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Activated phosphoinositide 3-kinase (PI3Kδ) Syndrome (APDS) is an inborn error of immunity (IEI) with a variable clinical presentation, characterized by infection susceptibility and immune dysregulation that may overlaps with other Primary Immune Regulatory Disorders (PIRDs). The rarity of the disease, its recent discovery, and the multiform /multifaced clinical presentation make it difficult to establish a correct diagnosis, especially at an early stage. As a result, the true prevalence of the pathology remains unknown. There is no treatment protocol for APDS, and drug therapy is primarily focused on treating symptoms. The most common therapies include immunoglobulin replacement therapy, antimicrobial prophylaxis, and immunosuppressive drugs. Hematopoietic stem cell transplantation (HSCT) has been used in some cases, but the risk-benefit balance remains unclear. With the upcoming introduction of specific medications, such as selective inhibitors for PI3Kδ, clinicians are shifting their attention towards target therapy. This review provides a comprehensive overview of APDS with a focus on diagnostic and treatments procedures available. This review may be useful in implementing strategies for a more efficient patients' management and therapeutic interventions. Main Text. [ABSTRACT FROM AUTHOR]

In Italy, procedures based upon concessions to the defendant in exchange for cooperation with the prosecution were ?rst established in 1981, but were organically laid out only in 1988, when an adversarial Code of Criminal Procedure came into force. Little of the original versions of the ‘summary proceeding’ and ‘application of a penalty upon request’ (the Italian equivalent of plea-bargaining) has survived the swinging reforms of the 1990s. Such reforms, driven at times by concerns of public interest and, at other times, by the endorsement of the fundamental rights of the accused, have culminated in the 1999 fair trial amendment to the Constitution. Negotiated justice also received constitutional legitimacy, albeit in an acutely controversial form. Despite the acknowledged indispensability of consensual means of con?ict resolution for reasons of procedural expediency, Italian commentators still struggle to reconcile the very concept of negotiated justice with engrained constitutional principles. Negotiations in Italian law can now be pro?tably grouped into two categories: negotiations ‘on the evidence’ upon which the court may base a judgment, and negotiations ‘on the sentence’ that the court may serve on the defendant. [ABSTRACT FROM PUBLISHER]

Background: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network., Methods: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method., Results: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction., Conclusions: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup., (© 2020 American Cancer Society.)

Background: RENASCENT is a prospective, multi-center first-in-human clinical study to evaluate the clinical performance of the novel sirolimus-eluting 150-μm strut thickness FORTITUDE® BRS for percutaneous coronary intervention of single de novo coronary lesions., Methods: FORTITUDE® BRS was tested in a prospective study in Italy and Colombia. Study objectives were in-scaffold angiographic late lumen loss (LLL) measured by quantitative coronary angiography and target vessel failure (TVF) defined as the composite rate of cardiac death, target vessel myocardial infarction or ischemia driven target lesion revascularization (TLR) at 9- and 24-months with clinical results up to 36-months., Results: A total of 63 patients were enrolled. All patients underwent lesion pre-dilatation and 22 patients (34.9%) underwent post-dilatation. Clinical device and procedural success was 98.4% (62/63 patients) and 96.8% (61/63 patients) respectively. At 9-months, TVF occurred in 3/61 (4.9%) of the patients including 2 peri-procedural MI and one ischemia-driven TLR. Between 9- to 24-months, ischemia-driven TLR occurred in 3 additional patients (4.9%) including 1 patient who presented with very late ST after stopping all medications. There were no further TVF between 24- and 36-months., Conclusions: In this multi-center prospective study, the FORTITUDE® BRS was shown to be safe and effective in the treatment of single coronary lesions with low levels of TVF and LLL at 9- and 24-months. It was shown to be clinically safe upto 36-months follow-up., Competing Interests: Declaration of Competing Interest Alaide Chieffo, MD: Proctorship fees from Amaranth Medical Inc. Juan F. Granada, MD: Scientific advisor and equity shareholder Amaranth Medical Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020. Published by Elsevier B.V.)

It is a well-recognized fact that implementing new guidelines in clinical practice may be difficult; therefore the Italian Society for Organ and Tissue Transplantation (SITO) set out to define practical immunosuppression tools for the management of liver transplantation patients. In 2017, an Italian Working Group of liver transplant experts and hepatologists issued a set of consensus statements along with evidence-based recommendations on the use of everolimus after liver transplantation. This article presents the evidence- and consensus-based algorithms developed within the Italian Working Group, which are aimed towards guiding clinicians in the selection of immunosuppressive regimens for the management of adult liver transplant recipients in real-life practice. The liver transplant recipient population, typically managed in clinical practice, was divided into the following categories: (1) standard patients; (2) critically ill patients; (3) patients with a specific etiology; (4) patients with hepatocellular carcinoma; (5) and patients with de novo malignancies. The algorithms are divided into two parts, according to the time from transplantation (0-3 months and > 3 months) and are discussed here along with relevant supporting literature, when available. Ultimately, it is hoped that the evidence- and consensus-based algorithms developed within the Italian Working Group, and presented here, contribute to simplify, personalize, and optimize immunosuppression of liver transplantation recipients in clinical practice.

The article announces that the region of Tuscany has agreed to join the annual award for the best paper published in the periodical "Journal of International Criminal Justice" by a young scholar. It notes that the contribution to the prize is part of an initiative to honor Giorgio La Pira on his centennial birth anniversary. It adds that the award will be referred to as the Premio Regione Toscana Giorgio La Pira which will be given during the annual public ceremony in Florence, Italy on January 9, 2005. Moreover, it presents a brief overview on La Pira's life and works.