Ospedali Riuniti di Ancona

Cement-bentonite (CB) mixtures, compacted soil-lime (SL), and compacted soil-lime-fly-ash (SLFA) mixtures are frequently used materials in environmental engineering. The properties of these materials change over time due to chemical reactions between the binder, soil, and/or water. The acceptance criteria for these materials are usually defined by specific property values, such as permeability, stiffness, and shear strength, measured at certain curing times. The small-strain shear modulus, G0, can be non-destructively measured using the Bender Element method. The present paper illustrates the trend of G0 in CB, SL, and SLFA mixtures over curing time until 60–90 days. In addition, the hydraulic conductivity, k, was also measured. Three different CB mixtures, one SL mixture, and one SLFA mixture were examined. It was observed that the G0 for the CB mixtures increased as the curing time progressed, while the k decreased noticeably. The ratio of cement to water in CBs seemed to play a key role in determining the G0, while other factors, like the use of additives, also significantly affected the k. For SL and SLFA mixtures, the G0 was found to rise with curing time, showing a pattern reflecting the advancement of pozzolanic reactions between the soil and binders, and the permeability correspondingly decreased within one order of magnitude.

To evaluate the effect of intraoperative administration of 1g of tranexamic acid (TXA) on perioperative and postoperative outcomes in patients receiving antithrombotic therapy undergoing endoscopic enucleation of the prostate (EEP). This multicenter, prospective, observational study included 932 patients across 30 centers (December 2024-June 2025). Patients were divided into four groups based on TXA use and continuation or discontinuation of blood thinners during EEP. The primary endpoint was bleeding complications within 30 days, defined as a composite of transfusion, clot retention, bleeding requiring restart of continuous bladder washout (CBWO), or surgical reintervention to control hemostasis. Multivariable Logistic regression analysis identified independent predictors of bleeding complications. There were 534 patients in Group 1 (stopped blood thinners, no TXA given), 316 in Group 2 (on blood thinners, no TXA given), 69 in Group 3 (stopped blood thinners, TXA given), and 13 in Group 4 (on blood thinners, TXA given). Median total operative time was longest in Group 2 (88min [IQR 70-127]) and shortest in Group 3 (55min [IQR 39-69]). Hemostasis time was shortest in TXA groups (p < 0.001). Transfusions occurred in 0.6-7.7% and surgical reinterventions in 0.6-7.7% across groups (p < 0.001). At 3 months, urinary symptoms and continence were comparable. On multivariable analysis, TXA reduced the odds of bleeding complications (OR 0.17, p < 0.001), while ongoing anticoagulant therapy (OR 2.93, p = 0.01), dual therapy (OR 4.31, p < 0.001), and longer operative time (OR 1.01, p < 0.001) increased the odds. Intraoperative TXA might mitigate perioperative bleeding and potentially protect patients at higher hemorrhagic risk.

Emerging evidence revealed an association between perfluorooctanoic acid (PFOA) exposure and reduced bone mass density, leading to osteoporosis disease. This confirms the bone as a target tissue for per- and polyfluoroalkyl substances (PFAS). However, it is still unclear during which phase, proliferation or differentiation, PFOA exerts the most significant harm on osteoblasts, the cells responsible for secreting bone matrix. To tackle the intriguing question of how PFOA treatment affects the process, this study investigated the impact of different concentrations of PFOA on 2D and 3D human fetal osteoblast (hFOB1.19) cell line cultures representing the proliferation and differentiation phases, respectively. In 2D cultures, a 6-day PFOA exposure impaired antioxidant defense without directly altering osteogenesis or calcium deposition. In 3D spheroids, PFOA disrupted spheroid morphology and the deposition of the organic component of extracellular matrix (ECM) in a time-dependent manner. Given the relevance of the endocannabinoid system (ECS) in bone remodeling, we further assessed cannabinoid receptor 1 (CB1) levels. In 2D cultures, 10 µM PFOA reduced CB1 protein levels in parallel with decreased collagen levels. Conversely, in 3D spheroids, exposure to 100 µM PFOA for 2 days significantly increased CB1 levels while reducing the levels of degraded collagen. These findings emphasize the non-monotonic, phase- and time-dependent effects of PFOA on osteoblast function and ECM deposition, underscoring the need for further research into its long-term impact on bone homeostasis and human health induced by this emerging concern contaminant.

Abstract Purpose Tibial spine avulsion fractures compromise ACL function and are common in children and adolescents. Traditional fixation methods may risk physeal injury and intra‐articular damage. Arthroscopic suture‐based techniques offer a minimally invasive, physeal‐sparing alternative. Methods Twenty‐five patients (mean age: 19 years) with type II–IV tibial spine fractures underwent arthroscopic anterior row suture fixation using knotless anchors. Functional outcomes as Lysholm, Internation Knee Documentation Committee rating score (IKDC), Range of motion (ROM), stability, and radiological healing were assessed over 24 months. Results All patients achieved radiographic union (mean: 16 weeks). Final follow‐up showed restoration of pre‐injury Lysholm (94 ± 5 to 93.6 ± 0.8), IKDC (84 ± 7 to 83.9 ± 0.7), and ROM (142°–140°). No instability, growth disturbance, or hardware‐related complications were observed. Conclusion This technique provides stable fixation, preserves the physis, and avoids intra‐articular hardware. Functional and radiological outcomes were excellent, supporting arthroscopic suture fixation as a safe and effective option for tibial spine avulsion fractures. Level of Evidence Level III, prospective study.

