IRIS UniSR (’Università Vita-Salute San Raffaele)
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Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS: Nine-Year Data From the OPERA Studies Open-Label Extension
Get PDFBackground and Objectives Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS). Methods Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies. Patients were randomized to OCR or interferon β-1a for 96 weeks (double-blind controlled treatment period [DBP]), before switching to OCR in the open-label extension (OLE). Efficacy assessments included no evidence of disease activity (NEDA-3), 24-week confirmed disability progression (CDP), MRI lesion activity, change in whole-brain volume; with safety outcomes assessed over a 9-year treatment period. Results Overall, 757 patients were included (interferon-treated n = 382, mean age 36.3 years, 65.7% female; OCR-treated n = 375, mean age 35.5 years, 64.0% female); 505 of 757 (66.7%) completed 9 years of follow-up. The difference in NEDA status between OCR-treated and interferon-treated patients achieved during the DBP (72.5% and 43.8%, respectively, odds ratio 3.48, 95% CI 2.52–4.81) was maintained throughout the 7-year OLE (48.2% vs 25.7%; odds ratio 2.72, 95% CI 1.94–3.82). No 24-week CDP was observed in 78.7% of OCR-treated patients over 9 years. Brain volume loss over the entire study period remained numerically higher among patients starting OCR later (p = 0.09 at OLE at week 336). During the DBP, safety profiles in both groups were similar; no new safety signals were observed during the OLE. Over >9 years of continuous OCR treatment, the rate of infections remained low and stable over time. Discussion A higher proportion of OCR-treated patients achieved NEDA status compared with interferon-treated patients during the DBP, which was maintained throughout the OLE. After switching to OCR, disability accrual and brain volume loss among interferon-treated patients became similar Glossary AE = adverse event; ARR = annualized relapse rate; cCDP = composite CDP; CDP = confirmed disability progression; COVID-19 = coronavirus disease 2019; CTCAE = Common Terminology Criteria for AEs; DBP = double-blind controlled treatment period; DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; Gd = gadolinium; HR = hazard ratio; IFN = interferon; IgG = immunoglobulin G; LLN = lower limit of normal; MMRM = mixed-effects model of repeated measures; MS = multiple sclerosis; NEDA = no evidence of disease activity; NfL = neurofilament light chain; OCR = ocrelizumab; OLE = open-label extension; PY = patient-years; RMS = relapsing MS; SAE = serious AE; SI = serious infection
Fissurectomy with or without anoplasty for chronic anal fissures is a valid alternative to lateral internal sphincterotomy: a retrospective cohort study of 475 patients
No full textBackground: After the failure of conservative therapy, the most effective surgical treatment for chronic anal fissures (CAFs) is lateral internal sphincterotomy. However, the choice of the procedure must be always evaluated carefully due to the risk of long-term anal continence impairment. The aim of the present study is to report the outcomes of fissurectomy with or without associated anoplasty. Methods: This study is a single-center retrospective study including patients with CAFs in whom conservative medical and non-medical treatments failed and who underwent fissurectomy with or without anoplasty from January 2015 to June 2023. Fecal continence, pain, and complications were assessed using specific questionnaires and scores. Results: Overall, 475 patients [280 males (58.9%)] with CAF underwent fissurectomy, with (n = 392; 82.5%) or without (n = 83; 17.5%) anoplasty. The majority of them (n = 379; 79.8%) had a posterior fissure. The mean follow-up was 49.9 months ± 26.13 months, with a minimum of 1 year, showing no intraoperative complications and a 4.2% postoperative complication rate. Missed healing occurred in 7.15% of patients at 6 months of follow-up, with higher recurrence and sphincterotomy rates in posterior fissures (p = 0.04). Cleveland Clinic Incontinence Scores were higher in patients who underwent anoplasty (p = 0.002). Interestingly, anoplasty led to a significant decrease in visual analogue scale (VAS) scores (p < 0.001), compared with those who did not undergo the procedure, with a consequent faster recovery. Conclusion: Our study showed that fissurectomy, whether performed with or without anoplasty, was a highly effective surgical option for treating CAFs, achieving an overall success rate of 92.8% without significant impairment of continence and with a low complication rate. Further randomized prospective trials are needed to confirm this finding. Interestingly, fissurectomy with anoplasty seems to allow for better short-term outcomes in terms of postoperative pain and recovery time compared with fissurectomy alone
