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Background: Preterm infants (PIs) are more susceptible to neurodevelopmental impairment compared with term newborns. Adequate postnatal growth has been associated with improved neurocognitive outcomes; therefore, optimization of nutrition may positively impact the neurodevelopment of PIs. Objective: This study focused on macronutrient parenteral nutrition (PN) intake during the Neonatal Intensive Care Unit stay and their associations with neurodevelopmental outcomes in PIs in the first two years of life. Methods: The Embase, MEDLINE, and Cochrane Library databases were searched using the following subject headings and terms (MeSH): "premature infants", "parenteral nutrition", "growth", "brain", "neurodevelopment", and "central nervous system diseases". All relevant papers' reference lists were manually searched. PN and neurodevelopment studies concerning the first two years of life were collected and analyzed. Results: 275 potential studies were retrieved, 64 were selected for full-text reading, and 22 were included (12 randomized controlled trials). While glucose intakes should be immediately provided and strictly monitored avoiding hyperglycemia, the long-term outcomes of aggressive PN caloric intakes are uncertain. Early amino acid (AA) supplementation is mandatory and improves short-term growth, though it is questionable whether increased AA and better neurodevelopment are directly related. Lipid infusion should be initiated right after birth, and further investigation will enable us to ascertain the potential impacts of lipid emulsions, particularly fish oil, on PI neurodevelopment. Conclusions: An aggressive PN and its possible metabolic complication could not favor neurodevelopment; the way forward could be a customized approach, depending on the patient's clinical state and tolerance. Long-term follow-up studies and the search for specific markers of tolerance are warranted. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles were synthesized using a vortex microfluidic system and subsequently functionalized with a primary shell of salicylic acid, recognized for its ability to increase the stability and biocompatibility of coated materials. In the second stage, the vortex platform was placed in a magnetic field to facilitate the growth and development of a porous silica shell. The selected drug for this study was micafungin, an antifungal agent well regarded for its effectiveness in combating fungal infections and identified as a priority compound by the World Health Organization (WHO). The resulting nanocomposite system was characterized using various techniques, including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), Brunauer–Emmett–Teller (BET) analysis, UV-Vis spectroscopy, and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The synthesis method produced nanoparticles with dimensions of 5–7 nm, highlighting the advantages of the chosen approach. A desorption profile was established using a continuous-flow, UV-Vis analysis system, indicating that the bioactive compound was released slowly; after two hours, approximately 50% of the loaded micafungin was detected in the release medium. Furthermore, the results obtained from the FT-ICR MS analysis provided molecular-level confirmation, thereby supporting the release mechanism of micafungin from the nanosystem. [ABSTRACT FROM AUTHOR]

Parvovirus B19 (B19V) infection is the cause of erythema infectiosum, or the "fifth disease", a widespread infection, potentially affecting 1–5% of pregnant women, in most cases without significant damage to the pregnancy or fetus. It follows a seasonal variation, with a higher prevalence in temperate climates, mainly in late winter and early spring. Women at increased risk include mothers of preschool and school-age children, and those working in nurseries, kindergartens, and schools. Vertical transmission occurs in 33% to 51% of cases of maternal infection. Parvovirus infection is an important cause of fetal perinatal infection resulting in increased morbidity through the development of fetal anemia, heart failure, and non-immune hydrops. A comprehensive literature review was conducted using PubMed, Cochrane Library, and Google Scholar, focusing on publications from the last 10 years and prioritizing studies related to parvovirus B19 infection in pregnancy. We summarized the existing data in the literature on the effects of parvovirus B19 infection during pregnancy and weighed if there is a need for screening in pregnant patients. Routine screening for parvovirus B19 infection can be considered in communities where infection is common, there is occupational exposure, or during endemic periods, with the reason being that accurate identification and treatment of fetuses affected by congenital B19V infection have been shown to improve perinatal outcomes. [ABSTRACT FROM AUTHOR]

The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile. [ABSTRACT FROM AUTHOR]

Background/Objectives: Invasive fungal infections (IFIs) are a prevalent complication of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the pediatric population and are associated with high morbidity and mortality. We aimed to identify the utilization of antifungal prophylaxis prescriptions and the associated clinical outcomes. Methods: A retrospective study included children (≤18 years old) diagnosed with hematological malignancies or undergoing HSCT who are at high risk for developing IFI and received systemic antifungal therapy between January 2018 and April 2024 at Sultan Qaboos University Hospital (SQUH), Oman. Results: A powered sample of 222 patients was included, and 208 (93.69%) received antifungal prophylaxis. Among those who received prophylaxis, 148 (66.67%) received appropriate prophylaxis, 86.06% (n = 179) received appropriate dosage. The patients who did not receive antifungal prophylaxis had higher rates of inpatient IFI requiring treatment (85.71% versus 12.02%, p < 0.01), a longer median length of hospital stay (LOS) (67.5 days versus 10 days, p = 0.015), and more incidence of 90-day all-cause mortality (21.43% versus 2.88%, p < 0.01) than those who received antifungal prophylaxis. Survival analysis demonstrated that these patients had a 12% higher risk for earlier death. Also, being on antifungal prophylaxis reduces the odds of inpatient IFI requiring treatment, with an adjusted odds ratio (aOR) of 0.13 [95% CI: 0.019–0.801]. Conclusions: Antifungal prophylaxis utilization was high, and it markedly decreases the occurrence and enhances the prognosis of IFI. Nonetheless, inconsistencies in practice and a lack of pediatric-specific data underscore the necessity for uniform guidelines and additional research to strengthen preventative methods in this population, and proper TDM utilization could provide more robust insights. [ABSTRACT FROM AUTHOR]

Sepsis is a pervasive condition that affects individuals of all ages, with significant social and economic consequences. The early diagnosis of sepsis is fundamental for establishing appropriate treatment and is based on warning scores and clinical characteristics, with positive microbiological cultures being the gold standard. Research has yet to identify a single biomarker to meet this diagnostic demand. Presepsin is a molecule that has the potential as a biomarker for diagnosing sepsis. In this paper, we present a narrative review of the diagnostic and prognostic performance of presepsin in different age groups. Given its particularities, it is identified that presepsin is a potential biomarker for sepsis at all stages of life. [ABSTRACT FROM AUTHOR]

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention. [ABSTRACT FROM AUTHOR]

