Azienda Ospedaliera San Giovanni Addolorata

Elevated low-density lipoprotein cholesterol (LDL-C) represents a key causal factor in atherosclerotic cardiovascular disease. Robust evidence demonstrates that early, marked, and sustained reduction of LDL-C is associated with a significant decrease in the risk of major adverse cardiovascular events. However, a substantial proportion of high-risk patients fail to achieve guideline-recommended LDL-C targets with statin therapy alone, thus requiring additional lipid-lowering treatments. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, particularly the monoclonal antibodies evolocumab and alirocumab, have been shown to reduce LDL-C levels by ∼60% and to provide clear cardiovascular outcome benefits in secondary prevention. More recently, the VESALIUS-CV trial extended these findings to the setting of primary prevention in high cardiovascular risk patients without prior major cardiovascular events. In this trial, evolocumab achieved a significant and sustained reduction in LDL-C levels and significantly reduced the risk of a first cardiovascular event, including myocardial infarction and ischaemia-driven revascularization, while maintaining a safety profile comparable to placebo. Overall, the available evidence supports the role of evolocumab as an effective and safe strategy for cardiovascular risk reduction across the entire risk continuum, from secondary to primary prevention, underscoring the importance of a personalized therapeutic approach based on the patient's global cardiovascular risk profile.

The widespread adoption of coronary computed tomography angiography (CCTA) has led to a growing detection of coronary artery anomalies in contemporary clinical practice, often as incidental findings during the evaluation of suspected or known coronary artery disease. Among these, anomalous aortic origin of a coronary artery (AAOCA) represents the most clinically debated entity, historically associated with myocardial ischaemia and sudden cardiac death, yet increasingly identified in asymptomatic or minimally symptomatic adults. Accumulating evidence indicates that most AAOCA diagnosed in adulthood are not associated with functionally relevant ischaemia and frequently follow a benign clinical course, highlighting the limitations of anatomy-based risk stratification alone. In this context, CCTA plays a pivotal role by accurately defining coronary origin and course, characterizing proximal vessel morphology, and assessing concomitant atherosclerotic disease, which often represents the predominant determinant of symptoms and prognosis in adult patients. Recent studies have demonstrated that quantitative CCTA-derived parameters can reliably exclude hemodynamically significant AAOCA and reduce unnecessary downstream testing. In selected cases, invasive functional assessment and intracoronary imaging provide incremental value by clarifying the presence and mechanisms of ischaemia but should be reserved for carefully selected patients. This review summarizes current evidence on coronary artery anomalies with a specific focus on AAOCA and proposes a pragmatic, stepwise approach integrating anatomical and functional assessment to guide clinical decision-making in daily practice.

Background: Thumb carpometacarpal (CMC) arthritis affects up to 25% of women and 8% of men over 70 years of age, significantly compromising their activities of daily living. With the rapid growth of the elderly population globally and their specific clinical needs, understanding optimal surgical treatment for this age group is crucial. This systematic review compares trapeziectomy with ligament reconstruction and tendon interposition (LRTI) versus dual-mobility prosthesis for treating thumb CMC arthritis in elderly patients over 70 years old. Methods: A systematic search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library for studies published up to August 2025. Studies that directly compared both techniques were included, with subgroup analyses performed for elderly patients over 70 years of age when data were available. Primary outcomes included pain relief, functional improvement, grip and pinch strength, complications, and patient satisfaction. Results: Five studies met the inclusion criteria for direct comparison of both techniques, encompassing 313 patients (324 thumbs). While none exclusively focused on patients over 70, elderly patients represented 25-41% of study populations. Due to the absence of age-stratified data in the original studies, our analysis encompasses all age groups with specific considerations for elderly patients where identifiable. Dual-mobility prostheses demonstrated faster pain relief and earlier functional improvement, particularly within the first 3-6 months postoperatively. Prostheses consistently provided superior grip and pinch strength outcomes throughout follow-up periods. Both procedures effectively preserved thumb function, but prostheses better maintained thumb length and metacarpophalangeal stability. While complication rates were comparable, LRTI complications were typically minor and self-limiting, whereas prosthesis complications, though rare, could potentially require revision surgery. Longer-term follow-up data (>3 years) remain limited, particularly regarding implant degradation and adverse local tissue reactions. Conclusions: Both procedures effectively treat thumb CMC arthritis in elderly patients, with distinct advantages. Dual-mobility prostheses offer faster recovery, enhanced strength, and better thumb length preservation, making them potentially advantageous for elderly patients prioritizing rapid functional recovery. Trapeziectomy with LRTI provides reliable long-term pain relief with fewer serious complications, making it suitable for patients with poor bone quality or significant comorbidities. Treatment selection should be individualized based on patient characteristics, functional demands, and surgeon expertise. Future research specifically focusing on elderly populations with longer follow-up periods (>5 years) is critically needed to provide stronger evidence for this growing demographic and to better understand long-term implant performance.

