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REASONABLENESS: OLD VIRTUE FOR A NEW ERA. GUEST EDITORS’ PREFACE
No full textThis special issue examines how the Rawlsian notion of reasonableness is strained by the epistemic and technological dynamics of digital democracy. Digital environments, defined by features such as echo chambers, misinformation, and fragmented public discourse, foster increasingly superficial and reactive forms of political engagement through social media and reduce citizens’ willingness to shoulder the burdens of judgment required by public reason. The contributions explore pedagogical strategies grounded in civic virtue ethics, culturally situated or weakened models of reasonableness, and non-ideal approaches introducing asymmetrical epistemic and civic duties. Together, they show why reasonableness remains normatively significant despite the pressures it faces today
A Comprehensive Systematic Review and Meta-analysis of the Role of Prostate-specific Membrane Antigen Positron Emission Tomography for Prostate Cancer Diagnosis and Primary Staging before Definitive Treatment
No full textBackground and objective: Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) in the diagnosis and primary staging of patients with prostate cancer (PCa) has an established role, but recent summative evidence on its actual diagnostic and staging value is still missing. We aimed to collect and analyze published studies reporting the accuracy of PSMA PET for the diagnosis of clinically significant prostate cancer (csPCa) and detection of distant metastases at primary staging before definitive treatment. Methods: We performed a systematic review of the literature, by searching the PubMed/MEDLINE, Cochrane library's CENTRAL, EMBASE, and Scopus databases, from inception to April 2024. Two coprimary outcomes were assessed: first, to evaluate the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of PSMA PET in detecting intraprostatic csPCa on a per-patient level, and second, to assess the positivity rates of metastatic disease in the primary staging, prior to definitive therapy. As a secondary outcome, the diagnostic accuracy of PET PSMA for the detection of lymph nodal invasion (LNI) was tested in a per-patient–level analysis of studies where pelvic lymph node dissection (PLND) was available as the reference standard. Positivity and detection rates were pooled using random-effect models. Preplanned subgroup analyses tested the diagnostic accuracy of PET PSMA across different study cohorts. Variation in PPV and NPV over csPCa and LNI prevalence was evaluated. Key findings and limitations: In total, 12 and 99 studies, with a total of 1533 and 18 649 participants, respectively, were included in the quantitative synthesis for intraprostatic diagnosis and staging. For intraprostatic disease, the sensitivity, specificity, PPV, and NPV of PSMA PET for csPCa were 82% (95% confidence interval [CI] 73–90%), 67% (95% CI 46–85%), 77% (95% CI 63–88%), and 73% (95% CI 56–87%), respectively. At a bivariate analysis, the diagnostic accuracy of PSMA PET estimated through a summary receiver operating characteristic curve–derived area under the curve was 84%, increasing up to 88% when combined with magnetic resonance imaging (MRI). On staging level, PSMA PET results were positive outside the prostate in 23% of the patients, with substantial variation in positivity rates between high-risk (31%) and intermediate-risk (12%) subcohorts. When using PLND as the reference standard (51 studies, 7713 patients), the sensitivity, specificity, PPV, and NPV of PSMA PET were, respectively, 54%, 94%, 77%, and 86%. With higher csPCa and LNI prevalence, a similar increase in PPV and a decrease in NPV were observed. Conclusions and clinical implications: The current updated systematic review and meta-analysis provides updated evidence on the diagnostic and staging accuracy of PSMA PET in PCa. We reported good accuracy of PSMA PET to discriminate csPCa, particularly when added to MRI, but NPV alone is insufficient to omit a biopsy. Regarding staging, PSMA PET cannot be used alone to determine the need for lymph node dissection (LND) and should be combined with additional clinical information within predictive tools. As such, further research should develop and validate models that incorporate PSMA PET to reliably inform biopsy or LND
THREE-HOUR INFUSION OF METHOTREXATE AT 3 g/m2 SIGNIFICANTLY REDUCES CNS RELAPSES AND IMPROVES SURVIVAL IN PATIENTS WITH LARGE B-CELL LYMPHOMAS AND INCREASED CNS RISK
No full textCardiovascular magnetic resonance parametric mapping in the risk stratification of patients affected by chronic myocarditis
