Search Results (67)

The Vesical Imaging Reporting and Data System (VI-RADS) is used to detect muscle-invasive bladder cancer, with emerging prognostic implications. Integrating imaging parameters with molecular biomarkers may improve risk stratification in bladder cancer. This study evaluated whether combining VI-RADS scores with serum cytokeratin fragment 19 (CYFRA 21-1) levels—a clinically relevant biomarker for bladder cancer—could improve overall survival (OS) prediction. We retrospectively analyzed 134 patients who underwent transurethral resection of bladder tumors, magnetic resonance imaging, and postoperative serum CYFRA 21-1 measurements. In total, 15 cancer-specific deaths were observed during follow-up. Receiver operating characteristic curve analysis identified optimal prognostic cut-off values: VI-RADS score ≥ 4 and CYFRA 21-1 level ≥ 1.8 ng/mL. The 1-, 2-, and 3-year OS in patients with both high VI-RADS scores and CYFRA 21-1 levels were 42.9%, 16.7%, and 8.3%, respectively, significantly lower than those in other groups (p < 0.001, 0.002, and 0.003, respectively). Multivariate Cox proportional hazards analysis demonstrated that such patients had the poorest OS (hazard ratio: 7.51; p = 0.002). This suggests that combining VI-RADS and CYFRA 21-1 improves prognostic accuracy in bladder cancer, demonstrating potential clinical utility by informing individualized treatment strategies; however, limitations include the retrospective study design and absence of external validation. Full article

The influence of foundation pit excavation on the bearing behavior of concrete tubular piles at the pit bottom remains unclear. Based on the Vesic cavity expansion theory, this paper proposes a method for calculating pile driving resistance, which takes into account the residual effect of vertical pressure changes on earth pressure during excavation. Furthermore, relying on the statistical regularity between Qu/Pu (ratio of ultimate bearing capacity to ultimate cavity expansion pressure) and L/d (length-to-diameter ratio), theoretical formulas for calculating the ultimate bearing capacity of tubular piles before and after foundation pit excavation are established, with their reliability and influencing factors analyzed. This method only requires determining the L/d of the tubular piles and the theoretical value of pile driving resistance. With its simple parameter requirements, it is suitable for estimating the ultimate bearing capacity of tubular piles affected by excavation. By comparing the computed penetration resistance, earth pressure, and driving resistance of tubular piles with field measurements, the computed results show good agreement with field measurements, and the accuracy of the proposed method meets the requirements of engineering design, verifying its feasibility as an empirical method. The fitting results of the Q_u/P_u ratios indicate that the deviations between the measured and computed values are 4.17% and 5.64% before and after excavation, respectively. Additionally, L/d and L/H (ratio of pile length to excavation depth) significantly affect the earth pressure, driving resistance, and vertical bearing capacity of monopoles. Smaller L/d and L/H ratios lead to greater earth pressure on the pile and more pronounced effects on driving resistance and vertical bearing capacity. The development of this method offers an approach for estimating the ultimate bearing capacity of tubular piles before and after foundation pit excavation during preliminary design, thereby holding substantial engineering significance. Full article

Alkylating agents, historically employed as chemical warfare agents and currently used as chemotherapeutic drugs, are known to induce significant pulmonary toxicity. Current clinical interventions often fail to fully prevent or reverse these pathological changes, highlighting the urgent need for safe, broad-spectrum therapeutic agents that are effective across diverse exposure scenarios. Melatonin has emerged as a promising protective agent due to its antioxidant, anti-inflammatory, and immunomodulatory properties, along with a well-established safety profile. This systematic review evaluates the potential of melatonin in mitigating vesicant-induced pulmonary damage, synthesizing and critically analyzing preclinical evidence in accordance with the PRISMA guidelines. Three in vivo rodent studies met the inclusion criteria and were analyzed. In all cases, melatonin demonstrated protective effects against alkylating agents such as mechlorethamine (HN2) and cyclophosphamide (CP). These effects were dose-dependent and observed across various animal models, administration protocols, and dosages (ranging from 2.5 to 100 mg/kg), highlighting the importance of context-specific considerations. The human equivalent doses (HEDs) ranged from 12 to 973 mg per day, suggesting that the effective doses may exceed those typically used in clinical trials for other conditions. Melatonin’s pleiotropic mechanisms, including a reduction in oxidative stress, the modulation of inflammatory pathways, and support for tissue repair, reinforce its therapeutic potential in both prophylactic and treatment settings for alkylating agent exposure. Nonetheless, this review underscores the critical need for further randomized clinical trials to establish the optimal dosing strategies, refine treatment protocols, and fully elucidate melatonin’s role in managing alkylating-agent-induced pulmonary toxicity. Full article