This study assessed the seroprevalence of Toxoplasma gondii and risk factors among 428 pregnant women attending Basic Health Units (BHUs) in Araçatuba, São Paulo, Brazil. The seroprevalence was 55.14%, indicating high exposure to the parasite in this population. Using a multi-level logistic regression model, this study analyzed these predictors to determine their association with a higher seropositivity rate, with BHUs included as a random factor. Predictors associated with higher seropositivity included older age (36–45 years), with a 71.64% prevalence in this group, and multiparity (61.65%). Women with lower educational levels were also more likely to be infected, with 59.46% seropositivity recorded among those who had only completed elementary school. Despite identifying several risk factors, no significant correlation was found between undercooked meat consumption or contact with soil and infection. These findings highlight the need for targeted public health interventions, particularly for educating high-risk groups about toxoplasmosis prevention, such as safe food handling and avoiding raw dairy products. Additionally, BHUs play a critical role in early detection and prevention. These units are important for providing healthcare access and preventive education for vulnerable populations. Given the high seroprevalence, this study underscores the urgency of implementing prenatal screening and educational programs to reduce the risks of congenital toxoplasmosis in this region. [ABSTRACT FROM AUTHOR]

PPHN is a common cause of neonatal respiratory failure and is still a serious condition that is associated with high mortality. Objectives: To analyze the clinical characteristics and outcomes of SARS-CoV-2 infection in neonates with PPHN to identify neonatal cases at risk to develop severe illness. Methods: For this systematic review, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched Medline, Embase, CINAHL, and PubMed for studies on the development of COVID-19 in neonates with PPHN, published from 1 December 2019 to 29 February 2024, with an English language restriction. Results: Of the 2406 papers that were identified, 21 articles were included in the systematic review. Studies involving thirty-six neonates with PPHN and infected with SARS-CoV-2 were analyzed (twenty-nine survived, six died, and one is still hospitalized). The main causes of PPHN in neonates who had COVID-19 were neonatal respiratory distress syndrome (NRDS) (41.7%), meconium-stained amniotic fluid (MSAF) (16.7%), preterm premature rupture of membranes (PPROM) (11.1%), hypoxic ischemic encephalopathy (HIE) (5.5%), pneumonia (5.5%), and idiopathic (2.8%). Most of those neonates were male (33.3%), belonged to Indian ethnicity (50%), and were delivered via caesarean section (44.4%). COVID-19 in cases with PPHN commonly occurred in neonates born with a pregnancy range from 32 to <37 weeks (moderate to late preterm) (36.1%). The maternal severity of COVID-19 was reported to be severe in three cases only (8.3%); however, SARS-CoV-2 infection in neonates with PPHN was either severe (44.4%) or critical (22.2%). Most of these neonates experienced acute respiratory distress syndrome (ARDS) (58.3%). Early and late multisystem inflammatory syndrome in neonates (MIS-N) were reported in 50% and 11.1%, respectively. A high proportion of neonates were admitted to the intensive care unit (ICU) (58.3%) or needed mechanical ventilation (MV) (47.2%). Neonates with concurrent PPHN and SARS-CoV-2 infection who died had worse severity of COVID-19 [i.e., severity of COVID-19 was critical in 10% (neonates with PPHN who survived group) vs. 83.3% (neonates with PPHN who died group); p = 0.026]. Neonates with PPHN and COVID-19 had a higher relative risk of death if they received more antibiotics (RR 4.14, 95% CI 0.64–6.88) and if their COVID-19 was defined as critical (RR 2.84, 95% CI 0.86–9.39). Male neonates with PPHN and COVID-19 (RR 2.60, 95% CI 0.30–1.17) and those requiring prolonged invasive positive pressure ventilation (RR 2.22, 95% CI 0.64–7.73) also showed an increased relative risk for death. Conclusions: COVID-19 in neonates with PPHN is challenging and may be associated with increased mortality, severity, ICU admission, ARDS, MIS-N, and MV usage. The results should be interpreted with caution owing to the small number of studies and substantial heterogeneity and indicate a need for future research in this area. Due to its benefits, testing for SARS-CoV-2 should be encouraged for newborns with symptoms consistent with COVID-19, especially in neonates with a history of SARS-CoV-2 exposure. Effective protection measures should be implemented during delivery and post-delivery care as necessary. [ABSTRACT FROM AUTHOR]

Background: Enteral nutrition can be delivered to the stomach using nasogastric or orogastric tubes, with each route having advantages and disadvantages. This meta-analysis aimed to compare the effects of these methods on growth, development, and the incidence of adverse outcomes. Methods: This analysis included studies that enrolled preterm infants who received nasogastric or orogastric tube feeding. We searched databases including PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. Only randomized controlled trials were selected. We used version 2 of the Cochrane tool to assess the risk of bias in randomized trials and Review Manager 5.4 software to perform the meta-analysis. Results: Six studies involving 265 preterm infants were included. The meta-analysis showed that orogastric tube feeding took significantly longer to establish full enteral tube feeding compared to nasogastric tube feeding (MD = 1.62, 95% confidence interval [CI]: 0.99–2.26, Z = 5.02, p < 0.01). However, no significant difference was observed between the two groups regarding time to regain birth weight (MD = −0.38, 95% CI: −2.2–1.44, Z = 5.02, p = 0.68). Data on adverse events were insufficient to perform a combined analysis. Conclusions: Preterm infants fed via nasogastric tubes took less time to reach full enteral feeding than those fed via orogastric tubes. Further research is required to evaluate the effect of feeding routes on adverse outcomes. [ABSTRACT FROM AUTHOR]