Real-world evidence on atogepant remains limited. GIANT2 explores the 24-week real-life effectiveness of atogepant in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) under routine clinical conditions. GIANT2 is a 24-week, prospective, multicenter, real-world, study including consecutive patients with HFEM or CM with ≥3 preventive treatment failures, treated with atogepant 60 mg once daily. Co-primary endpoints: proportions achieving ≥50% and ≥75% reductions in monthly migraine days for HFEM or monthly headache days for CM at weeks 21–24 versus baseline. Secondary endpoints: changes in migraine/headache days, analgesic intake, pain intensity, disability, patient global impression of change, 100% response rates, tolerability and safety. Response rates at weeks 21–24 were also evaluated in patients with prioranti-CGRP mAb failure. Exploratory analyses: proportion of >50% responders achieving >30% reduction in NRS scores and response rates in subgroups combining psychiatric comorbidities, CM, and medication overuse headache (MOH). Of 233 patients enrolled, 156 completed >24 weeks of treatment, with 37.2% having failed prior anti-CGRP mAbs. At weeks 21–24, 76.9% achieved a ≥ 50% response and 45.5% a ≥ 75% response, with ≥50% response more frequent in HFEM than CM (p = 0.005). A 100% response occurred in 5.1% of patients. All secondary endpoints improved significantly (p < 0.001) with greater benefits at week 24 than week 12. No difference in effectiveness was observed between mAb-naïve patients and those with prior mAb failures, who achieved ≥50% and ≥75% response rates of 70.7% and 39.7%. A combined ≥50% frequency reduction and ≥30% pain reduction was achieved by 54.5% of patients. Among patients with psychiatric comorbidities, 63.0% were ≥50% responders, while among CM patients rates were 62.1% in those with MOH and 40.0% in those with both psychiatric comorbidities and MOH (≥75% responder rates 42.4%, 37.0%, and 28.0%). Adverse events occurred in 11.2% of patients and led to discontinuation in 1.3%. GIANT2 shows that atogepant effectiveness increases from week 12 to 24 with a high proportion of responders and super-responders regardless of prior anti-CGRP mAb failure and reduces pain intensity in residual headaches in most patients. It is also effective in migraine subgroups combining psychiatric comorbidities, CM and MOH. NCT06136442.

