Publications

OBJECTIVE: The current study aims to describe the infection and infestation adverse events that may be associated with the use of ocrelizumab using real-world data.

METHODS: Infection and infestation adverse event reports with the generic name ocrelizumab as the primary suspect in the FAERS database from Q4 2003 to Q3 2024 were included in the study. The disproportionality analysis software package OpenVigil 2.1-MedDRA-v24, including the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) algorithms, was used to determine signal strength of infection and infestation adverse events associated with ocrelizumab. The signal intensity for ROR and PRR was classified as low, medium and strong according to signal strength.

RESULTS: The analysis of infection and infestation reports of the drug pharmacovigilance database on the use of ocrelizumab revealed 161 positive signals. The most common adverse event reported was COVID-19 (n=2287, ROR 24.303; PRR 22.681). According to the disproportionality analysis, the top six adverse events with the highest ROR and PRR were encephalitis enteroviral (ROR 101.831; PRR 101.809), meningitis enteroviral (ROR 76.019; PRR 76.005), fallopian tube abscess (ROR 51.225; PRR 51.221), nasal herpes (ROR 45.676; PRR 45.662), neuroborreliosis (ROR 28.563; PRR 28.559) and babesiosis (ROR 25.507; PRR 25.5).

CONCLUSION: Ocrelizumab may increase the risk of many infections and infestations, including enterovirus-related central nervous system infections, tick-borne infections, COVID-19-related disorders, genital tract infections and herpes infections, and therefore requires careful monitoring in clinical practice.

For goal-directed movements like throwing darts or shooting a soccer penalty, the optimal location to aim depends on the endpoint variability of an individual. Currently, there is no consensus on whether people can optimize their movement planning based on information about their motor variability. Here, we tested the role of different types of feedback for movement planning under risk. We measured saccades toward a bar that consisted of a reward and a penalty region. Participants either received error-based feedback about their endpoint or reinforcement feedback about the resulting reward. We additionally manipulated the feedback schedule to assess the role of feedback frequency and whether feedback focusses on individual trials or a group of trials. Participants with trial-by-trial reinforcement feedback performed best. They were less loss-aversive, had the least endpoint deviation from optimality, and showed more consistent performance at the group level. This combination of reduced between-participant variability and the improved alignment with optimality suggests that reinforcement feedback about a single movement is particularly effective to optimize movement planning under risk.

PURPOSE: To evaluate the 1-year progression of retinal capillary nonperfusion in eyes with mild to severe nonproliferative diabetic retinopathy (NPDR) using noninvasive retinal imaging.

METHODS: The CHART study (Clinicaltrials.gov: NCT04636307) is a multicenter, observational, longitudinal study involving five European research centers and included 202 eyes from 155 participants with type 2 diabetes and mild to severe NPDR. Participants underwent comprehensive ophthalmologic examinations at baseline and 3, 6, and 12 months, including best-corrected visual acuity, color fundus photography (Early Treatment Diabetic Retinopathy Study [ETDRS] severity scale), optical coherence tomography (OCT), and OCT angiography (OCTA). Disease progression was evaluated using mixed-effects models.

RESULTS: Of the 202 eyes, 81 eyes were graded as ETDRS level 35, 63 eyes as level 43, 46 eyes as level 47, and 12 eyes as level 53. At baseline, significant differences were observed in OCTA metrics between diabetic retinopathy severity groups. A total of 169 eyes (84%) completed the 1-year follow-up. Over 1 year, eyes with ETDRS levels 35 and 43 showed significant increases in capillary nonperfusion, identified by decreases in skeletonized vessel density in the superficial capillary plexus (rates of progression: β = -0.217 mm-1/y, P = 0.006 and β = -0.310 mm-1/y, P = 0.002, respectively). Eyes with level 47 showed only a borderline statistically significant decrease (P = 0.074), while eyes with level 53 remained stable. Microaneurysm turnover (MAT), formation, and disappearance rates increased in more severe NPDR stages (levels 47 and 53).

CONCLUSIONS: Retinal capillary nonperfusion progresses significantly over 1 year in mild to moderate NPDR, identified by changes in rates of progression of vessel and perfusion densities. In more severe stages (levels 47 and 53), capillary nonperfusion stabilizes, and a hyperperfusion response is identified by increases in MAT associated with the development of intraretinal microvascular abnormalities.