This study investigated the potential role of specific single-nucleotide polymorphisms (SNPs) in the genes Astrotactin 1 (ASTN1), EBF Transcription Factor 1 (EBF1), Eukaryotic Elongation Factor, Selenocysteine-tRNA Specific (EEFSEC), Microtubule-Associated Serine/Threonine Kinase 1 (MAST1), and Tumor Necrosis Factor Alpha (TNF-α) to assess whether these genetic variants contribute to the risk of spontaneous preterm birth (sPTB). A case-control study was conducted involving 573 women from Croatia and Slovenia: 248 with sporadic sPTB (positive personal and negative family history of sPTB before 37 weeks' gestation), 44 with familial sPTB (positive personal and family history of sPTB before 37 weeks' gestation), and 281 control women. The analysis of ASTN1 rs146756455, EBF1 rs2963463, EBF1 rs2946169, EEFSEC rs201450565, MAST1 rs188343966, and TNF-α rs1800629 SNPs was performed using TaqMan real-time PCR. p-values were Bonferroni-adjusted for multiple comparisons. EBF1 SNP rs2963463 was significantly associated with sPTB (p adj = 0.03). Women carrying the CC genotype had a 3–4-times lower risk of sPTB (p adj < 0.0001). In addition, a significant difference in the frequency of the minor C allele was observed when comparing familial sPTB cases with controls (p adj < 0.0001). All other associations were based on unadjusted p-values. The minor T allele of EBF1 SNP rs2946169 was more frequent in sPTB cases overall than in controls, especially in sporadic sPTB (p = 0.045). Similarly, the CC genotype of ASTN1 SNP rs146756455 was more frequent in sporadic sPTB cases compared to controls (p = 0.019). Finally, the TNF-α SNP rs1800629 minor A allele and AA genotype were more common in the familial sPTB group compared to sporadic sPTB and controls (p < 0.05). The EBF1 SNP rs2963463 polymorphism showed a protective effect in the pathogenesis of sPTB, particularly in women carrying the CC genotype. Moreover, EBF1 SNP rs2946169 and ASTN1 SNP rs146756455, as well as TNF-α SNP rs1800629, were associated with an increased risk of sPTB, representing suggestive potential risk factors for sporadic and familial sPTB, respectively. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii, an obligate intracellular parasite, is a globally prevalent pathogen capable of infecting a wide range of warm-blooded animals, including humans. Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications. This comprehensive review delves into the current understanding of T. gondii biology, exploring its complex life cycle, diverse transmission routes, and strain diversity. This article provides an in-depth analysis of the clinical manifestations of OT, which can result from both congenital and acquired infections, presenting a spectrum of signs and symptoms. The review examines various diagnostic strategies employed for OT, including clinical examination, multimodal imaging techniques such as fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA), as well as laboratory tests including serology and molecular methods. Despite extensive research, the specific mechanisms underlying ocular involvement in T. gondii infection remain elusive, and current diagnostic options have limitations. Moreover, the treatment of active and recurrent OT remains a challenge. While existing therapies, such as antimicrobial agents and immunosuppressants, can control active infections, they do not offer a definitive cure or completely prevent recurrence. The clinical endpoints for the management of active and recurrent OT are also not yet well-established, and the available treatment methods carry the potential for adverse effects. This article highlights the need for future research to elucidate the pathogenesis of OT, investigate genetic factors influencing susceptibility to infection, and develop more sensitive and specific diagnostic tools. Enhancing global surveillance, implementing robust prevention strategies, and fostering multidisciplinary collaborations will be crucial in reducing the burden of OT and improving patient outcomes. This comprehensive review aims to provide a valuable resource for clinicians, researchers, and policymakers, contributing to a better understanding of T. gondii infection and its impact on ocular health. [ABSTRACT FROM AUTHOR]

The document explores the molecular evolution and pathogenicity of Methicillin-Resistant Staphylococcus aureus (MRSA), a pathogen with the ability to acquire resistance to antibiotics and virulence factors. It discusses the emergence of MRSA strains, including community-associated and livestock-associated variants, and their impact on human and animal health. The research presented in the document covers a wide range of topics related to MRSA, including epidemiology, antimicrobial resistance, and virulence factors, highlighting the need for further research to understand and control infections caused by this pathogen. [Extracted from the article]

The article explores the significant role of clinical nutrition in enhancing patient outcomes across various medical conditions, emphasizing the management of sarcopenia, the effects of chronic intestinal failure on nutrition.

Fungal colonization poses a significant risk for neonates, leading to invasive infections such as fungemia. While Candida species are the most commonly identified pathogens, other rare yeasts are increasingly reported, complicating diagnosis and treatment due to limited data on antifungal pharmacokinetics. These emerging yeasts, often opportunistic, underscore the critical need for early diagnosis and targeted therapy in neonates. This systematic review aims to comprehensively analyze all published cases of neonatal fungemia caused by rare opportunistic yeasts, examining geographical distribution, species involved, risk factors, treatment approaches, and outcomes. Searching two databases (PubMed and SCOPUS), 89 relevant studies with a total of 342 cases were identified in the 42-year period; 62% of the cases occurred in Asia. Pichia anomala (31%), Kodamaea ohmeri (16%) and Malassezia furfur (15%) dominated. Low birth weight, the use of central catheters, prematurity, and the use of antibiotics were the main risk factors (98%, 76%, 66%, and 65%, respectively). 22% of the cases had a fatal outcome (80% in Asia). The highest mortality rates were reported in Trichosporon beigelii and Trichosporon asahii cases, followed by Dirkmeia churashimamensis cases (80%, 71%, and 42% respectively). Low birth weight, the use of central catheters, the use of antibiotics, and prematurity were the main risk factors in fatal cases (84%, 74%, 70%, and 67%, respectively). 38% of the neonates received fluconazole for treatment but 46% of them, died. Moreover, the rare yeasts of this review showed high MICs to fluconazole and this should be taken into account when planning prophylactic or therapeutic strategies with this drug. In conclusion, neonatal fungemia by rare yeasts is a life-threatening and difficult-to-treat infection, often underestimated and misdiagnosed. [ABSTRACT FROM AUTHOR]

Research is underway to develop a vaccine to prevent and cure infection from herpes simplex virus (HSV). It emphasizes the critical need for immunization to address public health issues and the shortcomings of existing treatment options. Furthermore, studies on the HSV vaccine advance the field of immunology and vaccine creation, which may help in the battle against other viral illnesses. The current lack of such a vaccine is, in part, due to herpes viral latency in sensory ganglions. Current vaccines rely on tissue-resident memory CD8+ T cells, which are known to provide protection against subsequent HSV reinfection and reactivation without correlating with other immune subsets. For that reason, there is no effective vaccine that can provide protection against latent or recurrent herpes infection. This review focuses on conventional methods for evaluating the efficacy of a herpes vaccine using differential CD8+ T cells and important unaccounted immune aspects for designing an effective vaccine against herpes. [ABSTRACT FROM AUTHOR]

