Azienda Ospedaliera Universitaria Senese

Psoriasis is a chronic inflammatory skin disease associated with significant physical and psychological burden. Tildrakizumab, an interleukin-23 p19 inhibitor, has demonstrated efficacy in treating moderate-to-severe plaque psoriasis both in clinical trials and real-world setting. However, limited data are available on the impact of the effective treatment of psoriasis on the psychological health of patients. The aim of this study was to assess changes in psychological well-being, as well as clinical and quality-of-life outcomes, in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in routine clinical practice in Italy. This was an interim analysis (IA) of a 52-week multicenter, prospective, observational study. Adults with moderate-to-severe plaque psoriasis initiating tildrakizumab were enrolled. Endpoints focused on well-being and psychological health and included changes, from baseline to week28, in Depression, Anxiety, and Stress Scale-21 (DASS-21) scores, Dermatology Life Quality Index (DLQI), European Social Survey (ESS) items, and World Health Organization-Five Well-Being Index (WHO-5). Effectiveness was also monitored via Psoriasis Area and Severity Index (PASI), and safety via treatment-emergent adverse event reporting. A total of 115 patients were included (mean age 52.5years, 60.8% male), 102 receiving ≥ 1 dose of tildrakizumab and completing DASS-21 evaluations at baseline and week28. At week28, improvements were observed in DASS-21 subscales [depression (-2.6, 95%CI -2.0 to -1.0), anxiety (-2.3, 95%CI -2.0 to -1.0), and stress (-3.4, 95%CI -4.0 to -2.0)], accompanied by marked PASI reduction (-13.7, 95%CI -12.8 to -10.1). DLQI, ESS, and WHO-5 scores also improved. Adverse events were generally mild or moderate, with no unexpected safety signals. In this real-world IA, tildrakizumab was observed to improve the psychological well-being of patients, reflected by a reduction in all items of the DASS-21 scale and, in parallel, confirmed its effectiveness in managing physical symptoms of psoriasis, establishing its role in the holistic management of psoriasis.

In Autoimmunology, interpretative comments can significantly improve the quality of information in laboratory reports. Laboratory autoimmunologists play an increasingly important role in supporting clinicians with the request and interpretation of tests, considering the growing complexity of autoimmune diagnostic and the increase in requests for autoimmune tests by non-specialist physicians. In 2024, the Study Group on Autoimmunology (GdS-AI) of the Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL) in collaboration with the Study Group of Extra-Analytical Quality (GdS-QuEA) developed a project with the aim to define interpretative comments for systemic autoimmune diseases and organ-specific autoimmune diseases. Based on the analysis of the comments used by GdS-AI laboratories in routine practice, the working group drafted a summary document including no. 47 interpretative comments (22 for systemic autoimmune diseases and 25 for organ-specific autoimmune diseases), representative of possible findings in autoimmune laboratory reports. The document is intended as a proposal of interpretative comments to support laboratory reporting. Furthermore, it defines the important role of the laboratory autoimmunologist in improving the informational quality of reports, while promoting harmonization and appropriateness of test ordering.

Background: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BiVp), but its implantation requires a specific learning curve. Early experience was dominated by His bundle pacing (HBP) with lumenless leads (LLL), whereas the subsequent adoption of left bundle branch area pacing (LBBAP) and the increasing procedural standardization led to a simplification of the technique and greater uniformity in its execution. This study evaluated the learning curve for CSP by analyzing the first consecutive implants of two electrophysiologists (operator 1: OP1 and operator 2: OP2). Methods: The first 55 CSP procedures performed by each operator (n = 110) were retrospectively analyzed. Implantation and fluoroscopy times were assessed in blocks of five cases. Univariate and multivariable linear regression were used to identify independent predictors of procedural complexity. Results: A total of 110 CSP implants (55 per electrophysiologist) were analyzed. Implantation time progressively decreased with experience, reaching a stable plateau after ~45 cases per operator, when inter-operator curves completely overlapped and differences were no longer significant. Fluoroscopy time stabilized earlier and showed no consistent differences between electrophysiologists. In the univariate analysis, longer procedural times were associated with larger left ventricular end-diastolic diameters (LVEDD: r: 0.43; p < 0.001), LLL (r: 0.25; p < 0.01) and earlier implant numbers (r: 0.36; p < 0.001). In the multivariable models, only LVEDD and implant number (IN) remained independent predictors of procedure duration (LVEDD: β: 2.04, p: 0.04; and IN: β: 3.26, p < 0.04). Conclusions: CSP implantation follows a distinct learning curve, with procedure duration stabilizing after approximately 45 cases per operator. Procedural complexity is mainly determined by patient factors (LVEDD) and operator-related factors, whereas differences between LLL and SL reflect historical experience rather than intrinsic technical characteristics.

