Search Results (248)

Background: RSV remains a leading cause of infant hospitalization worldwide, and the recently approved nirsevimab could represent an effective and safe prophylactic strategy to prevent severe infections in the general neonatal population. Objectives: We conducted a retrospective observational monocentric pilot study in a mixed preterm/term birth cohort to add real-world evidence of the efficacy and safety of nirsevimab in preventing severe RSV infection. Methods: We included a total of 2035 consecutive infants admitted to the Neonatal Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, from November 2024 to April 2025. We evaluated 30-day safety profiles and season-wide RSV infection rates, and the outcomes were also compared to newborns’ birth rate in the two previous seasons (2022–2023 and 2023–2024). Results: After the introduction of nirsevimab, a lower RSV infection rate was reported compared to previous seasons, and no adverse effects were observed. Compared to previous seasons, the clinical outcomes were more favorable, as only one unvaccinated neonate with RSV infection required invasive ventilation. Conclusions: In this real-world analysis, we demonstrated a good short-term safety profile of nirsevimab, as well as a potentially high efficacy in the general neonatal population with lower RSV infection incidence. However, future studies are needed to better assess its long-term safety and season-wide efficacy. Full article

ABG analysis is the gold standard for assessing acid–base balance, oxygenation, and ventilation in critically ill patients, but it is invasive and associated with patient discomfort and potential complications. Venous blood gas (VBG) analysis offers a less invasive alternative, although its clinical utility remains debated. This review evaluates the current evidence on VBG analysis, exploring its correlation with ABG, clinical applications, and limitations. Studies show a strong correlation between ABG and VBG for pH and a good correlation for bicarbonate and base excess in most cases, while the correlation for pCO₂ remains controversial. Predictably, pO₂ values differ significantly due to oxygen consumption gradients between the arterial and venous blood. VBG analysis is especially valuable for initial assessments, monitoring therapeutic responses, and guiding resuscitation in intensive care settings. It is not merely an alternative to ABG but a complementary tool that can provide unique insights, such as mixed venous oxygen saturation (SvO₂) or indices that require combined ABG and VBG data, like the pCO₂ gap. This review highlights the diagnostic equivalence of VBG in appropriate contexts and advocates for its use when arterial sampling is unnecessary or impractical. Furthermore, VBG analysis could enhance patient care by enabling the timely, less invasive assessment of hemodynamic and metabolic conditions. Future research should focus on refining interpretation algorithms and expanding the clinical applications of VBG to fully realize its potential in critical care practice. Full article

The hemostatic system in the newborn is a complex entity, characterized by dynamism in its development; therefore, the correct measurement of its potential is challenging. In this narrative review, we analyzed the current knowledge of the “developmental hemostasis” of the newborn; we also studied the performance of routine coagulation tests in its evaluation, with considerations about the establishment of neonatal age-specific normal ranges and about the role of preanalytical variables, in particular, hematocrit (which could represent an important cause of error); we also focused on the increasing importance of viscoelastic coagulation tests, which are becoming increasingly widespread (especially in some settings such as intensive care unit) and are able to quickly provide information about the hemostatic function of the newborn, even if they lack adequate standardization in the neonatal period. Full article

Gender-specific cardiology has gained increasing recognition in recent years, emphasizing the need for tailored management strategies for women with cardiovascular disease. Among these, cardiomyopathies—dilated, arrhythmogenic, hypertrophic, and restrictive—pose unique challenges throughout a woman’s reproductive life, affecting contraception choices, pregnancy outcomes, and breastfeeding feasibility. Despite significant advances in cardiovascular care, there is still limited guidance on balancing maternal safety and neonatal well-being in this complex setting. This review provides a comprehensive overview of the current evidence on reproductive counseling, pregnancy management, and postpartum considerations in women with cardiomyopathies. We discuss the cardiovascular risks associated with each cardiomyopathy subtype during pregnancy, highlighting risk stratification tools and emerging therapeutic strategies. Additionally, we address the safety and implications of breastfeeding, an often overlooked but increasingly relevant aspect of postpartum care. A multidisciplinary approach involving cardiologists, gynecologists, obstetricians, and anesthesiologists is crucial to optimizing maternal and fetal outcomes. Improved risk assessment, tailored patient counseling, and careful management strategies are essential to ensuring safer reproductive choices for women with cardiomyopathy. From now on, greater attention is expected to be given to bridging existing knowledge gaps, promoting a more personalized and evidence-based approach to managing these patients throughout different stages of reproductive life. Full article

Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient’s bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols. Full article

Glioblastoma (GBM), a highly malignant brain tumor, arises within a complex microenvironment that plays a critical role in facilitating tumor progression, ensuring survival, and enabling immune evasion, ultimately contributing to therapeutic resistance. Cancer-associated fibrosis is increasingly recognized as a key factor in the tumor pathophysiology, particularly in extracranial cancers, and reported therapeutic strategies in several cancers consist of the current use of the standard-of-care treatment combined with anti-fibrotic drugs. However, it remains unclear how the fibrotic changes associated with the GBM microenvironment contribute to the transformation of GBM from a chemosensitive state to a chemoresistant one. Here, we developed an in vitro model that mimics a fibrosis-like mechanism using the U-87MG GBM cell line. To achieve this, we identified the optimal experimental conditions (i.e., U-87MG cultured in serum-deprivation medium in the presence of recombinant TGF-B1 at 5 ng/mL for 72 h) that effectively induced fibrosis, as suggested by the counter-regulated expression of E- and N-cadherin and sustained levels of α-SMA and collagen I. As expected, U-87MG fibrotic cells were demonstrated to be more resistant to TMZ (predicted EC₅₀ = 35 µM) as compared to the non-fibrotic counterpart (EC₅₀ not achieved here; predicted EC₅₀ = 351 µM). Accordingly, the anti-fibrotic uPAcyclin—a new derivative cyclic compound inspired as a A6 decapeptide drug—showed a significant cytotoxic effect, sensitizing resistant U-87MG fibrotic cells to TMZ. This highlights that targeting fibrosis may help to overcome TMZ resistance in GBM. Full article

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) represent the most prevalent conditions among autoimmune bullous skin diseases, considered a major cause of severe morbidity and, in certain cases, mortality. The hallmark of the two diseases is the presence of autoantibodies directed against proteins located in the basement membrane of the skin, which determines the formation of blisters. In recent years, interest in the role of microbiota in relation to health-disease status has progressively increased. In particular, based on the gut–skin axis, accumulating evidence has emerged on the potential association between the composition and diversity of microbial communities in the gut, skin, and even in the oral cavity and the risk of developing BP and PV. Dysbiosis, characterized by a generally higher relative abundance of Firmicutes and a depletion of probiotics/beneficial species, might contribute to the pathogenesis of both diseases. Despite the still limited number of studies and the need for further large-scale multicenter studies, the knowledge gathered so far is suggestive of a novel modifiable risk factor representing a potential target for adjuvant treatments of these disabling and life-threatening conditions. Full article

Cryptococcosis, an opportunistic fungal infection predominantly caused by Cryptococcus neoformans, is the third most common invasive fungal disease in solid organ transplant recipients. While well-characterized in adult kidney transplant (KT) patients, pediatric data remain sparse. This article compares clinical presentation, immune response, renal involvement, and management strategies of cryptococcosis between adult and pediatric KT recipients. In adults, the disease typically presents as cryptococcal meningitis or pulmonary infection, often complicated by delayed diagnosis and high mortality. In contrast, children frequently exhibit non-specific respiratory symptoms or disseminated disease, reflecting immune immaturity and increased susceptibility to hematogenous spread. Key immunopathological differences include impaired Th1 type responses, macrophage dysfunction, and variable complement activity across age groups. Management involves similar antifungal regimens such as liposomal amphotericin B, flucytosine, and fluconazole, but requires weight-based dosing and careful toxicity monitoring in pediatric patients. Early diagnosis through serum cryptococcal antigen screening, appropriate adjustment of immunosuppressive therapy, and coordinated multidisciplinary care are essential. The findings underscore the need for pediatric specific research and clinical vigilance, emphasizing tailored antifungal dosing and individualized immune management to improve outcomes in this vulnerable population. Full article