Hybrid composite pile foundations face critical challenges in terms of optimizing load transfer mechanisms across variable soil densities, particularly in regions like Kano, Nigeria, characterized by loose to dense sandy deposits and fluctuating groundwater levels. This study addresses the need for sustainable, high-performance foundation systems that are adaptable to diverse geotechnical conditions. The research evaluates the mechanical behavior of steel–concrete and timber–concrete hybrid piles, quantifying skin friction dynamics, combining eight (8) classical ultimate bearing capacity (UBC) methods (Vesic, Hansen, Coyle and Castello, etc.) with numerical simulations, and assessing load distribution across sand relative densities (10%, 35%, 50%, 75%, 95%). Laboratory investigations included the geotechnical characterization of Wudil River well-graded sand (SW), direct shear tests, and interface shear tests on composite materials. Relative densities were calibrated using electro-pneumatic compaction. Increasing Dr from 10% to 95% reduced void ratios (0.886–0.476) and permeability (0.01–0.0001 cm/s) while elevating dry unit weight (14.1–18.0 kN/m³). Skin friction angles rose from 12.8° (steel–concrete) to 37.4° (timber–concrete) at Dr = 95%, with timber interfaces outperforming steel by 7.4° at Dr = 10%. UBC for steel–concrete piles spanned from 353.1 kN (Vesic, Dr = 10%) to 14,379 kN (Vesic, Dr = 95%), while timber–concrete systems achieved 9537.5 kN (Hansen, Dr = 95%). PLAXIS simulations aligned closely with Vesic’s predictions (14,202 vs. 14,379 kN). The study underscores the significance of soil density, material interfaces, and method selection in foundation design. Full article

Exposure to sulfur mustard can result in severe injury or even fatalities in humans. Therefore, the development of reliable and high-performance sensors for detecting sulfur mustard is critical. Herein, WO₃ thin films are prepared as sulfur mustard simulant (e.g., 2-chloroethyl ethylsulfide, 2-CEES) sensing materials using sputter deposition followed by high-temperature annealing. The 2-CEES gas sensors fabricated via WO₃ porous films realize high-performance detection of 2-CEES at 260 °C with an impressive detection limit (15 ppb), fast response (58 s), long-term stability, and good selectivity. Through systematic optimization of deposition and annealing parameters, WO₃ porous thin films with tailored oxygen vacancy concentrations were prepared, facilitating device fabrication. This approach provides an effective strategy for the batch production of miniaturized devices enabling real-time monitoring of vesicant agents. Full article

Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical recommendations about the diluent, pH, osmolarity, dosage, vesicant properties, and phlebitis rate of the most commonly used cardiological drugs evaluated in randomized controlled trials (RCTs) till 31 August 2024. The authors searched for available IV cardiological drugs in RCTs in PUBMED EMBASE^®, EBSCO-CINAHL^®, and Cochrane Controlled Clinical trials. Drugs’ chemical features were obtained online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, an osmolarity > 600 mOsm/L, and a high incidence of phlebitis reported in the literature, as well as vesicant drugs, require utmost caution during administration. A total of 857 papers were evaluated and 316 studies were included. A total of 84 cardiological drugs were identified, of which only 31 (37%) can be safely infused via a peripheral route. Thrombolytics and anticoagulants are considered the safest classes of drugs, with only one drug flagged as a “red flag” medication. However, a higher percentage of drugs in other categories meet the “red flag” criteria, including antiarrhythmics (52%), antiplatelet agents (67%), diuretics (67%), antihypertensives (70%), other drugs (77%), and vasoconstrictors and inotropics (89%). Understanding the physicochemical properties of cardiological drugs is essential for significantly improving patient safety and preventing administration errors and local side effects. Full article

