Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and ...metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors.
Spontaneous bacterial peritonitis is a complication of ascitic patients with end-stage liver disease(ESLD); spontaneous fungal peritonitis(SFP) is a complication of ESLD less known and described. ...ESLD is associated to immunodepression and the resulting increased susceptibility to infections. Recent perspectives of the management of the critically ill patient with ESLD do not specify the rate of isolation of fungi in critically ill patients,not even the antifungals used for the prophylaxis,neither optimal treatment. We reviewed,in order to focus the epidemiology,characteristics,and,considering the high mortality rate of SFP,the use of optimal empirical antifungal therapy the current literature.
Blockchain technology is a distributed ledger that guarantees the immutability of data and asset tracking. Its characteristics can result in an improvement to traditional agri-food Supply Chains. ...Blockchain-based traceability systems let producers improve their visibility and consumers trust the products they buy and where they come from. Actual literature lacks an exhaustive analysis of the benefits and drawbacks of Blockchain applied to the agri-food domain. This paper aims to overcome this issue: to understand the state-of-the-art related to the application of Blockchain in the agri-food sector, we screened 183 papers and performed a literature review answering six Research Questions. The work takes into consideration the advantages and disadvantages of implementing such paradigm, with an analysis on the role of industries. The main findings are related to research directions: they regard the lack of training both for industries and stakeholders, the involvement of additional technologies (i.e., Big Data, Edge Computing), and the absence of supporting tools for developers.
The current lack of reference datasets of road traffic mobility for network simulation jeopardizes the reliability and reproducibility of vehicular networking research. We contribute to the ongoing ...effort to develop dependable and publicly available mobility traces through the following: (1) implementing an original version of the Simulation of Urban Mobility (SUMO) road network conversion tool that allows importing OpenStreetMap (OSM) data in a neat automated fashion; (2) generating an original dataset of road traffic in Bologna, Italy; and (3) providing a novel validation methodology that builds on open data provided by navigation service, which we leverage to assess the quality of the proposed Bologna dataset. These three contributions are expected to benefit the whole research community, since they not only provide a new ready-to-use realistic dataset that can be input to network simulators but ease the generation and validation of further vehicular mobility traces for networking research as well.
Background
Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic ...Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document.
Methods
The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation.
Results
Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies.
Conclusions
Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.
Summary Background The current American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system does not have sufficient details to encompass the variety of ...soft-tissue sarcomas, and available prognostic methods need refinement. We aimed to develop and externally validate two prediction nomograms for overall survival and distant metastases in patients with soft-tissue sarcoma in their extremities. Methods Consecutive patients who had had an operation at the Istituto Nazionale Tumori (Milan, Italy), from Jan 1, 1994, to Dec 31, 2013, formed the development cohort. Three cohorts of patient data from the Institut Gustave Roussy (Villejuif, France; from Jan 1, 1996, to May 15, 2012), Mount Sinai Hospital (Toronto, ON, Canada; from Jan 1, 1994, to Dec 31, 2013), and the Royal Marsden Hospital (London, UK; from Jan 1, 2006, to Dec 31, 2013) formed the external validation cohorts. We developed the nomogram for overall survival using a Cox multivariable model, and a Fine and Gray multivariable model for the distant metastases nomogram. We applied a backward procedure for variables selection for both nomograms. We assessed nomogram model performance by examining overall accuracy (Brier score), calibration (calibration plots and Hosmer–Lemeshow calibration test), and discrimination (Harrell C index). We plotted decision curves to evaluate the clinical usefulness of the two nomograms. Findings 1452 patients were included in the development cohort, with 420 patients included in the French validation cohort, 1436 patients in the Canadian validation cohort, and 444 patients in the UK validation cohort. In the development cohort, 10-year overall survival was 72·9% (95% CI 70·2–75·7) and 10-year crude cumulative incidence of distant metastases was 25·0% (95% CI 22·7–27·5). For the overall survival nomogram, the variables selected applying a backward procedure in the multivariable Cox model (patient's age, tumour size, Fédération Française des Centres de Lutte Contre le Cancer FNCLCC grade, and histological subtype) had a significant effect on overall survival. The same variables, except for patient age, were selected for the distant metastases nomogram. In the development cohort, the Harrell C index for overall survival was 0·767 (95% CI 0·743–0·789) and for distant metastases was 0·759 (0·736–0·781). In the validation cohorts, the Harrell C index for overall survival and distant metastases were 0·698 (0·638–0·754) and 0·652 (0·605–0·699; French), 0·775 (0·754–0·796) and 0·744 (0·720–0·768; Canadian), and 0·762 (0·720–0·806) and 0·749 (0·707–0·791; UK). The two nomograms both performed well in terms of discrimination (ability to distinguish between patients who have had an event from those who have not) and calibration (accuracy of nomogram prediction) when applied to the validation cohorts. Interpretation Our nomograms are reliable prognostic methods that can be used to predict overall survival and distant metastases in patients after surgical resection of soft-tissue sarcoma of the extremities. These nomograms can be offered to clinicians to improve their abilities to assess patient prognosis, strengthen the prognosis-based decision making, enhance patient stratification, and inform patients in the clinic. Funding None.
Managing user mobility is historically one of the most critical issues in cellular radio access networks (RANs). That task will become an even greater challenge due to cellular users on board ...vehicles and networked cars that autonomously access Internet-based services, whose number is expected to grow dramatically in the next few years. There is thus a need to characterize RAN access from/by vehicles in a similar way to what has been done for traditional pedestrian access. In this paper, we propose a study of the macroscopic and microscopic features of pervasive vehicular access in a case-study large-scale urban environment in the presence of realistic data sets of the road traffic and RAN deployment. We find that pervasive vehicular access is characterized by unique temporal and spatial variability in the urban region, such that it may require a dedicated RAN capacity planning: The presence of stable vehicular access load patterns and mobility flows can help to that end. Moreover, we identify the theoretical distributions that best fit key metrics for RAN planning, i.e., the vehicular users' interarrival and residence times at cells, and discuss how their parameters vary over time and space.
To prospectively assess the behaviour of primary sporadic (not FAP associated) desmoid fibromatosis (DF) managed by active surveillance (AS).
This is an Italian prospective, multicenter, ...observational study (NCT02547831) including patients {greater than or equal to}16 years with primary sporadic DF at any site. Patients were assessed by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 . Primary end-point was progression-free survival (PFS) at 3 years. Treatment-free survival (TFS) was also analyzed. PFS and TFS were calculated by Kaplan-Meier plots and compared by log-rank test Cox proportional-hazard multivariable regression analyses were performed.
From 2013 to 2018 108 consecutive patients were included (82% female); median age was 39-yr; median size was 51 mm. CTNNB1 mutations were: T41A (50%); S45F (12%); other (19%); WT (19%). At 32.3-month median-FU, 42/108 (39%) showed RECIST progression. Spontaneous regression (SR) was initially observed in 27/108 (25%), while it followed dimensional progression in other 33/108 (31%). PFS at 36 months was 54.5% (95% CI, 44.9%-66.1%). Thirty-five/108 (32%) patients received active treatments, 18/108 (17%) after RECIST progression and 17/108 (15%) after symptomatic progression. TFS at 36 months was 65.9% (95% CI, 57.3%-75.9%). Larger tumor size and extremity location were associated to shorter TFS and a trend for S45F mutation was also observed (p=0.06), while none of the above variables was significantly associated to PFS.
In primary DF, AS can be proposed, since disease stabilization and SR frequently occur. However extra care should be taken for patients with tumors of larger size, extremity location and S45F mutation.
Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications ...that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions.
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