Search Results (20)

Maternal vaginal and rectal colonization by Streptococcus agalactiae (group B streptococcus, GBS) is the main risk factor for the development of newborn early-onset GBS disease (GBS-EOD). Much effort is in place for its prevention, including the development of vaccines. Currently, both a hexavalent glycoconjugate GBS vaccine against the most prevalent serotypes and a protein subunit vaccine have completed phase two clinical trials. GBS surveillance in both maternal carriage and neonatal disease is therefore important in establishing the coverage of the potential vaccines and in setting up the basis for pre- and post-marketing surveillance. A single-site study was conducted in the years 2020–2021 on the characteristics of 325 GBS strains (serotype distribution; identification of the alpha-like protein family member; and resistance to macrolides, tetracycline, and high-level gentamicin) isolated from the vaginal/rectal site in women in late pregnancy as well as in seven cases of GBS-EOD and one case of GBS-related stillbirth occurring in the same location and time period. The study indicated that the coverage of the developing vaccines was excellent (97.2% for the hexavalent glycoconjugate vaccine and 98.7% for the alpha-like protein subunit vaccine). However, the detection of the serotypes VI, VII, and IX—not covered by current vaccine formulations—accounting for 3.0% of isolates, as well as of negative alpha-like GBS strains from maternal carriage (1.2%), should be closely monitored over time. The high rates of GBS resistance to erythromycin (33.5%) and to clindamycin (29.5% in maternal carriage and 57.1% in GBS-EOD) was mostly due to the ever-increasing spread of the multidrug-resistant ST-17 subclone of serotype III. This finding, along with the newly emerging high-level gentamicin resistance in carriers (4.0%), mainly in serotype IV strains, poses a threat for the continued effectiveness of antibiotic therapy in invasive disease. Full article

Early-onset sepsis (EOS) remains a major cause of neonatal morbidity and mortality worldwide, with significant differences in the incidence and outcome of the disease in Europe. Eastern European countries face particular challenges due to differences in access to healthcare, diagnostic facilities, and prevention strategies. This review summarizes the results of recent research to provide insights into maternal risk factors, regional inequalities in access to healthcare, diagnostic biomarkers, pathogen patterns, and treatment protocols for EOS. This review also examines how healthcare infrastructure and socioeconomic factors influence EOS outcomes in Eastern Europe. Introduction: Early-onset sepsis (EOS) presents a significant health challenge for newborns, characterized by sepsis occurring within the first 72 h of life, primarily caused by the vertical transmission of pathogens from mother to child. Despite advancements in medical care, EOS remains particularly burdensome in resource-poor settings, especially in Eastern Europe, where disparities in healthcare access and maternal health are pronounced. This systematic review aims to provide insights into maternal risk factors, regional inequalities in healthcare access, diagnostic biomarkers, pathogen patterns, and treatment protocols for EOS. Background/Objectives: EOS is increasingly recognized as a public health issue, with outcomes significantly influenced by maternal health, socioeconomic status, and healthcare infrastructure. The review seeks to summarize the existing literature on EOS, particularly focusing on differences between high-income Western and low-resource Eastern European countries. The influence of maternal access to antenatal care, pathogen prevalence, and antibiotic resistance on EOS outcomes across regions will also be examined. Methods: To achieve the review’s objectives, a comprehensive search was conducted across multiple databases including PubMed, Google Scholar, ScienceDirect, and Scopus, adhering to PRISMA guidelines for systematic reviews. The inclusion criteria encompassed studies published within the last 20 years (January 2004–August 2024) that addressed EOS in late preterm or term infants, emphasizing maternal health, risk factors, diagnostic approaches, and treatment protocols pertinent to European populations. Exclusion criteria included non-English publications and studies lacking a focus on maternal and neonatal health. A total of 29 peer-reviewed articles meeting the specified criteria were ultimately included in the analysis. Results: The findings highlight significant regional disparities in EOS management between Western and Eastern Europe. Key issues include maternal risk factors, socioeconomic barriers to healthcare, diagnostic biomarkers, and pathogen resistance trends. Limited access to prenatal screenings and healthcare infrastructure in Eastern European countries, especially in rural regions in Romania, exacerbate the challenges faced by expectant mothers. Financial burdens, such as high out-of-pocket expenses, were shown to further restrict access to necessary maternal care. Conclusions: This systematic review emphasizes the urgent need for targeted investments in maternal healthcare infrastructure in Eastern Europe to mitigate the impacts of EOS. Enhanced screening programs, standardized surveillance systems, and ensuring equitable health policies are essential to improving neonatal outcomes. Additionally, tailored education and awareness campaigns for disadvantaged groups and comprehensive health policy reforms, including universal antenatal care and Group B Streptococcus (GBS), are essential to bridging healthcare gaps. Full article

