IRIS UniSR (’Università Vita-Salute San Raffaele)
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Zanubrutinib and Venetoclax for Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With and Without Del(17p)/ TP53 Mutation: SEQUOIA Arm D Results
No full textPURPOSESeveral chronic lymphocytic leukemia (CLL) studies have demonstrated promising efficacy with the combination of BCL2 and Bruton tyrosine kinase inhibitors; however, patients with CLL with del(17p) and/or TP53 mutation (TP53mut) comprised a small percentage of study populations or were excluded entirely. The purpose of the SEQUOIA Arm D cohort was to evaluate the combination of zanubrutinib + venetoclax in treatment-naïve (TN) patients with CLL/small lymphocytic lymphoma (SLL), in a large population of patients with TP53-aberrant disease.PATIENTS AND METHODSArm D is a nonrandomized cohort of patients aged 65 years and older (or 18-64 years with comorbidities). Patients received zanubrutinib from cycle 1 and venetoclax from cycle 4 (ramp-up) to cycle 28, followed by continuous zanubrutinib monotherapy until progressive disease (PD), unacceptable toxicity, or meeting undetectable minimal residual disease (uMRD)-guided stopping criteria.RESULTSBetween November 2019 and July 2022, 114 patients were enrolled: 66 (58%) with TP53-aberrant disease, 47 (41%) without TP53-aberrant disease, and 1 with missing TP53 results. At a median follow-up of 31.2 months, 85 patients (75%) remained on zanubrutinib monotherapy; 29 patients (25%) discontinued zanubrutinib because of adverse event, uMRD-guided stopping criteria, PD, or other. In the intention-to-treat population, 59% of patients achieved peripheral blood uMRD. The 24-month progression-free survival estimate was 92% (95% CI, 85% to 96%). The most common any-grade treatment-emergent AEs (TEAEs) were COVID-19 (54%), diarrhea (41%), contusion (32%), and nausea (30%). The most common grade ≥3 TEAEs were neutropenia (17%), hypertension (10%), diarrhea (6%), and decreased neutrophil count (6%).CONCLUSIONZanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL/SLL, regardless of the presence of TP53-aberrant disease
Advancing Therapeutic Targets in IBD: Emerging Goals and Precision Medicine Approaches
Full text linkInflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, relapsing conditions characterized by dysregulated immune responses and persistent intestinal inflammation. This review aims to examine new potential therapeutic targets in IBD starting from the STRIDE-II statements. Key targets now include clinical remission, endoscopic remission, and biomarker normalization (such as C-reactive protein and fecal calprotectin). Moreover, histologic remission, transmural remission, and in the future molecular targets are emerging as important indicators of sustained disease control. The treatment goals for inflammatory bowel disease are varied: to relieve symptoms, prevent permanent intestinal damage, promote inflammation remission, and minimize complications. Consequently, the therapeutic targets have evolved to become broader and more ambitious. Integrating these advanced therapeutic targets has the potential to redefine IBD management by promoting deeper disease control and improved patient outcomes. Further research is essential to validate these strategies and optimize their clinical implementation
Comorbidities, Socioeconomic Status, and Colorectal Cancer Diagnostic Route
Full text linkIMPORTANCE Reducing emergency cancer diagnoses is a public health priority, as they are associated with worse outcomes. Preexisting chronic conditions can influence screening participation and emergency cancer diagnosis; however, evidence is mixed, and data from Southern Europe are scant. OBJECTIVE To examine variations in the likelihood of colorectal cancer (CRC) diagnosis following an emergency presentation (EP) or screening by patient comorbidity status and socioeconomic characteristics and to investigate the association of patient characteristics, diagnostic route, and comorbidity status with short-term CRC mortality. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used linked cancer registry data and administrative health data from the Agency for Health Protection of Milan, Italy, for CRC cases diagnosed between July 1, 2014, and December 31, 2020, in the provinces of Milan and Lodi, Italy. Data were analyzed from January 1 to October 1, 2024. EXPOSURES Comorbidity status (number of comorbidities, specific preexisting comorbidities) and socioeconomic characteristics (including age, sex, and deprivation index). MAIN OUTCOMES AND MEASURES The primary outcomes were routes to cancer diagnosis (screening, emergency presentation, or inpatient or outpatient visits), cancer stage at diagnosis, and short-term mortality (30 days and 1 year). Multivariable and multinomial logistic regression models were used to estimate odds ratios (ORs) adjusted for socioeconomic and comorbidity factors. RESULTS Among 14 457 patients, 10 750 (74.4%) had colon cancer and 3707 (25.6%) had rectal cancer. The route to diagnosis was reconstructed for 10 514 patients with colon cancer (97.8%; median age, 73.1 years [IQR, 66-82 years]; 5563 [52.9%] male) and 3635 with rectal cancer (98.1%; median age, 70.3 years [IQR, 62-80 years]; 2079 [57.2%] male). Of those, 4697 patients with colon cancer (44.6%) and 2094 with rectal cancer (57.6%) had comorbidities, emergency diagnosis occurred in 3738 colon (35.6%) and 823 rectal (22.6%) cancer cases, and diagnosis while screening occurred in 881 colon (8.4%) and 347 rectal (9.5%) cancer cases. Emergency diagnosis was associated with having cerebrovascular (adjusted OR [AOR], 1.50; 95% CI, 1.23-1.82) and neurological (AOR, 1.67; 95% CI, 1.33-2.09) diseases or having 3 or more comorbidities compared with having none (AOR, 1.78; 95% CI, 1.47-2.16) among patients with colon cancer. Having 3 or more vs no comorbidities was associated with lower odds of screening-detected colon cancer (AOR, 0.64; 95% CI, 0.45-0.91). Higher 30-day (AOR, 4.84; 95% CI, 2.81-8.33) and 1-year (AOR, 2.77; 95% CI, 2.17-3.53) mortality was associated with emergency presentation. The COVID-19 period was associated with higher odds of emergency diagnoses compared with the prepandemic period (AOR, 1.32; 95% CI, 1.15-1.52). CONCLUSIONS AND RELEVANCE In this cohort study of patients with CRC in Italy, emergency diagnosis occurred for more than 1 in 3 patients with colon cancer. Having 3 or more comorbidities was associated with a lower likelihood of screening detection and higher odds of emergency diagnosis. Tailored interventions are needed to facilitate screening, to reduce emergency cancer diagnoses, and to improve outcomes for patients with chronic conditions
From intrinsic to adaptive clusters in breast cancer
No full textThe heterogeneity of breast cancers and the availability of several therapeutic options requires prognostic and predictive tools for tailoring adjuvant treatments. In this issue of Cancer Cell, Denkert et al. analyze longitudinal gene-expression data from the Penelope-B trial and identify five adaptive clusters with independent prognostic value to established signatures
Mitral valve surgery after failed transcatheter intervention for mitral regurgitation: surgical techniques, challenges and outcomes
No full textThe S-RACE Platform: A cloud-based solution for real-world health data, driving clinical translation and responsible governance of artificial intelligence
No full textThe S-RACE platform is a cloud-based AI solution for using real-world health data. It addresses data quality and governance challenges with an end-to-end pipeline, including on-premise anonymisation and tools for clinicians and data scientists. Aligned with responsible AI principles, it aims to accelerate the translation of AI research into clinical practice, improving patient care
The Effect of Plaque Detectors on the Color Stability of Two Types of Restorative Materials
Full text linkObjective: To investigate the color stability of a one-shade resin-based composite material (RC) and a glass-ionomer cement (GIC) after staining with plaque detectors (PDs) with different formulations and delivery forms. Materials and Methods: Rectangular-shaped specimens (7 × 3 × 2 mm) were produced with RC (Venus Diamond One, Kulzer) and GIC (Fujy IX GP, GC) (n = 30). Further, the following PDs were used on the specimens: (1) tablets (T; Plaq-Search, TePe); (2) mouthwash (M; Plaque Agent, Miradent); and (3) light-curing liquid (L; Plaque test, Ivoclar). The PDs were removed with dedicated toothbrushes (T1) and the specimens were repolished (T2). The protocol was repeated after 1 week of storage in artificial saliva (staining—T3 and repolishing—T4). Color measurement were performed at baseline (T0) and all testing times (T1—T4) using a recently introduced digital colorimeter (SmartColor, Smart Vision). Color changes (ΔEab) compared to T0 were automatically recorded by the digital instrument. The data were statistically analyzed (p < 0.05). Results: The type of PD, the polishing procedure and their interactions influenced the color stability of both restorative materials (p < 0.05). Particularly, after the second PDs application, M and L produced the highest color changes (p < 0.05), with GIC showing higher color variability than RC. Although