Neurotrophic factors and reactive oxygen species (ROS) modulate neuronal plasticity. In a model of a lower motor neuron lesioned bladder, somatic nerve transfer was used as a reinnervation strategy. Levels of neurotrophins, ROS, and TNF-α in bladder mucosa and muscle layers collected from three groups of adult female dogs: (1) Decentralized, via bilateral transection of coccygeal and sacral spinal roots, lumbar 7 dorsal roots, and hypogastric nerves, then 6–21 mo recovery; (2) reinnervated (ObNT-Reinn), after similar decentralization for 12 mo, then bilateral obturator-to-vesical nerve transfer and 8–12 mo recovery; and (3) Controls. In mucosa, BDNF and ROS levels were highest in ObNT-Reinn bladders, GDNF and TNF-α levels were restored to Control levels in ObNT-Reinn bladders (lowest in Decentralized). NT-3 and ARTN were lower in ObNT-Reinn and Decentralized bladders versus Controls. In muscle, ROS was lower in ObNT-Reinn muscle versus Controls. BDNF mucosa levels correlated with bladder axonal density and detrusor layer thickness; and GDNF mucosal correlated with bladder contraction after vesical or transferred obturator nerve electrical stimulation, as did BDNF and GDNF muscle levels. The increased BDNF and GDNF in bladders that underwent somatic nerve transfer with subsequent recovery suggest that BDNF and GDNF may help promote the reestablishment of bladder innervation. Full article

Background and Objectives: The Vesical Imaging–Reporting and Data System (VI-RADS) represents a standardized approach for interpreting multiparametric magnetic resonance imaging (mp-MRI) in bladder cancer (BC) evaluation. This systematic review aimed to assess the VI-RADS’ diagnostic performance and interobserver agreement in distinguishing muscle-invasive from non-muscle-invasive BC, a crucial differentiation for treatment planning. Materials and Methods: A systematic literature search was conducted through PubMed, Google Scholar, and Web of Science, over an initial five-year time span, from VI-RADS’ inception (May 2018) to November 2023. Studies reporting VI-RADS’ diagnostic performance with histopathological confirmation and interobserver agreement data were included. The diagnostic accuracy was assessed using sensitivity and specificity, while interobserver agreement was evaluated using Cohen’s κ coefficient. Results: Nine studies comprising 1249 participants met the inclusion criteria. Using a VI-RADS score cutoff of ≥3, the pooled sensitivity and specificity for detecting muscle invasion were 88.2% and 80.6%, respectively. Interobserver agreement showed excellent consistency with a mean κ value of 0.82. Individual study sensitivities ranged from 74.1% to 94.6%, while specificities varied from 43.9% to 96.5%. Conclusions: VI-RADS demonstrates high diagnostic accuracy and excellent interobserver agreement in BC staging, supporting its role as a reliable non-invasive diagnostic tool. However, it should be used as a complementary tool to, not a replacement for, histopathological confirmation. Moreover, the variability in specificity suggests the need for standardized training and interpretation protocols. Clinical correlation and adequate reader experience are essential for optimal implementation. Future integration with pathological data may further enhance its predictive value. Full article

Background: Bladder leiomyomas are rare benign tumors (<0.5% of all bladder tumors) arising from the bladder wall’s smooth muscle. Only 250 cases of this condition have been reported worldwide so far. While some leiomyomas present with irritative or obstructive symptoms, hematuria, or nonspecific abdominal pain, others are asymptomatic and are diagnosed incidentally. The surgical approach is based on the leiomyoma’s size and location. Given this tumor’s rarity, standardized management guidelines do not exist; however, transurethral resection of bladder tumor (TURBT), partial or radical cystectomy, or laparoscopic/robotic enucleation are viable therapeutic options. Case history: We report the case of a 64-year-old female presenting with recurrent colic and pelvic pain. An abdominal CT scan showed a 3 cm mass protruding from the posterior bladder wall toward the right vaginal fornix. A transvaginal ultrasound-guided through-cut biopsy confirmed the diagnosis of a bladder leiomyoma. Due to the tumor’s size and location, robotic enucleation was chosen to minimize the risk of bladder perforation. The mass was successfully excised via a transvesical approach. Results: The procedure was completed in 210 min without complications, with 50 mL blood loss. The patient recovered well, with resolution of symptoms and no recurrence at eighteen-month follow-up. Histopathological examination on the surgical specimen confirmed the diagnosis of bladder leiomyoma. Conclusions: This case highlights the feasibility and safety of robotic enucleation for large bladder leiomyomas, emphasizing minimal invasiveness, limited pelvic dissection, and preservation of bladder function. Further research and standardized guidelines are needed for managing this rare condition. Full article

