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The use of high-efficacy disease-modifying therapies in multiple sclerosis: recommendations from an expert Delphi consensus
Get PDFObjective: To establish recommendations based on an expert consensus on the early and appropriate use of high-efficacy disease-modifying therapies (HE-DMTs) in the management of multiple sclerosis (MS) patients, based on current clinical evidence and real-world practice in Italy. Material and methods: A Delphi panel comprising 65 neurologists from 54 Italian MS centers engaged in a two-round consensus process. Experts rated 43 statements across five domains: therapeutic goals, definitions of HE-DMT, MS patient profiling, and use of HE-DMT at diagnosis and later in MS course, using a 5-point Likert scale. A statement reached strong consensus if ≥80% of panelists agreed; whereas between 70% and 80% it was considered as moderate. Results: In Round 2, 53 experts completed the survey on 43 statements. Strong consensus was achieved for 33 (76.7%), and moderate consensus for 6 (14.0%) statements. Experts strongly supported early HE-DMT initiation to prevent irreversible disability, endorsed a multidimensional definitions of treatment efficacy, and recommended personalized approaches based on clinical, radiological, and biomarker indicators. Consensus supported initiating HE-DMTs in patients with poor prognostic features and identified magnetic resonance imaging (MRI) activity, neurodegeneration markers, and suboptimal clinical response as specific factors requiring escalation to HE-DMTs. Conclusion: This Italian Delphi underscores the importance of early, personalized HE-DMT use to optimize long-term outcomes in MS. The strong expert alignment reflects a paradigm shift toward proactive treatment and highlights actionable clinical, radiological, and biological indicators that should guide therapeutic decisions. These findings may support national policy changes and promote more equitable and evidence-based access to HE-DMTs across healthcare systems
Italian survey about intraperitoneal drain use in distal pancreatectomy
Get PDFIntraperitoneal prophylactic drain (IPD) use in distal pancreatectomy (DP) is still controversial. A survey was carried out through the Italian community of pancreatic surgeons using institutional emails, Twitter, and Facebook accounts of the Italian Association for the Study of the Pancreas (AISP) and the Italian Association of Hepato-biliary-pancreatic Surgery (AICEP). The survey was structured to learn surgeons’ practice in using IPD through questions and one clinical vignette. Respondents were asked to report their regrets for omission and commission regarding the IPD use for the clinical scenario, eliciting a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were built to identify respondents’ attitudes. One hundred six surgeons completed the survey. Sixty-three (59.4%) respondents confirmed using at least 1 drain, while 43 (40.6%) placed 2 IPDs. Only 13 respondents (12.3%) declared a change in IPD strategy in patients at high risk of clinically relevant postoperative pancreatic fistula (CR-POPF), while 9 (9.4%) respondents changed their strategy in low-risk POPF situations. Thirty-five (35.5%) respondents declared they would remove the IPD within the third postoperative day (POD) in the absence of CR-POPF suspicion. The median omission regret, which proved to be the wrong decision, was 80 (50–100, IQR). The median regret due to the commission of IPD, which turned out to be useless, was 2.5 (1–20, IQR). The CR-POPF probability threshold at which drainage omission was the less regrettable choice was 7% (1–35, IQR). The threshold to perceive drain omission as the least regrettable choice was higher in female surgeons (P < 0.001), in surgeons who modulated the strategies based on the risk of CR-POPF, and in high volume centers (p = 0.039). The threshold was lower in surgeons who performed minimally invasive distal pancreatectomy (P < 0.001), adopted a closed system (P < 0.001), placed two IPDs (P < 0.001), or perceived the IPD as important to prevent reintervention (p = 0.047). Drain management after DP remains very heterogeneous among surgeons. The regret model suggested that IPD omission could be performed in low-risk patients (7% of CR-POPF), leading to low regret in the case of the wrong decision, making it an acceptable clinical decision
Intercalated Disc Abnormalities Are Linked to Arrhythmias in Inflammatory Cardiomyopathy
