Search Results (285)

Background/Objectives: Amnioreduction prior to emergency cervical cerclage (ECC) has been proposed as a method to relieve the tension of the protruding amniotic membrane, thereby facilitating its intact retraction back into the uterine cavity. However, the effect of this procedure on pregnancy outcomes remains unclear. This study aims to evaluate the effect of amnioreduction on pregnancy outcomes in patients who received ECC during the second trimester. Methods: We conducted a retrospective analysis of the characteristics and pregnancy outcomes of patients who underwent ECC across four institutions between 1 July 2021 and 31 December 2024. Pregnancies were classified into the amnioreduction group and the non-amnioreduction group based on whether amnioreduction was performed prior to the ECC. The gestational age (GA) at delivery was the primary outcome measure. A multivariate linear regression model was employed to identify factors associated with GA at delivery. Additionally, a propensity score matching model was constructed for sensitivity analysis. A subgroup analysis was also conducted for pregnancies with cervical dilation ≥ 4 cm to evaluate the effect of amnioreduction in this specific subpopulation. Results: A total of 406 pregnancies were analyzed, and the results indicated no significant differences between the amnioreduction group and the non-amnioreduction group regarding GA at delivery (30.4 (25.7, 35.9) vs. 31.2 (26.0, 37.0) weeks, p = 0.655) or pregnancy latency (days from cerclage to delivery: 49.0 (15.0, 87.5) vs. 57.0 (18.0, 92.3) days, p = 0.397). The rates of preterm birth at <28 weeks (37.0% vs. 37.2%, p = 0.969), <32 weeks (54.6% vs. 52.3%, p = 0.684), <34 weeks (64.8% vs. 60.7%, p = 0.455), and <37 weeks (77.8% vs. 73.8%, p = 0.417) of gestation, as well as the rate of preterm premature rupture of membranes (26.9% vs. 22.5%, p = 0.360), were comparable between the two groups. No differences were observed in the neonatal birth weight or 5 min Apgar score between the groups. After balancing baseline characteristics using propensity score matching, all outcome measures remained similar between the two groups. Subgroup analysis of pregnancies with painless cervical dilation ≥ 4 cm also revealed no significant differences in any outcome measures between those who received amnioreduction and those who did not prior to ECC. Conclusions: Amnioreduction performed prior to ECC was not associated with adverse pregnancy outcomes based on the endpoints assessed in this cohort. Because procedure-specific complications were not systematically recorded, prospective studies collecting procedure-related safety data are required before amnioreduction can be definitively recommended. Full article

Introduction: Toxic epidermal necrolysis in children is a life-threatening emergency requiring prompt withdrawal of the culprit drug, transfer to an experienced center, and intensive supportive care. Case Report: An 11-year-old girl developed toxic epidermal necrolysis involving 90 percent of total body surface area after exposure to a nonsteroidal anti-inflammatory drug, with concomitant viral positivity. At the referring pediatric hospital, on day 2 the patient received high-dose intravenous immunoglobulin 2 g/kg and a single infusion of infliximab 5 mg/kg. She was transferred on day 6 to our Burn Unit. Histopathology confirmed complete epidermal loss. Treatment included IgM- and IgA-enriched intravenous immunoglobulin over 72 h and methylprednisolone 0.74 mg/kg/day for 30 days. Cryopreserved amniotic membrane was applied to trunk and limbs, and fluorescent light energy to the face. Complete re-epithelialization occurred within 14 days without complications. Pain resolved rapidly, with a Visual Analog Scale score of 0 on day 2. At 6 months, skin and mucosae were intact with only transient dyschromia. Conclusions: In this child with extensive toxic epidermal necrolysis and high predicted mortality, IgM/IgA-enriched immunoglobulin, low-dose corticosteroid and early staged cryopreserved amnion were associated with infection-free, complete re-epithelialization and full functional recovery. Full article