Background and Objectives: Abdominal compartment syndrome (ACS) is a severe clinical condition caused by intra-abdominal hypertension (IAH), often observed in surgical and trauma patients. However, ACS can also develop in non-surgical patients with massive ascites, leading to acute kidney injury (AKI) due to renal hypoperfusion. This study investigates the association between intra-abdominal pressure (IAP) changes, renal biomarkers, and mortality in patients with ACS-related AKI. Materials and Methods: A prospective cohort study was conducted on 24 hospitalized patients with ascites due to malignancy, cirrhosis, or heart failure. IAP was measured via the trans-vesical method on the first and seventh days of hospitalization. Serum and urinary biomarkers, including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-6 (IL-6), were assessed for their correlation with IAP changes. The primary outcome was in-hospital mortality, and the secondary outcomes included AKI progression and the effect of paracentesis on IAP reduction. Results: The overall in-hospital mortality rate was 50%. Patients who survived had significantly lower IAP on the seventh day compared to those who died (14.9 ± 3.5 mmHg vs. 20.2 ± 5.6 mmHg, p = 0.01). A 25% reduction in IAP was associated with improved kidney function and increased survival (p < 0.001). Urinary KIM-1 and serum NGAL levels showed a moderate correlation with IAP (r = 0.55, p = 0.02 and r = 0.61, p = 0.018, respectively), while IL-6 levels were significantly higher in non-survivors (p = 0.03). Paracentesis was associated with improved survival outcomes (p = 0.04). Conclusions: ACS is a critical but often overlooked cause of AKI in non-surgical patients with massive ascites. Lowering IAP significantly improves renal function and reduces mortality. Urinary KIM-1 and serum NGAL may serve as useful biomarkers for monitoring IAP changes. The early identification and management of IAH through timely interventions such as paracentesis and volume control strategies could improve patient outcomes. Full article

Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. Bronchoalveolar lavage fluid (BALF) was collected to measure total cells, protein, and cytokines. Lung injury, inflammatory signaling in alveolar macrophages (AMs), and matrix metalloproteinase-9 (MMP-9) activity were assessed via histological analysis, immunoblotting, and gelatin zymography, respectively. Results: CEES exposure led to an increase in immune cell infiltration, pro-inflammatory cytokines (IL-6 and TNF-α), and pro-MMP9 levels in the BALF, which were significantly decreased by HU308 treatment. The activation of CB2R attenuated CEES-induced NF-κB activation and reduced pro-inflammatory M1 markers (iNOS, and Cox-2) but did not alter the increase in the M2 marker arginase-1. CB2R activation mitigated CEES-induced oxidative stress, as evidenced by lower levels of heme oxygenase-1 (HO-1) and reactive oxygen species (ROS) in mouse AMs. Additionally, 4-hydroxynonenal (4-HNE) levels were reduced in the lungs of HU308-treated mice but were elevated after CEES exposure. Conclusions: These findings suggest that CB2R activation alleviates CEES-induced ALI and inflammation in mice, supporting its potential as a therapeutic approach for vesicant-induced pulmonary injury. Full article

