Stroke accounts for the second leading cause of death and a major cause of disability, with limited therapeutic strategy in both the acute and chronic phases. Blood-based biomarkers are intensively researched and widely recognized as useful tools to predict the prognoses of patients confronted with therapeutically limited diseases. We performed a systematic review of the circulating biomarkers in IS patients with prognostic value, with a focus on microRNAs and exosomes as predictive biomarkers of motor and cognitive recovery. We identified 63 studies, totalizing 72 circulating biomarkers with prognostic value in stroke recovery, as follows: 68 miRNAs and exosomal-miRNAs being identified as predictive for motor recovery after stroke, and seven biomarkers being predictive for cognitive recovery. Twelve meta-analyses were performed using effect sizes (random-effects and fixed-effects model). The most significant correlation findings obtained after pooling were with miR-21, miR-29b, miR-125b-5p, miR-126, and miR-335. We identified several miRNAs that were correlated with clinical outcomes of stroke severity and recovery after ischemic stroke, providing predictive information on motor and cognitive recovery. Based on the current state of research, we identified serum miR-9 and neutrophil miR-29b as the most promising biomarkers for in-depth follow-up studies, followed by serum miR-124 and plasma miR-125b.

BACKGROUND: Stroke-induced aphasia significantly impacts communication and quality of life. Despite the standard treatment being speech and language therapy, outcomes vary, highlighting the need for additional therapies. Cerebrolysin, a neuroprotective and neurotrophic agent, has shown potential in stroke management. This study addresses the notable gap in research about the combined use of Cerebrolysin and speech therapy, evaluating their synergistic potential in the treatment of aphasia. METHODS: The ESCAS trial (The Efficacy and Safety of Cerebrolysin in the Treatment of Aphasia After Acute Ischemic Stroke), a prospective, randomized-controlled, double-blinded study was conducted in 2 Romanian stroke centers. Participants included those with left middle cerebral artery territory ischemic stroke and nonfluent aphasia, enrolled 3 to 5 days poststroke. Inclusion criteria were right-handedness and Romanian as the mother tongue. Participants received Cerebrolysin or a placebo combined with speech and language therapy in 10-day cycles over 3 intervals, and evaluations were done at baseline, 30, 60, and 90 days respectively. The main outcome measure was Western Aphasia Battery for language function. Changes at days 30, 60, and 90 compared with baseline were quantified, and the effect estimand used was the difference in means between groups. Secondary outcome measurements were the National Institutes of Health Stroke Scale for neurological deficit, the modified Rankin Scale for global disability, and the Barthel Index for activities of daily living. RESULTS: Out of 132 enrolled patients, 123 were included in the intention-to-treat analysis, and 120 in the per-protocol analysis. Overall, both groups showed improvement at subsequent visits compared with the baseline for Western Aphasia Battery and the National Institutes of Health Stroke Scale. The Cerebrolysin group showed greater improvements in Western Aphasia Battery (visit 4 mean increase of 35.579±16.316 [95% CI, 31.289–39.869] points; P <0.001) compared with the placebo group (20.774±12.486 [95% CI, 17.603–23.945] points; P <0.001), a difference in means of 14.805 (95% CI, 9.521–20.089) points ( P <0.001). The Cerebrolysin group also showed significant improvements (higher decreases) in National Institutes of Health Stroke Scale scores compared with the placebo group (2.085 [95% CI, 1.076–3.094] points; P <0.001). Safety analysis raised no concerns (number of patients with adverse events P =0.105, number of adverse events per patient P =0.134). Additionally, the Cerebrolysin group showed greater improvements in functional independence (Barthel Index) and a trend toward reduced disability (modified Rankin Scale) compared with the placebo group. CONCLUSIONS: Cerebrolysin combined with speech and language therapy offers promising potential for enhancing recovery in poststroke nonfluent aphasia. Significant improvements were observed in language and neurological deficits, underscoring the importance of adjunctive therapies in nonfluent aphasia rehabilitation. Further research with larger cohorts is needed to fully establish the efficacy of this combination therapy. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: ISRCTN54581790.

Vitamin D, its importance in different processes taking place in the human body, the effects of abnormal levels of this hormone, either too low or too high, and the need for supplementation have been extensively researched thus far. Variances in exposure to sunlight can cause vitamin D levels to fluctuate. Indoor activity can be a factor for these fluctuations and can lead to a decrease in vitamin D levels. We conducted a systematic review and meta-analysis aiming to identify whether indoor compared to outdoor training has a significant influence on vitamin D levels; we also performed subgroup analyses and multivariate meta-regression. The type of training has an impact on vitamin D levels that is influenced by multiple cofounders. In a subgroup analysis not considering cofounders, the mean serum vitamin D was 3.73 ng/mL higher in outdoor athletes, a difference which barely fails to achieve significance (p = 0.052, a total sample size of 5150). The indoor–outdoor difference is only significant (clinically and statistically) when considering studies performed exclusively on Asian athletes (a mean difference of 9.85 ng/mL, p < 0.01, and a total sample size of 303). When performing the analyses within each season, no significant differences are observed between indoor and outdoor athletes. To control for multiple cofounders (the season, latitude, and Asian/Caucasian race) simultaneously, we constructed a multivariate meta-regression model, which estimated a serum vitamin D concentration lower by 4.446 ng/mL in indoor athletes. While a multivariate model suggests that outdoor training is associated with slightly higher vitamin D concentrations when controlling for the season, latitude, and Asian/Caucasian race, the type of training has a numerically and clinically small impact. This suggests that vitamin D levels and the need for supplementation should not be decided based on training type alone.

Considered as the most frequent contaminations that do not require hospitalization, urinary tract infections (UTIs) are largely known to cause significant personal burdens on patients. Although UTIs overall are highly preventable health issues, the recourse to antibiotics as drug treatments for these infections is a worryingly spread approach that should be addressed and gradually overcome in a contemporary, modernized healthcare system. With a virtually alarming global rise of antibiotic resistance overall, nanotechnologies may prove to be the much-needed ‘lifebuoy’ that will eventually suppress this prejudicial phenomenon. This review aims to present the most promising, currently known nano-solutions, with glimpses on clinical and epidemiological aspects of the UTIs, prospective diagnostic instruments, and non-antibiotic treatments, all of these engulfed in a comprehensive overview.

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018–2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non-BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease. This study explored the association between human leukocyte antigen (HLA) and ESRD. The interaction between genetic and environmental factors may also play a role in the development of ESRD. The study included 2392 ESRD patients who were awaiting renal transplantation. Blood samples were genotyped by SSOP and SSP-PCR methods. Multivariate logistic regression analysis showed that HLA-A*11 (p = 0.027), HLA-A*34 (p = 0.017), HLA-A*69 (p = 0.012), HLA-B*41 (p < 0.001), HLA-B*50 (p = 0.004), HLA-DRB1*10 (p = 0.027), and HLA-DRB1*14 (p = 0.004) were positively associated with ESRD (OR > 1); HLA-DRB1*07 (p < 0.001), HLA-DRB1*08 (p = 0.005), and HLA-DRB1*13 (p < 0.001) were protective against ESRD (OR < 1); and the three-locus haplotype HLA-A*02–B*41–DRB1*03, containing one susceptible allele, was strongly associated with ESRD (p < 0.001, OR = 3.15). In conclusion, this retrospective analysis of HLA typing in patients with ESRD of various etiologies suggests that molecular data on the HLA polymorphism should be collected in order to identify high-risk ESRD patients and to improve graft survival after kidney transplantation.