The management of chronic lymphocytic leukemia (CLL) in older patients requires careful balancing of therapeutic efficacy with the risks of treatment intolerance. Frailty assessment is increasingly recognized as a critical determinant of clinical outcomes, but its specific role in guiding therapy with second-generation Bruton tyrosine kinase inhibitors remains poorly defined. We conducted a prospective, multicenter investigation of 326 consecutive CLL patients aged 65years or older who received zanubrutinib across 52 Italian centers, aiming to evaluate whether the Clinical Frailty Scale (CFS) could predict treatment discontinuation in real-world practice. The cohort was characterized by advanced age (median 78.1years, range 65.1-94.5), with over half of the patients presenting with Binet stage C disease. Two-thirds were treated in the frontline setting, while the remainder received zanubrutinib as salvage therapy. After a median follow-up of 8 months, 48 patients (14.7%) discontinued treatment, most commonly due to toxicity or disease progression. Receiver operating characteristic curve analysis identified a CFS of 3 as the optimal threshold for predicting discontinuation, with an area under the curve of 0.65 (95% CI 0.56-0.73, p<0.001). At 12months, the discontinuation rate was significantly higher among patients with a CFS >3 (29.2%) compared with those with a CFS ≤3 (8.8%) (p<0.001); among conventional prognostic variables, only relapsed/refractory disease demonstrated an independent association with TTD. These findings highlight the CFS as a simple yet powerful clinical tool that provides incremental prognostic information beyond standard disease-related factors. Incorporating frailty assessment into treatment planning may enhance patient selection and optimize therapeutic strategies for elderly CLL patients in daily practice.

Immediate breast reconstruction (IBR) with polyurethane (PU)-coated implants has usually been performed to mitigate the capsular contracture (CC) rate, particularly in patients requiring post-mastectomy radiotherapy (PMRT). This retrospective study aimed to evaluate the long-term outcomes of direct-to-implant (DTI) reconstruction using Microthane® PU-coated implants placed prepectorally without additional devices. A total of 143 consecutive patients underwent mastectomy, followed by IBR with Microthane® implants in the prepectoral position. Demographic and clinical data, including complications and CC incidence, were retrospectively collected. Statistical analyses comprised descriptive statistics, Kaplan-Meier survival curves, and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire for patient-reported outcomes. Over a median follow-up of 4.5 years, 18.9 % of patients experienced at least one complication, with adjuvant radiotherapy being the only factor significantly associated with increased complications (p = 0.0229). Kaplan-Meier analysis indicated a complication-free survival rate of 57.85 % for the patient and 58.00 % for the implant, and a contracture-free survival rate of 79.46 % and 81.56 %, respectively. Severe CC (Baker grade III/IV) occurred only in 9.1 % of patients, including several who underwent adjuvant radiotherapy (p = 0.0215). These rates remain notably lower than those historically reported with textured implants. Moreover, DASH scores revealed minimal disability (an overall mean score of 8.17 %), reflecting favorable patient-reported outcomes. Microthane® breast implants in a prepectoral position demonstrated low CC rates and high patient satisfaction, even among those receiving radiotherapy, benefiting from all the prepectoral surgical approaches. In addition, this technique obviates the need for supplementary devices such as meshes or acellular dermal matrices (ADMs), thereby reducing costs, operative times, and potential complications. The large cohort size and substantial follow-up strengthen these findings. The results support prepectoral reconstruction with Microthane® implants as a safe and effective option in breast reconstruction, offering both aesthetic and functional benefits.

BackgroundWith the increasing adoption of the suprapatellar approach for intramedullary tibial nailing in diaphyseal tibial fractures, this study compared intraoperative and postoperative outcomes between infrapatellar nailing (IPN) and suprapatellar nailing (SPN).MethodsA retrospective analysis was conducted on 51 SPN and 58 IPN procedures performed at a single trauma center between October 2018 and June 2023. Operative time, postoperative blood loss, functional outcomes using the Lysholm score, and the incidence of anterior knee pain (AKP) at follow-up were compared.ResultsThere were no significant differences in age or sex between the groups. Mean follow-up was 36.74 ± 18.11 months for SPN and 35.98 ± 15.11 months for IPN. Mean operative time was significantly shorter in the SPN group (79.7 ± 34.0 min) compared to the IPN group (91.9 ± 36.0 min, p < 0.05). The SPN group showed significantly higher Lysholm scores (89.45 ± 9.2 vs. 85.1 ± 10.5, p = 0.017) and a lower incidence of AKP. No significant difference was observed in postoperative blood loss.ConclusionCompared to the IPN approach, SPN for diaphyseal tibial fractures may reduce operative time, decrease the incidence of AKP, and improve postoperative functional outcomes.

