IRIS UniSR (’Università Vita-Salute San Raffaele)
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Erythema multiforme major presenting in a teenager with anti-N-Methyl-D-Aspartate receptor encephalitis
No full textHead-to-head comparison of nephrometry scores for partial nephrectomy: implications for clinical guidelines
No full textIntroduction: Several nephrometry scores aim to predict partial nephrectomy (PN) outcomes. Since consensus regarding the best score is lacking, we performed a prospective head-to-head comparison of the most widely used. Materials and methods: A dedicated uroradiologist prospectively reviewed preoperative CT scan to assign points to variables of interest included in RENAL, PADUA, SPARE, C-Index, DAP, and MAP score, in 202 renal cell carcinoma (RCC) surgical candidates. The primary outcome was surgical success, defined as PN completion, absence of grade > II Clavien-Dindo complications, ischemia time ≤20 min, and negative surgical margins. The secondary outcome was PN completion relative to radical nephrectomy (RN). Multivariable logistic regression (MLR) models predicted study outcomes after adjusting for age, gender, ECOG performance status, preoperative renal function, and surgical approach. Receiver operating characteristic (ROC) and area under the curve (AUC) compared each nephrometry accuracy. Results: Surgical success and PN completion rates were 31 % and 60 %, respectively. At MLR, RENAL, PADUA, SPARE, DAP, and MAP scores independently predicted both outcomes (p < 0.001). The highest predictive accuracy for surgical success and PN completion was recorded for SPARE (AUC: 0.79 and 0.89). Intermediate accuracy was recorded for RENAL (AUC: 0.78 and 0.85), PADUA (AUC: 0.78 and 0.86), DAP (AUC: 0.76 and 0.85) and C-Index (AUC: 0.73 and 0.77). The lowest accuracy was recorded for MAP (AUC: 0.65 and 0.68). Conclusion: Nephrometries are associated with surgical success and PN completion. In clinical practice, the use of SPARE should be privileged based on the highest predictive accuracy for both endpoints
2025 ESVM Guidelines on interventional treatment of venous thromboembolism
No full textThe number of endovascular interventional procedures for catheter-based therapy (CBT) of acute venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), has been increasing over the past years. The development of more efficient thrombectomy systems for CBT of VTE has potentially enhanced the efficacy of interventional treatment of VTE. Nevertheless, indications for CBT of VTE, i.e. catheter-directed thrombolysis (CDT) or catheter-based mechanical thrombus removal, need to be established based on existing data and expert consensus. Vascular experts should be involved in the decision-making process on CBTs in patients with acute VTE, and thrombus removal procedures should be performed in centers with experience in interventional treatment of VTE. This guideline document of the European Society of Vascular Medicine (ESVM) provides recommendations on indications and management of CBT in acute VTE and is endorsed by the European national societies of Vascular Medicine
Fibroblasts and hiPS-Derived Astrocytes From CoPAN Patients Showed Different Levels of Iron Overload Correlated With Senescent Phenotype
No full textCOASY protein-associated neurodegeneration (CoPAN) is a rare autosomal recessive disorder within the Neurodegeneration with Brain Iron Accumulation spectrum, resulting from mutations in COASY. This gene encodes the bifunctional enzyme essential for the final steps of coenzyme A biosynthesis. To elucidate the pathophysiology and iron dyshomeostasis underlying CoPAN, we analyzed fibroblasts and human induced pluripotent stem (hiPS)-derived astrocytes from two patients carrying distinct COASY mutations. Our findings reveal that CoPAN fibroblasts display altered iron homeostasis, characterized by iron aggregates, elevated cytosolic labile iron pool, and impaired tubulin acetylation. Patients hiPS-derived astrocytes showed mitochondrial morphological abnormalities and compromised vesicular trafficking. Notably, both cell types demonstrated evidence of ferroptosis, but the astrocytes exhibited more pronounced iron accumulation and lipid peroxidation. These results demonstrate that astrocytes may more accurately recapitulate the pathological phenotype of CoPAN compared to fibroblasts. Interestingly, astrocytes exhibited different levels of iron accumulation concomitant with cellular senescence, indicating a possible role of iron-induced cellular senescence. This finding suggests that the accumulation of cytosolic iron, possibly caused by mitochondrial dysfunction, actively promotes senescence. Our data emphasize the potential therapeutic efficacy of drugs that enhance mitochondrial functionality to attenuate the effects of CoPAN
Home-based prehabilitation: a systematic review and meta-analysis of randomised trials