Anderson–Fabry disease (AFD) is a genetic lysosomal storage disorder caused by mutations in the α-galactosidase A gene, leading to impaired lysosomal function and resulting in both macrovascular and microvascular alterations. AFD patients often exhibit increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating non-atherosclerotic arterial thickening and the potential for cardiovascular events. Nailfold capillaroscopy, a non-invasive diagnostic tool, has shown potential in diagnosing and monitoring microcirculatory disorders in AFD, despite limited research. This study evaluates nailfold capillaroscopy findings in AFD patients, exploring correlations with GLA gene variant subgroups (associated with classical or late-onset phenotypes and variants of uncertain significance (VUSs)), and assessing morpho-functional differences between sexes. It aims to determine whether capillaroscopy can assist in the early identification of individuals with multiorgan vascular involvement. A retrospective observational study was conducted with 25 AFD patients from AOUP “G. Rodolico-San Marco” in Catania (2020–2023). Patients underwent genetic testing, enzyme activity evaluation, and nailfold capillaroscopy using Horus basic HS 200 videodermatoscopy. Parameters like angiotectonic disorder, vascular areas, capillary density, and intimal thickening were assessed. The study identified significant differences in capillaroscopy findings among patients with different GLA gene variant subgroups. Classic AFD variant patients showed reduced capillary length and signs of erythrocyte aggregation and dilated subpapillary plexus. No correlation was found between enzymatic activity and capillaroscopy parameters. However, Lyso-Gb3 levels were positively correlated with average capillary length (ῤ = 0.453; p = 0.059). Sex-specific differences in capillaroscopy findings were observed in neoangiogenesis and average capillary length, with distinct implications for men and women. This study highlights the potential of nailfold capillaroscopy in the diagnostic process and clinical management of AFD, particularly in relation to specific GLA gene mutations, as a valuable tool for the early diagnosis and monitoring of AFD. Full article

Recent data described that patients with lysosomal storage disorders (LSDs) may have clinical schizophrenia (SCZ) features. Disruption of lipid metabolism in SCZ pathogenesis was found. Clinical features of schizophrenia (SCZ) have been demonstrated in patients with several lysosomal storage disorders (LSDs). Taking into account the critical role of lysosomal function for neuronal cells’ lysosomal dysfunction could be proposed in SCZ pathogenesis. The current study analyzed lysosomal enzyme activities and the alpha-synuclein level in the blood of patients with late-onset SCZ. In total, 52 SCZ patients with late-onset SCZ, 180 sporadic Parkinson’s disease (sPD) patients, and 176 controls were recruited. The enzymatic activity of enzymes associated with mucopolysaccharidosis (alpha-L-Iduronidase (IDUA)), glycogenosis (acid alpha-glucosidase (GAA)) and sphingolipidosis (galactosylceramidase (GALC), glucocerebrosidase (GCase), alpha-galactosidase (GLA), acid sphingomyelinase (ASMase)) and concentration of lysosphingolipids (hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), and lysosphingomyelin (LysoSM)) were measured using LC-MS/MS. The alpha-synuclein level was estimated in magnetically separated CD45+ blood cells using the enzyme-linked immunosorbent assay (ELISA). Additionally, NGS analysis of 11 LSDs genes was conducted in 21 early-onset SCZ patients and 23 controls using the gene panel PGRNseq-NDD. Decreased ASMase, increased GLA activities, and increased HexSpn, LysoGb3, and LysoSM concentrations along with an accumulation of the alpha-synuclein level were observed in late-onset SCZ patients in comparison to the controls (p < 0.05). Four rare deleterious variants among LSDs genes causing mucopolysaccharidosis type I (IDUA (rs532731688, rs74385837) and type III (HGSNAT (rs766835582)) and sphingolipidosis (metachromatic leukodystrophy (ARSA (rs201251634)) were identified in five patients from the group of early-onset SCZ patients but not in the controls. Our findings supported the role of sphingolipid metabolism in SCZ pathogenesis. Aberrant enzyme activities and compounds of sphingolipids associated with ceramide metabolism may lead to accumulation of alpha-synuclein and may be critical in SCZ pathogenesis. Full article