Background/Objectives: Oxidative stress is a major cause of impaired oocyte quality and early embryo development, a challenge that still needs to be addressed in assisted reproduction. Mesenchymal stem cell secretomes have been investigated as cell-free therapeutics with antioxidant activity and relevant anti-apoptotic effects. This study aimed to evaluate the effects of human amniotic membrane-derived mesenchymal stem cell-conditioned saline (AMSC-CS) as an injectable formulation on oxidative stress–related markers in ovarian tissue and preimplantation developmental outcomes. Methods: AMSC-CS was administered intravenously to female mice in a dose-dependent manner. Safety assessments were conducted to evaluate systemic and target organ toxicity within the dosage range. In vitro fertilization (IVF) outcomes and oxidative status in ovaries, oocytes, and embryos were evaluated following treatment with low, medium, and high doses of AMSC-CS (1, 3, and 5 μL/g). Results: As an injectable formulation, the safety assessments did not reveal systemic or target organ toxicity of AMSC-CS within the dosage range. Medium-to-high doses of AMSC-CS improved the expression of folliculogenesis-related genes and decreased oxidative stress and apoptosis signaling in ovarian tissue. At the high dose, AMSC-CS promoted preimplantation embryo development to the blastocyst and hatched blastocyst stages, along with improved blastocyst quality and reduced oxidative stress in oocytes and blastocysts. Conclusions: These findings suggest that AMSC-CS at medium-to-high doses, as an injectable formulation with antioxidant activity, may be a promising adjunct for assisted reproductive technologies. Full article

Human placenta-derived amniotic membrane (hAM) and its derivatives have attracted growing interest as bioactive materials for tissue engineering, regenerative medicine, and biomaterial design. This review summarizes the anatomical and cellular characteristics of hAM and examines the interplay between its regenerative and immunomodulatory properties. Key hAM-derived biomolecules are discussed, with an emphasis on their roles in immune regulation, angiogenesis, extracellular matrix remodeling, and tissue repair across diverse regenerative contexts. Current applications of hAM-based materials in tissue engineering and regenerative biomaterials are reviewed, including emerging studies involving soft tissue applications. In addition, recent efforts to integrate hAM derivatives into 3D bioprinting approaches are examined, including their use as bioink components or biofunctional additives to hydrogel-based systems. Although studies involving hAM-based bioprinted constructs remain limited, the available findings suggest promising regenerative, proangiogenic, and bioactive effects. Challenges related to material processing, printability, standardization, and reproducibility are also discussed. Overall, this review highlights the biomaterial potential of hAM derivatives and their emerging relevance to biofabrication strategies aimed at developing biologically instructive constructs for regenerative medicine. Full article

This systematic review assessed transcriptomic evidence on the molecular mechanisms underlying spontaneous preterm birth (sPTB). Major electronic databases were searched from inception to October 2025. Eligible studies examined RNA transcriptomic profiles from maternal pregnancy-related tissues or biofluids in spontaneous preterm labor (sPTL) or preterm prelabor rupture of membranes (PPROM), while indicated or iatrogenic preterm births were excluded. Two reviewers independently screened studies, extracted differentially expressed genes (DEGs), and assessed study quality. DEGs were summarized by tissue type, and recurrent concordant genes were analyzed using Gene Ontology, Reactome, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, with false discovery rate < 0.05 considered significant. Twenty studies were included. Transcriptomic data were derived from placental villi, maternal peripheral blood, decidua, fetal membranes, myometrium, amniotic fluid, and vaginal secretions. Placental villi findings suggested proliferative-metabolic reprogramming and impaired maternal–fetal immune–structural homeostasis, whereas maternal blood profiles reflected systemic immune–inflammatory activation and dysregulated lipid-metabolic pathways. sPTL and PPROM showed potentially distinct signatures involving extracellular matrix disruption, collagen remodeling, matrix degradation, and myeloid/neutrophil-associated inflammation. Transcriptomic profiling may support non-invasive sPTB risk assessment, but standardized, phenotype-specific longitudinal studies are needed to confirm predictive value and clinical utility. Full article

