The PANSS Autism Severity Score (PAUSS) has recently become a popular measure of autistic features in psychosis populations, but evidence on its longitudinal reliability and factor configuration is poor. The aims of this investigation were to examine psychometric characteristics of the PAUSS in young patients with First Episode Psychosis (FEP) treated in an early intervention service, with primary interest for its long-term stability across 2 years of follow-up and factor configuration. All FEP participants completed the Positive And Negative Syndrome Scale (PANSS) and Autism Quotient (AQ) at baseline and across the follow-up. Statistical analysis mainly included Cronbach’s α to examine internal consistency of the PAUSS, Cohen’s k statistics and Spearman’s ρ correlation coefficients for its longitudinal stability and convergent validity with AQ scores, and exploratory factor analysis to explore its dimensions’ configuration. 301 FEP participants were recruited (170 with Schizophrenia Spectrum Disorder [SSD]). Cronbach’s α value for the PAUSS was 0.806, but with unacceptable inter-item correlations for PANSS G5 and G15 items. K value for examining PAUSS convergent validity with AQ score was unacceptable (0.295), as well as ρ and k values to quantify long-term test-retest reliability (< 0.750 and < 0.600, respectively). No long-term stability of the PAUSS scores across the follow-up was also found using Wilcoxon’s test for repeated measure. Our EFA found a 2-factor model in the FEP total sample and a 3-factor configuration in the SSD subgroup. Our results suggest that the PAUSS does not represent a valid instrument to assess autistic features in FEP and SSD. Indeed, the it probably captures psychotic symptom severity rather than autistic features, especially reflecting negative symptom load.
Enzalutamide (ENZA), a next-generation non-steroidal androgen receptor (AR) inhibitor, plays a pivotal role in the management of both hormone-sensitive (HSPC) and androgen deprivation-resistant prostate cancer (ARPC). This paper presents real-world clinical outcomes of ENZA in a subgroup of metastatic HSPC (mHSPC) patients included in the ARON-3 study. Clinical information was extracted retrospectively from medical records at 29 cancer centres in 9 countries worldwide. Overall Survival (OS) was calculated from starting ENZA to death from any cause and the time on treatment (ToT) from ENZA initiation to discontinuation for any reason. The Kaplan–Meier method was used to estimate OS and ToT. PSA90 was defined as a ≥90% PSA reduction from baseline, and PSA0.2 as the achievement of an ultra-low PSA level ≤0.2 ng/ml. Adverse events (AEs) were categorised according to Common Terminology Criteria for Adverse Events v5.0. The study population comprised 424 patients treated with ENZA for mHSPC, of whom 80 (19%) had lymph node-only metastases, 265 (63%) bone-only metastases, and 50 (12%) visceral metastases. 273 patients (64%) had synchronous metastases and 151 (36%) had developed metachronous metastases. A total of 228 patients were diagnosed with low-volume disease, and 196 patients (46%) with high-volume disease. The median ToT was 31.8 months, and the median OS was not reached. The median time to PSA90 (achieved in 76% of patients) and PSA0.2 (59% of patients) was 6.0 months and 8.3 months, respectively. Statistically significant associations were identified between lymph node-only patterns, PSA90 and ultra-low PSA responses, and longer treatment duration and better overall survival. Grade 3–4 AEs were observed in 9% of patients <70 years and in 10% ≥70 years. Real-world clinical practice corroborates the findings from clinical trials, confirming the effectiveness and safety of ENZA in mHSPC patients.
Hepatocellular carcinoma (HCC) is one of the most common cancers and the third leading cause of cancer-related death worldwide. The prognosis is poor, with a median survival of 12–15 months in patients with advanced-stage disease. Early diagnosis and the development of new, more effective therapeutic strategies are needed to address the challenges posed by this malignancy. Although immune checkpoint inhibitors have replaced multikinase inhibitors as first-line therapy, sorafenib continues to represent a valuable option for patients with contraindications to newer treatments. Based on genome-wide RNA-seq analysis, which identified mitochondrial oxidative phosphorylation (OxPhos) and Hmox1 upregulation as potential pro-survival mechanisms in sorafenib-resistant cells, we investigated whether SR9009, a synthetic agonist of the nuclear receptor REV-ERBα/β, heme competitor, and inhibitor of mitochondrial respiration, could enhance the antitumor efficacy of sorafenib in liver cancer models. Co-treatment with SR9009 and sorafenib significantly enhanced cytotoxic effects in both mouse and human liver cancer cells. This synergistic activity was associated with increased levels of free heme and a complete inhibition of mitochondrial OxPhos. In vivo xenograft studies confirmed that the combination was effective even in sorafenib-resistant tumors. Furthermore, in a N-Nitrosodiethylamine (DEN)-induced HCC model, the combination therapy led to a reduction in size in over 90% of tumor nodules, representing a significant improvement over sorafenib alone. The combination was well tolerated, with no evident signs of acute toxicity. These findings support the concept that the efficacy of anticancer therapies can be enhanced by targeting the metabolic adaptations that tumor cells rely on for survival. Combining sorafenib with agents like SR9009, that disrupt metabolic homeostasis, may offer a promising strategy for treating advanced HCC.
