Search Results (852)

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide new knowledge of the mechanisms responsible for the immune adaptation of the fetus to extrauterine life. FcGBP concentrations were measured by ELISA in the first-pass meconium and amniotic fluid samples collected from 120 healthy neonates delivered by either vaginal birth (n = 35) or cesarean section (n = 85) at 36 to 41 weeks gestation. The meconium FcGBP concentrations (405.78 ± 145.22 ng/g) decreased (r = −0.241, p = 0.007) over the course of 36 to 41 weeks gestation, but there were no significant changes (p > 0.05) in the amniotic fluid FcGBP (135.70 ± 35.83 ng/mL) in the same period. Both meconium and amniotic fluid FcGBP concentrations were higher (p < 0.05) in neonates delivered by cesarean section. Decreases in the meconium FcGBP concentrations correlated (r = −0.37, p = 0.027) with the gestational age in neonates delivered by vaginal birth but not in those delivered by cesarean section (p > 0.05). No association was found between the FcGBP concentrations in meconium and amniotic fluid and the birth weight (p > 0.05). With the development of the mucosal immune system in the fetal intestine over the course of the third trimester of gestation, the meconium FcGBP concentrations decrease. Increased FcGBP concentrations measured in the meconium and amniotic fluid of neonates delivered by cesarean section may possibly indicate altered intestinal mucosal function. Intrauterine growth is not associated with the intestinal mucosal barrier maturation involving FcGBP. Full article

Purpose: Our understanding of the influence of preterm birth and related perinatal exposures on early brain development is limited, hampering personalized optimization of neuroprotective strategies. This study assesses the effect of gestational age (GA) at birth on brain volumes at term-equivalent age (TEA) in infants without overt brain injury born across the GA spectrum. Methods: A cohort of infants born across the GA spectrum (25–40 weeks’ gestation) underwent 3T brain MRI around TEA (40–46 weeks postmenstrual age). Eight brain regions, intracranial and total tissue volumes were segmented using MANTiS (morphologically adaptive neonatal tissue segmentation toolbox). Segmentations were visually quality-checked and excluded if segmentation failed. Absolute TEA volume in relation to GA was assessed using univariate and multivariate (correction for postmenstrual age) linear regression analysis. Statistical significance was set at p < 0.05. Post hoc scatter plots of brain volumes relative to intracranial volumes were created. Results: Fifty infants were included (mean GA = 35.0 [SD = 3.3, range = 25.7–40.1] weeks). A higher GA at birth was significantly related to lower cerebrospinal fluid (p = 0.004) and amygdala (p = 0.02) volumes; no significant relation was found between GA and other volumes. Post hoc analyses showed positive trends between GA and several brain structures, including total brain tissue, cortical gray matter, deep gray matter, hippocampus, cerebellum and brainstem volumes. Conclusions: Our results suggest that GA has an effect on TEA brain volumes that is independent of brain lesions, with lower GA being associated with smaller brain tissue volumes and significantly larger cerebrospinal fluid volume. Preterm birth and related exposures may thus affect early brain growth and contribute to neurodevelopmental challenges encountered by preterm-born children. Full article

The genotoxin colibactin, a complex secondary metabolite, targets eukaryotic cell cycle machinery and contributes to neonatal sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) XM, which produces this genotoxin, is an agent of poultry diseases with zoonotic potential. In this study, we confirmed that clbF was necessary for the APEC XM strain to produce colibactin, but it did not affect the growth, adhesion, or invasion of cells. Deletion of clbF substantially diminished both virulence and systemic dissemination, but it also changed the gene expression of the antiserum survival factor, adherence and invasion, iron acquisition genes, and the secretion system. In conclusion, clbF is necessary for the synthesis of the genotoxin colibactin and affects the development of APEC meningitis in mice. Full article