Objectives: The aim of this study was to evaluate the association between amniotic fluid volume at preterm prelabor rupture of membranes (PPROM) diagnosis and latency, short-term delivery risk, and perinatal outcomes across different gestational ages. Methods: This retrospective cohort study included singleton pregnancies with PPROM before 34 weeks’ gestation managed at a tertiary referral center. Amniotic fluid (AF) volume was categorized according to the deepest vertical pocket (≤20 mm vs. >20 mm). Fetal and neonatal outcomes were analyzed as predefined composite outcomes. Latency to delivery was assessed using Kaplan–Meier estimates. Multivariable Cox regression models were used to evaluate associations after adjustment for clinically relevant confounders. Results: A total of 263 pregnancies were included, of which 66.5% had an AF pocket ≤ 20 mm at presentation. Lower AF volume was associated with a higher incidence of the fetal composite outcome (74.3% vs. 52.3%, p < 0.001) and a higher short-term risk of delivery across gestational-age strata. In multivariable analysis, AF pocket > 20 mm remained independently associated with lower risk of fetal composite outcome. AF volume was not associated with overall latency to delivery (Spearman ρ = 0.03, p = 0.598). Although lower AF volume was associated with higher crude neonatal morbidity, this association was attenuated after adjustment for gestational age. Conclusions: Reduced AF volume at PPROM presentation was associated with adverse fetal outcomes and higher short-term delivery risk, whereas neonatal morbidity was mainly driven by gestational age at delivery. AF volume should therefore be interpreted as a contextual prognostic marker rather than an isolated determinant of outcome. Full article

Background: Preterm premature rupture of membranes (PPROM) before 32 weeks of gestation with prolonged latency is associated with substantial neonatal morbidity, including Dry Lung Syndrome (DLS), pulmonary hypoplasia (PH), bronchopulmonary dysplasia (BPD), and death. Accurate individualized risk stratification remains elusive, as the interacting contributions of amniotic fluid dynamics, inflammatory status, and microbiological burden are inadequately captured by traditional statistical approaches. Methods: We performed a retrospective, exploratory–predictive analysis of 66 pregnancies complicated by second-trimester PPROM with latency exceeding 14 days. Elastic Net and Random Forest models were trained across six clinically defined predictor domains using a multi-stage block modelling strategy. To address the clinically relevant distinction between antenatal and postnatal information, results are reported separately for Model A—comprising exclusively antenatal predictors available during expectant management (gestational age at PPROM, latency, amniotic fluid trajectory, inflammatory status, vaginal microbiome at admission)—and Model B, which additionally incorporates postnatal variables and characterizes the full mechanistic perinatal risk trajectory. Binary and ordinal outcomes included DLS, PH, BPD, intraventricular hemorrhage (IVH), and neonatal death. Pairwise interaction models were additionally computed to identify cross-domain risk constellations. Results: Distinct predictor architectures emerged per outcome. Pulmonary hypoplasia was most strongly associated with temporal features of oligohydramnios—particularly the persistence and timing of SDP < 1 cm—rather than isolated measurements. For DLS, the antenatal model (Model A) achieved AUC 0.776, driven by gestational maturity and inflammatory status; surfactant administration—a postnatal variable reflecting therapeutic response rather than an antenatal risk factor—dominated only the mechanistic Model B. Neonatal death was driven by a combined profile of respiratory support burden, amniotic fluid persistence, and co-morbidity. IVH showed consistently high ordinal predictability (accuracy 0.863), with amniotic fluid dynamics and microbiological burden as leading contributors. BPD remained the least linearly separable endpoint across all configurations. Conclusions: Multi-domain machine learning reveals outcome-specific, cross-domain risk architectures following second-trimester PPROM that are invisible to conventional statistical models. Longitudinal amniotic fluid trajectory is the dominant antenatal determinant of structural pulmonary morbidity, while microbiological burden independently shapes neurological risk. These findings support prospective validation of integrated ML-based risk stratification tools for individualized antenatal counselling in this high-risk population. Full article