No full textBackground: The relationship between intercalated disc abnormalities (IDAs) and arrhythmias in inflammatory cardiomyopathy (ICM) remains incompletely understood. Objectives: This study presents a pilot research that aimed to: 1) investigate the link between IDAs and arrhythmias in humans with ICM; and 2) compare findings in humans and mice with experimental autoimmune myocarditis (EAM). Methods: Humans with ICM (N = 316) investigated for either genetic or autoimmune IDAs were identified at a referral center. Ultrastructural analysis on biobanked tissue was performed to determine the average intercellular cleft width (ICW) between cardiac myocytes. IDA+ cases were compared with IDA- control subjects matched 1:1 by age, sex, and race/ethnicity. The primary endpoint was the occurrence of clinically demanding supraventricular or ventricular arrhythmias, recorded either by Holter electrocardiography or implanted devices during a 24-month prospective follow-up. The relationships between ICW and arrhythmias were compared in humans and male mice with EAM (n = 12). Results: Of 316 humans with ICM (mean age 45 ± 15 years, 63% male), 70 (22%) were IDA+ and 107 (34%) had arrhythmias on admission. IDA+ patients had greater ICW than control subjects (44 ± 8 nm vs 28 ± 4 nm; P < 0.001) and higher incidence of clinically demanding arrhythmias both at presentation (31 of 70 vs 9 of 70; P < 0.001) and during follow-up (44 of 70 vs 10 of 70; P < 0.001). In a multivariable model, IDAs predicted the occurrence of major ventricular arrhythmias by 24 months (HR: 3.0; 95% CI: 1.4-6.4; P = 0.004). In mice, arrhythmias were documented in 7 of 12 EAM cases and 0 of 6 control animals (P = 0.038). Increased ICW was found in close relationship with arrhythmias in both species (humans: 32 of 44 with vs 4 of 52 without arrhythmias; P < 0.001; mice: 7 of 8 with vs 0 of 4 without arrhythmias; P = 0.010), as well as with abnormal ventricular electrograms on viable murine myocardial tissue (5 of 6 vs 0 of 6; P = 0.015). Conclusions: As a shared trait between genetic and autoimmune ICM, IDAs are linked to arrhythmias in humans and find promising applications in the EAM mouse model
Implementation of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction (OpTIMa-HF Registry)
No full textAims: The last released European guidelines on the management of heart failure (HF) recommend in patients with chronic HF with reduced ejection fraction (HFrEF) a pharmacological approach based on four fundamental drugs to be rapidly implemented and then uptitrated to modify disease progression. The aim of the Optimization of Therapy in the Italian Management of Heart Failure (OPTIMA-HF) registry is to collect data on chronic HF outpatients in different settings of care. In the present analysis, we report the first analysis of the OPTIMA-HF registry, focusing on the real-life use of guideline-directed medical therapy in patients affected by HFrEF. Methods: OPTIMA-HF is an observational, cross-sectional, multicentre, real-life Italian registry conducted in two different clinical settings: HF outpatients' clinics of Italian hospitals and community HF outpatients' services. The study comprises a T0 phase—retrospective data collection, in which data of consecutive HF outpatients seen between January and October 2022 were collected; an educational activity phase; and a T1 phase—prospective data collection, in which data of consecutive HF outpatients seen between September 2023 and November 2023 were collected. In the present analysis, we describe the T0 phase focusing on HFrEF drug prescription rates, types, doses, combination therapy, the presence of contraindications and reasons of non-optimized treatment. Results: Twenty-nine centres enrolled 2110 HF patients, of which 1390 (65.9%) had HFrEF [69.5 ± 11.9 years, 76.2% males, 4.1 years since HF diagnosis, median ejection fraction (EF) 33%]. Among HFrEF patients, 89.1% were on treatment with renin–angiotensin–aldosterone system inhibitor (RAASi)/angiotensin receptor neprilysin inhibitor (ARNI) (72% ARNI and 17.1% RAASi), 95.1% with beta-blockers, 75.8% with mineralocorticoid receptor antagonists (MRA) and 63.2% with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Despite high prescription rates, a non-negligible number of patients with no contraindications were not treated with each specific drug. Patients taking all four drug classes, as recommended by guidelines, were mere 46.9%. Regarding doses, a still low number of patients on RAASi/ARNI and beta-blockers were treated with a dose ≥50% of the target doses recommended by the European guidelines. Conclusions: The OPTIMA-HF registry reported that HFrEF fundamental drugs are prescribed in most Italian patients; however, <50% of patients receive optimal combination therapy, and still not a satisfying number of patients receive target doses. Strategies to improve implementation of guideline-directed medical therapy are needed to improve HF prognosis
