complexes. Methods In this study, to investigate HOX C13 expression in melanoma progression, we have compared its expression pattern between naevi, primary melanoma and metastasis. In addition HOXC13 profile pattern of expression has been evaluated in melanoma cell lines. Results Our results show the strong and progressive HOX C13 overexpression in metastatic melanoma tissues and cytological samples compared to nevi and primary melanoma tissues and cells. Conclusions The data presentated in the paper suggest a possible role of HOX C13 in metastatic melanoma switch.</p

Peritumoral Immune Infiltrate as a Prognostic Biomarker in Thin Melanoma

Thin melanomas are tumors less than 1&nbsp;mm thick according to Breslow classification. Their prognosis is in most cases excellent. However, a small subset of these tumors relapses. These clinical findings emphasize the need of novel prognostic biomarkers to identify this subset of tumors. Characterization of tumor immune microenvironment (TIME) is currently investigated as a prognostic and predictive biomarker for cancer immunotherapy in several solid tumors including melanoma. Here, taking into account the limited availability of tumor tissues, by characterizing some of the characteristics of TIME such as number of infiltrating lymphocytes, HLA class I antigen and PD-L1 expression, we show that number of infiltrating CD8+ and FOXP3+ T cells as well as CD8+/FOXP3+ T cell ratio can represent a useful prognostic biomarker in thin melanoma. Although further investigations in a larger patient cohort are needed, these findings have potential clinical significance since they can be used to define subgroups of thin melanoma patients who have a worse prognosis and might need different treatment modalities

The ratio of grzb+ − foxp3+ over cd3+ t cells as a potential predictor of response to nivolumab in patients with metastatic melanoma

The understanding of the molecular pathways involved in the dynamic modulation of the tumor microenvironment (TME) has led to the development of innovative treatments for advanced melanoma, including immune checkpoint blockade therapies. These approaches have revolutionized the treatment of melanoma, but are not effective in all patients, resulting in responder and non-responder populations. Physical interactions among immune cells, tumor cells and all the other components of the TME (i.e., cancer-associated fibroblasts, keratinocytes, adipocytes, extracellular matrix, etc.) are essential for effective antitumor immunotherapy, suggesting the need to define an immune score model which can help to predict an efficient immunotherapeutic response. In this study, we performed a multiplex immunostaining of CD3, FOXP3 and GRZB on both primary and unmatched in-transit metastatic melanoma lesions and defined a novel ratio between different lymphocyte subpopulations, demonstrating its potential prognostic role for cancer immunotherapy. The application of the suggested ratio can be useful for the stratification of melanoma patients that may or may not benefit from anti-PD-1 treatment