Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. Methods: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. Results: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. Conclusions: Our results suggest that early treatment is more important than combined therapy.

Pro-inflammatory mediators play an important role in the pathogenesis of pulmonary tuberculosis. Consecutively, 26 pulmonary tuberculosis patients were enrolled in our study based on the exclusion criteria. We have used Spearman’s correlation analysis, hierarchical clustering and regression modelling to evaluate the association of 11 biomarkers with culture status after antituberculosis treatment. The results of our study demonstrated that six inflammatory biomarkers of 11, C-reactive protein (CRP), white blood cells (WBC), neutrophils, interferon gamma inducible protein 10, C-reactive protein (CRP) to albumin ratio (CAR) and neutrophil to albumin ratio (NAR), were significantly associated with culture negativity. The predictive ability of a composite model of seven biomarkers was superior to that of any single biomarker based on area under the receiver operating characteristic curve (AUC) analysis, indicating an excellent prediction efficacy (AUC:0.892; 95% CI:0.732-1.0). We also found that the highest significant trends and lower levels of CRP and IP-10 were observed in the two-month treated tuberculosis (TB) patients. We believe that our study may be valuable in providing preliminary results for an additional strategy in monitoring and management of the clinical outcome of pulmonary tuberculosis. Using a panel of predictors added a superior value in predicting culture status after anti-TB therapy.

Our study objective was to construct models using 20 routine laboratory parameters on admission to predict disease severity and mortality risk in a group of 254 hospitalized COVID-19 patients. Considering the influence of confounding factors in this single-center study, we also retrospectively assessed the correlations between the risk of death and the routine laboratory parameters within individual comorbidity subgroups. In multivariate regression models and by ROC curve analysis, a model of three routine laboratory parameters (AUC 0.85; 95% CI: 0.79–0.91) and a model of six laboratory factors (AUC 0.86; 95% CI: 0.81–0.91) were able to predict severity and mortality of COVID-19, respectively, compared with any other individual parameter. Hierarchical cluster analysis showed that inflammatory laboratory markers grouped together in three distinct clusters including positive correlations: WBC with NEU, NEU with neutrophil-to-lymphocyte ratio (NLR), NEU with systemic immune-inflammation index (SII), NLR with SII and platelet-to-lymphocyte ratio (PLR) with SII. When analyzing the routine laboratory parameters in the subgroups of comorbidities, the risk of death was associated with a common set of laboratory markers of systemic inflammation. Our results have shown that a panel of several routine laboratory parameters recorded on admission could be helpful for early evaluation of the risk of disease severity and mortality in COVID-19 patients. Inflammatory markers for mortality risk were similar in the subgroups of comorbidities, suggesting the limited effect of confounding factors in predicting COVID-19 mortality at admission.

Aim and Objectives: The objective of our retrospective study was to investigate the changes in pNFH levels in cerebrospinal fluid, which is a reliable marker of neuronal damage, after the loading dose of nusinersen in different types of spinal muscular atrophy. Materials and Methods: We analyzed the spinal muscular atrophy types, the number of copies of the SMN2 gene, and the progression of the motor status using specific motor function scales in a group of 38 patients with spinal muscular atrophy types 1, 2, and 3. Results: We found a significant inverse correlation between pNFH levels and patient age, progress on functional motor scales, and nusinersen administration. Our results also revealed that the neurofilament levels in the cerebrospinal fluid were higher in patients with 2 SMN2 copies than those with more than 2 copies, although the association was not statistically significant due to the abnormal distribution of the values. Conclusions: We identified several predictors of favorable evolution under nusinersen treatment, including spinal muscular atrophy type 1, children aged ≤ 30 months, and the presence of only 2 copies of SMN2. Our study provides important insights into the use of pNFH as a biomarker to monitor disease progression and responses to treatment in patients with spinal muscular atrophy.

The investigation of unexplained global developmental delay (GDD)/intellectual disability (ID) is challenging. In low resource settings, patients may not follow a standardized diagnostic process that makes use of the benefits of advanced technologies. Our study aims to explore the contribution of chromosome microarray analysis (CMA) in identifying the genetic etiology of GDD/ID. A total of 371 Romanian patients with syndromic or non-syndromic GDD/ID, without epilepsy, were routinely evaluated in tertiary clinics. A total of 234 males (63.07%) and 137 (36.93%) females, with ages ranging from 6 months to 40 years (median age of 5.5 years), were referred for genetic diagnosis between 2015 and 2022; testing options included CMA and/or karyotyping. Agilent Technologies and Oxford Gene Technology CMA workflows were used. Pathogenic/likely pathogenic copy number variations (pCNVs) were identified in 79 patients (21.29%). Diagnosis yield was comparable between mild ID (17.05%, 22/129) and moderate/severe ID 23.55% (57/242). Higher rates were found in cases where facial dysmorphism (22.97%, 71/309), autism spectrum disorder (ASD) (19.11%, 26/136) and finger anomalies (20%, 27/96) were associated with GDD/ID. GDD/ID plus multiple congenital anomalies (MCA) account for the highest detection rates at 27.42% (17/62). pCNVs represent a significant proportion of the genetic causes of GDD/ID. Our study confirms the utility of CMA in assessing GDD/ID with an uncertain etiology, especially in patients with associated comorbidities.