Background: Nutrition is of paramount importance during early development, since suboptimal growth in this period of life is linked to adverse long- and mid-term outcomes. This is particularly relevant for preterm infants, who fail to thrive during the first weeks of life and develop extrauterine growth restriction (EUGR). This group of premature babies represents an interesting population to investigate using a metabolomic approach to optimize nutritional intake. Aims: To analyse and compare the urinary metabolomic pattern at birth of preterm infants with and without growth restriction at 36 weeks of postmenstrual age or at discharge, searching for putative markers of growth failure. Methods: We enrolled preterm infants between 23 and 32 weeks of gestational age (GA) and/or with a birth weight <1500 g, admitted to the Neonatal Intensive Care Unit (NICU) at the Department of Women’s and Children’s Health of Padova University Hospital. We collected urinary samples within 48 h of life and performed untargeted metabolomic analysis using mass spectrometry. Results: Sixteen EUGR infants were matched with sixteen non-EUGR controls. The EUGR group showed lower levels of L-cystathionine, kynurenic acid, L-carnosine, N-acetylglutamine, xanthurenic acid, aspartylglucosamine, DL5-hydroxylysine-hydrocloride, homocitrulline, and L-aminoadipic acid, suggesting a lower anti-inflammatory and antioxidant status with respect to the non-EUGR group. Conclusions: Metabolomic analysis suggests a basal predisposition to growth restriction, the identification of which could be useful for tailoring nutritional approaches. Full article

Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article

Background/Objectives: Infants with high-output enterostomies often require prolonged parenteral nutrition (PN), increasing risks of infections, liver dysfunction, and impaired growth. Mucous fistula refeeding (MFR) is proposed to enhance intestinal adaptation, weight gain, and distal bowel maturation. This systematic review and meta-analysis assessed its effectiveness, safety, and technical aspects. Methods: Following PRISMA guidelines, studies reporting MFR-related outcomes were included without data or language restrictions. Data sources included PubMed, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Library, and UpToDate. Bias risk was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis employed random- and fixed-effects models, with outcomes reported as odds ratios (ORs) and 95% confidence interval (CI). Primary outcomes assessed were weight gain, PN duration, and complications and statistical comparisons were made between MFR and non-MFR groups. Results: Seventeen studies involving 631 infants were included; 482 received MFR and 149 did not. MFR started at 31 postoperative days and lasted for 50 days on average, using varied reinfusion methods, catheter types, and fixation strategies. MFR significantly improved weight gain (4.7 vs. 24.2 g/day, p < 0.05) and reduced PN duration (60.3 vs. 95 days, p < 0.05). Hospital and NICU stays were also shorter (160 vs. 263 days, p < 0.05; 122 vs. 200 days, p < 0.05). Cholestasis risk was lower (OR 0.151, 95% CI 0.071–0.319, p < 0.0001), while effects on bilirubin levels were inconsistent. Complications included sepsis (3.5%), intestinal perforation (0.83%), hemorrhage (0.62%), with one MFR-related death (0.22%). Conclusions: Despite MFR benefits neonatal care, its practices remain heterogeneous. Standardized protocols are required to ensure MFR safety and efficacy. Full article

The first few days following the birth are a vulnerable time for the neonate. Sick infants experience various interventions during their stay in the neonatal unit in order to stay alive and grow. Acquisition of gut microbes is critical for the short- and long-term health of the neonate. At a time when the gut microbiome is starting to take shape, crucial interventions directed at improving the growth, development and survival of the neonate impact its development. Events prior to and after the birth of the neonate, such as maternal conditions, antibiotic exposure, type of feeds, supplemental probiotics, and neonatal intensive care environment, contribute significantly to shaping the gut microbiome over the first few weeks and maintain its healthy balance crucial for long-term health. In this comprehensive review, we address common interventions the neonate is exposed to in its journey and their impact on gut microbiome, and discuss various interventions that minimize the dysbiosis of the gut. Full article

