Italian Experience Research Articles

Article: DAC6: Some (potential) Incompatibility Profiles with Article 6 ATAD

From a comparative analysis of Article 6 Anti Tax Avoidance Directive (ATAD) and the Directive Administrative Cooperation (DAC)6, it would seem that the disclosure requirements of the latter are in accordance with the concept of tax avoidance (or ‘abuse of rights’) introduced by the general clause of Article 6 ATAD. Nevertheless, notwithstanding the consistency of the DAC6 with the general anti-abuse clause of the ATAD, at least two types of uncertainties appear to arise. The first concerns the consistency of the directive mentioned previously with the ultimate purpose of the anti-avoidance regulations (which is to exclusively prevent and counteract avoidance conduct). The second involves the compatibility of the disclosure requirements imposed by the directive with the general anti-abuse clauses currently in force in some European legal systems (for all, reference will be made to the Italian experience). The comparison outlined above would appear to demonstrate that the reporting obligations established by the DAC6 are overly broad and that they do not adequately take account of the ‘non-tax reasons’ that may justify the cross-border mechanism even for a transaction from which tax advantages may arise at the same time. ATAD, General Anti Avoidance Rule (GAAR), DAC-6, exchange of information, tax avoidance, Article 10-bis

Charmaine Lee (1949–2021)

Charmaine Lee (1949–2021) Wendy Pfeffer Charmaine Lee. Who was this scholar with an English name, based in Italy, producing edition after edition, writing in flawless Italian? Under what rock had she hidden, such that we had not met, not even crossed paths, at one conference or another over the years? When we did finally meet, I discovered a bubbly and warm individual, with much of a mother hen to her. She was friendly and forthcoming, happy to meet me. As she did for me, she must have done many times beforehand, opening her arms broadly. Her willingness to share her research and findings, not just in the form of publications and conference papers, but also as *.pdf's and attachments to emails, was remarkable. I would ask her a question about Jaufre and receive in return not only her thoughts and specific line numbers, but also illustrations from the manuscripts to make her point. She used her British upbringing and her Italian experience to overcome most of the vicissitudes of life. These were a very winning combination when wielded by Charmaine. I remember most distinctly trying to figure out with her how we could get a copy of Tenso into her hands on a regular basis. Mail the copy to England, so she could pick it up when she visited relatives? Try using her home address, to avoid things getting lost in the university mail room? Send her copy to some colleague somewhere—anywhere outside of Italy—who could then convey the issue to Charmaine? The woes of Tenso and the Italian postal system are decades-old; I joke that somewhere in the depths of the system sits an Italian postal worker with a remarkable interest in Occitan, as issue after issue of Tenso disappears into that deep. Somehow, though, Charmaine and I did figure something out. It was long overdue when I asked Charmaine to serve on the editorial board of Tenso. She was an obvious choice, because of her expertise and because of her ability to negotiate the multiple languages of the journal. A few recent Tenso authors were able to benefit from the insights and suggestions of this blind reader. I regret that she joined the Tenso team late and was unable to serve long. [End Page 267] One of her very last public appearances was as a panelist in a session organized by the Société Guilhem IX in Kalamazoo, Michigan (May 2021). Thanks to Zoom, Charmaine was able to participate and share with us some of the adventures of being on the production set as a multi-episode television show, Eco's Romance of the Rose no less, is being created. I did not know Charmaine as well as many, certainly not as well as her Italian colleagues and students, nor her collaborators. But I take her loss as personally as they do and feel honored to have known her. [End Page 268] Wendy Pfeffer University of Louisville University of Pennsylvania Copyright © 2023 Société Guilhem IX ...

Палладианский ландшафт как культурное наследие

The article is devoted to the formal and semantic unity of architecture and its natural environment. The author considers the Palladian landscape as a harmonious combination of elements dating back to the architecture of the late Renaissance, to the work of Andrea Palladio. The study identifies examples of the use of compositional techniques to create an artistic and symbolic unity of the building and landscape space, natural or man-made. The Italian experience of the Renaissance is projected onto the evolution of the building art of Modern and Contemporary times. The environment of the monument is understood as cultural heritage. The problems of preserving urban clusters, as well as suburban and rural areas of historical and cultural value, are outlined. The utilitarian nature of the use of «free spaces» during compacted development, which destroys the optical connections of historical locations, which must be preserved to achieve visual effects in the process of comprehending the aesthetic and semiotic essence of architectural heritage objects, is revealed.