Fabry disease (FD) is an X-linked lysosome storage disease that results in the accumulation of globotriaosylceramide (Gb3) throughout the body leading to irreversible target organ damage. As the role of secondary mediators (inflammatory molecules) and their mechanisms has not been fully elucidated, we focused on the interleukin (IL)-6 system in adult FD patients and in matched healthy subjects. To obtain insights into the complex regulation of IL-6 actions, we used a novel approach that integrates information from plasma and exosomes of FD patients (n = 20) and of healthy controls (n = 15). Soluble IL-6 receptor (sIL-6R) levels were measured in plasma with the ELISA method, and membrane-bound IL-6R was quantified in plasma and urinary exosomes using flow cytometry. In FD patients, the levels of soluble IL-6R in plasma were higher than in control subjects (28.0 ± 5.4 ng/mL vs. 18.9 ± 5.4 ng/mL, p < 0.0001); they were also higher in FD subjects with the classical form as compared to those with the late-onset form of the disease (36.0 ± 11.4 ng/mL vs. 26.1 ± 4.5 ng/mL, p < 0.0001). The percentage of urinary exosomes positive for IL-6R was slightly lower in FD (97 ± 1 vs. 100 ± 0% of events positive for IL-6R, p < 0.05); plasma IL-6 levels were not increased. These results suggest a potential role of IL-6 in triggering the inflammatory response in FD. As in FD patients only the levels of sIL-6Rs are consistently higher than in healthy controls, the IL-6 pathogenic signal seems to prevail over the homeostatic one, suggesting a potential mechanism causing multi-systemic damage in FD. Full article

Anderson–Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to α-galactosidase A (α-Gal A) deficiency. The disease’s X-linked inheritance leads to more severe, early-onset presentations in males, while females exhibit variable, often insidious, manifestations, notably impacting cardiac health. This study aims to examine gender-based AFD cardiac manifestations in correlation with the variant type: classical (CL), late-onset (LO), or variants of uncertain significance (VUS). We analyzed data from 72 AFD patients (53 females, 19 males) referred to the “G. Rodolico” University Hospital, employing enzyme activity measurements, genetic analysis, periodic lyso-Gb3 monitoring, comprehensive medical histories, and advanced cardiac imaging techniques. Statistical analysis was performed using SPSS version 26. Our AFD cohort, with an average age of 45 ± 16.1 years, comprised 12 individuals with hypertrophy (AFD-LVH) and 60 without (AFD-N). Women, representing about 75% of the subjects, were generally older than men (47.2 ± 16.2 vs. 38.8 ± 14.6, p = 0.046). In the female group, 17% had CL variants, 43.3% LO, and 39.6% had VUS, compared to 21.1%, 36.8%, and 31.6% in the male group, respectively. Females exhibited significantly higher α-Gal A values (median 7.9 vs. 1.8 nmol/mL/h, p < 0.001) and lower lyso-Gb3 levels (1.5 [IQR 1.1–1.7] vs. 1.9 [1.5–17.3] nmol/L, p = 0.02). Regarding the NYHA class distribution, 70% of women were in class I and 28% in class II, compared to 84% and 16% of men, respectively. Among women, 7.5% exhibited ventricular arrhythmias (10.5% in men), and 9.4% had atrial fibrillation (10.5% in men). Cardiac MRIs revealed fibrosis in 57% of examined women, compared to 87% of men. Even among patients without LVH, significant differences persisted in α-Gal A and lyso-Gb3 levels (p = 0.003 and 0.04), as well as LVMi (61.5 vs. 77.5 g/sqm, p = 0.008) and GLS values (−20% vs. −17%, p = 0.01). The analysis underscored older age, decreased lyso-Gb3 deposition, reduced hypertrophy, and lesser GLS compromise in females, suggesting later disease onset. Severe cardiac patterns were associated with classic variants, while more nuanced manifestations were noted in those with VUS. Early GLS impairment in males, irrespective of hypertrophy, emphasized the role of subclinical damage in AFD. Full article