Background/Objectives: Maternal dietary behaviors, including meal frequency patterns, may influence fetal growth. This study examined the associations between maternal meal frequency patterns during pregnancy—categorized as structured, moderately irregular, or highly irregular—and neonatal anthropometric outcomes, including weight, length, head, chest, and abdominal circumferences, and Apgar score. A secondary objective was to assess whether maternal education and household income modify these associations. Methods: This cross-sectional study included 1025 mother–newborn pairs from a socioeconomically diverse Romanian cohort. Maternal meal frequency patterns were classified based on self-reported weekly consumption. Neonatal anthropometric outcomes were obtained from medical records. Multivariable linear regression models, adjusted for maternal and neonatal characteristics, assessed the associations between meal frequency patterns and birth outcomes. Interaction terms evaluated effect modification by maternal education and income. Results: Structured maternal meal frequency patterns were associated with a slight but significant reduction in neonatal length compared to highly irregular patterns (β = −0.36 cm; 95% CI: −0.68 to −0.04; p = 0.02). A borderline inverse association with birth weight was also observed (β = −63.82 g; 95% CI: −128.87 to 1.23; p = 0.05). No significant differences were found for other anthropometric indicators or Apgar score. Maternal education modified the association between moderately irregular patterns and chest circumference (β = 0.15 cm; 95% CI: 0.04 to 0.25; p = 0.003), while household income modified the association with abdominal circumference (β = 0.14 cm; 95% CI: 0.02 to 0.26; p = 0.02). Conclusions: Maternal meal frequency patterns were modestly associated with neonatal length, while socioeconomic factors modified specific anthropometric outcomes. These findings highlight the importance of considering social context in prenatal nutritional recommendations. Full article

Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, Ligilactobacillus salivarius LSM231, and Lactiplantibacillus plantarum LPM239, which exhibited synergistic growth, potent acid/bile salt tolerance, and broad-spectrum antimicrobial activity against pathogens. In vitro, the probiotic combination disrupted pathogen ultrastructure and inhibited PEDV replication in IPI-2I cells. In vivo, PEDV-infected piglets administered with the multi-strain probiotic exhibited decreased viral loads in anal and nasal swabs, as well as in intestinal tissues. This intervention was associated with the alleviation of diarrhea symptoms and improved weight gain. Furthermore, the multi-strain probiotic facilitated the repair of intestinal villi and tight junctions, increased the number of goblet cells, downregulated pro-inflammatory cytokines, enhanced the expression of barrier proteins, and upregulated antiviral interferon-stimulated genes. These findings demonstrate that the multi-strain probiotic mitigates PEDV-induced damage by restoring intestinal barrier homeostasis and modulating immune responses, providing a novel strategy for controlling PEDV infections. Full article

Background: The worldwide prevalence of FGR is about 13% and can lead to various adverse perinatal outcomes, including preterm birth, stillbirth, and neonatal mortality. Hypoxia-Inducible Factor-1 (HIF-1) is an important regulator of oxygen homeostasis in humans and is crucial for placental development. The aim of this study is to determine the pattern of HIF-1A expression in placenta, and to correlate its association with preeclampsia, fetal growth restriction and adverse perinatal outcomes. Methods: This study comprised a total of 158 cases with 42 cases of mother having babies with fetal growth restriction (FGR), 39 cases of mother with preeclampsia (PE), 35 cases of mother with preeclampsia and fetal growth restriction and 42 controls. The expression of HIF-1A was evaluated in various placental cell types, including cytotrophoblasts, syncytiotrophoblasts, fetal endothelial cells, maternal endothelial cells, and decidual cells. Results: The expression of HIF-1A in placental decidual cells of mother with FGR (21/42, 50%, p < 0.0001), PE (25/39, 64.1%, p < 0.0001) and PE with FGR (12/35, 34.3%, p < 0.0001) were significantly increased compared to controls (1/42). Intriguingly, HIF-1A expression was significantly reduced in the placental cytotrophoblasts and syncytiotrophoblasts of mother with PE and FGR (2/35, 5.7%) compared to PE alone (11/39, 28.2%) (p = 0.0142). Conclusions: We found that increased HIF-1A expression in the nuclei of decidual cells was observed in the mothers of babies with FGR, both with and without PE. While HIF-1A expression in the cytotrophoblasts and syncytiotrophoblasts was significantly reduced between mothers with PE and mothers with PE and FGR. This suggests HIF-1A expression might play a role in the pathogenesis of FGR. Full article