Covid-19 in Patients with Hematological Disorders: An Italian Single Center Experience before Covid-19 Vaccination

Covid-19 in Patients with Hematological Disorders: An Italian Single Center Experience before Covid-19 Vaccination

The COVID-19 Pandemic Between Bio-Ethics, Bio-Law and Bio-Politics: A Case Study on The Italian Experience of The DuPre Commission

The aim of this qualitative study was to consider the question of whether the Italian political management of the pandemic respected the European bio-ethical and bio-juridical approaches in light of the principles of autonomy, dignity, integrity and vulnerability. As no specific consolidated literature exists on the subject, the Italian situation was taken into consideration, specifically the work of a spontaneous commission (DuPre) that collected the reflections of academics and researchers interested in discussing political decisions for the management of the emergency, which was the coronavirus disease (COVID-19) pandemic. The analysis took into account the contributions of scholars during two conferences (without proceedings), which were transcribed and examined. From the texts processed with a thematic analysis, three main themes emerged: ‘pandemic as a state of exception, sovereignty and crisis of democracy’, ‘the value of doubt and refutation’ and ‘elimination of informed consent between persuasion and blackmail’. In this paper, the final bio-political considerations on the European approach and the management of the COVID-19 pandemic in Italy are presented.

Transanal hemorrhoidal dearterialization (THD) for hemorrhoidal disease: An Italian single-institution 5-year experience analysis and updated literature review.

Hemorrhoidal disease is a highly prevalent, chronic disorder that usually compromise patients' quality of life. Despite recent advances in pharmacologic and surgical therapeutic options, a clear treatment "gold standard" is lacking. Our aim is to analyze the outcomes following Transanal Hemorrhoidal Dearterialization (THD) procedure. Patients who failed conservative treatment and underwent THD Doppler between 2017 and 2021 were enrolled. Follow-up interviews (consisting of clinical examination, Visual Analog Scale for pain-VAS, Vaizey incontinence score, Hemorrhoid Severity Score) were administered 1 week, 2weeks, 1 month and 6 months after surgery. Forty-seven out of 75 patients were male, and the mean age was 50 (±17.9) years. Hemorrhoids were classified as Goligher's degree II in 25 cases, III in 40 and IV, simple irreducible without ischemic changes, in 10. The mean operative time was 35 (28-60) minutes, and most procedures were performed with epidural anesthesia (80%). No intraoperative complications occurred, and 73 patients (97.3%) were discharged within post-operative day 1. Early post-operative pain and bleeding occurred in 37.3% and 8% of patients, respectively. No patients experienced anal incontinence and severe symptoms at 6 months after surgery. The overall success rate was 97.3%. THD is safe and effective in hemorrhoidal disease at degree II if bleeding, III, and IV without ischemic changes, both as a first intervention and on recurrence. Physician and patient need to understand each other's expectations, weight the risks and benefits, and customize the treatment.