Background/Objectives: We have demonstrated in human cadavers and canines that nerve transfer to bladder vesical nerve branches is technically feasible for bladder reinnervation after nerve injury. We further clarify here that sacral (S) ventral rami contribute to these vesical branches in 36 pelvic sides (in 22 human cadavers). Methods: Gross post-mortem visualization and open anterior abdominal approaches were used, as was micro-CT of sacral nerve bundles, for further confirmation when needed. Results: Considerable between and within-subject variation was observed. Sacral (S) ventral rami contributions to vesical nerves were observed as shared contributions from several rami or, in a few cases, from single rami: S2 alone (6%), S3 alone (6%), S2 and S3 (28%), S3 and S4 (28%), S2–S4, 14%, L5 in combination with S1–S4 (6%), S1 and S2 (6%), and S3–S5 (3%). The most common contributor to these shared or single rami contributions was from the S3 ventral ramus, which contributed 100% of the time on the left side and 79% on the right side. Side-to-side asymmetry was observed in 10 of 14 cadavers examined bilaterally (71%). Conclusions: This characterization of the anatomical variation in sacral ventral rami contributions to the bladder will ultimately aid in developing therapeutics for patients with bladder dysfunction. Full article

Sulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In order to identify relevant biomarkers and to obtain a deeper understanding of the underlying biochemical events, we performed an untargeted metabolomics analysis using liquid chromatography coupled to high-resolution mass spectrometry of plasma samples from New Zealand white rabbits ocularly exposed to vapors of SM. Metabolic profiles (332 unique metabolites) from SM-exposed (n = 16) and unexposed rabbits (n = 8) were compared at different time intervals from 1 to 28 days. The observed time-dependent changes in metabolic profiles highlighted the profound dysregulation of the sulfur amino acids, the phenylalanine, the tyrosine and tryptophan pathway, and the polyamine and purine biosynthesis, which could reflect antioxidant and anti-inflammatory activities. Taurine and 3,4-dihydroxy-phenylalanine (Dopa) seem to be specifically related to SM exposure and correspond well with the different phases of ocular damage, while the dysregulation of adenosine, polyamines, and acylcarnitines might be related to ocular neovascularization. Additionally, neither cysteine, N-acetylcysteine, or guanine SM adducts were detected in the plasma of exposed rabbits at any time point. Overall, our study provides an unprecedented view of the plasma metabolic changes post-SM ocular exposure, which may open up the development of potential new treatment strategies. Full article

Background: Gross Hematuria is a relevant cause of admission to the emergency department in the general population and particularly in older adults (≥80 years). This specific urological symptom is often underestimated and usually associated with benign conditions such as urinary infections or poor hydration. Nevertheless, hematuria could lead to severe acute complications or be the first symptom of urological cancers. Methods: We retrospectively analyzed clinical data from 1169 patients aged ≥80 years consecutively admitted to the emergency department for hematuria. The primary endpoint of the study was to identify risk factors for major complications, and the secondary endpoint was to analyze risk factors for urological cancer diagnosis. The median age was 85 years (IQR 82–88 years), and 908 (77%) were males. Among them, 449 (38.4%) had a past medical history of urological neoplasm (kidney, ureter, bladder, prostate, or urethral cancer). Results: Overall, 87 patients (7.4%) had major complications (patient death, septic shock, and admission to the intensive care unit). Worse vital signs at admission, fever, and confusion (p < 0.001, OR 18.0 IC 95% [5.5–58.7]; p = 0.015, OR 2.0 IC 95% [1.1–3.5]; p = <0.001, OR 4.2 IC 95% [1.9–3.5], respectively), as well as lower hemoglobin values and higher Charlson comorbidity index (p < 0.001, OR 0.8 IC 95% [0.7–0.9]), p = 0.002, OR = 1.2 [1.1–1.3]) were independent predictive factors for major complications. The multivariate analysis identified as risk factors for diagnosis of urological cancer older age, male sex and higher comorbidity (OR 1.05 IC95% [1–1.09]; OR 2.19 IC95% [1.42–3.39] and OR 1.11 IC95% [1.2–1.2], respectively); interestingly the presence of indwelling vesical catheter (IVC) (OR 0.44 IC95% [0.24–0.82]) resulted as an independent factor for absence of urological cancers. Conclusions: Hematuria is a frequent symptom in older adults admitted to the emergency department. While this is often associated with benign conditions, there are some risk factors for major complications and for urological cancer that must be taken into account to identify the patients who need further evaluation or prompt hospital admission. Full article

Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette–Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy’s role in BC management, ultimately improving patient outcomes. Full article