Background: Hydatid disease, caused by the larval form of Echinococcus granulosus, is a rare but potentially life-threatening condition during pregnancy, with an estimated incidence of 1 in 20,000 to 30,000 gestations. Physiological immunosuppression and increased placental steroid levels during pregnancy may promote cyst growth, elevating the risk of rupture, which can result in anaphylactic shock, sepsis, or widespread peritoneal dissemination. Diagnostic imaging, particularly ultrasonography, plays a central role in detection, while treatment decisions are complicated by the lack of standardized guidelines and the need to balance maternal–fetal safety. Methods: This case report describes a 29-year-old pregnant woman at 22 weeks’ gestation who was incidentally diagnosed with two large hepatic hydatid cysts during a routine ultrasound. Results: Given the high rupture risk, she underwent successful laparoscopic surgery in the second trimester, followed by careful monitoring and elective cesarean delivery at term. A third retroperitoneal cyst, initially managed conservatively, was excised postpartum. Conclusions: This case highlights the critical importance of individualized, multidisciplinary management in achieving favorable maternal and neonatal outcomes in complex presentations of hydatid disease during pregnancy. Full article

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population. Full article

Introduction: Fetal ovarian cysts are known to be a common form of fetal abdominal masses in female fetuses, often resulting from hormonal stimulation in utero. Although many resolve spontaneously without sequelae, others can develop into more complex pathologies, such as intracystic hemorrhage or torsion, which can compromise ovarian integrity and long-term reproductive outcomes. Early detection and appropriate follow-up evaluation are therefore crucial for optimal perinatal management. Materials and Methods: We conducted a retrospective study of 12 cases of fetal ovarian cysts diagnosed by routine prenatal ultrasound examinations over a two-year period at our institution. Inclusion criteria were the presence of a cystic adnexal lesion detected in utero, detailed prenatal ultrasound documentation, and a comprehensive postnatal examination. Sonographic features such as cyst size, internal echogenicity, and signs of vascular compromise were recorded. The mother’s clinical variables, including gestational age at diagnosis and relevant medical conditions, were noted. Postnatal follow-up evaluation consisted of ultrasound examinations and, if indicated, pediatric surgical consultation. Results: Of the 12 cases, 9 were characterized by a simple cystic morphology. All spontaneously regressed postnatally and did not require surgical intervention. Three were defined as complex cysts showing septations or echogenic deposits; one of these cysts required immediate surgical exploration for suspected torsion. No cases with a malignant background were identified. All infants showed a favorable course with normal growth and development until follow-up evaluation. Conclusions: This series emphasizes that most fetal ovarian cysts are benign and often resolve without intervention, highlighting the benefit of systematic prenatal imaging. Nevertheless, complex or large cysts require close prenatal and neonatal monitoring to diagnose complications such as torsion. Full article

Previous research has demonstrated sex-specific differences in muscle cells regarding sex hormone release and steroidogenic enzyme expression after testosterone exposure. The present study aims to elucidate sex-related differences in intracellular processes involved in myogenesis and regeneration. Neonatal 46XX and 46XY human primary skeletal muscle cells were treated with increasing doses of testosterone (0.5, 2, 5, 10, 32, and 100 nM) for 24 h. The molecular pathways involved in muscle metabolism and growth, as well as the release of myokines involved in satellite cell activation, were analyzed using western blot, real-time PCR, and a Luminex assay. The unpaired Student’s t-test and one-way ANOVA for repeated measures were used to determine significant variations within and between groups. An increase in the expression and release of MYF6, IGF-I, IGF-II, and CXCL1, as well as a decrease in GM-CSF, IL-9, and IL-12, was observed in 46XX cells. Conversely, testosterone up-regulated GM-CSF and CXCL1 in 46XY cells but did not affect the release of the other myokines. Preferential activation of the MAPK pathway was observed in 46XX cells, while the PI3K/AKT pathway was preferentially activated in 46XY cells. In conclusion, our findings demonstrate differential responses to androgen exposure in 46XX and 46XY cells, resulting in the activation of muscle cell growth and energy metabolic pathways in a sex-specific manner. Full article