Background: This study aims to analyze the clinical, radiological, and histopathological features, as well as the long-term follow-up, of patients with breast carcinoma orbital metastases. Methods: The study was a multicentric retrospective observational case series. The medical records of 32 female patients affected by breast carcinoma orbital metastases referred to three tertiary referral centers from January 2016 to December 2023 were reviewed. The demographic characteristics of the population, clinical ophthalmological presentation, histological features, orbital metastasis latency, disease-related survival (DRS), and mortality rate were analyzed. Results: The median age of the patients was 62.50 years (interquartile range (IQR): 74.50–57.50). The prevalent histotype of the orbital metastases of breast cancer was lobular carcinoma (75.00% of cases). The median orbital metastasis latency time was 39.50 months (IQR: 134.00–10.25). The median disease-related survival (DRS) during the observational period was 35 months, and the 24-month survival rate was 70.73%. The overall mortality rate in our population was 50%. Conclusions: The most frequent histotype of breast cancer orbital metastasis is lobular carcinoma. The primary tumor precedes the onset of orbital metastasis in most cases and usually presents as a mass occupying space and infiltrating the orbit. Orbital metastases are a sign of an advanced stage of the disease, which has a high mortality rate and a low DRS. Full article

Childhood leukemia survivors are at risk of long-term complications. Data on bone remodeling in childhood acute lymphoblastic leukemia (ALL) are limited. This 2-year prospective longitudinal study investigated bone remodeling and bone turnover markers at diagnosis, during treatment, and until stopping treatment, in ALL patients < 18 years, to clarify the influence of leukemia itself and/or chemotherapy on bone. Methods: A total of 22 ALL children (12 males, age 5.5 ± 3.6 years) underwent blood sampling at the 5 time point (T0−T4). Osteoprotegerin (OPG), receptor-activator-NF-B-ligand (RANKL), osteocalcin (OC), C-terminal-telopeptide-type-I-collagen (CTX), bone-alkaline-phosphatase (bALP), tartrate-resistant acid-phosphatase-5b (TRACP5b), procollagen-type-I-N-terminal-propeptide (P1NP), Dickkopf-1 (DKK-1), and sclerostin were assessed. Data from patients at T0 were compared to a control group of healthy children. We used the principal component analysis (PCA) for statistics. Results: Levels of CTX, OC, P1NP, and bALP resulted lower in ALL children than controls (p = 0.009 for CTX and p < 0.001 for the others), also DKK1 and sclerostin (p < 0.0001 and p = 0.023). RANKL ed OPG were higher in patients. During T0−T4, CTX, OC, P1NP, TRACP5b, and bALP showed a significant increase, in particular at T0−T1 (end-of-induction). Less evident changes were detected onwards. Conclusions: The onset of leukemia has been revealed as a key point in determining a slowing of bone remodeling in ALL children. Full article

Primary osteoporosis in children and young adults often suggests a monogenic disease affecting bone microarchitecture and bone mineral density. While Osteogenesis Imperfecta (OI) is the most recognized genetic cause of recurrent fractures, many other genes involved in bone metabolism may contribute to osteoporosis. Among them, FGFR2 plays a critical role in bone growth and development by regulating osteoblast differentiation and proliferation, as well as chondrogenesis. Germline pathogenic FGFR2 variants are typically associated with syndromic craniosynostosis, conditions not characterized by bone fragility or osteoporosis. A report recently identified FGFR2 as a potential cause of dominant early-onset osteoporosis and bone fractures in a family. We report the case of a child affected by severe osteoporosis with multiple fractures. We performed clinical exome sequencing in trio to investigate potential genetic causes of the observed phenotype and identified a likely mosaic pathogenic FGFR2 variant, absent in both parental samples. Our findings provide further evidence that FGFR2 pathogenic variants can lead to a novel non-syndromic bone mineralization disorder, reinforcing the role of FGFR2 in the pathogenesis of early-onset osteoporosis. Full article

Background/Objectives: Microbial infections represent a significant threat to public health due to the emergence and spread of antimicrobial resistance. Adjunctive and alternative therapeutic strategies are explored to tackle this issue, including the use of natural or synthetic antimicrobial peptides. Previous research showed that antibody-derived peptides possess antimicrobial, antiviral, and immunomodulatory properties. This study aimed to characterize newly designed antibody-derived peptides and evaluate their effectiveness against representative strains of Staphylococcus aureus, including drug-resistant isolates. Methods: Colony-forming unit assays and confocal microscopy studies were performed to evaluate peptide activity against planktonic microbial cells. Cytotoxicity tests were performed on THP-1 human monocytic cells. Circular dichroism (CD) and nuclear magnetic resonance (NMR) were employed for the conformational characterization of peptides. Results: The half-maximal effective concentrations of the peptides against bacterial reference strains and drug-resistant isolates ranged from 0.17 to 18.05 µM, while cytotoxic effects were not observed against mammalian cells. A killing kinetics analysis and observation by confocal microscopy of the interaction between peptides and bacteria suggested a mechanism of action involving membrane perturbation. CD studies showed that all peptides predominantly exhibit a random coil arrangement in aqueous solution. NMR spectroscopy revealed that the most active peptide adopts a helical conformation in the presence of membrane mimetics. Conclusions: The structural characterization and evaluation of the newly designed peptides’ antimicrobial activity may lead to the selection of a candidate to be further studied to develop an alternative treatment against microbial infections caused by drug-resistant strains. Full article