No full textBackground: Prehabilitation aims to enhance preoperative functional capacity through exercise, nutrition, and psychological programs. Home-based prehabilitation represents an alternative to hospital prehabilitation, with the advantage of not utilising hospital resources. This review aims to evaluate adherence and clinical effectiveness of home-based prehabilitation. Methods: We searched PubMed, Cochrane, and Embase up to October 1, 2024 for randomised controlled trials comparing home-based prehabilitation with standard care. The primary outcome was the proportion of patients with postoperative complications. Secondary outcomes included protocol adherence, and 6-min walking test. We used risk ratios (RR) and mean differences to summarise the results. The risk of bias was assessed using RoB 2 tool. Results: We included 29 randomised trials for a total of 3508 patients. Median adherence to home-based prehabilitation programs was 82%. Home-based prehabilitation reduced the proportion of patients with postoperative complications (508/1322 [38.4%] vs 578/1335 [43.3%], risk ratio 0.84, 95% confidence interval [CI] 0.72–0.98, P=0.02, I2=44%, low certainty). After home-based prehabilitation, 6-min walking test performance was better compared with control (MD 28.2 m (95% CI 9.5–46.9; P<0.01, I2=48). Preoperative depression (MD −0.65, 95% CI −0.87 to −0.43; P<0.001, I2=0%), postoperative anxiety (MD −0.50, 95% CI −0.75 to −0.25; P<0.001, I2=0%, low certainty) and length of hospital stays (MD −0.32 days, 95% CI −0.61 to −0.03; P=0.03, I2=45%, low certainty) were lower with home-based prehabilitation. Conclusions: Home-based prehabilitation reduced the proportion of patients with postoperative complications, but with low certainty of evidence. It also improved preoperative functional capacity, reduced hospital stays, depression and anxiety scores, with good adherence to the intervention. Systematic review protocol: PROSPERO (CRD42024591208).Background: Prehabilitation aims to enhance preoperative functional capacity through exercise, nutrition, and psychological programs. Home-based prehabilitation represents an alternative to hospital prehabilitation, with the advantage of not utilising hospital resources. This review aims to evaluate adherence and clinical effectiveness of home-based prehabilitation. Methods: We searched PubMed, Cochrane, and Embase up to October 1, 2024 for randomised controlled trials comparing home-based prehabilitation with standard care. The primary outcome was the proportion of patients with postoperative complications. Secondary outcomes included protocol adherence, and 6-min walking test. We used risk ratios (RR) and mean differences to summarise the results. The risk of bias was assessed using RoB 2 tool. Results: We included 29 randomised trials for a total of 3508 patients. Median adherence to home-based prehabilitation programs was 82%. Home-based prehabilitation reduced the proportion of patients with postoperative complications (508/1322 [38.4%] vs 578/1335 [43.3%], risk ratio 0.84, 95% confidence interval [CI] 0.72–0.98, P=0.02, I2=44%, low certainty). After home-based prehabilitation, 6-min walking test performance was better compared with control (MD 28.2 m (95% CI 9.5–46.9; P<0.01, I2=48). Preoperative depression (MD −0.65, 95% CI −0.87 to −0.43; P<0.001, I2=0%), postoperative anxiety (MD −0.50, 95% CI −0.75 to −0.25; P<0.001, I2=0%, low certainty) and length of hospital stays (MD −0.32 days, 95% CI −0.61 to −0.03; P=0.03, I2=45%, low certainty) were lower with home-based prehabilitation. Conclusions: Home-based prehabilitation reduced the proportion of patients with postoperative complications, but with low certainty of evidence. It also improved preoperative functional capacity, reduced hospital stays, depression and anxiety scores, with good adherence to the intervention. Systematic review protocol: PROSPERO (CRD42024591208)
Clinical and transcriptomic characterization of patients with chronic lymphocytic leukemia harboring t(14;19): an ERIC study
No full textIn chronic lymphocytic leukemia (CLL), the role of complex karyotype (CK) for prognostic stratification remains a topic of debate, and the impact of specific cytogenetic abnormalities is still unclear. This study aims to investigate the clinical and biological features of CLL with t(14;19)(q32;q13) (tCLL) involving the BCL3 gene. Patients with tCLL were younger and more commonly presented unmutated IGHV gene, subset #8 stereotypy, trisomy of chromosome 12, and complex karyotype than other patients without t(14;19) (oCLL). The presence of t(14;19) was associated with a shorter time to treatment and overall survival compared to oCLL. Gene expression analysis revealed a unique transcriptome profile in tCLL, characterized by the upregulation of BCL3 and the activation of B-cell receptor, PI3K-Akt. Conversely, apoptosis-related pathways were suppressed in tCLL. While the BTK gene was upregulated, the BCL2L11 gene, coding for the pro-apoptotic protein BIM, was downregulated. Notably, patients with tCLL were characterized by a trend (p = 0.058) for a longer time to the next treatment with BTK inhibitors (BTKi) compared to those treated with a venetoclax-based (Ven-based) regimen. We underscore the adverse outcomes of tCLL, its distinct molecular features and gene expression patterns. Therefore, our data suggest that identifying tCLL could help tailor therapeutic approaches
Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types
No full textGlucagon-like peptide-1 receptor (GLP-1R) agonists, such as exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), albiglutide (Tanzeum), dulaglutide (Trulicity), lixisenatide (Lyxumia, Adlyxin), semaglutide (Ozempic, Rybelsus, Wegovy), and tirzepatide (Mounjaro, Zepbound), are widely used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. While these agents are well known for their metabolic benefits, there is growing interest in their potential effects on cancer biology. However, the role of GLP-1R agonists in cancer remains complex and not fully understood, particularly across different tumor types. This study aimed to evaluate the prognostic significance of GLP1R expression on overall survival across various cancer types. Using a comprehensive analysis of gene expression data and survival outcomes a large cohorts of different tumor types, we employed Cox proportional hazards survival analyses, coupled with false discovery rate determinations, to