Background and Objectives: The study aims to explore the potential for transplacental transmission of SARS-CoV-2, focusing on its pathophysiology, placental defense mechanisms, and the clinical implications for maternal and neonatal health. Materials and Methods: A comprehensive review of the current literature was conducted, analyzing studies on SARS-CoV-2 infection in pregnancy, the expression of key viral receptors (ACE2 and TMPRSS2) in placental cells, and the immune responses involved in placental defense. The review also examined the clinical outcomes related to maternal and neonatal health, including adverse pregnancy outcomes and neonatal infection. Results: The expression of ACE2 and TMPRSS2 in the placenta supports the biological plausibility of SARS-CoV-2 transplacental transmission. Histopathological findings from the infected placentas reveal inflammation, vascular changes, and the evidence of viral particles in placental tissues. Clinical reports indicate an increased risk of preterm birth, intrauterine growth restriction, and neonatal infection in pregnancies affected by COVID-19. However, the frequency and mechanisms of vertical transmission remain variable across studies, highlighting the need for standardized research protocols. Conclusions: SARS-CoV-2 can potentially infect placental cells, leading to adverse pregnancy outcomes and neonatal infection. While evidence of transplacental transmission has been documented, the risk and mechanisms are not fully understood. Ongoing research is essential to clarify these aspects and inform obstetric care practices to improve maternal and neonatal outcomes during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Toxoplasmosis is a parasitism transmitted by Toxoplasma gondii, part of the TORCH complex, the most prevalent parasitism worldwide. It is asymptomatic in immunocompetent individuals but causes severe infections and developmental abnormalities in pregnant women, mainly affecting the central nervous system and the gastrointestinal system. Methods: In our prospective study, we analyzed cases of recent maternal Toxoplasma infections confirmed by serological testing between 1996 and 2020 at the Department of Obstetrics and Gynecology, Semmelweis University. Amniocentesis, followed by PCR, was performed in cases of recent infection confirmed by serological testing during pregnancy. After birth, a neonatological, microbiological, pediatric neurological and ophthalmological examination and a follow-up was carried out. Results: During the study period, a total of 238 cases of amniotic fluid Toxoplasma PCR testing due to Toxoplasma recent infection were performed. In terms of pregnancies, there were 219 deliveries and seven abortions. Twelve cases had no data available on the outcome of the pregnancy. In total, 133 cases of ultrasound abnormalities were detected during pregnancy, while in 105 cases, no abnormalities were detected on ultrasound examination. During amniocentesis, eight cases of Toxoplasma infection were revealed in amniotic fluid samples by PCR, and in 230 cases, the result was negative. Neonatal follow-up was performed in 139 cases, with no abnormalities during follow-up in 117 cases, and in 22 cases, there was a detectable complication that was likely to be related to Toxoplasma infection. In all 22 cases, amniotic fluid PCR Toxoplasma testing was negative. Conclusions: The most common ultrasound abnormalities involve the nervous system and the gastrointestinal system. In cases of suspicion, it is recommended to perform amniocentesis Toxoplasma PCR testing besides the indirect methods to help the pregnant woman decide whether to carry the pregnancy to term. During follow-up, a multidisciplinary team experienced in pregnancies complicated by toxoplasmosis must carry out the follow-up, care and subsequent development. [ABSTRACT FROM AUTHOR]

Pediatric chronic intestinal failure (PIF) is a rare and heterogeneous condition characterized by the inability of the patient's intestine to adequately absorb the required fluids and/or nutrients for growth and homeostasis. As a result, patients will become dependent on home parenteral nutrition (HPN). A MEDLINE search was performed in May 2024 with keywords "intestinal failure", "parenteral nutrition" and "pediatric". Different underlying conditions which may result in PIF include short bowel syndrome, intestinal neuromuscular motility disorders and congenital enteropathies. Most common complications associated with HPN are catheter-related bloodstream infections, catheter-related thrombosis, intestinal failure-associated liver disease, small intestinal bacterial overgrowth, metabolic bone disease and renal impairment. Treatment for children with PIF has markedly improved with a great reduction in morbidity and mortality. Centralization of care in specialist centers and international collaboration between centers is paramount to further improve care for this vulnerable patient group. A recently promising medical therapy has become available for children with short bowel syndrome which includes glucagon-like peptide 2, a naturally occurring hormone which is known to delay gastric emptying and induce epithelial proliferation. Despite advances in curative and supportive treatment, further research is necessary to improve nutritional, pharmacological and surgical care and prevention of complications associated with parenteral nutrition use. [ABSTRACT FROM AUTHOR]

Since the 1950s, invasive prenatal diagnostics have played an integral role in perinatal management. However, its significance extends beyond detecting genetic abnormalities. This paper comprehensively reviews the indications for amniocentesis and chorionic villus sampling. Additionally, it examines various methods of genomic, infectious, and biochemical analysis, with a particular emphasis on the achievements of the last decade. [ABSTRACT FROM AUTHOR]

Background/Objectives: Retinopathy of Prematurity (ROP) remains a leading cause of vision impairment in premature infants, especially those with Respiratory Distress Syndrome (RDS) necessitating respiratory support. This study aimed to identify correlations between plasma levels of Insulin-like Growth Factor 1 (IGF1) and Tumor Necrosis Factor-alpha (TNF-alpha), and the risk of developing ROP. Additionally, it explored the association of ROP severity grades with plasma levels of glucose, lactate dehydrogenase (LDH), creatin phosphokinase (CPK), and other biomarkers, aiming to uncover predictive markers for ROP risk and severity in this population. Methods: This prospective study included premature neonates admitted with RDS requiring respiratory support, conducted over 18 months at the Neonatal Intensive Care Unit of the Louis Turcanu Emergency Clinical Hospital for Children, Timisoara. Plasma levels of IGF1 and TNF-alpha were measured on days 1 and 14 post-birth, alongside the initial assessment of glucose, LDH, and CPK levels. Results: Significant correlations were observed between lower gestational age and elevated LDH levels on day 7–10 (rho = −0.341, p = 0.0123) and between TNF-alpha levels at 2 weeks and ROP severity (rho = 0.512, p = 0.0004). Elevated IGF1 levels were protective against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second, suggesting their potential as biomarkers for ROP risk assessment. Higher levels of TNF-alpha at 2 weeks were associated with an increased risk of ROP (Beta = −0.45, p = 0.0014), whereas higher IGF1 levels offered protective effects against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second. Elevated LDH levels on day 7–10 post-birth were linked to an increased risk of ROP (Beta = 0.29, p = 0.0214). Conclusions: These findings highlight the potential of IGF1 and TNF-alpha as predictive biomarkers for ROP, offering avenues for early intervention and improved management strategies in this high-risk group. [ABSTRACT FROM AUTHOR]

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case–control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at −80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP. [ABSTRACT FROM AUTHOR]

Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes. [ABSTRACT FROM AUTHOR]

The incidence of Neonatal Systemic Inflammatory Response Syndrome (SIRS) is a critical concern in neonatal care. This study aimed to identify maternal laboratory parameters predictive of SIRS in newborns, focusing on the establishment of diagnostic cutoffs and evaluating the predictive power of these biomarkers. This prospective cohort study was conducted from January 2023 to January 2024 across several regional hospitals specializing in neonatal care. It included 207 mother-newborn pairs, divided into groups based on the neonatal development of SIRS (66 cases) or its absence (141 controls). Key maternal parameters measured included inflammatory markers and liver enzymes, analyzed using standard biochemical methods. The study applied receiver operating characteristic (ROC) analysis to establish optimal cutoff values and conducted multivariate logistic regression to determine hazard ratios (HRs) for SIRS prediction, with adjustments for potential confounders. The study identified significant ROC/AUC values for several biomarkers. The neutrophil-to-lymphocyte ratio (NLR) demonstrated an AUC of 0.926, with a cutoff value of 3.64, achieving 81.8% sensitivity and 90.9% specificity (p < 0.001). The systemic immune–inflammation index (SII) showed an AUC of 0.819 and a cutoff of 769.12, with 75.8% sensitivity and 81.8% specificity (p < 0.001). Multivariate regression analysis highlighted that neonates with maternal SII values above this cutoff were three times more likely to develop SIRS (HR 3.09, 95% CI 2.21–4.17, p < 0.0001). Other notable biomarkers included dNLR and ALRI, with respective HRs of 1.88 (p = 0.018) and 1.75 (p = 0.032). These findings confirm the significant predictive value of specific maternal inflammatory markers for neonatal SIRS. These findings support the utility of these biomarkers in prenatal screening to identify neonates at increased risk of SIRS, potentially guiding preemptive clinical interventions. [ABSTRACT FROM AUTHOR]