The amniotic membrane is widely recognized in regenerative medicine due to its rich content of extracellular matrix proteins and growth factors that confer anti-inflammatory and pro-regenerative properties. However, its rapid degradation restricts its standalone clinical use. To overcome these limitations, we developed biofilms by incorporating decellularized human amniotic membrane matrix (dHAM) into polycaprolactone (PCL) and polyvinylpyrrolidone (PVP) matrices using spin-coating. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were used to evaluate film biocompatibility through cell viability, proliferation, and wound healing migration assays. Surface characterization was performed using contact angle measurements, Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy, and scanning electron microscopy. Soluble dHAM extracts (4–6 mg/mL) significantly enhanced BM-MSC proliferation at 48 h compared to controls (p ≤ 0.01 and p ≤ 0.0001). Both PCL-dHAM and PVP-dHAM biofilms exhibited high cell viability (>90%) and improved initial adhesion. Notably, dHAM incorporation significantly increased wound closure rates at 24 h, reaching 98.47% for PCL-dHAM and 93.13% for PVP-dHAM, compared to 76.56% and 64.20% for pure polymers (p = 0.0001). All scaffolds maintained hydrophilic surfaces (<90°), favorable for cell interaction. The integration of dHAM into PCL and PVP by spin-coating produces biofilms biocompatible with enhanced regenerative potential, representing promising candidates for wound healing applications. In conclusion, these coatings support BM-MSC adhesion, proliferation, and migration, while significantly accelerating wound closure, underscoring their value as advanced bioactive coatings for regenerative medicine. Full article

Background/Objectives: Chorioamnionitis (CA), an inflammation, with or without infection, involving the amniotic fluid, placenta, fetal membranes or decidua, can significantly impact fetal and neonatal development. This study aimed to determine the prevalence of chorioamnionitis and confirm its correlation with neonatal morbidity and mortality, in a single tertiary center. Methods: This observational, retrospective study was conducted over three years (2019–2021) in a tertiary neonatal intensive care unit, examining 80 preterm infants born at 23–28 weeks of gestation. Spearman rank correlation, χ² tests, and multivariate logistic regression were used to assess associations between chorioamnionitis exposure and neonatal outcomes. Results: Among the 80 newborns analysed, clinical chorioamnionitis was identified in 12 preterm infants, while 65 (81.3%) presented histological chorioamnionitis. No significant association was found between histological chorioamnionitis stage and gestational age at birth (Spearman ρ = −0.15, p = 0.195). Premature rupture of membranes was significantly more frequent in the CA-exposed group (46.2% vs. 13.3%, p = 0.019). In unadjusted analyses, histological chorioamnionitis exposure was associated with higher rates of adverse neonatal outcomes, including early-onset sepsis (46.2% vs. 26.7%), intraventricular haemorrhage (73.8% vs. 60.0%), bronchopulmonary dysplasia (15.9% vs. 6.7%), and retinopathy of prematurity (11.3% vs. 0.0%); however, most of these differences did not reach statistical significance. After multivariate adjustment, histological chorioamnionitis remained independently associated with severe respiratory distress syndrome (adjusted OR 25.84, 95% CI 2.49–268.44, p = 0.006). Mortality was numerically lower in the CA-exposed group (27.7% vs. 46.7%); however, this difference did not reach statistical significance (p = 0.216). Conclusions: Histological chorioamnionitis was independently associated with severe respiratory distress syndrome. Associations with early onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity were observed in unadjusted analyses but were not independently significant after adjustment for perinatal confounders. No significant association was found between chorioamnionitis and neonatal mortality. While clinical diagnostic criteria for chorioamnionitis demonstrated good specificity, their poor sensitivity underscores the urgent need for improved diagnostic tools, including routine histological examination of the placenta. Full article

Background/Objectives: Acute myocardial infarction (AMI) remains a major cause of global morbidity and mortality and is a leading factor in the development of heart failure. This study investigated the regenerative potential of decellularized human amniotic membrane (HAM) and Wharton’s jelly (WJ) in a rat model of left ventricular dysfunction induced by acute myocardial infarction (AMI). Methods: Twenty-three rats underwent left anterior descending coronary artery ligation and were randomized into three groups: control (saline), WJ (decellularized WJ), and HAM (decellularized HAM). Results: After 30 days, echocardiographic, histopathological, and immunohistochemical assessments were performed. No significant differences in ventricular function were observed among groups. However, the HAM-treated group showed a significant reduction in myocardial fibrosis compared with the control (p = 0.009), suggesting attenuation of post-infarction remodeling. Despite the absence of measurable functional recovery, HAM demonstrated potential to promote more favorable tissue organization. Study limitations include the lack of a sham-operated group, short follow-up period, and absence of quantitative decellularization validation. Conclusions: Overall, the results indicate that decellularized HAM may act as a structural modulator of myocardial remodeling, warranting further studies with longer follow-up and combination approaches, such as cell-based or growth factor-enhanced therapies. Full article