Textbook outcome in liver surgery for intrahepatic cholangiocarcinoma: defining predictors of an optimal postoperative course using machine learning
No full textBackground: We sought to define textbook outcome in liver surgery (TOLS) for intrahepatic cholangiocarcinoma (ICC) by considering the implications of perioperative outcomes on overall survival (OS). Methods: Using a multi-institutional database, TOLS for ICC was defined by employing novel machine learning (ML) models to identify perioperative factors most strongly predictive of OS ≥ 12 months. Subsequently, clinicopathologic factors associated with achieving TOLS were investigated. Results: A total of 1556 patients with ICC were included. The ML classification models demonstrated that the absence of post-hepatectomy liver failure, intraoperative blood loss <750 mL, absence of major infectious complications, and R0 resection were the perioperative outcomes associated with prolonged OS, thereby defining TOLS for ICC. On multivariable analysis, older age, ASA class >2, lymph node metastasis, receipt of neoadjuvant therapy, advanced T status, poor histological grade and microvascular invasion were independently associated with lower odds of achieving TOLS (all p-values<0.05). Overall, 60.2 % (n = 936) of the patients achieved TOLS, demonstrating markedly improved OS and recurrence-free survival (RFS) than individuals who did not (both p < 0.05). Conclusion: A standardized definition of TOLS for ICC was established that may be used to evaluate hospital performance at the patient level and help optimize surgical outcomes for patients with ICC
Home-based, computer-assisted cognitive rehabilitation for attention in pediatric onset multiple sclerosis: a randomized, multicenter pilot study
No full textObjective: Cognitive impairment affects approximately 30% of pediatric onset Multiple Sclerosis (POMS) patients with a negative impact on everyday life. The aim of this study was to evaluate the feasibility and effectiveness of a home-based, computer-assisted training of attention in patients with POMS. Methods: This was a randomized double-blind study. Subjects were randomized to specific training (ST) or non-specific training (n-ST), delivered through a customized module based on attention exercises (COGNI-TRAcK2). The main feature of the ST is the implementation of working load algorithms and procedures for intensiveness regulation. The effectiveness of the ST on attention was primarily assessed on the Symbol Digit Modalities Test (SDMT), using the Wilcoxon signed-rank test. Secondary objectives included effectiveness on other cognitive tests. The evaluations were performed at baseline, end of training and 3-month follow-up. Results: 22 relapsing-remitting patients were included: data of 8 subjects in n-ST and 5 subjects in ST were available. As for the primary outcome, SDMT score improved in the ST group (from 31.2 at baseline to 42.4 after 3 months, p = 0.043). There was no benefit in other neuropsychological measures. Conclusions: These preliminary findings point to a potential benefit of a home-based, computer-assisted training of attention in patients with POMS
Evaluating Mitral TEER in the Management of Moderate Secondary Mitral Regurgitation Among Heart Failure Patients
Get PDFBackground: Moderate secondary mitral regurgitation (SMR) represents a subgroup of heart failure (HF) patients with treatment restricted to medical therapy. Outcomes in patients with moderate SMR treated with mitral transcatheter edge-to-edge repair (M-TEER) are less well known. Objectives: The aim of this study was to assess the safety and effectiveness of M-TEER in subjects with moderate SMR using the EXPANDed studies. Methods: One-year outcomes in subjects from the EXPANDed studies (EXPAND [A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices] and EXPAND G4 [A Post-Market Study Assessment of the Safety and Performance of the MitraClip G4 System] MitraClip studies) with baseline moderate SMR (2+), per echocardiographic core laboratory (ECL) assessment, were compared with subjects with baseline severe SMR (≥3+). Results: There were 335 subjects with moderate SMR and 525 with severe SMR at baseline per ECL review. Baseline characteristics were similar