repolishing reduced the color changes of RC (p < 0.05), it could not reestablish the initial color of GIC, irrespective of the PD used (p < 0.05). Except for RC associated with T, all materials exhibited discoloration above the clinical perceptibility (1.77) and acceptability (2.66) thresholds. Conclusions: The influence of PDs on the color stability of RC and GIC was material-dependent. GIC showed higher color instability than RC. Repolishing could not reestablish the original color of GIC and only attenuated the color changes of the one-shade RC. The newly introduced digital colorimeter was an important tool to standardize and simplify color measurement evaluations. Clinical Significance: PDs can pose a potential risk to the color stability of restorative materials. Dental practitioners should be careful when recommending the frequency of at-home application of PDs, taking into consideration the material properties and the position of the restorations of each patient
Predicting the complexity of minimally invasive liver resection for hepatocellular carcinoma using machine learning
No full textBackground: Despite technical advancements, minimally invasive liver surgery (MILS) for hepatocellular carcinoma (HCC) remains challenging. Nonetheless, effective tools to assess MILS complexity are still lacking. Machine learning (ML) models could improve the accuracy of such tools. Methods: Patients who underwent curative-intent MILS for HCC were identified using an international database. An XGBoost ML model was developed to predict surgical complexity using clinical and radiological characteristics. Results: Among 845 patients, 186 (22.0 %) were classified as high-risk patients. In this subgroup, median Charlson Comorbidity Index (CCI) (5.0, IQR 3.0–7.0 vs. 2.0, IQR 2.0–5.0, p < 0.001) and tumor burden score (TBS) (median 4.12, IQR 3.0–5.1 vs. 4.22, IQR 3.2–7.1, p < 0.001) were higher. The model was able to effectively predict complexity of surgery in both the training and testing cohorts with high discriminating power (ROC-AUC: 0.86, 95%CI 0.82–0.89 vs. 0.73, 95%CI 0.65–0.81). The most influential variables were CCI, TBS, BMI, extent of resection, and sex. Patients predicted to have a complex surgery were more likely to develop severe complications (OR 4.77, 95%CI 1.82–13.9, p = 0.002). An easy-to-use calculator was developed. Conclusion: Preoperative ML-prediction of complex MILS for HCC may improve preoperative planning, resource allocation, and patient outcomes
Predictability of ClinCheck in Overbite Correction with Aligners: A Systematic Review
No full textBackground: The use of aligner therapy for open bite and deep bite correction has increased in contemporary society. There is no evidence that unify the results present the in literature regarding a real comparison between clinical outcomes and the results predicted by the ClinCheck software 3.0 (Align Technology, Santa Clara, CA, USA). Furthermore, the literature shows conflicting data about the protocols and not all authors compare the programmed movements and the clinical results obtained for the overbite correction. Therefore, the aim of this systematic review is to assess the predictability of ClinCheck in the correction of vertical discrepancies by comparing the planned outcomes with the actual clinical results performed with clear aligners. Methods: The research question focused on the effectiveness of ClinCheck in predicting the actual correction of deep bite AND open bite in adult patients. Five electronic databases (PubMed, Scopus, Embase, Web of Science and Cochrane Library) were investigated, with the following keywords: overbite AND aligners. A quality assessment was performed using the Newcastle-Ottawa scale, while the risk of bias was evaluated using the ROBINS-I tool 2.0. PROSPERO ID: CRD420251078610. Results: Out of a total of 838 records initially screened, seven studies fulfilled the inclusion criteria and were ultimately selected for this systematic review. The analysis focused on assessing the divergence between the overbite correction predicted by ClinCheck and the outcomes observed in clinical practice. Conclusions: ClinCheck demonstrated a predictability of 62.1% for overbite correction in open bite cases and 41.5% in deep bite cases. However, not all studies report the planned tooth movements. Among the studies that addressed this aspect, the majority reported no significant association between the overbite correction predicted during treatment planning and the results ultimately achieved—except for one study, which demonstrated significant accuracy in achieving absolute extrusion in the correction of open bite