Firearm ownership and suicide: Has the time come to discuss uniformity of health and social assessments in aid of regulation? Reflection from a retrospective study on a forensic case series
No full textBackground: Firearm-related deaths are an issue of ongoing public interest, from a health and economic perspective. Worldwide, firearm prevalence in suicides varies widely, depending on multiple factors including the availability of weapons in each country. Although several studies have shown that national laws about gun ownership, reducing legal access to guns, decrease the risk of suicide by firearm, the current situation clashes with widely differing legislations. Study design: Retrospective study on a forensic case series. Methods: Autopsy reports assessed at the Section of Legal Medicine of Milan (Italy) from January 2014 to December 2023 were retrospectively documented. Only firearm suicides were considered. For each case, a close analysis of the criminal offence reports has been performed to obtain information about the gender and age of the victim, as well as the legal possession of firearms, psychiatric disorders, alcohol, and illicit drug abuse. Results: Among all the 1,164 suicides assessed at the Section of Legal Medicine of Milan over a 10-year-period, 101 cases (8.7%) were firearm-related. The male to female ratio was therefore about 13:1. No seasonal trends were observed. Most of the individuals owned the firearm license. Of the entire dataset, 35.6% suffered from psychiatric disorders, 4% of alcohol abuse and 2% of drug addiction. Among the owners of a firearm license, 42.3% had psychiatric disorders. Conclusions: Knowledge about firearm suicide and its relation to firearm legal possession is limited and current preventive laws should be reconsidered. Present administrative and clinical examinations required to obtain a firearm license in Italy and in some European territories are dealt with. The evaluation of the firearm-related risk of abuse is an essential but complex procedure, which requires not only clinic-anamnestic data but also in-deep psychiatric information. There is a need to develop and reinvigorate a debate that currently presents very heterogeneous solutions, but which would probably benefit from a common vision of the prevention strategies that can be implemented and enacted for the benefit of the entire community.Background. Firearm-related deaths are an issue of ongoing public interest, from a health and economic perspective. Worldwide, firearm prevalence in suicides varies widely, depending on multiple factors including the availability of weapons in each country. Although several studies have shown that national laws about gun ownership, reducing legal access to guns, decrease the risk of suicide by firearm, the current situation clashes with widely differing legislations. Study Design. Retrospective study on a forensic case series. Methods. Autopsy reports assessed at the Section of Legal Medicine of Milan (Italy) from January 2014 to December 2023 were retrospectively documented. Only firearm suicides were considered. For each case, a close analysis of the criminal offence reports has been performed to obtain information about the gender and age of the victim, as well as the legal possession of firearms, psychiatric disorders, alcohol, and illicit drug abuse. Results. Among all the 1,164 suicides assessed at the Section of Legal Medicine of Milan over a 10-year-period, 101 cases (8.7%) were firearm-related. The male to female ratio was therefore about 13:1. No seasonal trends were observed. Most of the individuals owned the firearm license. Of the entire dataset, 35.6% suffered from psychiatric disorders, 4% of alcohol abuse and 2% of drug addiction. Among the owners of a firearm license, 42.3% had psychiatric disorders. Conclusions. Knowledge about firearm suicide and its relation to firearm legal possession is limited and current preventive laws should be reconsidered. Present administrative and clinical examinations required to obtain a firearm license in Italy and in some European territories are dealt with. The evaluation of the firearm-related risk of abuse is an essential but complex procedure, which requires not only clinic-anamnestic data but also in-deep psychiatric information. There is a need to develop and reinvigorate a debate that currently presents very heterogeneous solutions, but which would probably benefit from a common vision of the prevention strategies that can be implemented and enacted for the benefit of the entire community
Erratum: Correction for Kajaste-Rudnitski et al., "TRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements" (Journal of virology (2011) 85 10 DOI: 10.1128/JVI.02302-10.)