Neurogenesis is considered the most robust form of plasticity in the adult brain. To better decipher this process, we evaluated the potential crosstalk of Kisspeptin and Endocannabinoid Systems (KPS and ECS, respectively) on hippocampal neurogenesis. Male adolescent rats were exposed to kisspeptin-10 (KP10) and the endocannabinoid anandamide (AEA) administered alone or in combination with the type 1 cannabinoid receptor (CB1R) antagonist SR141716A. The expression of Kiss1 and Kisspeptin receptor (Kiss1R) has been characterized for the first time in rat hippocampus together with the expression of the CB1R and the Transient Receptor Potential Vanilloid 1 ion channel receptor (TRPV1). Results show that both systems inhibit neurogenesis by reducing the extracellular signal-regulated kinase (ERK) signaling. Despite little differences in the expression of Kiss1R and CB1R, TRPV1 is enhanced by both KP10 and AEA treatments, suggesting TRPV1 as a common thread. KP10 administration reduces CB1R expression in the dentate gyrus, while AEA does not. KPS, unlike ECS, promotes the expression of estrogen receptor α (ER-α) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also upregulating sirtuin 1 (SIRT1), brain-derived-neurotrophic factor (BDNF), and c-Jun. These findings suggest that the interaction between ECS and KPS could be involved in the fine-tuning of neurogenesis, highlighting a novel role for KPS. Full article

Background: Chronic migraine (CM) is a debilitating neurological disorder that imposes substantial burdens on individuals and society, including diminished quality of life and increased healthcare utilization. While the efficacy of botulinum neurotoxin type A (BoNT-A) has been demonstrated in controlled trials, this longitudinal, real-world study offers unprecedented evidence of its long-term benefits, with patients followed for a median of 15 months (interquartile range: 6–36 months) and up to 11 years. Methods: This retrospective analysis included 579 patients diagnosed with CM who were newly treated with BoNT-A, according to the PREEMPT protocol, receiving injections every 12 weeks at doses of 155–195 units across 31–39 sites. Outcomes were assessed through changes in monthly headache days, frequency, symptomatic medication use, and migraine-related disability using Migraine Disability Assessment (MIDAS) scores up to 60 months from recruitment. Safety was evaluated by recording treatment-emergent adverse events (TEAEs), with a focus on long-term tolerability and subgroup variability. Results: Patients showed sustained improvements, with the mean number of monthly headache days decreasing from 22.7 to 5.5, and symptomatic medication use dropping from 33.4 to 3.7 mean doses at 60 months. Additionally, over 60% of patients improved from severe (MIDAS Grade IV) to minimal disability (MIDAS Grade I). Subgroup analysis revealed variability in response rates, emphasizing the need for personalized approaches. TEAEs were predominantly mild, with no new adverse events reported after 36 months, supporting the long-term safety of BoNT-A in real-world settings. Conclusions: This real-world study provides significant evidence for the long-term efficacy, safety, and tolerability of BoNT-A in the preventive treatment of CM. The findings highlight the importance of real-world data to account for patient variability and tailoring treatment strategies. Full article

Mesenchymal tumors of the breast constitute a rare and heterogeneous group of neoplasms, representing only 0.5% to 1% of all breast tumors. Originating from mesenchymal tissues, these tumors include various histological subtypes. They are particularly aggressive, characterized by a high propensity for local recurrence and an overall poor prognosis. The rarity of these cases has impeded the development of comprehensive clinical studies, leading to a lack of standardized diagnostic protocols and treatment guidelines. This review provides a thorough synthesis of current knowledge on breast mesenchymal tumors with a specific focus on malignant variants such as phyllodes tumors and breast sarcomas. It also addresses the diagnostic challenges faced by clinicians, evaluates current therapeutic strategies, and emphasizes the crucial role of surgical treatment. Additionally, it examines the evolving roles of chemotherapy and radiotherapy in enhancing patient outcomes. Full article