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.

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.

We evaluated in this cohort study the predictive ability of 23 peripheral blood parameters and ratios for treatment outcomes after the 2-month intensive phase in patients with PTB. In 63 patients out of 90 that turned culture negative, a significant decrease in white blood cell count, neutrophils, monocyte, hemoglobin, platelet, plateletcrit, erythrocyte sedimentation rate, MLR, NLR, PLR and SII values after anti-TB therapy compared to pretreatment was observed (p <0.001). Logistic regression analysis generated a model of predictors consisting of nine covariates. Spearman’s correlation analysis revealed significant positive correlations between NLR with NEU (r = 0.79, p<0.01), SII with NEU (r = 0.846, p<0.01), PLT with SII (r = 0.831, p<0.01), PLT with PCT (r = 0.71, p<0.01) and MPV with P-LCR (r = 0,897, p<0.01) in 63 patients out of 90 that turned culture negative after 2 months of treatment. ROC curve analysis indicated that all areas under the curve (AUC) revealed no statistically significant results, except lymphocyte for culture conversion. In summary, here we observed a set of hematological parameters that declined significantly as the disease was treated in patients that turned culture negative. Despite some limitations, our findings are useful for further studies aiming to identify hematological profiles that could predict the treatment outcome.

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Spinal muscular atrophy (SMA) is a spectrum of genetically and clinically heterogeneous diseases leading to the progressive degeneration of peripheric motor neurons with subsequent muscle weakness and atrophy. More than 95% of the cases of SMA are represented by homozygous mutations of the SMN1 gene (5q-SMA). Because this disease represents the leading cause of death due to a genetic cause and due to the availability of genetic therapies which can now save the life of the patient and stop the progress of the disease, early diagnosis is crucial. This report presents the case of a 13-year-old patient admitted to our hospital in 2018 who presented a phenotype typical to 5q-SMA. Next-generation sequencing (NGS) and Sanger sequencing of the SMN1 gene were performed, and a negative result was obtained. Consequently, we continued testing using whole-exome sequencing and discovered three mutations in the ASAH1 gene (one pathogenic and two variants of uncertain significance). Pathogenic mutations in the ASAH1 gene are responsible for spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and Farber disease, which overlapped with our patient’s phenotype. Currently, there are 45 SMA cases caused by mutations in the ASAH1 gene reported worldwide; however, the present case is the first reported in Romania.

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.

1q44 microdeletion syndrome (1q44 monosomy) is a newly described genetic syndrome characterized by the haploinsufficiency of a 6 Mb locus on the long arm of chromosome 1. The main features are global developmental delay, seizures, hypotonia and craniofacial dysmorphism. With a prevalence below one in a million cases, this syndrome is very rare and, hence, often passes undiagnosed. We present the case of a one year old girl admitted to our hospital with global developmental delay and several congenital abnormalities suggesting a plurimalformative syndrome. Microarray analysis detected a 967 kb deletion in the 1q44 region as well as a a 530 kb microduplication in the 14q31.1q31.2 region, the latter having unknown clinical significance as it contains no currently known OMIM genes. The patient’s phenotype was in accordance to 1q44 microdeletion syndrome. Furthermore, after studying the 1q44 microdeletion syndrome cases reported so far in the literature, we have noticed that our patient presented previously undescribed features of this syndrome, namely prenatal hydronephrosis, bifid hallux and grey matter heterotopy. Based on the cerebral, renal and skeletal involvement in 1q44 microdeletion syndrome, we suspect these might be additional, previously unreported features of 1q44 microdeletion syndrome.

Fibroza chistică, numită și mucoviscidoză, este cea mai frecventă boală pulmonară ereditară și este produsă de mutații în gena CFTR, ce codifică un canal anionic pentru clor și bicarbonat cu rol în reglarea metabolismului bicarbonatului și sării. În momentul de față, aproximativ jumătate din totalul pacienților cu fibroză chistică pot beneficia de terapie personalizată cu ajutorul modulatorilor, substanțe care restaurează sau îmbunătățesc funcționalitatea și stabilitatea CFTR. Mai mult, la ora actuală se află în stadiul de studiu clinic și alte tipuri de terapii, ca de exemplu terapia genică utilizând sistemul CRISP/CAS-9, oligonucleotide antisens modificate sau inserția genei sălbatice utilizând particule nanolipidice sau vectori virali. Acest articol își propune să treacă în revistă principalele tipuri de terapii aprobate sau aflate în stadiul de studiu clinic pentru tratamentul fibrozei chistice.