958 IMPACT OF CARDIAC SYMPATHETIC DENERVATION ON ELECTRICAL STORMS IN PATIENTS WITH CARDIOMIOPATHIES

Abstract Background Cardiac Sympathetic Denervation (CSD) has been recently proposed for the treatment of refractory ventricular arrhythmias (VAs) in patients with cardiomyopathy (CMP). A multicentric American and Indian case series suggested a greater efficacy of bilateral denervation (BCSD), compared to the left-side only procedure (LCSD), albeit with the potential prize of an increased need for atrial pacing due to the right-side innervation of the sinus node. The impact of CSD on the risk of electrical storms (ES) in CMP has never been evaluated. Aim To describe our multicenter Italian experience with CSD in CMP patients with drug and/or catheter ablation refractory VAs, with a specific focus on ES incidence. Methods Thirty patients with CMP and refractory VAs underwent either LCSD or BCSD between April 2016 and June 2022. Among them, one patient received first LCSD and then right-side denervation due to ES recurrence after LCSD: to properly assess the risk of ES after LCSD and BCSD he was included in both groups with the corresponding follow-up, leading to 5 cases of LCSD and 26 cases of BCSD. All patients had a Video–Assisted Thoracoscopic Surgery (VATS), in 8 cases associated with the robotic technique. The main reason (3/5 cases, 60%) to perform LCSD instead of BCSD since the beginning was sinus bradycardia in single ICD lead recipients. Results 87% of pts were male, the mean age was 56 ± 16 yrs and the mean LVEF 31± 12%; most (n=26, 85%) suffered non-ischemic cardiomyopathy and 37% were in NYHA functional class ≥3. Main indications for CSD were represented by refractory polymorphic/fast VAs (cycle length <250 msec) in 60% of pts and by refractory monomorphic VAs episodes in the rest. Except for 5 patients (17%) with previous thyrotoxicosis, the majority were either on amiodarone (n=19, 63%) or on sotalol (n=3, 10%) before CSD and 53% had previously undergone ≥1 catheter ablation for VAs. The median follow-up (FU) after denervation was 15 months (IQR 5-42 months). No major complication directly related to the procedure occurred. Overall, 11 patients (37%) either died during FU (n=8, 27%), mostly due to end-stage heart failure, or underwent heart transplant (n=3, 10%). After denervation, the percentage of patients with ES decreased from 77% to 40% (p<0.01), while patients with appropriate shocks decreased from 100% to 60%. The antiarrhythmic benefit was even more pronounced among the 26 patients who received BCSD: ES incidence decreased from 85% to 39% (p<0.01), appropriate shock incidence from 100% to 54% (p<0.01), while no significant changes in ES and ICD shock incidence were observed after the few LCSD procedures (n=5). A NYHA class <3 was associated with a trend toward a better response after BCSD (37% vs 54% incidence of ICD shock, p=0.05). Conclusions Our case series of CSD in cardiomyopathies represents the largest reported in Europe and the first ever to specifically evaluate the impact of denervation on electrical storms. The occurrence of electrical storm was more than halved by bilateral CSD confirming the powerful protective effect of BCSD also on this ominous phenomenon. The greater antiarrhythmic benefit observed among patients with better functional class suggests the opportunity to perform this procedure earlier on in the trajectory of patients with progressive heart failure.

Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery: An Italian initial experience.

The aim of this study is to evaluate the initial feasibility, safety, and outcomes of hysterectomy performed by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) at three institutions in Italy. All women who underwent vNOTES hysterectomy ± salpingo-oophorectomy for benign indications at three tertiary referral medical centers between July 2019 and April 2021 were included in a retrospective analysis. All vNOTESs were performed with the use of Alexis® and Vpath Gel paths® (Applied Medical). Perioperative data were extracted from patient records. Patient satisfaction and dyspareunia were prospectively inquired about at 60 days and 6 months. Forty-six patients underwent vNOTES in the study period. Indications for surgery included myomas ± metrorrhagia (52.2%), H-Sil/in situ cervical cancer (10.7%), adenomyosis ± metrorrhagia (8.7%), BRCA 1-2 mutations (6.5%), endometrial hyperplasia (6.5%), ovarian cyst + history of breast cancer (6.5%), metrorrhagia (6.5%), and hydatidiform mole (2.2%). The mean operation time was 91.1 (±32.6) minutes. The mean hemoglobin drop was 1.2 (±0.8). The mean visual analog scale at 24 h for post-operative pain was 3.3 (±1.8). Secondary to our limited experience with the surgical technique, we favor discharge only from day 1. The mean length of hospital stay was 2 (±1.4) days. Two conversions to conventional laparoscopy were reported (4.3%), due to an obliterated pouch of Douglas and a preoperative complication. Two post-operative complications were reported (4.3%). Overall, our data on peri- and post-operative outcomes are similar to those already published for vNOTES. Our initial experience suggests that introducing vNOTES as an alternative to conventional surgery is feasible and may offer some advantages in selected women.