Background and Objectives: Group B streptococcus (GBS) is the leading cause of infections in neonates with high fatality rates. GBS is caused by the streptococcus bacterium known as streptococcus agalactiae, which is highly contagious and can be transmitted from pregnant women to infants. GBS infection can occur as an early onset or late-onset infection and has different treatment strategies. Antibiotics are effective in treating GBS infections at early stages. The aim of this systematic review was to summarize the clinical characteristics and treatment strategies for GBS, with a focus on antibiotics. Material and Methods: The findings of this review were reported in accordance with the PRISMA 2020 guidelines and a flow diagram of the study selection process, a summary of the included studies, a description of the study characteristics, a summary of the results, a discussion of the implications of the findings, and a conclusion are included. Overall, the authors followed a rigorous methodology to ensure that this review is comprehensive and inclusive of relevant studies on GBS infection and its treatment. Results: Overall, 940 studies were reviewed and only the most relevant 22 studies were included in the systematic review. This review describes the characteristics of patients in different studies related to early onset GBS disease and presents various treatment strategies and outcomes for GBS infection in pediatrics. The studies suggest that preventive measures, risk-based intrapartum antibiotic prophylaxis, and maternal vaccination can significantly reduce the burden of GBS disease, but late-onset GBS disease remains a concern, and more strategies are required to decrease its rate. Improvement is needed in the management of the risk factors of GBS. A conjugate vaccine with a serotype (Ia, Ib, II, III, and V) has been proven effective in the prevention of GBS in neonates. Moreover, penicillin is an important core antibiotic for treating early onset GBS (EOD). Conclusions: This systematic review summarizes the treatment comparison for GBS infections in neonates, with a primary focus on antibiotics. IAP (intrapartum antibiotic prophylaxis) according to guidelines, antenatal screening, and the development of a conjugate vaccine may be effective and could lower the incidence of the disease. Full article

