Centro Clinico Nemo

Background and Objectives Observational data can provide evidence of treatment effects in a low-burden, cost-effective manner. Using a causal inference framework to address selection bias, we illustrate the approach in ALS by examining previously researched associations, baseline function and sex, and evaluating metformin’s survival benefits. Methods Data are from the ALS Natural History Study collected in the United States, Israel, and Italy from 2015 to 2025. We employ propensity score matching, two approaches to address loss to follow-up (i.e. a naive exclusion and principal stratification), and randomization-based inference to evaluate difference in 18-month restricted mean survival time. Results For the function investigation, estimated survival is 16.39, 16.14, 16.09, and 16.24 months for the high ALSFRS-R group and 14.04, 14.42, 14.72, and 14.60 months for the low ALSFRS-R group using the non imputed and imputed datasets 1-3, respectively (p<0.0001, N=450; p<0.00001, N=1,485; p<0.00001, N=1,492; p<0.00001, N=1,600). Using principal stratification, estimated survival is 16.38, 16.14, 16.09, and 16.23 months for the high ALSFRS-R group and 14.04, 14.42, 14.72, and 14.59 months for the low ALSFRS-R group with the non imputed and imputed datasets 1-3, respectively (p<0.0001, N=449; p<0.00001, N=1,483; p< 0.00001, N=1,491; p<0.00001, N=1,596). For the sex investigation, estimated survival is 15.20, 15.16, 15.20, and 15.17 months for females and 15.41, 14.84, 14.91, and 14.97 months for males using the non imputed and imputed datasets 1-3, respectively (p≈0.594, N=612; p≈0.155, N=2,081; p≈0.200, N=2,104; p≈0.359, N=2,111). Using principal stratification, estimated survival is 15.20, 15.16, 15.20, and 15.17 months for females and 15.41, 14.83, 14.91, and 14.97 months for males with the non imputed and imputed datasets 1-3, respectively (p≈0.598, N=612; p≈0.146, N=2,079; p≈0.195, N=2,102; p≈0.364, N=2,110). For the metformin investigation, estimated survival is 14.77, 14.87, and 14.57 months for metformin users and 14.59, 14.43, and 13.97 months for non metformin users using imputed datasets 1-3, respectively (p≈0.391, N=289; p≈0.257, N=279; p≈0.191, N=301). Using principal stratification, estimated survival is 14.75, 14.85, and 14.55 months for metformin users and 14.68, 14.58, and 13.97 months for non metformin users with imputed datasets 1-3, respectively (p≈0.458, N=286; p≈0.351, N=275; p≈0.201, N=300). Discussion We reject the sharp null hypothesis for the function investigation and fail to reject it for the sex and metformin investigations. Trial Registration Information ClinicalTrials.gov Identifier: NCT05966038 .

Unlike other immune-based combinations for hepatocellular carcinoma (HCC), long-term data for atezolizumab-bevacizumab (AB) are lacking, as the IMbrave150 trial closed after a median follow-up of 15.6 months. Consequently, reports of long-term outcomes for AB rely mainly on real-world evidence. We evaluated long-term effectiveness, safety, and clinically relevant on-treatment events in a large prospective real-world cohort of patients treated with AB. We analyzed 538 patients prospectively enrolled in the Italian ARTE database. Outcomes included overall survival (OS), safety, liver decompensation, rate of patients achieving drug-free disease-free status. On-treatment events were modelled as time-dependent covariates in Cox regression models. After a median follow-up of 24.2 months, median OS was 19.7 months (95% CI 17.2-22.2), with a 36-month survival rate of 30.0%. Independent factors influencing OS included ECOG-PS >0, ALBI grade >1, AFP >400ng/mL, multinodularity, macrovascular invasion, and on-treatment events (objective response, progression, or liver decompensation). Grade ≥3 AEs occurred in 36.8% of patients; 5 late-onset severe toxicities arose beyond 24 months. Liver decompensation unrelated to tumor progression occurred in 14.1% patients. Eighty patients (14.9%) underwent surgical or locoregional procedures after the initiation of AB; 24 (4.4%) achieved a drug-free disease-free status. Our data confirmed the sustained effectiveness of AB without new safety concerns. Surgical/locoregional treatments after the start of AB and liver decompensation were common, highlighting the need for a multidisciplinary and integrated approach in advanced HCC.

Patient: Female, 40-year-oldFinal Diagnosis: ObesitySymptoms: ObesityClinical Procedure: —Specialty: SurgeryObjective: Unusual clinical courseBackgroundMetabolic and bariatric surgeries (MBS) are effective treatments for obesity and related comorbidities, such as diabetes and hypertension. In patients with morbid obesity and challenges like hepatomegaly, conventional procedures may increase risks. Staged MBS was developed to address these issues, enhancing safety. This report highlights the successful use of isolated intestinal transit bipartition with duodeno-ileal anastomosis, preserving the duodenum, as the first stage of the duodenal switch.Case ReportA 40-year-old woman with a BMI of 40.2 kg/m2 was booked for MBS. Severe hepatomegaly impaired safe access to the esophagogastric junction, leading to the performance of only the intestinal stage of the duodenal switch. A duodeno-ileal anastomosis was created 250 cm from the ileocecal valve, preserving the stomach and partial duodenal function. Without the gastric stage, the patient achieved 50 kg of weight loss (equivalent to 78.7% excess weight loss) over 19 years, without requiring additional surgery. Minor complications included occasional diarrhea, meteorism, and difficulties with vitamin supplementation, all managed effectively through dietary adjustments and nutritional guidance. A benefit was increased satiety.ConclusionsIsolated intestinal transit bipartition with duodeno-ileal anastomosis is an approach that may be used in exceptional cases, such as with this patient. Despite the favorable long-term follow-up results, further studies are necessary to better understand this approach. This method demonstrated sustained weight loss and long-term metabolic control, potentially representing a promising initial treatment option for patients with lower BMIs, including those with type 2 diabetes.