The accurate identification of infections is critical for effective treatment in intensive care units (ICUs), yet current diagnostic methods face limitations in sensitivity and specificity, alongside cost and accessibility issues. Consequently, there is a pressing need for a marker that is economically feasible, rapid, and reliable. Presepsin (PSP), also known as soluble CD14 subtype (sCD14-ST), has emerged as a promising biomarker for early sepsis diagnosis. PSP, derived from soluble CD14, reflects the activation of monocytes/macrophages in response to bacterial infections. It has shown potential as a marker of cellular immune response activation against pathogens, with plasma concentrations increasing during bacterial infections and decreasing post-antibiotic treatment. Unlike traditional markers such as procalcitonin (PCT) and C-reactive protein (CRP), PSP specifically indicates monocyte/macrophage activation. Limited studies in critical illness have explored PSP's role in sepsis, and its diagnostic accuracy varies with threshold values, impacting sensitivity and specificity. Recent meta-analyses suggest PSP's diagnostic potential for sepsis, yet its standalone effectiveness in ICU infection management remains uncertain. This review provides a comprehensive overview of PSP's utility in ICU settings, including its diagnostic accuracy, prognostic value, therapeutic implications, challenges, and future directions. [ABSTRACT FROM AUTHOR]

Point-of-care ultrasound (POCUS) integration into neonatology offers transformative potential for diagnostics and treatment, enhancing immediacy and precision of clinical decision-making in this vulnerable patient population. This systematic review aims to synthesize evidence on POCUS applications, benefits, challenges, and educational strategies in neonatology. Literature search was conducted using SPIDER scheme keywords and MeSH terms related to POCUS and neonatology. Studies focusing on POCUS applications, its impact on clinical outcomes, and educational interventions for skill acquisition were included and analyzed using standardized tools, followed by a narrative synthesis of the findings. The search yielded 68 relevant publications, encompassing original research, reviews, and guidelines. POCUS applications varied across cardiovascular, pulmonary, neurological, and abdominal assessments. Key benefits included a reduced need for invasive procedures and rapid bedside diagnosis. Challenges included steep learning curves for clinicians and the need for standardized training and guidelines. Educational strategies highlighted the effectiveness of simulation-based training in enhancing ultrasound proficiency among neonatal care providers. POCUS represents a significant advancement in neonatal medicine, offering benefits for patient care. Addressing identified challenges through comprehensive training programs and developing standardized guidelines is crucial for optimized use. Future research should focus on evaluating educational outcomes and long-term impacts of POCUS integration into neonatal care. [ABSTRACT FROM AUTHOR]

Congenital syphilis presents a significant global burden, contributing to fetal loss, stillbirth, neonatal mortality, and congenital infection. Despite the target established in 2007 by the World Health Organization (WHO) of fewer than 50 cases per 100,000 live births, the global incidence is on the rise, particularly in low- and middle-income regions. Recent data indicate a rate of 473 cases per 100,000 live births, resulting in 661,000 total cases of congenital syphilis, including 355,000 adverse birth outcomes such as early fetal deaths, stillbirths, neonatal deaths, preterm or low-birth-weight births, and infants with clinical congenital syphilis. Alarmingly, only 6% of these adverse outcomes occurred in mothers who were enrolled, screened, and treated. Unlike many neonatal infections, congenital syphilis is preventable through effective antenatal screening and treatment of infected pregnant women. However, despite available screening tools, affordable treatment options, and the integration of prevention programs into antenatal care in various countries, congenital syphilis remains a pressing public health concern worldwide. This review aims to summarize the current epidemiology, transmission, and treatment of syphilis in pregnancy, as well as to explore global efforts to reduce vertical transmission and address the reasons for falling short of the WHO elimination target. [ABSTRACT FROM AUTHOR]

TORCH infections usually result in mild maternal morbidity, but may cause severe congenital abnormalities. Therefore, it is important to detect maternal infections, monitor the fetus after the disease has been recognized, and define the seronegative women who are at risk of primary infection during pregnancy. From 2014 to 2023, serum samples from 1032 childbearing-aged and pregnant women (16–45 years) were tested for IgM/IgG antibodies to the most common TORCH pathogens: Toxoplasma gondii, rubella virus (RUBV), cytomegalovirus (CMV), and herpes simplex viruses (HSV-1 and HSV-2). The overall IgG seroprevalence rates were 20.1% for T. gondii, 91.3% for RUBV, 70.5% for CMV, 66.8% for HSV-1, and 3.5% for HSV-2. Only HSV-2 seroprevalence was age-related, with a significant progressive increase in seropositivity from 0% in those aged less than 26 years to 9.3% in those older than 40 years. The seroprevalence of T. gondii was higher in residents of suburban/rural areas than in residents of urban areas (27.4% vs. 17.1%). In addition, participants from continental regions were more often toxoplasma-seropositive than those from coastal regions (22.2% vs. 15.3%). HSV-1 seroprevalence was also higher in suburban/rural areas (71.7% vs. 64.7%). Obstetric history was not associated with TORCH seropositivity. Univariate and multivariate risk analysis showed that suburban/rural areas of residence and continental geographic regions were significant risk factors for T. gondii seroprevalence. Furthermore, suburban/rural area of residence was a significant risk factor for HSV-1 seroprevalence, while older age was a significant risk factor for HSV-2 seroprevalence. A declining trend in the seroprevalence of all TORCH pathogens was observed compared to previous Croatian studies (2005–2011). Similarly, the proportion of women simultaneously IgG-seropositive to two or three pathogens decreased over time. The maternal serology before pregnancy could potentially reduce the burden of congenital TORCH infections. [ABSTRACT FROM AUTHOR]

The nutrition of preterm infants remains contaminated by wrong beliefs that reflect inexactitudes and perpetuate old practices. In this narrative review, we report current evidence in preterm neonates and in preterm neonates undergoing surgery. Convictions that necrotizing enterocolitis is reduced by the delay in introducing enteral feeding, a slow advancement in enteral feeds, and the systematic control of residual gastric volumes, should be abandoned. On the contrary, these practices prolong the time to reach full enteral feeding. The length of parenteral nutrition should be as short as possible to reduce the infectious risk. Intrauterine growth restriction, hemodynamic and respiratory instability, and patent ductus arteriosus should be considered in advancing enteral feeds, but they must not translate into prolonged fasting, which can be equally dangerous. Clinicians should also keep in mind the risk of refeeding syndrome in case of high amino acid intake and inadequate electrolyte supply, closely monitoring them. Conversely, when preterm infants undergo surgery, nutritional strategies are still based on retrospective studies and opinions rather than on randomized controlled trials. Finally, this review also highlights how the use of adequately fortified human milk is strongly recommended, as it offers unique benefits for immune and gastrointestinal health and neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18–24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04–2.65), NDI (aOR, 2.09; 95% CI, 1.71–2.55), and growth failure (aOR, 1.57; 95% CI, 1.16–2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03–1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77–3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18–24 months. [ABSTRACT FROM AUTHOR]

