IRIS UniSR (’Università Vita-Salute San Raffaele)
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Predictors of failure to rescue after fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms
No full textObjective: Failure to rescue (FTR), defined as mortality due to failure in responding to in-hospital complications, is an important quality indicator. This study aimed to assess incidence and predictors for FTR among centers performing fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysms (TAAA). Methods: Consecutive patients treated by FB-EVAR for TAAAs between 2005 and 2022 in 27 centers of the International Multicenter Aortic Research Group were analyzed. Data were obtained from the United States Aortic Research Consortium, which contains prospectively collected data of physician-sponsored investigational device exemption studies from 10 centers, and retrospective center data from Europe and New Zealand. FTR was defined as in-hospital mortality following ≥1 major adverse event (MAE). Primary endpoints were rates of postoperative MAEs, including major cardiac (myocardial infarction, cardiovascular collapse, acute congestive heart failure) and respiratory events, major stroke, paraplegia, acute kidney injury (AKI), and bowel ischemia requiring surgical resection or escalation of care and FTR. Multivariate analysis was performed to identify predictors for MAEs and FTR. Results: There were 3634 patients (68% males; mean age, 71 ± 9 years) treated by FB-EVAR for TAAAs. Technical success was achieved in 94%, with 5% in-hospital mortality. Median incidences of MAEs and FTR were 27% (interquartile range, 18%-33%) and 15% (interquartile range, 6%-21%). There was a significantly (33% vs 20%; P <.001) higher rate of MAEs among centers with annual volume below the median (11 cases). Independent predictors for MAEs included age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P =.02), chronic kidney disease (OR, 1.88; 95% CI, 1.54-2.29; P ≤.001), ASA class ≥3 (OR, 1.70; 95% CI, 1.21-2.38; P =.002), previous aortic repair (OR, 0.74; 95% CI, 0.60-0.91; P =.004), symptomatic/ruptured (OR, 1.76; 95% CI, 1.36-2.28; P <.001), extent I to III TAAA (OR, 2.28; 95% CI, 1.75-2.97; P <.001), and lower annual volume (<11 cases/year: OR, 1.83; 95% CI, 1.40-2.38; P <.001). Symptomatic/ruptured TAAA was an independent predictor for FTR (OR, 2.99; 95% CI, 1.62-5.52; P <.001). Conclusions: FB-EVAR was performed with low in-hospital mortality. Lower volume centers had higher rates of MAEs, but center volume was not related to FTR. Symptomatic/ruptured TAAAs were independently predictive of FTR
Cancer incidence in people with HIV in Italy: Comparison of the ICONA COHORT with general population data
Get PDFThe cancer risk of people with HIV (PWH) enrolled in the Italian COhort of Naives to Antiretrovirals (ICONA) with HIV diagnosis occurred between 01/1997 and 12/2023 has been compared to that of the corresponding general population of Italy. Incident cancers were grouped according to their association with viral infections. Standardized incidence ratios (SIRs) were estimated as the ratio between the observed number of cancers among PWH and the expected ones among the general population. Competing risks cumulative incidence curves and Gray's test were used to compare incidence between groups (gender and CD4+ T-cells values at diagnosis) with death as a competing risk. Overall, 17,298 PWH (79.1% males) contributing to 133,851 person-years of follow-up were included; 763 (4.4%) developed > = 1 incident cancers, the most frequent cancers being KS (N = 204), NHL (N = 127) and lung-trachea-bronchus (N = 66). PWH were at 1.6-times higher risk for all cancers compared to the general population (SIR = 1.6, 95% CI: 1.5–1.8), with significantly increased SIR for almost all virus-related cancers, including KS (SIR = 145), NHL (SIR = 5.8), ICC (SIR = 6.0), anal cancer (SIR = 21.0) and Hodgkin lymphoma (SIR = 10.0). Apart from lung cancer risk (SIR = 1.3), none of the non-virus-related cancers turned out to be more frequent among PWH. PWH with CD4 + <200 cells/mm3 at cART initiation showed the highest cancer incidence, 5% after 5 years, versus 3% for CD4+ 200–349 and 2% for CD4+ >350 (p <.001). These findings underscore the need to continue prevention efforts in PWH, including behavioral risk reduction, early cART initiation, screening, and vaccination
EANM/SNMMI guideline/procedure standard for [18F]FDG hybrid PET use in infection and inflammation in adults v2.0