Background: Fabry cardiomyopathy is characterized by left ventricular hypertrophy, myocardial fibrosis, arrhythmia, and premature death. Treatment with migalastat, an oral pharmacological chaperone, was associated with a stabilization of cardiac biomarkers and a reduction in left ventricular mass index, as measured by echocardiography. A recent study, using cardiac magnetic resonance (CMR) as the gold standard, found a stable course of myocardial involvement after 18 months of treatment with migalastat. Our study aimed to provide long-term CMR data for the treatment with migalastat. Methods: A total of 11 females and four males with pathogenic amenable GLA mutations were treated with migalastat and underwent 1.5T CMR imaging for routine treatment effect monitoring. The main outcome was a long-term myocardial structural change, reflected by CMR. Results: After migalastat treatment initiation, left ventricular mass index, end diastolic volume, interventricular septal thickness, posterior wall thickness, estimated glomerular filtration rate, and plasma lyso-Gb3 remained stable during the median follow-up time of 34 months (min.: 25; max.: 47). The T1 relaxation times, reflecting glycosphingolipid accumulation and subsequent processes up to fibrosis, fluctuated over the time without a clear trend. No new onset of late gadolinium enhancement (LGE) areas, reflecting local fibrosis or scar formation of the myocardium, could be detected. However, patients with initially present LGE showed an increase in LGE as a percentage of left ventricular mass. The median α-galactosidase A enzymatic activity increased from 37.3% (IQR 5.88–89.3) to 105% (IQR 37.2–177) of the lower limit of the respective reference level (p = 0.005). Conclusion: Our study confirms an overall stable course of LVMi in patients with FD, treated with migalastat. However, individual patients may experience disease progression, especially those who present with fibrosis of the myocardium already at the time of therapy initiation. Thus, a regular treatment re-evaluation including CMR is needed to provide the optimal management for each patient. Full article

Group B Streptococcus (GBS) is a Gram-positive bacterium commonly found in the genitourinary tract and is also a leading cause of neonatal sepsis and pneumonia. Despite the current antibiotic prophylaxis (IAP), the disease burdens of late-onset disease in newborns and non-pregnant adult infections are increasing. Recently, inactivation of the pathogens via gamma radiation has been proven to eliminate their replication ability but cause less damage to the antigenicity of the key epitopes. In this study, the non-capsule GBS strain was inactivated via radiation (Rad-GBS) or formalin (Che-GBS), and we further determined its immunogenicity and protective efficacy as vaccines. Notably, Rad-GBS was more immunogenic and gave rise to higher expression of costimulatory molecules in BMDCs in comparison with Che-GBS. Flow cytometric analysis revealed that Rad-GBS induced a stronger CD4⁺ IFN-γ⁺ and CD4⁺IL-17A⁺ population in mice. The protective efficacy was measured through challenge with the highly virulent strain CNCTC 10/84, and the adoptive transfer results further showed that the protective role is reversed by functionally neutralizing antibodies and T cells. Finally, cross-protection against challenges with prevalent serotypes of GBS was induced by Rad-GBS. The higher opsonophagocytic killing activity of sera against multiple serotypes was determined in sera from mice immunized with Rad-GBS. Overall, our results showed that the inactivated whole-cell encapsulated GBS could be an alternative strategy for universal vaccine development against invasive GBS infections. Full article

Group B Streptococcus is a Gram-positive bacterium that typically colonizes 10–30% of pregnant women, causing chorioamnionitis, preterm birth, and stillbirth, as well as neonatal sepsis and meningitis with early-onset disease (EOD) or late-onset disease (LOD) due to ascending infection or transmission during delivery. While there are some differences between EOD and LOD in terms of route of transmission, risk factors, and serotypes, the only preventive approach currently is maternal intrapartum antibiotic prophylaxis (IAP) which will not be able to fully address the burden of the disease since this has no impact on LOD. Probiotics and immunization in pregnancy may be more effective than IAP for both EOD and LOD. There is mixed evidence of probiotic effects on the prevention of GBS colonization, and the data from completed and ongoing clinical trials investigating different GBS vaccines are promising. Current vaccine candidates target bacterial proteins or the polysaccharide capsule and include trivalent, tetravalent, and hexavalent protein–polysaccharide conjugate vaccines. Some challenges in developing novel GBS vaccines include the lack of a correlate of protection, the potential for serotype switching, a need to understand interactions with other vaccines, and optimal timing of administration in pregnancy to maximize protection for both term and preterm infants. Full article

Group B Streptococcus (GBS, Streptococcus agalactiae) is a Gram-positive bacterium that is commonly found in the gastrointestinal and urogenital tracts. However, its colonization during pregnancy is an important cause of maternal and neonatal morbidity and mortality worldwide. Herein, we specifically looked at GBS in relation to the field of Obstetrics (OB) along with the field of Gynecology (GY). In this review, based on the clinical significance of GBS in the field of OBGY, topics of how GBS is being detected, treated, and should be prevented are addressed. Full article