OBJECTIVES:The primary objective of this study was to identify potential prognostic factors influencing disease control and survival outcomes in patients with neck metastases (NLM) and/or intraparotid metastases (PLM) arising from cutaneous squamous cell carcinoma (cSCC) of the head and neck. A secondary aim was to compare patients with isolated NLM, isolated PLM, and concurrent NLM/PLM. STUDY DESIGN AND METHODS:An observational, retrospective multicenter study included 68 patients with nodal metastatic cSCC treated at the Head and Neck Units of Bologna, Modena, and Pescara (2014-2024). Clinical, pathological, and treatment variables were analyzed for associations with survival using univariate and multivariate Cox regression models (IBM SPSS). RESULTS:The cohort included 30 patients with isolated NLM (44%), 14 with isolated PLM (21%), and 24 with both NLM and PLM (35%). At 5 years, DFS was 33.8%, DSS 70.6%, and OS 69.1%. DFS was reduced by extranodal extension (ENE) in PLM (HR 3.95, 95% CI 1.65-9.48, p = .002). DSS was negatively influenced by perineural invasion (HR 4.53, 95% CI 1.02-34.44, p= 0.016), NLM ENE (HR 5.60, 95% CI 1.72-18.19, p = 0.004), and PLM ENE (HR 8.90, 95% CI 2.51-18.90, p < 0.001). OS was independently worsened by PNI (HR 6.16, 95% CI 1.20-31.39, p = 0.029), NLM ENE (HR 5.18, 95% CI 1.67-16.03, p= 0.004), and PLM ENE (HR 7.03, 95% CI 2.24-22.07, p < 0.001). Female sex (36% in isolated PLM vs 3% in isolated NLM, p = .004) and immunosuppression (67% in patients with both NLM and PLM, p = 0.02) were significantly associated with nodal dissemination pattern, but not with survival. CONCLUSION:This study highlights the prognostic relevance of PNI, ENE, advanced nodal stage, and lack of adjuvant RT in nodal metastatic cSCC. Immunosuppression and female sex appear more related to higher nodal dissemination patterns than to survival.
BackgroundThe concept of tumor-vessel detachment (R1 vascular [R1v]), has recently gained attention within the minimally invasive (MI) setting, but its oncological adequacy remains poorly defined. This meta-analysis aims to assess the outcomes of MI-R1v hepatectomy for hepatocellular carcinoma (HCC) and colorectal liver metastases (CLM).Patients and MethodsA literature search was conducted in MEDLINE, Embase, and Cochrane Library to identify studies reporting local recurrence (LR) rates following MI-R1v for HCC and CLM. Secondary outcomes included the extent of hepatectomy (major versus parenchyma-sparing), tumor burden (monofocal versus multifocal), intrahepatic recurrence, and overall survival (OS).ResultsIn total, eight studies comprising 839 patients (410 HCC and 429 CLM) were included. In HCC, LR rates were comparable between R1v and R0 (5.6% versus 7.9%; odds ratio [OR] 1.2, 95% confidence interval [CI] 0.25-6.1; p = 0.79), whereas in CLM, LR was higher after R1v (12.3% versus 6.4%; OR 3.4, 95% CI 1.10-10.54; p = 0.03). Robotic and laparoscopic R1v resections showed similar LR rates in both HCC (2.8% versus 4.8%; p = 0.82) and CLM (15% versus 12%; p = 0.08). No significant differences were observed between MI-R1v and MI-R0 resections in terms of extent of hepatectomy, tumor burden, intrahepatic recurrence, or OS in either group.ConclusionsThe comparable LR rates suggest that the R1v approach is oncologically acceptable for HCC in the MI setting, supporting its use when R0 cannot be achieved without a major hepatectomy. The higher LR rates in R1v for CLM resections require cautious patient selection and further standardization. Prospective studies are needed to define clear oncological benchmarks for MI-R1v procedures.