between the 2 subgroups. After treatment with M-TEER, significant MR reduction was achieved in both groups. Significant left ventricular (LV) reverse remodeling was observed through 1 year, with a >20 mL decrease in LV end-diastolic and end-systolic volumes on average in the moderate SMR group. Significant 1-year improvements in NYHA functional class (>78% NYHA functional class I or II) and quality of life (>20 points on the Kansas City Cardiomyopathy Questionnaire–Overall Summary) were observed in subjects with moderate SMR. Similarly, low rates of major adverse events, all-cause mortality, and HF hospitalizations were observed between the 2 subgroups through 1 year. Conclusions: In the EXPANDed studies, subjects with moderate SMR treated with M-TEER had improvements similar to subjects with severe SMR in quality of life and positive LV remodeling at 1 year. Future studies are needed to evaluate if M-TEER would be beneficial for HF patients with moderate SMR
Evidence Generation and Implementation of Transcatheter Interventions for Atrioventricular Valvular Heart Disease in Heart Failure: Current Status and Future Directions
Get PDFMitral regurgitation and tricuspid regurgitation are the most common valvular heart diseases in patients with heart failure and have independent prognostic value. Transcatheter interventions are now available for the treatment of valvular heart disease, and their efficacy and safety have been tested in randomized controlled trials. However, evidence is still limited and sometimes inconclusive because several aspects of these trials limit their interpretation or consistency. These include heterogeneity in the pathogenesis and clinical characteristics of patients, the dynamic nature of secondary atrioventricular valve disease severity, the role of heart failure medications and devices, dependency on procedural results and operators’ skills, smaller number of patients enrolled and the power to detect differences in trials, and limitations to use patients’ reported outcomes with unblinded study protocols. These specific aspects of trials in patients with atrioventricular valve disease are reviewed in this article with a focus on possible solutions to generate further evidence for the efficacy and safety for transcatheter treatments of atrioventricular valve disease in patients with heart failure
Screening and surveillance practices for Multiple Endocrine Neoplasia type 1-related Neuroendocrine Tumours in European Neuroendocrine Tumor Society Centers of Excellence (ENETS CoE)—An ENETS MEN1 task force questionnaire study
Get PDFMultiple Endocrine Neoplasia type 1 (MEN1) Clinical Practice Guidelines (2012) are predominantly based on expert opinion due to limited available evidence at the time, leaving room for interpretation and variation in practices. Evidence on the natural course of MEN1-related neuroendocrine tumours (NET) and the value of screening programs has increased and new imaging techniques have emerged. The aim of this study is to provide insight in the current practices of screening and surveillance for MEN1-related NETs in ENETS Centers of Excellence (CoEs). A clinical practice questionnaire was distributed among all 65 ENETS CoEs. Response rate was 91% (59/65). In 14% of CoEs <10 patients, in 50% 10–49, in 31% 50–100 and in 3 centres (5%) >100 patients with MEN1 are seen. Practices with regard to screening and surveillance of NETs were markedly heterogeneous. Differences between countries were noted in the use of gut hormones for biochemical screening and the choice for imaging modality for screening/surveillance of pancreatic NETs (PanNETs). Magnetic resonance imaging (MRI) is the preferred modality for screening and surveillance of PanNETs, whereas this is computed tomography (CT) for thoracic NETs. Practices regarding screening for thoracic NETs were more homogeneous among larger volume CoEs, with longer screening intervals. The majority of CoEs tailored the surveillance of small pancreatic and lung NETs to observed growth rate. 68% of CoEs advise patients with clinical MEN1 with negative genetic testing to undergo periodic screening like mutation-positive patients. In conclusion, there is still marked heterogeneity in practice, although there are also common trends. Differences were sometimes associated with volume or country, but often no association was found. This underscores the need for clear and evidence-based practice recommendations
Filosofia della fotografia. I prodigi di un insospettabile "obiettivo"
No full textRiflessione filosofica intorno all'arte fotografica