explore correlations between GLP1R expression and survival. The integrated database included thousands of cancer specimens with available overall survival time and event data from numerous independent cohorts, providing a robust platform for survival analysis. Our findings reveal that increased GLP1R expression is associated with improved overall survival in cancers such as bladder cancer, breast cancer, esophageal adenocarcinoma, renal clear cell carcinoma, and thyroid carcinoma. Conversely, higher GLP1R expression is linked to poorer survival outcomes in cervical squamous cell carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Additionally, GLP1R expression showed no significant impact on overall survival in cancers such as esophageal squamous cell carcinoma, colon cancer, head-neck squamous cell carcinoma, renal papillary cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, ovarian cancer, and pancreatic cancer. In conclusion, GLP1R expression levels serve as an important biomarker with potential prognostic significance across multiple cancers, demonstrating both protective and adverse associations depending on the tumor type. These findings highlight the complex role of GLP-1R agonists in cancer risk and survival, suggesting that the therapeutic use of these agents should be carefully tailored to the individual patient’s cancer risk profile
Patients’ Attitude toward Less Frequent Surveillance of Low-Risk Pancreatic Cysts: A Multicenter European Cohort Study
No full textBackground: Recent studies show that low-risk pancreatic cysts may require less frequent monitoring. Future guidelines will likely adapt their recommendations accordingly. Our goal was to explore the willingness of individuals with a low-risk pancreatic cyst to undergo less frequent surveillance and to identify associated characteristics with such willingness. Methods: This is a side study of the international PACYFIC study, which prospectively collects data on cyst surveillance, including questionnaires to assess participants’ attitude toward surveillance. Individuals with low-risk cysts at baseline, without given standardized information by the study protocol, were enrolled. Their responses to the baseline question, “Would you prefer less frequent surveillance? Yes/No,” were correlated with baseline characteristics using multivariable logistic regression, namely, age, country of residence, symptoms, medical and family history, time since first cyst detection, and Hospital Anxiety Depression Scale score. Results: Of the 215 participants included from the Netherlands (n = 185) and Italy (n = 30), only 47 (22%) were willing to undergo less surveillance. Characteristics positively associated with this willingness were older age (odds ratio [OR] 1.87 per 10 y, 95% confidence interval [CI]: 1.15–3.04) and Italian residency (OR 16.35, 95% CI: 5.65–47.31). A medical history of cancer was negatively associated (OR 0.28, 95% CI: 0.09–0.90). No other associations were observed. Conclusion: Most participants appear unwilling to undergo less frequent cyst surveillance. Older age and residing in Italy were associated with a greater willingness toward less rigorous surveillance, while a history of cancer did the opposite. Identifying which individuals are hesitant to undergo less frequent surveillance may help clinicians tailor their counseling and can support implementation of future guideline with fewer surveillance recommendations. Highlights: Most low-risk individuals were reluctant toward less frequent pancreatic cyst surveillance.Older age and residency in Italy were associated with a higher willingness.A medical history of cancer was associated with an unwillingness.Standardized patient information may increase the willingness, but such information has yet to be developed
The Relevance of Right Ventricular Function and Dimension in Patients Undergoing Transcatheter Tricuspid Edge-to-Edge Repair
No full textBackground: Patients with severe tricuspid regurgitation (TR) often present with abnormal right ventricular (RV) function and dimensions. Objectives: The aim of this study was to investigate the impact of RV dysfunction and dilation on clinical outcomes in patients undergoing transcatheter tricuspid edge-to-edge repair (T-TEER). Methods: Patients from the international EuroTR registry undergoing T-TEER between 2016 and 2023 at 20 heart valve centers across Europe were included. RV dysfunction was defined as tricuspid annular plane systolic excursion <17 mm, and RV dilation was defined as RV mid-diameter >35 mm, determined on baseline echocardiography. Results: A total of 2,191 patients (mean age 78 ± 7 years, 53% [1,111 of 2,092] women) were analyzed. TR was successfully reduced to a severity grade of ≤2+ in 80% of patients (1,608 of 2,001). In multivariable analysis, significant predictors of mortality after T-TEER included RV dysfunction (HR: 1.05 per 1-mm tricuspid annular plane systolic excursion decrease; 95% CI: 1.03-1.08), RV dilation (HR: 1.02 per 1-mm RV mid-diameter increase; 95% CI: 1.00-1.03), and residual TR after T-TEER (HR: 1.70 for TR grade ≤2; 95% CI: 1.36-2.13). These parameters were also predictive of the combined endpoint of mortality and heart failure hospitalization. The worst prognosis was observed in patients exhibiting both RV dysfunction and dilation. Conclusions: RV size and function, along with residual TR severity, were significant predictors of clinical outcomes, including all-cause mortality and heart failure hospitalization. Accordingly, early intervention to prevent RV dilation and dysfunction, as well as achieving maximal TR reduction, appears crucial for improving prognosis in patients undergoing T-TEER