No full textObjectivesChronic myocardial inflammation is the substrate for arrhythmias and dilated cardiomyopathy onset, causing morbidity and mortality. Cardiovascular magnetic resonance (CMR) is the noninvasive gold standard for myocardial inflammation detection, due to the high sensitivity of the parametric mapping techniques. However, the potential prognostic capabilities of CMR mapping have not been studied in the setting of chronic myocarditis.MethodsThis is a retrospective study on consecutive patients undergoing CMR with suspicion of chronic myocarditis from September 2017 to November 2021. CMR was acquired according to 2018 Lake Louise Criteria recommendations. The outcome (chronic heart failure, recurrent chronic myocarditic chest pain, ICD/PM implantation, arrhythmias [Lown class >= 2]) was collected at follow-up. The extent and degree of native T1, T2, and extracellular volume fraction alterations were used to create multivariate binary logistic regression models for outcome prediction, with or without left ventricle ejection fraction; their AUCs were compared with DeLong test. Differences between other parameters were assessed using Chi-square test, Fisher's exact test, or Mann-Whitney U-test.ResultsThe population included 88 patients (age 43 [32-52] yo), mostly male (53/88, 60%). After a median follow-up of 21 (17-34) months, 31/88 (35%) patients experienced the outcome. The model based on the extension of mapping alterations and LV dysfunction reached a good predictability (AUC 0.71). The model based on the intensity of mapping alterations and LV dysfunction had a very good performance (AUC 0.80).ConclusionThe quantitative analysis of CMR mapping parameters indicative of myocardial damage severity may improve risk stratification in patients with chronic myocarditis.Clinical relevance statementThe intensity of myocardial damage, assessed as the degree of native T1, T2, and ECV alteration, together with left ventricle dysfunction, improved patient risk stratification. Further prospective studies will be necessary for validation before clinical application
Correction to: Safety of laparoscopic compared to open right hepatectomy after portal vein occlusion: results from a multicenter study (Surgical Endoscopy, (2025), 39, 3, (1839-1847), 10.1007/s00464-025-11532-8)
No full textThe original online version of this article was revised to correct the presentation of the name of coauthor Nadia Russolillo, and to correct the affiliation information for corresponding author Serena Langella. The original article has been corrected
Data-driven subtypes of subjective cognitive decline: neuropsychological profiles, Alzheimer’s disease biomarkers, and clinical trajectories
No full textObjectives: Subjective Cognitive Decline (SCD) is a heterogeneous condition recognized as the earliest manifestation of Alzheimer's disease (AD). We hypothesized that the heterogeneity of SCD may be synthesized in distinct subtypes. Methods: We analyzed data from the AD Neuroimaging Initiative (ADNI) database. For all participants, demographic variables, cognitive measures, APOE genotype, CSF biomarkers, brain MRI, and FDG-PET data were available. Participants underwent follow-up visits every 6 or 12 months. Results: 542 cognitively normal (CN), 346 SCD, and 423 early mild cognitive impairment (E-MCI) individuals were included. A data-driven approach based on cognitive measures identified three SCD clusters (k1, k2, k3) that performed differently in verbal memory (k2 outperformed all the groups and k3 showed the poorest performance, p < 0.001) and in executive function (k1 had the lowest scores, p = 0.006). Regarding CSF biomarkers, k2 exhibited lower p-tau (20.6 ± 9.2 vs. 24.2 ± 13.6, p = 0.03) and k3 had higher Aβ42 levels (1131.3 ± 379.8 vs. 942.87 ± 355.3, p = 0.01) compared to the E-MCI group, while there were no differences between k1 and E-MCI. Regarding brain FDG-PET, k1 demonstrated reduced uptake compared to CN, k2, and k3 (p < 0.001). During follow-up, k1 exhibited a higher rate of progression to MCI or dementia compared to k2 and k3 (Log-rank χ2 = 18.18, p = 0.0002) and a steeper decline in general cognition and long-term verbal memory compared to k2. Interpretation: We proposed a three-subgroup system classification for SCD, reflecting different cognitive profiles and longitudinal trajectories. Classifying individuals with SCD may enhance diagnostic pathways and inform personalized interventions
The Effect of Intraoperative Hypothermia on Anastomotic Leakage After Esophagectomy