Італійське «економічне диво»: успішний досвід управління повоєнним відновленням

The research is based on the historical experience of rebuilding Italy’s economy, destroyed as a result of World War II. The purpose of the article is historical and economic assessment of the process of restoration of the Italian economy in the post-war period for extrapolation of this experience in the revival of the economy of Ukraine at the present stage. The study results in analysis of the main reforms, highlighting the peculiarities of the Italian government’s economic policy and revealing the consequences of internal and external efforts in economic recovery, as well as substantiation of prospects of the use of this historical experience in modern Ukraine. The article analyzes the specifics of the post-war revival of the Italian economy by the government of Christian Democrats, who introduced a policy of strict regulation of the monetary system, state intervention in industrial policy, promoted the development of innovative entrepreneurship, creation of high-tech industries. It was proved that the agrarian reform, which laid the foundations for the formation of efficient farm production, helped market reorientation of agriculture in general. Italian experience of leveling regional imbalances in economic development for national integrity and unity is useful for Ukraine. The correlation of external patronage influence and internal efforts in the rapid rise of the Italian economy, which was called «economic miracle», was revealed. It is justified to use the strategy of economic development of the post-war Italy in preparing programs of economic reconstruction of Ukraine destroyed by the aggressive war of Putin's russia.

A European Credit Council? Lessons from the History of Italian Central Banking after World War II

Abstract By formulating a proposal for the “democratisation” of the ECB through the establishment of a European Credit Council, Eric Monnet makes a fundamental contribution to the contemporary debate on central banking. This idea appears to be in line with other critiques that often see the post-World War II institutional set-up as a model to be revived to bring central banks back to democracy after the neoliberal disengagement of the 1980s. However, I argue in this article that the intellectual optimism with which these historical experiences are often viewed can be misleading. Going beyond the French “ideal type” and focusing instead on the “twin case” of Italy, I intend to show how the attempt to democratically control the central bank has not always been linear nor necessarily democratic and successful. The establishment of a credit council did not prevent the Bank of Italy from enjoying a high degree of independence and ability to influence policy. At the same time, the widespread system of credit policy that the central bank has explicitly promoted in pursuit of the country’s development agenda has often degenerated into irrational and opaque practices, revealing the side effects of an economy in which a sustainable boundary between fiscal and monetary policy struggles to emerge. While the Italian experience might show how problematic and “fictitious” the relationship between the credit council and the central bank can be, it can also offer interesting insights for a better articulation of it.

Development of sustainable control strategies for citrus under the threat of climate change for the prevention of HLB entry into the EU: the Italian experience (LIFE18 CCA/ES/001109)

ISHS III International Organic Fruit Symposium and I International Organic Vegetable Symposium Development of sustainable control strategies for citrus under the threat of climate change for the prevention of HLB entry into the EU: the Italian experience (LIFE18 CCA/ES/001109)

Use of Flash Glucose Monitoring technology in type 2 diabetic patients in basal-bolus insulin therapy improves metabolic control and generates saving health costs: fake or reality.

Since few years Glucose monitoring, which contributes to good metabolic control, has available a new tool, sensors, which automatically and continuously measure interstitial glucose levels in two modes: continuous (Continuous Glucose Monitoring) and flash (Flash Glucose Monitoring). Flash Glucose Monitoring has been shown to be efficient and improve the quality of life in type 1 diabetic patients; and also for type 2 diabetic patients there are a growing number of studies, which have evaluated efficacy, the frequency of hypoglycemia and glycemic variability in these patients. The purpose of this review is to take stock of use of Flash Glucose Monitoring in type 2 diabetic patients by examining international studies and Italian experiences, also reporting data on the costs and savings generated by use of this new technology. KEY WORDS Flash Glucose Monitoring; type 2 diabetes; basal-bolus insulin therapy; elderly with type 2 diabetes; diabetes costs.

Translational and transdisciplinary approach to the human papilloma virus - Preliminary evidence from the Italian "HPV board: a future without papilloma virus" project.