Neonatal myocardial infarction is a rare and often life-threatening condition, particularly in preterm neonates, with nonspecific clinical presentations that complicate diagnosis. While diagnosis relies on ECG changes, elevated cardiac markers, and echocardiographic abnormalities, management guidelines and validated biomarker cut-offs for neonates are lacking. Conventional inotropic support is often necessary, but its efficacy in immature myocardium can be limited. Levosimendan, a calcium sensitizer with inotropic, lusitropic, and vasodilatory effects, offers potential advantages by improving contractility without increasing myocardial oxygen consumption, but evidence in neonates, especially preterm infants, remains scarce. We report the case of an extremely preterm neonate (26 + 6 weeks gestation) who developed severe myocardial ischemic injury and refractory cardiogenic shock following perinatal hypoxic-ischemic insult. Despite aggressive resuscitation and conventional inotropic support with Dobutamine, Noradrenaline, and Milrinone, the infant’s condition remained critical with persistent severe left ventricular dysfunction. Given the lack of response to conventional therapy, off-label levosimendan was initiated. Within 48 h, significant clinical and echocardiographic improvement was observed, including shock resolution and recovery of left ventricular ejection fraction. This case highlights the successful use of Levosimendan in a preterm neonate with severe myocardial ischemic injury and refractory cardiogenic shock, where conventional inotropes failed to improve cardiac function. Levosimendan’s unique mechanism of action, which enhances contractility without increasing myocardial oxygen demand, proved beneficial in the context of an immature myocardium. While further studies are needed to standardize its application and establish clear guidelines, this case suggests that Levosimendan may be a valuable therapeutic option for acute heart failure in preterm neonates, particularly in cases unresponsive to traditional treatments.

Several studies have previously demonstrated an increased risk of dementia and brain amyloid deposition in individuals with heterozygous NPC1 mutations. Moreover, in a recent study, we identified the first family with autosomal dominant late-onset Alzheimer's disease (AD) caused by a heterozygous NPC1 mutation. Unfortunately, there are currently no effective treatments available for this condition. Miglustat, which impacts the metabolism of oxysterols, has been shown to exert an anti-amyloidogenic effect in a human cellular model of AD. In our exploratory uncontrolled study, three patients from the previously published family were orally treated with miglustat for 12 months. They underwent monthly clinical evaluations and routine blood tests. Additionally, neuropsychological evaluations, brain amyloid-PET imaging, and biochemical analyses on plasma and CSF were performed. All three patients achieved clinical stability, showed a sustained reduction in serum oxysterol levels, and experienced a marked decrease in brain amyloid burden. Based on our preliminary observations and hypothesis-generating findings, along with the growing evidence suggesting AD as a lipid disorder, miglustat should be further tested in a larger cohort of heterozygous NPC1 mutated patients and probably evaluated as a potential disease-modifying treatment for AD.

Intravenous (IV) iron therapy is a cornerstone in the management of iron deficiency anemia, yet its administration is associated with significant side effects, most notably hypophosphatemia. This adverse event is not a class effect but is disproportionately linked to specific formulations, particularly ferric carboxymaltose (FCM). This review synthesizes the current clinical evidence, elucidates the central pathophysiological role of fibroblast growth factor 23 (FGF23), and explores a potential pharmacogenomic basis for individual susceptibility. Clinical data from numerous randomized controlled trials and meta-analyses confirm that FCM induces hypophosphatemia in over 50% of patients, a rate far exceeding that of other IV iron preparations. The proposed underlying mechanism involves a “two-hit” process: pre-existing iron deficiency upregulates FGF23 gene transcription, while FCM administration is thought to inhibit the proteolytic cleavage of the FGF23 protein. This uncoupling of production and degradation leads to a surge in active, intact FGF23 (iFGF23), causing renal phosphate wasting. We explore the potential for genetic polymorphisms in FGF23 and its key processing enzymes, such as FURIN, GALNT3, and FAM20C, to modulate individual risk. Understanding this complex interplay is crucial for risk stratification, appropriate formulation selection, and patient monitoring to mitigate the acute and chronic consequences of iatrogenic hypophosphatemia, including debilitating fatigue and osteomalacia.

Background: Endovascular Aneurysm Repair (EVAR) is a proven, safe, and effective treatment; however, its application may be limited by the potential adverse effects of iodinated contrast medium (ICM), which can exacerbate renal function and may be contraindicated in patients with renal insufficiency. Purpose: This review aims to provide an overview of "zero-iodine contrast EVAR," which uses CO2 exclusively, as a strategy to mitigate the risk of acute kidney injury (AKI) associated with ICM. Research design: A systematic literature review was conducted in PubMed, Embase, and Cochrane databases following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify EVAR cases performed using carbon dioxide. The Medical Subject Headings (MeSH) terms used were "endovascular repair AND abdominal aortic aneurysm AND contrast medium" and "endovascular repair AND abdominal aortic aneurysm AND carbon dioxide," with inclusion criteria limited to articles in English published until December 2024. Results: The literature search yielded 1167 papers. After removing duplicates, titles and abstracts were screened, and 68 papers underwent full-text review. A total of 16 studies were included in the analysis, encompassing 1625 patients. Of these, 837 patients underwent EVAR with ICM, and 788 patients underwent EVAR with CO2. Of these, 510 patients were treated with EVAR using CO2 exclusively. Conclusions: Although this method still faces inherent limitations due to the physicochemical characteristics of CO2, its use, when combined with additional technical precautions, enables the achievement of zero-contrast results in standard EVAR procedures.