Get PDFIntroduction: Hybrid [18F]FDG PET imaging is currently the method of choice for a wide variety of infectious and inflammatory disorders and was recently adopted in several clinical guidelines. A large amount of evidence-based articles, guidelines and appropriate use criteria have been published since the first version of this guideline in 2013. Purpose: To provide updated evidence-based information to assist physicians in recommending, performing and interpreting hybrid [18F]FDG PET examinations for infectious and inflammatory disorders in the adult population. Methods: A systematic literature search of evidence-based articles using whole-body [18F]FDG hybrid imaging on the indications covered within this guideline was performed. All systematic reviews and meta-analyses published within the last 10 years until January 2023 were identified in PubMed/Medline or Cochrane. For each indication covered in this manuscript, diagnostic performance was provided based on meta-analyses or systematic reviews. If not available, results from prospective or retrospective studies were considered based on predefined selection criteria. Results and conclusions: Hybrid [18F]FDG PET is extremely useful in the work-up and management of adults with infectious and inflammatory diseases, as supported by extensive and rapidly growing evidence-based literature and adoption in clinical guidelines. Practical recommendations are provided describing evidence-based indications as well as interpretation criteria and pitfalls. Monitoring treatment response is the most challenging but insufficiently studied potential application in infection and inflammation imaging
Raphe-Type Bicuspid Aortic Valve as a Risk Factor for Transcatheter Aortic Valve Replacement Failure: Improving Outcomes Using the LIRA Method and the Medtronic FX Prosthesis
No full textTranscatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis and raphe-type bicuspid aortic valve (BAV) is still associated with poor outcomes in terms of increased risk of paravalvular regurgitation, stroke, and permanent pacemaker implantation. There is no definitive consensus on the optimal sizing method for prosthesis selection in this setting. The LIRA method is a supra-annular tailored sizing method specifically designed for bicuspid anatomy that might increase accuracy of prosthesis choice in BAV patients and improve TAVR outcomes. This is the first report of the combination of the novel LIRA method for prosthesis sizing together with the adoption of the technological improvements introduced by the Evolut FX prosthesis as a useful tool for improving outcomes in this high risk subgroup of patients.Transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis and raphe-type bicuspid aortic valve (BAV) is still associated with poor outcomes in terms of increased risk of paravalvular regurgitation, stroke, and permanent pacemaker implantation. There is no definitive consensus on the optimal sizing method for prosthesis selection in this setting. The LIRA method is a supra-annular tailored sizing method specifically designed for bicuspid anatomy that might increase accuracy of prosthesis choice in BAV patients and improve TAVR outcomes. This is the first report of the combination of the novel LIRA method for prosthesis sizing together with the adoption of the technological improvements introduced by the Evolut FX prosthesis as a useful tool for improving outcomes in this high risk subgroup of patients
Lo spazio europeo dei dati sanitari: una questione di etica pubblica
No full textThe crisis of Europe is a recurring theme, made evident by the difficulty of member countries in responding effectively to military and economic conflicts, as well as threats to the independence of the European Union. It is argued by many that Europe is not a true union, but merely an ideal detached from reality, where fundamental rights, considered acquired, are constantly at risk due to the influence of external powers. However, it is important to recognize the value of achievements made in the name of unity. Among these, the European Health Data Space (EHDS) represents a significant example. In this contribution, I will briefly examine, from a public ethics perspective, the meaning of this achievement, its objectives, the principles that support it, the potential criticalities that could compromise it
Consensus of the Italian Primary Immunodeficiency Network on the use and interpretation of genetic testing for diagnosing inborn errors of immunity