Human papillomavirus (HPV) is considered to be one of the viral infections associated with cancers and other diseases. HPV is detected asymptomatically in the oral mucosa. The presence of human papillomavirus in the oral mucosa appears to be closely associated with a series of benign and malign oral lesions. The aim of this paper is to report the Italian experience in applying translational protocols, using new technologies and multidisciplinary strategies in Human Papilloma virus detection and treatment. The "HPV board: a future without papilloma virus" project was born, promoted by CNEL (Italian Council of Economics and Labor) with the collaboration of numerous scientific societies to commonly approach to public knowledge of HPV-related oral lesions and their clinical management. The preliminary results are related to the assessment of the proof-of-concept of this new project. More in details, "HPV Board" is a project that plans the presence of a working group, made up of otolaryngologists, dentists, oral and maxillofacial surgeons, in close contact with gynecologists, oncologists and pediatricians; this working group manages to combine very transversal skills, in order to promote primary prevention projects, early diagnosis and adequate therapies. The "HPV BOARD" project will give the opportunity to increase the attention of patients and doctors on the early diagnosis of oncological diseases dependent on infection by the infectious agent HPV. In this panorama, dentists will have the role of "first sentinel" of public health because oral health is an indicator, too often overlooked, for the prevention of numerous diseases.

How the work of respiratory physiotherapists changes the tracheostomy management and decannulation in a NICU department: an Italian experience.

Tracheotomy is a clinical procedure that is often necessary though not without complications, hence the need for appropriate and timely decannulation. The inclusion of trained respiratory physiotherapists (RPT) in the staff and the use of shared protocols could help the team to manage the patient with tracheotomy cannula. The objective of this study was to describe the difference in the rate of decannulation and clinical outcomes of tracheostomized patients admitted to a NeuroIntensive Care Unit (NICU) team after the inclusion of a group of physiotherapists specialized in respiratory physiotherapy and a new phoniatric protocol. It is a 6-year retrospective study, in which two periods of 3 years each were compared: in the first period (P1: September 2013-August 2016) physiotherapists were called to treat NICU patients on a consultative basis (2 hours/day for 5 days a week); in the second period (P2: September 2016-August 2019) two full-time respiratory physiotherapists were present on the ward (7 hours/day, 6/7 days/week). In P2 period, a decannulation protocol was used. Patients who had undergone a tracheotomy procedure and who were alive at the time of discharge were retrospectively evaluated. We described the number of decannulations, the length of stay in NICU and decannulation time; the diagnosis of decannulated patients and the number of deaths. 928 total patients were analysed: 468 in P1, 460 in P2. Total length of stay or number of deaths did not change significantly between the two periods, while the number of decannulated patients before the discharge was higher in P2 143 (64%), compared with P1 79 (36%) p<0.001. More patients with neurological pathologies involving possible swallowing disorders, such as cerebral haemorrhage, head trauma and stroke, have been successfully decannulated in P2 than in P1 (120 patients in P2 vs 54 in P1). A multidisciplinary approach, including respiratory physiotherapist, dedicated to tracheostomy management, decannulation and early mobilization in NICU is safe, feasible and seems to improve the number of severe patients decannulated, even if no change was observed in NICU length of stay or deaths. Further studies must confirm our results in other ICU settings.

The Italian policy of mandating SARS-CoV-2 vaccination for healthcare workers: Analysis of the policy processes and preliminary outcomes

BackgroundItaly experienced the first outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Europe, and was among the most hardly hit European countries. Growing evidence suggests healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. Infection in HCWs can lead to cross-transmission and increase community transmission. Italy was the first country in Europe to introduce mandatory vaccinations against SARS-CoV-2 for HCWs, on April 1, 2021. AimTo describe the policy processes and preliminary results of the introduction of compulsory vaccination against SARS-CoV-2 for HCWs in Italy. Results and conclusionIn Italy, the adoption of the policy was possible in the context of the public health and economic crisis resulting from the pandemic, with support from the scientific community and among favorable political conditions. Preliminary data suggest the policy has so far had a positive impact on increasing vaccine uptake and lowering infection rates among HCWs. Hopefully, the lack of serious vaccine-related adverse events and the growing evidence on vaccine effectiveness will progressively strengthen vaccine confidence among HCWs. In the context of a global pandemic, the Italian experience could provide insight for policymakers in other countries considering similar policies. Further, the ethical, legal, and policy challenges raised by the current public health emergency could be used to inform future pandemic preparedness plans.