Anti-hypotensive treatment, which includes dopamine, dobutamine, epinephrine, norepinephrine, milrinone, vasopressin, terlipressin, levosimendan, and glucocorticoids, is a long-established intervention in neonates with arterial hypotension (AH). However, there are still gaps in knowledge and issues that need clarification. The main questions and challenges that neonatologists face relate to the reference ranges of arterial blood pressure in presumably healthy neonates in relation to gestational and postnatal age; the arterial blood pressure level that potentially affects perfusion of critical organs; the incorporation of targeted echocardiography and near-infrared spectroscopy for assessing heart function and cerebral perfusion in clinical practice; the indication, timing, and choice of medication for each individual patient; the limited randomized clinical trials in neonates with sometimes conflicting results; and the sparse data regarding the potential effect of early hypotension or anti-hypotensive medications on long-term neurodevelopment. In this review, after a short review of AH definitions used in neonates and existing data on pathophysiology of AH, we discuss currently available data on pharmacokinetic and hemodynamic effects, as well as the effectiveness and safety of anti-hypotensive medications in neonates. In addition, data on the comparisons between anti-hypotensive medications and current suggestions for the main indications of each medication are discussed. [ABSTRACT FROM AUTHOR]

Background: Nocturnal infant crying is often empirically treated with acid suppressants. The aim of this study was to evaluate the prevalence and characteristics of gastroesophageal reflux (GER) in infants with unexplained persistent crying. Methods: We enrolled all infants (0–12 months) referred for suspected GER disease who underwent esophageal impedance–pH monitoring (MII-pH) for unexplained persistent crying not improved by parental reassurance, dietary modification or alginate. Gastrointestinal malformation/surgery, neurological impairment and infections were exclusion criteria. Demographic and anthropometric parameters, GER symptoms and questionnaires (I-GERQ-R) and MII-pH data were recorded and analyzed. Normal MII-pH was defined when acid exposure was <3%, symptom index was <50% and symptom association probability was <95%. Acid exposure >5% and >10% was also considered. Statistical analysis was performed using Chi-Square and univariate and multivariable regression analysis. Results: We included 50 infants (median age 3.5 months) who fulfilled the study criteria: 30 (60%) had normal MII-pH. I-GERQ-R score was abnormal in 33 (66%) infants, and 21/33 (64%) had normal MII-pH (p = 0.47). In the 26 (52%) infants with nocturnal crying, MII-pH was normal in 16 (54%) (p = 0.82). Associated regurgitation (>3 or >10 episodes/die) did not predict abnormal MII-pH (p = 0.74, p = 0.82, respectively). Univariate and multivariable regression analysis did not identify any clinical variable significantly associated with abnormal MII-pH. Conclusions: Infants with persistent unexplained and nocturnal crying should not be empirically treated with acid inhibitors. [ABSTRACT FROM AUTHOR]

Extrauterine growth restriction (EUGR) has been used in the literature and clinical practice to describe inadequate growth in preterm infants. Significant variability is seen in the criteria for EUGR, with no standard definition reached to date. Moreover, no consensus on the optimal timing for assessment or the ideal growth monitoring tool has been achieved, and an ongoing debate persists on the appropriate terminology to express poor postnatal growth. To ensure an adequate understanding of growth and early intervention in preterm infants at higher risk, it is critical to relate the diagnostic criteria of EUGR to the ability to predict adverse outcomes, such as neurodevelopmental outcomes. This narrative review was conducted to present evidence that evaluates neurodevelopmental outcomes in preterm infants with EUGR, comparing separately the different definitions of this concept by weight (cross-sectional, longitudinal and "true" EUGR). In this article, we highlight the challenges of comparing various published studies on the subject, even when subclassifying by the definition of EUGR, due to the significant variability on the criteria used for each definition and for the evaluation of neurodevelopmental outcomes in different papers. This heterogeneity compromises the obtention of a single firm conclusion on the relation between different definitions of EUGR and adverse neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Background: Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch–Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than in adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. Objective: Many studies have failed to demonstrate an association between vasculitis diseases and vaccination; this study examines possible associations. Methods: Herein, the Vaccine Adverse Event Reporting System (VAERS) database is retrospectively examined for associations between vasculitis diseases and immunizations. Results: For some vaccines, the number of rare cases of KD, MIS, and HS are higher than the background rates. These rare cases are predicted to occur in individuals with (1) genetic risk factors with (2) antibody titer levels above the primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets, resulting in cell activation and the release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and possibly histamine drive initial vasoconstrictions, disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms (CAA) or lesions (CAL) in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset. Conclusion: The proposed model of immune complexes driving disease initial disease etiology by Fc receptor activation of immune cells and platelets, resulting in elevated histamine and serotonin levels, is testable and is consistent with disease symptoms and current treatments. [ABSTRACT FROM AUTHOR]

Integrin receptors are heterodimeric surface receptors that play multiple roles regarding cell–cell communication, signaling, and migration. The four members of the β2 integrin subfamily are composed of an alternative α (CD11a–d) subunit, which determines the specific receptor properties, and a constant β (CD18) subunit. This review aims to present insight into the multiple immunological roles of integrin receptors, with a focus on β2 integrins that are specifically expressed by leukocytes. The pathophysiological role of β2 integrins is confirmed by the drastic phenotype of patients suffering from leukocyte adhesion deficiencies, most often resulting in severe recurrent infections and, at the same time, a predisposition for autoimmune diseases. So far, studies on the role of β2 integrins in vivo employed mice with a constitutive knockout of all β2 integrins or either family member, respectively, which complicated the differentiation between the direct and indirect effects of β2 integrin deficiency for distinct cell types. The recent generation and characterization of transgenic mice with a cell-type-specific knockdown of β2 integrins by our group has enabled the dissection of cell-specific roles of β2 integrins. Further, integrin receptors have been recognized as target receptors for the treatment of inflammatory diseases as well as tumor therapy. However, whereas both agonistic and antagonistic agents yielded beneficial effects in animal models, the success of clinical trials was limited in most cases and was associated with unwanted side effects. This unfavorable outcome is most probably related to the systemic effects of the used compounds on all leukocytes, thereby emphasizing the need to develop formulations that target distinct types of leukocytes to modulate β2 integrin activity for therapeutic applications. [ABSTRACT FROM AUTHOR]