No full textBackground: Inborn errors of immunity (IEIs) comprise more than 500 different rare congenital disorders of the immune system and are characterized by susceptibility to infection and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High-throughput sequencing techniques may allow a timely genetic definition. Guidelines for the use and the interpretation of genetic testing produced by the American College of Medical Genetics and Genomics (ACMG) and the European Society of Human Genetics (ESHG) do not cover specifics for their application to IEIs. Objective: The aim of this consensus study was to define the best approach to genetic testing for IEIs. Methods: A panel of experts in the context of the Italian Primary Immunodeficiency Network (IPINet) composed a list of statements that were evaluated by the Delphi method. Results: The experts recommend that genetic testing for IEIs should be offered to selected patients with warning signs for IEIs and highlight the crucial role of thorough phenotyping and functional tests for the conclusive diagnosis of IEI. Comprehensive educational programs targeted to health care professionals and the public should be developed to increase IEIs awareness and reduce diagnostic delay. Ethical issues should be pondered over the diagnostic advantages of genetic tests requested for diagnostic purposes. Conclusion: Adherence to guidelines on the use and interpretation of genetic tests for diagnosing IEIs should help limit the inappropriate use of these techniques, thereby reducing the risk of misdiagnosis and patient apprehension regarding inconclusive genetic results
Generalized epileptic discharges leading into focal onset seizure: GOFE seizures as the initial diagnosis of epilepsy
No full textBcor loss promotes Richter transformation of chronic lymphocytic leukemia associated with Notch1 activation in mice: Lymphoma
No full textRichter’s transformation (RT) is an aggressive lymphoma occurring upon progression from chronic lymphocytic leukemia (CLL). Despite advances in deciphering the RT genetic architecture, the mechanisms driving this disease remain unknown. BCOR disruptive mutations were found in CLL and frequently associated with NOTCH1 aberrations, a common feature in CLL and RT. We engineered mice to knock-out Bcor in B and CLL cells of Eμ-TCL1 mice. Bcor loss resulted in alterations of the B cell compartment and favored CLL transformation into an aggressive lymphoma with reduced survival in Eμ-TCL1 mice. RNA-sequencing demonstrated a molecular signature reminiscent of human RT and implied the involvement of the T cell tumour microenvironment in the disease onset. Bcor deficiency was associated with Notch1 activation in splenic CD19 + CD5+ cells to accelerate Eμ-TCL1 mice lymphoproliferation. Notch1 inhibition progressively reduced circulating CD19+ CD5+ and RT cells infiltrating the spleen of diseased mice with concomitant reduction of PD-1 expressing T cells and improved survival. Our data demonstrated an interplay between the tumour suppressor activity of Bcor and Notch1 in RT pathogenesis with potential for tumour targeting. This model represented a new platform to uncover promising alternatives for this incurable tumour
Autoimmune gastritis: an organ-specific disease or a model of systemic autoimmunity? Parallels, divergences, and emerging insights
No full textIntroduction: Autoimmune gastritis (AIG) is traditionally classified as an organ-specific autoimmune disease; however, emerging evidence highlights its immunological overlap with systemic autoimmunity, warranting a reevaluation of its pathophysiological framework. Areas covered: This review delineates the immunopathogenic basis of AIG, with particular emphasis on the breakdown of central and peripheral tolerance, the predominance of autoreactive CD4+ T-cell subsets, and the contributions of Th1 and Th17 cytokine profiles. The role of humoral immunity, including autoantibodies as potential biomarkers, is critically appraised. Literature was selected through a targeted search of PubMed and Scopus, prioritizing mechanistic studies, translational research, and recent therapeutic advances, covering the period from January 2000 to March 2025. Expert opinion: AIG represents a paradigm of localized autoimmunity with systemic immunological features, including cytokine dysregulation and epitope spreading. Although serologic markers are valuable for screening, their prognostic utility remains limited. Therapeutic approaches currently focus on complication prevention rather than immune modulation. Future research should prioritize the identification of predictive biomarkers of disease progression and the development of targeted immunotherapies aimed at restoring immune tolerance and preserving gastric mucosal integrity