Intrathecal onasemnogene abeparvovec (OAV101 IT) may enable a one-time gene transfer therapy, addressing an unmet need across the broader spinal muscular atrophy (SMA) population. STRENGTH ( NCT05386680 ) was a 52-week, phase 3b, single-arm, open-label, multicenter study evaluating OAV101 IT in participants with SMA aged 2 to <18 years who discontinued nusinersen or risdiplam. The primary objective was safety/tolerability. Twenty-seven participants were enrolled (mean (s.d.) age at OAV101 IT, 7.4 (3.35) years; range, 2.4-17.7 years) with prior nusinersen or risdiplam (mean (s.d.) duration of 4.3 (1.07) years; range, 1.86-6.18 years or 3.0 (2.02); range, 0.39-6.28 years). All (n = 27) experienced at least one adverse event (AE), most frequently nasopharyngitis (n = 15, 55.6%), pyrexia (n = 14, 51.9%) and vomiting (n = 13, 48.1%). Thirteen participants (48.1%) experienced treatment-related AEs, most frequently vomiting (n = 6, 22.2%), headache (n = 4, 14.8%) and pyrexia (n = 3, 11.1%). Serious adverse events (SAEs) were reported for four participants (n = 4, 14.8%) (mostly respiratory infection related). No AEs leading to death or study discontinuation were reported. Adverse events of special interest (AESI) reported were in categories of transient thrombocytopenia (n = 8, 29.6%), hepatotoxicity (n = 4, 14.8%) and signs and symptoms that may be suggestive of dorsal root ganglia toxicity (n = 2, 7.4%). The OAV101 IT safety profile was consistent with findings in treatment-naïve patients. Trial registration: ClinicalTrials.gov identifier: NCT05386680 .

Clinical research is a strategic priority for the Italian healthcare system, with significant benefits for patients, economy and public health. The Clinical Advancement & Research Excellence (CARE) project identified the main obstacles that limit the full expression of the potential of clinical trials in Italy and proposed concrete solutions. Starting with an online survey and following a simplified Delphi method, a multidisciplinary panel of experts identified the main barriers to clinical research in Italy and proposed a set of programmatic instances designed to improve the present situation. The final instances were formulated also based on the review by external stakeholders. The following programmatic instances were developed: 1) support the compliance with trial contract signing times; 2) create a national standard for Clinical Trial Sites (CTS) and a dedicated portal; 3) define the role of General Practitioners; 4) promote campaigns to raise awareness on the importance of clinical research. The instances presented offer concrete insights to optimize the effectiveness and efficiency of clinical trials in Italy, ensuring international competitiveness and allowing patients to benefit from innovative therapies.

Introduction:Injuries of the pre-pubic aponeurotic complex (PPAC) are a significant cause of groin pain syndrome. These injuries tend to have limited self-healing capacity because the injured area is kept apart by opposing forces exerted by the rectus abdominis (RA) and adductor longus muscles. Recently, botulinum toxin type A (BTX-A) has been successfully used in a case report describing a patient with PPAC injuries. This study aims to evaluate the efficacy of BTX-A in a series of patients with PPAC injuries.Materials and Methods:Ten male athletic subjects with PPAC injuries underwent infiltrative therapy with BTX-A at the level of the RA and adductor longus, followed by an 8-week rehabilitation program.Results:Ultrasound assessment performed after the rehabilitation program showed that 9 subjects (90%) achieved complete restitutio ad integrum of the PPAC injury area, while 1 subject (10%) exhibited partial repair. At 12 months of follow-up, 9 patients (90%) returned to sports activity, 8 (80%) at the same level, and 1 (10%) at a lower level, but not due to residual pain. No adverse effects were recorded.Conclusion:BTX-A infiltrative therapy appears to be a safe, effective, and promising treatment for PPAC injuries, enabling a quick return to sporting activity.

BACKGROUND Sleeve gastrectomy (SG) is widely used in obesity treatment, although it is associated with new onset of gastroesophageal reflux disease (de novo GERD) and weight regain. Roux-en-Y gastric bypass (RYGB) is the standard revisional procedure for GERD, though it offers limited additional weight loss. Ileal-based procedures have demonstrated superior outcomes regarding weight loss but have uncertain results in GERD. This study presents preliminary findings on gastric bipartition with functional duodenal exclusion (GBp-FDE) as a revisional approach following SG in this scenario. CASE REPORT A retrospective data analysis was conducted on 10 patients who underwent GBp-FDE due to de novo GERD and obesity recurrence after SG (mean BMI: 37.2±3.2 kg/m²). Nine patients presented with hiatal hernia and 8 with sleeve dilation. GERD was assessed pre- and postoperatively using a validated questionnaire, endoscopy, and contrast radiology. The surgical technique involved a pre-pyloric antroileostomy in Roux-en-Y configuration using a 40% proportion biliopancreatic limb. One-year postoperative findings included pyloric spasm (endoscopy), very preferential contrast flow to the ileum (radiology), and endoscopic access preservation to the duodenum. GERD symptoms resolved in 90% (P=0.0059) and esophagitis healed in 80% (P=0.008), likely due to gastric decompression. Mean percent total weight loss and percent excess weight loss were 35.2±6.6 and 108.0±11.14, respectively. CONCLUSIONS GBp-FDE seems to be a promising surgery for managing de novo GERD and obesity recurrence after SG, through SG pouch decompression and ileal stimuli, promoted by the antroileostomy. Further controlled studies with extended follow-up are necessary to validate these findings.