There have been increasing reports of Guillain–Barré syndrome (GBS), a rare but debilitating neurological disease, occurring post-COVID-19 vaccination. However, the outcomes and relationships between patient demographics and clinical outcomes of post-COVID-19 vaccination GBS remain unclear. To bridge this gap, our study investigates the outcomes and clinical factors associated with poorer GBS outcomes following COVID-19 vaccination. We conducted a review and pooled analysis of detailed data extracted from 57 published cases with the relevant search strategies and criteria. The groups compared included male versus female patients, 1st dose versus 2nd dose and early onset versus late onset of GBS. Multivariate regression analysis was performed to compare the vaccine type, clinical severity and post-treatment outcomes between these groups of patients. Our results highlight for the first time that females were significantly more likely to have severe clinical presentation and poorer outcomes compared to males. Additionally, viral vector vaccines were the predominant vaccine type administered in early-onset post-COVID-19-vaccination GBS and GBS occurring after the 1st vaccination dose. It was also shown that reported cases of post-vaccination GBS generally displayed a positive response to conventional treatment and had favourable post-treatment outcomes. Through this study, we have established important links and provided assuring evidence for treatment response and post-treatment outcomes of GBS occurring post-COVID-19 vaccination. While the COVID-19 vaccination brings about much greater benefits than risks, our findings provide further impetus for greater vigilance in certain patient groups and more studies to explore the mechanisms behind these links. Full article

Invasive infections by group B streptococci (iGBS) are the leading cause of sepsis and meningitis in the first three months of life worldwide. The clinical and microbiological characteristics of neonatal and infant iGBS in Italy during the years 2015–2019 were investigated. Voluntary-based surveillance reported 191 cases (67 early-onset (EOD) and 124 late-onset disease (LOD)) and 89 bacterial isolates were received. The main clinical manifestations were sepsis (59.2%) followed by meningitis (21.5%), bacteremia (12.0%) and septic shock (6.3%). Hospitalized preterm babies accounted for one third of iGBS and constituted the most fragile population in terms of mortality (8.2%) and brain damage (16.4%). GBS serotype III was predominant in EOD (56%) and caused almost all LOD (95%). The rate of resistance to clindamycin reached 28.8%. Most of clindamycin-resistant GBS strains (76%) were serotype III-ST17 and possessed the genetic markers of the emerging multidrug resistant (MDR) CC-17 sub-clone. Our data revealed that iGBS is changing since it is increasingly reported as a healthcare-associated infection (22.6%), mainly caused by MDR-CC17. Continuous monitoring of the clinical and microbiological characteristics of iGBS remains of primary importance and it represents, at present, the most effective tool to support prevention strategies and the research on the developing GBS vaccine. Full article

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat. Full article

Fabry disease (FD) is a lysosomal storage disorder caused by deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene, resulting in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes different pathogenic mechanisms in which several mediators could be implicated, inducing multiorgan lesions, mainly in the kidney, heart and nervous system, resulting in clinical manifestations of the disease. Enzyme replacement therapy was shown to delay disease progression, mainly if initiated early. However, a diagnosis in the early stages represents a clinical challenge, especially in patients with a non-classic phenotype, which prompts the search for biomarkers that help detect and predict the evolution of the disease. We have reviewed the mediators involved in different pathogenic mechanisms that were studied as potential biomarkers and can be easily incorporated into clinical practice. Some accumulation biomarkers seem to be useful to detect non-classic forms of the disease and could even improve diagnosis of female patients. The combination of such biomarkers with some response biomarkers, may be useful for early detection of organ injury. The incorporation of some biomarkers into clinical practice may increase the capacity of detection compared to that currently obtained with the established diagnostic markers and provide more information on the progression and prognosis of the disease. Full article