Early relapse in multiple myeloma (MM) is a major predictor of poor prognosis, regardless of cytogenetic risk or treatment intensity. Here we analyzed 1026 MM patients treated across 12 Italian hematology centers. FHR was defined as progression-free survival (PFS) ≤18 months in transplant-eligible (TE) and ≤12 months in non-transplant-eligible (NTE) patients. Logistic regression and ROC analysis were used to identify significant predictors of FHR and build a risk score. FHR status was identified in 175 patients (17%). These patients had significantly shorter PFS (7 vs. 57.5 months) and overall survival (19 months vs. not reached; p < 0.001). FHR status was associated with higher median LDH, lower Hb level, higher creatinine level and lower platelets count. Modified EASIX formula was built by these significant continuous variables, to be tested in a logistic analysis: [(LDH × creatinine)/(Hb × PLT) × 100]. A significantly higher rate of FHR was found with a score > 2.0 (89% vs. 11%, p < 0.001). Multivariate logistic analysis selected the above formula, ECOG PS ≥ 2 and ISS III as factors associated with FHR. Scoring these variables according to OR, three groups of patients were segregated with a rate of FHR patients of 7%, 29.5%, and 63.5%, respectively. Treatment with anti-CD38 monoclonal antibodies was associated with lower FHR frequency. This study proposes a simple, clinically applicable model to identify FHR MM patients early in their disease course. However, very in-depth biological tools, not available in clinical practice, are needed to identify singularly risk of becoming FHR.

Background: The interaction between probiotics and the vitamin D/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, but its effect on the VDR pathway remains unexplored in humans. Aim: To test the hypothesis that LGG can stimulate the vitamin D/VDR pathway and modulate mucosal-adherent microbiota. Methods: In this study, we analyzed a subgroup of 13 patients from the LGGinUC trial, in which UC patients with mild-to-moderate disease activity received LGG monotherapy for four weeks. Colonic biopsy samples were collected before and after treatment to evaluate VDR expression via RT-qPCR and immunohistochemistry. Mucosal-adherent microbiota was also analyzed by DNA extraction and next-generation sequencing (NGS). Results: LGG administration significantly increased VDR mRNA expression in colonic mucosa (p < 0.05), with a corresponding rise in VDR protein levels in both epithelial and sub-epithelial compartments. Microbiota analysis revealed a reduction in α-diversity, primarily due to a decrease in commensal bacterial species, while β-diversity remained largely unchanged. Conclusions: Although the present results have to be considered preliminary, this is the first human study demonstrating that probiotic supplementation can upregulate VDR expression in colonic mucosa. We propose that LGG may exert its beneficial effects in UC by stimulating the VDR pathway, which in turn modulates mucosal immunity and microbiota composition. Further studies with larger sample sizes and longer treatment durations are needed to validate these findings and explore their therapeutic implications.

Peripheral Artery Disease (PAD) with Chronic Limb Threatening Ischemia (CLTI) is a severe condition at risk of amputation, and often conventional surgical and endovascular procedures and/or medical therapy are insufficient. The present review considers current knowledge regarding autologous cell therapy and regenerative medicine for PAD with CLTI. We evaluated cell-based therapies in the recent literature, that are pivotal in treating vascular disorders by promoting angiogenesis, vascular restoration, and tissue regeneration; furthermore, we provided an overview of the relevant main clinical studies. Clinical conditions and risk factors of patients correlate with the performance of autologous cell-based therapies and the probability of success. Nevertheless, the current evidence indicates that these therapies are promising, necessitating further research. Autologous cell therapy and regenerative medicine can offer additional support for treating PAD with CLTI. These advanced techniques are becoming more tailored and substantial for their application in clinical practice. Personalized Medicine represents a contemporary paradigm that calls for consideration of individual patient's clinical conditions, risk factors, and biomarkers.