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59–0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education. [ABSTRACT FROM AUTHOR]

Fever of unknown origin (FUO) can be caused by four etiological categories of diseases. The most common cause of FUO in children is represented by infections, followed by inflammatory conditions and neoplastic causes; a decreasing quote remains still without diagnosis. Despite the fact that several diagnostic and therapeutic approaches have been proposed since the first definition of FUO, none of them has been fully validated in pediatric populations. A focused review of the patient's history and a thorough physical examination may offer helpful hints in suggesting a likely diagnosis. The diagnostic algorithm should proceed sequentially, and invasive testing should be performed only in select cases, possibly targeted by a diagnostic suspect. Pioneering serum biomarkers have been developed and validated; however, they are still far from becoming part of routine clinical practice. Novel noninvasive imaging techniques have shown promising diagnostic accuracy; however, their positioning in the diagnostic algorithm of pediatric FUO is still not clear. This narrative review aims to provide a synopsis of the existent literature on FUO in children, with its major causes and possible diagnostic workup, to help the clinician tackle the complex spectrum of pediatric FUO in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Background: To date, there is no licensed vaccine for preventing herpes simplex virus type 2 (HSV-2). The current treatment to address the infection and prevent its transmission is not always satisfactory. Methods: We constructed two recombinant vectors, one encoding HSV-2 glycoprotein D (gD, SeV-dF/HSV-2-gD) and one encoding HSV-2-infected cell protein 27 (ICP27, SeV-dF/HSV-2-ICP27), based on a replication-defective Sendai virus through reverse genetics, collectively comprising a combinatorial HSV-2 therapeutic vaccine candidate. The immunogenicity and proper immunization procedure for this vaccine were explored in a murine model. The therapeutic effect that helps prevent recurrent HSV-2 disease was evaluated in HSV-2-infected guinea pigs. Results: Both a robust humoral immune response and a cellular immune response, characterized by the neutralizing antibody titer and the IFN-γ level, respectively, were elicited in BALB/c mice. A further study of cellular immunogenicity in mice revealed that T lymphocytes were successfully enhanced with the desirable secretion of several cytokines. In HSV-2-seropositive guinea pigs, vaccination could reduce the severity of HSV-2 in terms of recurrent lesions, duration of recurrent outbreak, and frequency of recurrence by 58.66%, 45.34%, and 45.09%, respectively, while viral shedding was also significantly inhibited in the vaccine-treated group compared to the group treated with phosphate-buffered saline. Conclusions: The replication-defective recombinant Sendai viruses conveying HSV-2-gD and ICP27 proteins showed great immunogenicity and potential for preventing recurrent HSV-2 disease. [ABSTRACT FROM AUTHOR]

Human parvovirus B19 (B19V) has a wide clinical spectrum, ranging from an asymptomatic infection to a life threatening one. During pregnancy, it can lead to fetal loss and hydrops fetalis. This retrospective study examined the incidence rates of B19V in Israel, analyzing anonymized electronic medical records of 2.7 million individuals between January 2015 and September 2023. A generalized linear model with a Poisson distribution was fit to the data, adjusting for potential confounders. A marked increase in B19V was observed in 2023, with an adjusted incidence rate ratio (IRR) of 6.6 (95% CI 6.33–6.89) when comparing 2023 to previous years. When specifically comparing 2023 to COVID-19 years (2020–2022), adjusted IRR climbs to 9.21 (8.66–9.80). Moreover, in 2023, previously existing seasonality has largely disappeared. High SES characterized most infected individuals with a marked discrepancy in social sectors; the Arab population was significantly less likely to be found B19V positive, even when adjusting for SES. Most infections occurred in school-aged children (6–11 years old). Pregnant women experienced the most significant rise in B19V, with an adjusted IRR of 11.47 (9.44–13.97) in 2023 compared to previous years; most cases were diagnosed in the first trimester. This study demonstrates that Israel is currently experiencing the largest and longest reported outbreak of B19V to date. Policymakers should consider setting screening policies in place, at least for populations at risk, while specifically studying and potentially targeting low socioeconomic populations and specific social sectors to avoid health inequalities. [ABSTRACT FROM AUTHOR]

Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEβCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments. [ABSTRACT FROM AUTHOR]

Childbirth education classes represent an antenatal tool for supporting pregnant women and couples in increasing knowledge on pregnancy, delivery, breastfeeding, and newborn care. The aim of this study was to investigate the impact of an additional lesson during the prenatal course regarding the advantage of vaccination to mitigation of maternal anxiety. An observational study was designed that included participants in childbirth education classes and compared courses enhanced by the extra lesson on vaccination during pregnancy versus those who did not receive it. Assessment of the impact of prenatal educational on vaccination was measured by using validated questionnaires (State-Trait Anxiety Inventory, STAI; Perceived Stress Scale, PSS; World Health Organization- Five Well-Being Index, WHO-5). A total of 145 pregnant women participated to the investigation by answering to the online survey. Of them, 33 patients (22.8%) belonged to the course without a lesson on vaccine, while 112 (77.2%) participated to online prenatal education that included an additional meeting on the usefulness of getting vaccinated during pregnancy. No statistical differences were found between study groups in terms of demographics and perinatal outcomes. Participants in the enriched course reported lower basal anxiety levels than those without the vaccine lesson (STAI-State, normal score < 40, 30 vs. 19%, p-value 0.041; STAI-State, mild score 40–50, 78 vs. 67%, p-value 0.037). With reference to the prior two weeks, maternal wellbeing level was improved by the added class (score > 13 as measurement of wellbeing: 62% vs. 80%, p-value < 0.05). Moderate perceived stress assessed by PSS was found in those pregnant women without prenatal education on vaccination (64 vs. 50%, p-value 0.042). The introduction of a lesson regarding vaccination during pregnancy in the program of prenatal education courses improved maternal anxiety levels and wellbeing, in addition to reducing perceived stress. [ABSTRACT FROM AUTHOR]

Critically ill patients have a hyper-inflammatory response against various offending injuries that can result in tissue damage, organ failure, and fatal prognosis. The origin of this detrimental, uncontrolled inflammatory cascade can be found also within our gut. In detail, one of the main actors is our gut microbiota with its imbalance, namely gut dysbiosis: learning about the microbiota's dysfunction and pathophysiology in the frame of critical patients is of crucial and emerging importance in the management of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Multiple pieces of evidence indicate that the bacteria that populate our gut efficiently modulate the immune response. Treatment and pretreatment with probiotics have shown promising preliminary results to attenuate systemic inflammation, especially in postoperative infections and ventilation performance. Finally, it is emerging how immunonutrition may exert a possible impact on the health status of patients in intensive care. Thus, this manuscript reviews evidence from the literature on gut microbiota composition, its derangement in critically ill patients, its pathophysiological role, and the described and emerging opportunities arising from its modulation. [ABSTRACT FROM AUTHOR]