Preterm birth is a major cause of neonatal morbidity and mortality, and many spontaneous cases remain idiopathic. Increasing evidence suggests that intrauterine inflammation may occur in the absence of detectable infection, leading to the recognition of sterile intrauterine inflammation as an important mechanism contributing to threatened preterm labor and spontaneous preterm birth. This review summarizes current knowledge regarding the role of damage-associated molecular patterns (DAMPs), alarmins, pattern recognition receptors, inflammasome activation, cellular senescence, and pyroptosis in the initiation of sterile inflammatory pathways associated with labor. Key mediators including HMGB1, IL-1α, fetal cell-free DNA, platelet-activating factor, and S100 proteins appear to promote inflammatory activation within fetal membranes and the amniotic cavity. The review also discusses the emerging contribution of fetal immune activation, maternal–fetal immune dysregulation, maternal microchimerism, and epigenetic mechanisms to idiopathic preterm birth. Current diagnostic and therapeutic options remain limited, and no targeted treatment for sterile intrauterine inflammation has yet been established. Future approaches may include precision biomarkers, multiomics-based risk stratification, targeted immunomodulatory therapies, and modulation of maternal–fetal immune interactions. Improved understanding of sterile inflammatory mechanisms may ultimately support development of personalized strategies to prevent preterm birth and improve perinatal outcomes. Full article

Chronic wound management remains a significant clinical challenge, requiring adaptive therapeutic approaches to achieve wound closure that nonetheless frequently prove fruitless. Balancing the initial pro-inflammatory response with debris removal and tissue rebuilding remains elusive in most cases, leading to pain, drastic quality-of-life deterioration, and, eventually, amputation. Meanwhile, patient adherence is an overarching theme. Furthermore, non-surgical alternatives that effectively promote tissue rebuilding are essential for patients seeking to avoid further invasive procedures. We report a patient with a recalcitrant ulcer managed using human amniotic membrane dressing (hAM-pe) and a bovine collagen matrix (BCM) in spatially distinct areas as an intra-patient control. Methodology included clinical monitoring and ad hoc molecular and histological analyses to assess inflammatory markers and tissue architecture. Following 59 days of observation, the superior evolution of the hAM-pe-treated zone led to the clinical decision to extend hAM-pe treatment over the adjacent BCM area, resulting in total wound closure. The hAM-pe-treated site demonstrated accelerated closure and clinical resolution of inflammation without the presence of a granulomatous response. Molecular analysis revealed downregulated pro-inflammatory mediators (IL-1β, TNF-α, CXCL-10) and upregulated markers associated with angiogenesis (VEGF, CD34) and tissue repair (Arginase-1). In this case, the non-surgical hAM-pe treatment was associated with a favorable healing trajectory, characterized by superior inflammation resolution and enhanced tissue organization (collagen type I/III maturation). While these descriptive findings suggest the potential advantages of amniotic membrane dressings in promoting advanced tissue repair, they remain limited to this individual observation. Further research in larger cohorts is required to validate these mechanisms. Full article