Joining the fight: the Italian foreign fighters contingent of the Kurdish People's Protection Units

AbstractSince the emergence of the Islamic State (ISIS) as one of the leading insurgent forces in Syria and Iraq in the 2010s, the academic literature has increasingly focused on the phenomenon of foreign fighters. Most studies have analyzed transnational insurgents joining the ISIS; however, research on non-jihadi foreign fighters remains underdeveloped. The article sheds much-needed light on the factors motivating non-jihadi fighters to join conflicts abroad. Specifically, it presents the findings of an in-depth analysis of the factors leading Italian nationals to join the Kurdish People's Protection Units (YPG/YPJ)1 after 2011, their military contribution on the battlefield, and their reasons for returning to Italy. The contributions of the paper are twofold. First, it enriches our general understanding of the motivations of non-jihadi foreign fighters through detailed qualitative analysis, including first-hand accounts and an analysis of fighters' biographies. Second, it offers a more complete picture of the specific factors informing the Italian experience of transnational non-jihadi fighters in recent years. The qualitative data highlight the role of non-material factors in triggering the armed mobilization of foreign fighters. The findings indicate that the Italian foreign fighters contingent within the YPG/YPJ and the SDF has been highly committed, made up mostly of young males with no military experience, and had little to no impact on the battlefield.

End-to-end test for lung SBRT: An Italian multicentric pilot experience

PurposeSet up a lung SBRT end-to-end (e2e) test and perform a multicentre validation. Material and methodsA group of medical physicists from four hospitals and the Italian Institute of Ionizing Radiation Metrology designed the present e2e test. One sub-group set up the test, while another tested its feasibility and ease of use. A satisfaction questionnaire was used to collect user feedback.Each participating centre (PC) received the ADAM breathing phantom, a microDiamond detector and radiochromic films. Following the e2e protocol, each PC performed its standard internal procedure for simulating, planning, and irradiating the phantom. Each PC uploaded its planning and treatment delivery data in a shared Google Drive. A single centre analyzed all the data. ResultsThe e2e test was successfully performed by all PCs. Participants' comments indicated that ADAM was well suited to the purpose and the protocol well described. All PCs performed the test in static and dynamic modes. The ratio between measured and planned point dose obtained by PC1, PC2, PC3, PC4 was: 0.99, 0.96, 1.01 and 1.01 (static track) and 0.99, 1.02, 1.01 and 0.94 (dynamic track). The gamma passing rates (3 % global, 3 mm) between planned and measured dose maps were 98.5 %, 94.0 %, 99.1 % and 94.0 % (static track) and 99.5 %, 96.5 %, 86.0 % and 94.5 % (dynamic track) for PC1, PC2, PC3 and PC4, respectively. ConclusionsAn e2e test for lung SBRT has been proposed and tested in a multicentre framework. The results and user feedback prove the validity of the proposed e2e test.

Italian Nicodemites amidst Radicals and Antitrinitarians

Abstract Many Italians in exile ‚religionis causa‘ had learned to dissimulate well before they left their homeland: nicodemism was part of the necessary life preparation for becoming a radical or an antitrinitarian. Examining the careers of Italian refugees in the mid-sixteenth century, this essay shows that, by the time they crossed the Alps, they were already programmed to keep quiet, evade and deceive. Initially, exile felt like utopia: yet there was also a dawning realisation that restraint, evasion and silence would remain essential in relatively closed Swiss cities. When the exiles’ views turned to dangerous topics like the Trinity, baptism, the immortality of the soul or ‚il cielo aperto‘, they already knew the core nicodemite strategies: evasion, secrecy, ambiguity, pretence, being terse and hiding risky ideas within humanist dialogue form. Three examples are taken from those in and around Basel in the troubled 1550s: Bernardino Ochino, Celio Secondo Curione, and Lelio Sozzini. The burning of Miguel Servetus in nearby Geneva in 1553 appalled all three, crystallised their resistance to the dogma of reformers, and pointed to the dangers of not remaining a nicodemite. Concealment learned in Italy served to keep them alive in Swiss cities. Italian experience had also prepared them to write in forms whereby they might elude the attention of the authorities: spiritual letters (Curione), dialogues (Ochino) and ambiguous comments (Sozzini). All three spread their views by tactics known to nicodemites all over Europe but especially in Italy.