Get PDFBackground/Objectives: Inadvertent intraoperative hypothermia is a common occurrence during major surgery, and some preclinical studies have reported its association with postoperative anastomotic leakage (AL). In the present study, we demonstrated the correlation between intraoperative hypothermia and postoperative outcomes after Ivor Lewis (IL) esophagectomy for cancer. Methods: Retrospectively, patients were divided into three groups on the basis of their time-weighted average temperatures (TWA): normothermia (N-TWA 36–37.5 °C), mild hypothermia (M-TWA 35–36 °C), and severe hypothermia (S-TWA < 35 °C). Results: Starting from 254 consecutive patients, 95 were included in the final analysis, classified according to intraoperative temperature: S-TWA = 19 (20%), M-TWA = 62 (65.3%), and N-TWA = 14 (14.7%). S-TWA was related to lower BMI (p = 0.001), diagnosis of squamous cell carcinoma (p = 0.029), and shorter operation times (p = 0.006). In the same way, AL was more related to S-TWA when compared with M-TWA and N-TWA (31.6% vs. 6.5% vs. 14.3%, p = 0.015). After multivariate analysis, S-TWA remained as the only predictive factor of AL (OR 5.385, 95%CI 1.502; 19.310; p = 0.010). Instead, higher BMI was found to be a protective factor for S-TWA (OR 0.818, 95%CI 0.723; 0.926: p = 0.001). Conclusions: S-TWA seems to be a major independent risk factor for AL after IL esophagectomy. Implementation of perioperative measures, aimed to prevent severe intraoperative hypothermia, could potentially be crucial to improve surgical outcomes
Relationships between hypometabolism and both β‐amyloid and tau PET in corticobasal syndrome
Get PDFINTRODUCTION: Alzheimer's disease (AD) pathology causes corticobasal syndrome (CBS) in 21%-50% of patients. Studies have assessed hypometabolism in CBS according to beta-amyloid (A) positron emission tomography (PET), but the understanding of the association of both AD-tau (T) and A with hypometabolism is incomplete. METHODS: Thirty-three CBS patients and 45 controls underwent fluorodeoxyglucose (FDG), flortaucipir, and Pittsburgh compound-B PET and were classified as A +/- and T +/-. FDG-PET uptake was extracted for 12 regions-of-interest in dominant (most affected) and non-dominant hemispheres and compared across A/T groups. RESULTS: A+T+ patients had greater hypometabolism in temporo-parieto-occipital cortices than A+T- and A-T- groups, with no differences observed between the A+T- and A-T- groups. FDG asymmetry was more accentuated in A+T+ patients. Medial temporal and basal ganglia metabolism were similar across AT groups. DISCUSSION: Amyloid and tau positivity contribute synergistically to hypometabolism and asymmetry in temporo-parieto-occipital cortices in CBS, with AD-like patterns of hypometabolism observed only in A+T+ patients
Atezolizumab plus bevacizumab versus Lenvatinib for patients with Barcelona clinic liver cancer stage B (BCLC-B) hepatocellular carcinoma (HCC): A real-world population
Get PDFBackground: The aim of the present study was to perform a real-world analysis on a large patient cohort with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (A + B) or with Lenvatinib. Methods: The study population included patients affected with Barcelona Clinic Liver Cancer stage B (BCLC-B) hepatocellular carcinoma not suitable for locoregional therapies (LRTs) from eastern and western populations, who received atezolizumab plus bevacizumab (A + B) or Lenvatinib as first-line treatment. Univariate and multivariate analyses were used to evaluate predictive factors for overall survival (OS) and time to progression (TTP) while prognostic factors were analyzed by univariate and multivariate analysis using Cox regression model. Results: 919 patients with BCLC-B HCC were analyzed in the study. Lenvatinib was administered to 561 (61%) patients while 358 (39%) received A + B. The median overall survival (mOS) for patients receiving Lenvatinib was 21.3 months compared to 15.8 months for patients receiving A + B as first-line treatment (Lenvatinib v A + B), hazard ratio (HRs) 0.84 P = 0.22. The median time to progression (mTTP) for patients receiving Lenvatinib was 7.3 months compared to 8.7 months for patients receiving A + B as first-line treatment (Lenvatinib v A + B): HR 1.15 P = 0.10. Multivariate analysis confirmed no different in terms of mOS and mTTP between the two treatments. Objective response rate (ORR) was 47.1% for patients receiving Lenvatinib and 27.1% for patients receiving A + B P < 0.000001. Patients receiving Lenvatinib experienced a significantly higher incidence of hand-foot skin reaction (HFSR), hypertension, diarrhea, fatigue, decrease appetite, hypothyroidism, and other toxicity compared to patients receiving A + B. Favorable prognostic factors for OS in Lenvatinib group were platelets (PLT) >100.000 (HR 0.68 P = 0.02), HCC nonalcoholic steatohepatitis/nonalcoholic fatty liver disease (NASH/NAFLD) related (HR 0.53, P = 0.03). No favorable prognostic factors were found for A + B group. Favorable prognostic factors for TTP in the A + B group were in TACE refractory patients (HR 0.76, P = 0.02), PLT <100.000 (HR 0.62, P = 0.0067), and neutrophil-to-lymphocyte ratio (NLR) < 3 (HR 0.78, P = 0.04). Conclusion: Although Lenvatinib had a higher response rate, the study showed no statistically significant differences between Lenvatinib and A + B in terms of efficacy, in patients with BCLC-B HCC