Background: RSV often leads to hospitalization, and accurate knowledge of risk factors is crucial. Methods: We retrospectively analyzed laboratory-confirmed RSV hospitalizations regarding pregnancy factors, birth status, cigarette smoke exposure, nutrition, social conditions, clinical presentation, and severe disease defined as a need for passive oxygen therapy (pO2Tx), the presence of pneumonia, respiratory failure, intensive care unit (ICU) transfer, and prolonged hospitalization. Results: A univariate analysis included 594 children (median age 4 months) and revealed a pO2Tx relationship with age ≤ 3 months (OR = 1.56), prematurity (OR = 1.71), being born during RSV season (OR = 1.72), smoke exposure during pregnancy (both parents (OR = 2.41, father (OR = 1.8)), dyspnea (OR = 5.09), and presence of apnea (OR = 5.81). Pneumonia was associated with maternal smoke exposure (OR = 5.01), fever (OR = 3.92), dyspnea (OR = 1.62), history of aspiration (OR = 4.63), and inversely with age ≤ 3 months (OR = 0.45). Respiratory failure was associated with prematurity (OR = 3.13) and apnea (OR = 18.78), while the lower odds were associated with older age (OR = 0.57 per month) and presence of fever (OR = 0.11). ICU transfer was associated with apnea (OR = 17.18), but an inverse association was observed with age (OR = 0.54) and fever (OR = 0.11). A prolonged hospital stay was associated with prematurity (OR = 1.76), low birth weight (OR = 2.89), aspiration (OR = 4.93), and presence of fever (OR = 1.51). Conclusions: Age (up to 3 months), prematurity, and presence of apnea are risk factors for a severe RSV course. [ABSTRACT FROM AUTHOR]

Prompt empirical broad-spectrum antibiotic therapy and source control of infection are the most effective treatment strategies in sepsis. As reported above, the dysregulated host response to infection, leading to sepsis and septic shock, is a life-threatening event that is associated with high mortality rate, despite advances in organ support and antimicrobial therapy. Moreover, as sepsis and septic shock are characterized by a dysfunction of the immune response, adjunctive immune-modulatory treatments have been developed in support of antibiotic therapies to restore immune response. The complex interaction between microorganisms, the host's immune response, and the release of pro- and anti-inflammatory factors influence the evolution of sepsis. [Extracted from the article]

Droplet digital PCR (ddPCR) recently has been shown to be a potential diagnostic tool for adults with bloodstream infections (BSIs); however, its application in children remains obscure. In this study, 76 blood samples of children with suspected BSIs were synchronously detected by traditional blood cultures (BCs) and ddPCRs. Our team validated the diagnostic performance of ddPCR including sensitivity, specificity, and positive and negative predictive values. The 76 pediatric patients from the hematology department (67.1%), the pediatric intensive care unit (PICU, 27.6%), and other departments (5.2%) were enrolled. The positive rate of ddPCR results was 47.9%, whereas that for BC was 6.6%. In addition, the time consumption of ddPCR was shorter, only for 4.7 ± 0.9 h, in comparison with the detection timing of BC (76.7 ± 10.4 h, p < 0.01). The levels of agreement and disagreement between BC and ddPCR were 96.1% and 4.2%, and the negative agreement reached 95.6%. The sensitivity of ddPCR was 100%, with corresponding specificities ranging from 95.3 to 100.0%. In addition, a total of nine viruses were identified by ddPCR. In China, the multiplexed ddPCR first could be a tool for the rapid and accurate diagnosis of children with suspected BSIs and can be an early indicator of the possibility of viraemia in children with immunosuppression. [ABSTRACT FROM AUTHOR]

Background. Pregnant women are more susceptible to severe disease associated with SARS-CoV-2 infection. We performed a prospective study to analyze the inflammatory and immune profile after SARS-CoV-2 infection occurring in vaccinated or non-vaccinated pregnant women and their newborns. Methods. Twenty-five pregnant women with SARS-CoV-2 infection were enrolled, and sixteen cord blood samples were obtained at delivery. Results. We observed that IL-1β, TNF-α, Eotaxin, MIB-1β, VEGF, IL-15, IL-2, IL-5, IL-9, IL-10 and IL-1ra levels were significantly higher in vaccinated than non-vaccinated mothers. Furthermore, the newborns of the vaccinated mothers produced higher levels of IL-7, IL-5 and IL-12 compared to the newborns of non-vaccinated mothers. Anti-Spike (S) IgG levels were significantly higher in all vaccinated mothers and their newborns compared to the non-vaccinated group. We found that 87.5% of vaccinated women and 66.6% of non-vaccinated women mounted an S-specific T-cell response quantified by ELISpot assay. Moreover, 75.0% of vaccinated mothers and 38.4% of non-vaccinated mothers showed S-specific CD4+ T-cell proliferative response. The T-helper subset response was restricted to CD4+ Th1 in both vaccinated and non-vaccinated women. Conclusion. A higher level of cytokines, IgG antibodies and memory T cells was noted in the vaccinated women. Furthermore, the maternal IgG antibody trans-placental transfer occurred more frequently in vaccinated mothers and may protect the newborn. [ABSTRACT FROM AUTHOR]

Herein, we present a newborn female with congenital vocal cord paralysis who required a tracheostomy in the neonatal period. She also presented with feeding difficulties. She was later diagnosed with a clinical picture of congenital myasthenia, associated with three variants of the MUSK gene: the 27-month follow-up was described. In particular, the c.565C>T variant is novel and has never been described in the literature; it causes the insertion of a premature stop codon (p.Arg189Ter) likely leading to a consequent formation of a truncated nonfunctioning protein. We also systematically collected and summarized information on patients' characteristics of previous cases of congenital myasthenia with neonatal onset reported in the literature to date, and we compared them to our case. The literature reported 155 neonatal cases before our case, from 1980 to March 2022. Of 156 neonates with CMS, nine (5.8%) had vocal cord paralysis, whereas 111 (71.2%) had feeding difficulties. Ocular features were evident in 99 infants (63.5%), whereas facial-bulbar symptoms were found in 115 infants (73.7%). In one hundred sixteen infants (74.4%), limbs were involved. Respiratory problems were displayed by 97 infants (62.2%). The combination of congenital stridor, particularly in the presence of an apparently idiopathic bilateral vocal cord paralysis, and poor coordination between sucking and swallowing may indicate an underlying congenital myasthenic syndrome (CMS). Therefore, we suggest testing infants with vocal cord paralysis and feeding difficulties for MUSK and related genes to avoid a late diagnosis of CMS and improve outcomes. [ABSTRACT FROM AUTHOR]