Tagraxofusp Administered Concomitantly with Intrathecal Chemotherapy in Patients with BPDCN who Either Have or are Considered High-risk to Develop CNS Disease is a Safe and Effective Treatment Strategy: An Italian Multicenter Experience

Background: The precise frequency of central nervous system involvement (CNS+) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) is currently unclear, with some studies reporting an incidence of 10% at baseline and 30% at first relapse. The CNS, a "sanctuary" for any systemic treatment, can lead to disease recurrence even after systemic response. Intrathecal (IT) chemotherapy is aimed at eradication of the disease from the CNS, with modest systemic side effects, and it is currently indicated as both prophylaxis and primary treatment. Tagraxofusp (TAG), a first-in-class CD123-targeted therapy comprising human interleukin-3 fused to a truncated diphtheria toxin payload, was approved by the US Food and Drug Administration for the treatment of pts ≥2 years of age with newly diagnosed or relapsed/refractory BPDCN in 2018, and in 2021 by the European Medicines Agency for treatment of BPDCN in first-line adult pts. Data from 5 pts with BPDCN with/without CNS+ receiving TAG and CNS treatment/prophylaxis were retrospectively collected in our center in Genoa. The aim was to evaluate if CNS treatment/prophylaxis impacts pts' prognosis and the efficacy and safety of systemic treatment with TAG. Methods: A diagnosis of BPDCN was confirmed by histopathologic or cytologic samples with biomarkers, including CD123, CD4, and CD56, and CNS involvement was confirmed by presence of cells with the characteristic morphology and by 8-color flow cytometry for CD123. Pts received TAG intravenous infusions at 12 mcg/kg once daily on days 1-5 of a 21-day cycle. TAG was repeated for 1-4 cycles, depending on the level of response and potential bridge to hematologic stem cell transplant (HSCT). Hospitalization was mandatory for the first cycle; the following cycles were administered in an outpatient setting if no severe complications occurred during the first cycle. IT chemotherapy (methotrexate 12.5 mg, dexamethasone 4 mg, and cytarabine 50 mg) was administered at each cycle at the same doses until negative cerebrospinal fluid (CSF) was observed in CNS+ pts. After 4 treatment cycles, response was evaluated, including CSF examination. Results: TAG was administered in 5 first-line pts with BPDCN; 3 had CNS+ (1 clinically evident case and 2 with cytofluorometric positivity only). All pts received IT chemotherapy, either as a primary-intention treatment in the 3 CNS+ pts, or as prophylaxis in the 2 CNS-negative pts. The Table reports the main pt characteristics. Three of the 5 pts had CNS+ disease and achieved remission with no relapses reported at the time of the data cut for this analysis. Two pts received IT chemotherapy as CNS prophylaxis. Of these, 1 was treated with TAG followed by HSCT and continues in complete response (CR) after 32 months. The other pt received high-dose chemotherapy, achieved a partial remission after TAG, underwent HSCT, and remains alive after 7 months. Capillary leak syndrome was the most common adverse event (AE), occurring in 4/5 pts: grade (G)1, n = 1; G2, n = 2; G4, n = 1; all cases resolved. Other AEs included pulmonary aspergillosis (n = 1); sepsis (n = 1). Conclusion: These cases illustrate that IT chemotherapy can be safely administered in pts receiving systemic TAG. Baseline disease and CNS involvement did not appear to predispose pts to different efficacy results or treatment-related AEs. IT chemotherapy effectively cleared and controlled CNS involvement. Because CNS can be a sanctuary site in BPDCN, the information from these initial cases can be helpful in the management of the disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long Term Survival in Multiple Myeloma Patients: A Multicenter Italian Experience

Long Term Survival in Multiple Myeloma Patients: A Multicenter Italian Experience