A hydatidiform mole (HM) is the most common form of gestational trophoblastic disease (GTD). Differentiating hydatidiform moles (HMs) from non-molar pregnancies and distinguishing complete HMs (CHMs) from partial HMs (PHMs) remains challenging due to overlapping morphological features and a high rate of misclassification. This study aimed to evaluate reliable immunohistochemical markers for improving diagnostic accuracy and addressing the limitations of current molecular techniques. We retrospectively analyzed 64 cases of HMs and hydropic abortions (HAs), diagnosed in women aged 17–36 years between 2010 and 2024, at the Pathology Department of “Elena Doamna” Clinical Hospital, Iași, Romania. Routine histology was supplemented with immunohistochemistry (IHC) using p57, Ki-67, β-hCG, and E-cadherin, with semiquantitative immunoscores applied. Histology revealed 38 PHMs (59.37%), 16 CHMs (23.88%), and 10 HAs (15.62%). p57 was positive in 100% of PHMs and HAs but only in 18% of CHMs. Ki-67 expression was predominantly strong in CHMs, variable in PHMs, and weak in all HAs. β-hCG showed the highest expression in CHMs, followed by PHMs and HAs, while E-cadherin was strongest in HAs. Morphological features alone are insufficient for HM diagnosis; thus, ancillary techniques like p57 IHC and DNA genotyping are crucial to differentiate complete, partial moles, and non-molar specimens by revealing unique genetic patterns, especially p57 absence in CHMs and ploidy/parental origin in PHMs. In this context, an algorithmic approach integrating histology, immunohistochemistry, and genotyping reduces interobserver variability and refines diagnostic precision.

Abstract The performance of bio-inspired fibrillar adhesives can be compromised by surface roughness, manufacturing imperfections or impurities. Previous studies investigated the cases of distributed defects on the array, and defects at the level of single fibrils. However, the influence of localized, macroscopic defects remains largely unexplored. Using numerical simulations of a discrete mechanical model for a fibrillar adhesive with a thick backing layer, we investigate how the size and location of a single circular defect affect the established scaling law between the adhesion force (F) and the effective compliance of the system (β), i.e, F ∝ β−1/2. We find that edge defects are generally more detrimental than central ones, as they act as pre-cracks that amplify stress concentrations at the adhesive's edge, accelerating a crack-like failure. Consequently, the established adhesion scaling law is preserved, with the defect only reducing the effective contact area. In contrast, a central defect fundamentally alters the mechanics of detachment. By transforming the contact geometry into an annulus, it promotes more uniform load sharing across the remaining fibrils and mitigates the edge-dominated failure mechanism. This change makes the adhesive strength less sensitive to the compliance of the system, as reflected by a less negative scaling exponent. The transition between these two regimes appears to occur for defects whose boundary merges with the one of the adhesive.

Acute myeloid leukemia (AML) includes genetically defined subsets. In allogeneic hematopoietic cell transplantation (allo-HCT), the frequency and prognosis of gene-gene interactions may differ from those of patients treated with chemotherapy alone. In this study, adult patients (N = 952) with AML allografted between 2015 and 2023, with available next generation sequencing (NGS) at diagnosis were included. Most frequent mutations were DNMT3A (24%), FLT3-ITD (21%), NPM1 (21%), RUNX1 (16%), NRAS (16%), TET2 (14%), and IDH2 (12%). Multiple correspondence analysis identified distinct groups of co-occurring mutations. Outcome analysis was performed on 646 AML patients allografted in first complete remission (CR1). Six non-overlapping groups were constructed: 1) TP53 mutation (N = 47); 2) NPM1 mutation (N = 129); 3) FLT3-ITD and/or DNMT3A mutation (N = 128); 4) SRSF2 and/or ASXL1 and/or RUNX1 mutation (SAR group) (N = 132); 5) IDH1 and/or IDH2 and/or TET2 mutation (N = 43); and 6) all ten genes unmutated (N = 167). In multivariable analysis, TP53 mutation, adverse karyotype, and age negatively affected leukemia-free survival (LFS) and overall survival (OS). OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

The availability of immune checkpoint inhibitors (ICIs) has expanded perioperative treatment options for urothelial carcinoma. Our aim was to evaluate the effect of neoadjuvant ICI-based regimens on oncological outcomes for patients with muscle-invasive bladder cancer (MIBC). We systematically searched MEDLINE, Embase, Web of Science, and ClinicalTrials.gov in September 2024 for studies on neoadjuvant therapies for MIBC. A proportion meta-analysis and network meta-analysis (NMA) using random-effect models were conducted to evaluate pooled pathological complete response (pCR) rates and to compare overall survival (OS) and adverse events. The review is registered on PROSPERO (CRD42024587964). We included 12 randomized controlled trials (RCTs; 5004 patients) and 35 non-RCTs (2964 patients). ICI-chemotherapy combination therapy was associated with a significantly higher pCR rate versus chemotherapy alone (40.6% vs 17.9%; p<0.01). In the two phase 3 RCTs included (1556 patients) there was no significant difference in OS between dose-dense methotrexate+vinblastine+Adriamycin+cisplatin (ddMVAC) and durvalumab+gemcitabine+cisplatin (GC; hazard ratio 1.06, 95% confidence interval [CI] 0.72-1.55; p=0.8). ddMVAC significantly increased the risk of grade ≥3 anemia (risk ratio [RR] 2.81, 95% CI 1.62-4.88) and asthenia (RR 3.46, 95% CI 1.68-7.14) in comparison to GC, while durvalumab+GC did not. Limitations include data heterogeneity across studies and the limited number of studies included in the NMA. ICI addition to chemotherapy in the neoadjuvant MIBC setting significantly increased pCR rates in comparison to chemotherapy alone. However, there was no difference in OS between durvalumab+GC and ddMVAC. Further studies are needed to clarify the OS benefit of ICI-based combination therapy in comparison to the current standard chemotherapy regimen.