Purpose: To evaluate the clinical efficacy and safety of eye drops containing lyophilized amniotic membrane (AM) in the treatment of dry eye disease (DED), with a focus on tear film stabilization and epithelial–immune balance. Methods: In this prospective cohort study, 40 patients (80 eyes) with DED were followed over six visits. The primary outcome was tear break-up time (TBUT). Secondary outcomes included corneal and conjunctival staining graded by the Oxford scale, meibomian gland parameters, corneal sensitivity (Cochet–Bonnet esthesiometry), best-corrected visual acuity, intraocular pressure (IOP), and Schirmer I test. Continuous variables were analyzed using repeated-measures ANOVA with Greenhouse–Geisser correction and Bonferroni post hoc testing; ordinal outcomes were analyzed using the Friedman test with Dunn–Bonferroni correction. Results: TBUT increased significantly in both eyes (OD: +5.3 s; OS: +4.9 s; both p < 0.001; ηp² ≈ 0.33). Corneal and conjunctival staining scores decreased (p < 0.001), meibomian gland quality and expressibility improved (p < 0.001), and corneal sensitivity increased (p < 0.001), while visual acuity and IOP remained stable. Schirmer I values showed no significant change. The combined pattern of changes (TBUT ↑, staining ↓, meibum/expressibility ↑, sensitivity ↑) indicates tear film stabilization and ocular surface improvement with a preserved safety profile. Conclusions: Lyophilized AM eye drops significantly prolong TBUT and improve clinical signs of DED, presumably by restoring the extracellular matrix (ECM) niche and the heavy-chain hyaluronan/pentraxin 3 (HC-HA/PTX3) complex, reducing proteolytic burden, and promoting a pro-resolving immune balance, with potential neurotrophic effects. These findings support the adjunctive use of AM-derived eye drops within contemporary TFOS DEWS II-based management algorithms for dry eye disease. Full article

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited disorder characterized by extreme epithelial fragility and progressive cicatrization, frequently leading to severe ocular surface disease and early visual impairment. Surgical interventions such as ocular surface reconstruction (OSR) in childhood are often delayed because of anesthetic risks and concerns regarding recurrence. Consequently, the effectiveness of OSR, including amniotic membrane transplantation (AMT), and its impact on visual development remain poorly documented. Methods: We report a case series of two pediatric patients (three eyes) with genetically confirmed RDEB who underwent single-step OSR using AMT. Clinical outcomes, long-term visual acuity, perioperative management, and histopathological findings were evaluated. Results: Ocular manifestations included corneal epithelial damage, symblepharon, and pseudopterygium extending over the cornea. One patient underwent symblepharon lysis, superficial keratectomy, and AMT onto the bare sclera in the right eye at age 4 and in the left eye at age 8, both under intubated general anesthesia. The other patient underwent the same procedure in the right eye at age 6. Best spectacle-corrected visual acuity improved from ≤20/300 to 20/30 in all eyes, and pupillary zone clarity was maintained during the follow-up period (up to 6 years). Histopathology confirmed pseudopterygium with squamous metaplasia, goblet cell loss, and fibrovascular stroma. Safe general anesthesia was achieved through meticulous multidisciplinary perioperative planning involving anesthesiologists, dermatologists, and pediatricians. No systemic complications related to anesthesia or perioperative management were observed. Conclusions: Single-step OSR with on-lay AMT can restore and preserve visual function in pediatric RDEB. Early surgical intervention may prevent profound amblyopia and provide durable ocular surface stability. A multidisciplinary approach enables safe general anesthesia and perioperative management. Full article

Eyelid anomalies represent a relevant cause of corneal injury, including epithelial instability and recurrent erosions up to progressive stromal thinning, corneal melt, and, in severe cases, perforation leading to permanent visual impairment. Correction of eyelid dysfunction is the first step in managing these lesions. However, corneal damage may persist or progress despite adequate eyelid treatment. Therefore, a corneal surgical approach is necessary to preserve ocular surface integrity and visual function. This review synthesizes literature published between 2008 and 2025 on corneal complications secondary to eyelid anomalies and postoperative eyelid procedures. We analyzed the mechanisms of eyelid-induced corneal injury, indications for surgical treatment, and corneal surgical strategies, from surface-stabilizing techniques to tectonic interventions. Entropion and ectropion are the most common eyelid abnormalities associated with mechanical trauma and exposure-related corneal disease. Although definitive eyelid correction is necessary for corneal recovery, persistent epithelial defects, stromal thinning, corneal melt, and perforation frequently require corneal surgical management. Surface-stabilizing procedures, such as amniotic membrane transplantation, are effective in early disease stages, whereas progressive stromal defects necessitate tectonic approaches such as lamellar patch grafting or therapeutic keratoplasty. Interventions aimed at visual rehabilitation should be postponed until sustained ocular surface stability has been achieved. Effective management of eyelid-related corneal damage requires both eyelid surgical correction and corneal management. Close collaboration between corneal and oculoplastic surgeons helps achieving good anatomical outcomes and long-term ocular surface stability. Full article