No full textMinimally invasive versus open liver resection for nonmetastatic hepatocellular carcinoma staged BCLC – B and – C: an Italian multicentric analysis
No full textBackground: Recent papers report significant survival gain after liver resection in BCLC-B and -C HCC patients. The results of minimally invasive liver surgery (MILS) in such patients have not been widely investigated so far. Methods: Data regarding patients undergoing MILS or open liver resection (OLR) for HCC staged BCLC -B and -C were extracted from the HERCOLES database. An inverse probability of treatment weighting (IPTW) method was adopted to balance the confounders. The primary outcome was a composite endpoint including post-hepatectomy liver failure, severe postoperative complications and in-hospital mortality. Results: 627 patients were included (459 undergoing OLR and 168 receiving MILS). After IPTW, no difference was found in the composite endpoint between MILS and OLR (OR 0.86 [95%CI 0.46-1-60]; p = 0.62). MILS reduced the risk of receiving intra-operative transfusions (OR 0.28 [95%CI 0.13-0.58]; p < 0.001) and of developing postoperative ascites (OR 0.56 [95%CI 0,32-0,98]; p = 0.039), with reduced length of stay (OR 0.82 [95%CI 0.66-1.01]; p = 0.045). The survival analysis showed no differences between MILS and OLR for both OS (p = 0.13) and DFS (p = 0.491). Conclusion: MILS was shown to be safe and feasible for selected non-metastatic HCC patients staged BCLC B and C, reducing the risk of perioperative transfusions and postoperative ascites, and shortening the length of stay
Sex-Specific Inflammatory Profiles Affect Neuropsychiatric Issues in COVID-19 Survivors
No full textPost-COVID syndrome has unveiled intricate connections between inflammation, depressive psychopathology, and cognitive impairment. This study investigates these relationships in 101 COVID-19 survivors, focusing on sex-specific variations. Utilizing path modelling techniques, we analyzed the interplay of a one-month 48-biomarker inflammatory panel, with three-months of depressive symptoms and cognitive performance. The findings indicate that cognitive impairment is influenced by both inflammation and depression in the overall cohort. However, prominent sex-specific differences emerged. In females, a lingering imbalance between pro- and anti-inflammatory responses—likely reflecting the long-lasting immune alterations triggered by COVID-19—significantly affects cognitive functioning and shows a marginal, though not statistically significant, association with depressive symptoms. This suggests that a mixed inflammatory profile may contribute to these outcomes. Conversely, in males, inflammation was inversely associated with depression severity, with protective effects from regulatory mediators (IL-2, IL-4, IL-6, IL-15, LIF, TNF-α, β-NGF) against depression. In males, cognitive impairment appeared to be driven mainly by depressive symptoms, with minimal influence from inflammatory markers. These results highlight distinct sex-specific pathways in immune and inflammatory responses post-COVID-19, potentially shaped by endocrine mechanisms. The findings suggest that persistent inflammation may foster long-term neuropsychiatric sequelae, possibly through its effects on the brain, and underscore the need for sex-tailored therapeutic strategies to address the lasting impact of COVID-19
Multidisciplinary Screening of a Novel Founder LMNA Mutation Associated With Cardiomyopathy in a Geographic Isolate
No full textOutcomes of Octogenarians Undergoing Edge-to-Edge Transcatheter Valve Repair for Tricuspid Regurgitation: Inverse Propensity Score-Weighted Analysis
No full textThere is a scarcity of data for perioperative outcomes of octogenarians undergoing tricuspid transcatheter edge-to-edge repair (TEER), despite both the potential procedural effectiveness in treating tricuspid regurgitation and a low incidence of severe complications observed in the nonelderly population. We assessed the characteristics and outcomes of TEER in octogenarians compared to those in patients under 80 years old treated at a referral tertiary teaching hospital. We retrospectively enrolled all adult patients undergoing tricuspid TEER. The population was stratified based on age: ≥80 and <80 years. Inverse probability of treatment weighting (IPTW) propensity score was used to mitigate the risk of selection bias. Between January 2017 and September 2023, 101 patients underwent tricuspid TEER. Thirty-six (36%) were octogenarians. Crude treatment estimates indicated that preoperative Tricuspid Annular Plane Systolic Excursion (TAPSE) was significantly higher in octogenarians compared to younger patients (19 mm [IQR: 17 to 21] vs. 17 mm [IQR: 14–18]; p = 0.005). At discharge, octogenarians showed a TAPSE 2.71 mm higher than that observed in the <80 age group (95% CI: 0.79 to 4.62; p = 0.006) according to crude treatment estimates. After adjusting with IPTW-weighting, the TAPSE difference remained significant, with octogenarians having a 2.44 mm higher TAPSE (95% CI: 0.54 to 4.35; p = 0.012). IPTW-adjusted analyses indicated comparable clinical outcomes between the two groups. Adverse events and survival in octogenarians were similar to those observed in patients aged <80 years. Our findings indicate that age alone should not be the sole criterion to deny TEER