Local treatment with electrochemotherapy of superficial angiosarcomas: Efficacy and safety results from a multi-institutional retrospective study

Background: Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated. Methods: This multicenter retrospective analysis reviewed patients who underwent electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated. Results: Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n¼5), breast(n¼8), other skin sites (n¼3), and soft tissue (n¼3). Target lesions (n¼54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients). Conclusions: Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas

Correction of hypovitaminosis D improved global longitudinal strain earlier than left ventricular ejection fraction in cardiovascular older adults after orthopaedic surgery

Background Cardiovascular diseases and insufficient levels of vitamin D are risk factors for adverse surgical outcomes, and they are both commonly present among older adults undergoing orthopaedic surgery. Giving the cardiovascular effects of vitamin D, pre-operative diagnosis of hypovitaminosis D would be a valuable step for the implementation of supplementation protocols. We investigated if the normalization of serum 25 [OH] D could ameliorate cardiac performance of older adults suffering from cardiovascular diseases. Methods We enrolled 47 older adults scheduled for major orthopaedic surgery and suffering from hypovitaminosis D. Patients underwent 6-months calcifediol supplementation with a starting dose at first post-operative day of 50 \u3bcg/die in liquid preparation. Down-Titration to 20 \u3bcg/die at 3-months assessment was planned. Cardiac performance was evaluated by measuring left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) during pre-operative assessments and at 1-month, 3-months, 6-months follow-ups. Results Six months of calcifediol supplementation were associated with a significant improvement of both LVEF (+ 3.94%; 95% CI: -4.0789 to -0.8232; P < 0.01) and GLS (+ 18.56%; Z = -5.895; P < 0.0001). Conclusions Calcifediol supplementation normalized serum 25 [OH] D concentration after 1-month treatment. GLS offered better insights into myocardial contractile amelioration than LVEF, thus being useful for detecting earlier subclinical changes that may anticipate hemodynamic modifications

Management of patients with lower-risk myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis with abnormal blood cell development (dysplasia) leading to cytopenias and an increased risk for progression to acute myeloid leukemia (AML). Patients with MDS can generally be classified as lower- (LR-MDS) or higher-risk (HR-MDS). As treatment goals for patients with LR-MDS and those with HR-MDS differ significantly, appropriate diagnosis, classification, and follow-up are critical for correct disease management. In this review, we focus on the diagnosis, prognosis, and treatment options, as well as the prediction of the disease course and monitoring of treatment response in patients with LR-MDS. We discuss how next-generation sequencing, increasing knowledge on mechanisms of MDS pathogenesis, and novel therapies may change the current treatment landscape in LR-MDS and why structured assessments of responses, toxicities, and patient-reported outcomes should be incorporated into routine clinical practice

Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis.

The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. METHODS: A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. RESULTS: Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR. CONCLUSIONS: In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC

Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors

BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade 653, 7.8%) was lower in patients with tumors <2 cm (p 640.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs

Use of sonic tomography to detect and quantify wood decay in living trees.

Premise of the studyField methodology and image analysis protocols using acoustic tomography were developed and evaluated as a tool to estimate the amount of internal decay and damage of living trees, with special attention to tropical rainforest trees with irregular trunk shapes.Methods and resultsLiving trunks of a diversity of tree species in tropical rainforests in the Republic of Panama were scanned using an Argus Electronic PiCUS 3 Sonic Tomograph and evaluated for the amount and patterns of internal decay. A protocol using ImageJ analysis software was used to quantify the proportions of intact and compromised wood. The protocols provide replicable estimates of internal decay and cavities for trees of varying shapes, wood density, and bark thickness.ConclusionsSonic tomography, coupled with image analysis, provides an efficient, noninvasive approach to evaluate decay patterns and structural integrity of even irregularly shaped living trees

LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity.

Inflammasomes are cytosolic innate immune sensors of pathogen infection and cellular damage that induce caspase-1-mediated inflammation upon activation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and can be detrimental, such as in coronavirus disease (COVID-19). However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine-rich repeat (LRR) protein ribonuclease inhibitor (RNH1), which shares homology with LRRs of NLRP (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing) proteins, attenuates inflammasome activation. Deletion of RNH1 in macrophages increases interleukin (IL)-1β production and caspase-1 activation in response to inflammasome stimulation. Mechanistically, RNH1 decreases pro-IL-1β expression and induces proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and lipopolysaccharide (LPS)-induced endotoxemia, which are dependent on caspase-1, respectively, show increased neutrophil infiltration and lethality in Rnh1 &lt;sup&gt;-/-&lt;/sup&gt; mice compared with wild-type mice. Furthermore, RNH1 protein levels were negatively related with disease severity and inflammation in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity

La progettazione psicosociale nei progetti del Sistema di Accoglienza e Integrazione/SAIUn modello di intervento

The authors, psychologists, social workers, educators, care workers of the "Don Vincenzo Matrangolo" Association, aware that in the field of Reception and Inte-gration there is no shared methodology to define in detail the process of psychosocial planning, present the validation of an accurate and meticulous proposal in which they define the "phases, tools and timing" of a professional work that faces the complex emergency of migration

Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis

Cellular decision-making is mediated by a complex interplay of external stimuli with the intracellular environment, in particular transcription factor regulatory networks. Here we have determined the expression of a network of 18 key haematopoietic transcription factors in 597 single primary blood stem and progenitor cells isolated from mouse bone marrow. We demonstrate that different stem/progenitor populations are characterized by distinctive transcription factor expression states, and through comprehensive bioinformatic analysis reveal positively and negatively correlated transcription factor pairings, including previously unrecognized relationships between Gata2, Gfi1 and Gfi1b. Validation using transcriptional and transgenic assays confirmed direct regulatory interactions consistent with a regulatory triad in immature blood stem cells, where Gata2 may function to modulate cross-inhibition between Gfi1 and Gfi1b. Single-cell expression profiling therefore identifies network states and allows reconstruction of network hierarchies involved in controlling stem cell fate choices, and provides a blueprint for studying both normal development and human disease

Honey, a Gift from Nature to Health and Beauty: A Review

Benefits of honey are contributed by the composition of its elements such as glucose, fructose, glucose oxidase, vitamins and phenolic compounds. For health, honey can be used to treat wounds due to the antibacterial activity conferred by the hydrogen peroxide produced by glucose oxidase in honey. Anti-inflammatory, anti-oxidant, deodorizing and tissue regeneration activities in honey also help in the wound healing process. It can also be an alternative sweetener for diabetic patients to ensure compliance to a healthy diet. Moreover, honey exerts several effects such as lowering low density lipids and increasing high density lipids, thus reducing risk of atherosclerosis. In terms of beauty, honey can be used on skin and hair. It moisturizes skin through its natural humectant properties contributed by high contents of fructose and glucose. Honey treats acne on the skin due to its antibacterial activity, anti-inflammatory action and tissue repair. The hair can benefit from honey in such a way that the hair has abundance, and becomes easier to comb. However, there have not been as many studies regarding the use of honey in skin in comparison to its use for health. Therefore, future studies on honey could research its use, action and benefits in both cosmetics and dermatology