TRANSLATIONAL RELEVANCE: This study provides quantitative data on 1-year progression of retinal capillary nonperfusion in NPDR using noninvasive imaging, offering the basis for future interventional trials.

Glossopharyngeal neuralgia (GN) is a rare neuropathic disorder characterized by sudden, unilateral, electric shock-like pain in the areas innervated by the glossopharyngeal nerve. Its diagnosis is frequently delayed because of its clinical overlap with odontogenic and otorhinolaryngological conditions. In the context of the COVID-19 pandemic, different cranial neuropathies have been reported, suggesting possible post-infectious mechanisms. We describe the case of a 54-year-old male dentist, without relevant medical history, who developed recurrent episodes of intense pain in the right pharynx and base of tongue after confirmed SARS-CoV-2 infection. Symptoms were triggered by swallowing, coughing, and salivary stimulation, reaching maximum intensity on the visual analogue scale (EVA 10/10). Brain and neck magnetic resonance imaging revealed no structural abnormalities. Treatment with carbamazepine (600 mg/day) partially reduced frequency and severity of attacks, while pregabalin (300 mg/day) showed no benefit. This case highlights the need to consider SARS-CoV-2 infection as a potential trigger of GN, underscores the importance of recent infectious history in the differential diagnosis, and emphasizes the relevance of early pharmacological management in clinical improvement.

Cirrhosis is the fourteenth leading cause of death globally and significantly increases the risk of hepatocellular carcinoma (HCC). Polymorphisms in the vitamin D receptor (VDR) can influence inflammation, fibrosis progression and cancer susceptibility. We analysed the association of genetic polymorphisms of the VDR (VDR-rs2228570, VDR-rs731236 and VDR-rs7975232) in cirrhosis with or without HCC, considering clinical, biochemical profiles and survival. A total of 158 patients with cirrhosis, with or without HCC, were studied and distributed into Group 1 (G1 = 60): cirrhosis and HCC; Group 2 (G2 = 98): isolated cirrhosis and control group (G3 = 225): without liver disease. Genetic polymorphisms were analysed by real-time polymerase chain reaction; clinical and biochemical profiles were obtained from medical records. A significance level of α = 5% was adopted. The homozygous mutant for VDR-rs731236 and rs7975232 predominated in G1 compared to other groups (p < 0.05). For VDR-rs2228570, the homozygous mutant predominated in patients, while heterozygotes were found in controls (p > 0.05). A positive correlation between vitamin D and parathyroid hormone was observed in patients (R² = 0.3273). VDR-rs2228570 emerged as a protective factor for G2 (p = 0.0057) and was associated with increased survival, as was rs7975232. In conclusion, VDR-rs731236 and VDR-rs7975232 are associated with cirrhosis and HCC, with VDR-rs7975232 identified as independent predictors for isolated cirrhosis. VDR-rs2228570 confers protection and is associated with increased survival in cirrhosis, as well as a better clinical profile for both conditions in the Brazilian cohort. These findings highlight the potential clinical relevance of VDR polymorphisms as biomarkers for risk assessment and prognosis in cirrhosis and HCC.

Multiple myeloma (MM) represents a significant global health challenge, with its incidence and mortality rates steadily increasing over recent decades. This review critically examines the current landscape of MM management, with a specific focus on resource-limited settings, where the disparities in diagnostic capabilities and treatment options are most pronounced. A comprehensive literature search was performed using multiple databases, encompassing peer-reviewed articles, clinical guidelines and conference abstracts from 2010 to 2024. Our analysis delineates the stark differences between therapeutic approaches in high-income versus low- and middle-income countries (LMICs). In high-income settings, the standard of care involves advanced induction regimens, autologous stem cell transplantation and maintenance therapy with novel agents, which collectively have contributed to improved patient outcomes. Conversely, LMICs often rely on more affordable yet less effective treatments, such as bortezomib- or thalidomide-based regimens, largely due to limited access to advanced diagnostics and high-cost therapies. Key challenges identified include late presentation, inadequate diagnostic infrastructure, economic constraints and a paucity of trained healthcare personnel. To address these issues, we propose a multifaceted strategy that emphasises the enhancement of diagnostic capacity, the adaptation of resource-stratified treatment guidelines and the strengthening of healthcare systems through targeted policy interventions and international collaborations. By bridging the gap between evidence-based MM care and the practical realities of under-resourced healthcare systems, this review aims to inform future clinical practice and policy, ultimately improving survival outcomes and reducing global health inequities in MM management.