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Objective: Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825)., Methods: Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.0-6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 mg. Following dose escalation, new patients in Group A were randomized (1:1) to receive a single 600 mg intravenous ocrelizumab dose or the candidate subcutaneous dose, which was predicted to result in similar exposure as the 600 mg intravenous dose while being safe and well tolerated. The area under the concentration-time curve for both formulations was used to select the subcutaneous ocrelizumab dose. Patients in all cohorts could enter a dose-continuation phase., Results: Eighty-eight and 47 patients were enrolled into Group A and B, respectively; most patients were female (72.7%/63.0%), and mean age at baseline was 45.7 and 39.7 years, respectively. Subcutaneous ocrelizumab was well tolerated across all doses tested. The 920 mg subcutaneous ocrelizumab dose was selected for the OCARINA II study based on pharmacokinetic and safety data., Interpretation: Subcutaneous ocrelizumab may provide patients with multiple sclerosis with an additional treatment option., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The aim of this study was to assess the reliability of three diagnostic methods (near-infrared transillumination (NIRT), bitewing radiographs (BW), and clinical images (CI)) to detect occlusal carious lesions in a low caries risk population. This retrospective analysis included one hundred and eighty-eight occlusal surfaces, scored as sound surface, early lesion, or distinct lesion. We evaluated the agreement between and within the methods over time. Kappa statistics tested the correlation between the methods. Examiners detected occlusal early lesions more frequently with visual examination and NIRT and the same lesions were confirmed on the 2-year follow-up. Within the limitations of this study, we were able to establish that early occlusal lesions can be detected and monitored over time using NIRT and visual exam, while BW scores showed mostly sound surfaces at both examinations. NIRT combined with clinical examination can be considered appropriate to detect and monitor early enamel caries on the occlusal surface in low caries-risk populations.

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation were assigned to receive gantenerumab, 52 solanezumab and 40 placebo. Both drugs engaged their Aβ targets but neither demonstrated a beneficial effect on cognitive measures compared to controls. The solanezumab-treated group showed a greater cognitive decline on some measures and did not show benefits on downstream biomarkers. Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. Amyloid-related imaging abnormalities edema was observed in 19.2% (3 out of 11 were mildly symptomatic) of the gantenerumab group, 2.5% of the placebo group and 0% of the solanezumab group. Gantenerumab and solanezumab did not slow cognitive decline in symptomatic DIAD. The asymptomatic groups showed no cognitive decline; symptomatic participants had declined before reaching the target doses., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Extracellular vesicles (EVs) are natural particles formed by the lipid bilayer and released from almost all cell types to the extracellular environment both under physiological conditions and in presence of a disease. EVs are involved in many biological processes including intercellular communication, acting as natural carriers in the transfer of various biomolecules such as DNA, various RNA types, proteins and different phospholipids. Thanks to their transfer and targeting abilities, they can be employed in drug and gene delivery and have been proposed for the treatment of different diseases, including cancer. Recently, the use of EVs as biological carriers has also been extended to cancer immunotherapy. This new technique of cancer treatment involves the use of EVs to transport molecules capable of triggering an immune response to damage cancer cells. Several studies have analyzed the possibility of using EVs in new cancer vaccines, which represent a particular form of immunotherapy. In the literature there are only few publications that systematically group and collectively discuss these studies. Therefore, the purpose of this review is to illustrate and give a partial reorganization to what has been produced in the literature so far. We provide basic notions on cancer immunotherapy and describe some clinical trials in which therapeutic cancer vaccines are tested. We thus focus attention on the potential of EV-based therapeutic vaccines in the treatment of cancer patients, overviewing the clinically relevant trials, completed or still in progress, which open up new perspectives in the fight against cancer.

Pediatric Index of Mortality (PIM) 2 score is used in pediatric intensive care unit (PICU) to predict the patients' risk of death. The performance of this model has never been assessed in Switzerland. The aim of this study was to evaluate the performance of the PIM2 score in the whole cohort and in pre-specified diagnostic subgroups of patients admitted to PICUs in Switzerland. All children younger than 16 years admitted to any PICU in Switzerland between January 1, 2012 and December 31, 2017 were included in the study. A total of 22,382 patients were analyzed. Observed mortality was 2%, whereas mortality predicted by PIM2 was 4.2% (SMR = 0.47, 95% CI, 0.42-0.52). Calibration was also poor across the deciles of mortality risks (p < 0.001). The AUC-ROC for the entire cohort was 0.88 (95% CI, 0.87-0.90). Calibration varied significantly according to primary diagnosis.Conclusion: The performance of the PIM 2 score in a cohort of Swiss patients is poor with adequate discrimination and poor calibration. The PIM 2 score tends to under predict the number of deaths among septic patients and in patients admitted after a cardiorespiratory arrest. What is Known: •PIM2 score is a widely used mortality prediction model in PICU. •PIM2 performance among uncommon but clinically relevant diagnostic subgroups of patients is unknown. •The performance of PIM2 score has never been assessed in Switzerland. What is New: •The performance of the PIM 2 score in a cohort of Swiss patients is poor with adequate discrimination and poor calibration. •Calibration varies significantly according to primary diagnosis. The PIM 2 score under predict the number of deaths among septic patients and in patients admitted after a cardiorespiratory arrest.