Search

Intraventricular hemorrhage (IVH) occurs in approximately 30–50% patients with spontaneous intracerebral hemorrhage (ICH), with a high 30-day mortality rate. Excess accumulation of parenchymal or ventricular blood associated with the development of acute hydrocephalus leads to poor outcomes. The prediction of shunt dependency is important to identify patients susceptible to requiring permanent shunt placement and benefit from the diversion. This retrospective analytical study aimed to establish a predictive model of shunt dependency in patients with IVH. This study included 179 patients with primary IVH with supratentorial origin or spontaneous ICH with extension into the ventricles between 2015 and 2021. Patients were grouped into "shunt required" and "shunt not required" groups. Variables, including age, sex, preexisting hypertension and diabetes, initial Glasgow Coma Scale scores, ICH location and volume, urokinase administration, modified Graeb score (mGraeb score), and bicaudate index, were analyzed. The shunt required group had significantly higher mGraeb scores (12.0 (6.5–15.0) vs. 7.0 (4.0–12.0), p = 0.001) and higher bicaudate index (0.20 (0.17–0.23) vs. 0.16 (0.13–0.18), P < 0.001) than the shunt not required group. The receiver operating characteristic curve (ROC curve) analysis revealed that a cut-off value of 0.16 of the bicaudate index was significantly related to shunt dependency. The subgroup statistical analysis revealed that neither urokinase administration (p = 0.533) nor urokinase dosage (p = 0.117) showed significant relevance in shunt dependency in patients who received external ventricular drainage. In logistic regression adjusted for the confounders, thalamic ICH (odds ratio (OR) 3.55; 95% confidence interval [(95%CI), 1.13–11.18], an mGraeb score greater than 8 (OR, 3.93; 95%CI, 1.84–8.38), and a bicaudate index greater than 0.16 (OR, 9.87; 95%CI, 3.79–25.73) were factors associated with a higher tendency for shunting. The findings of this study may help identify patients at risk for a permanent shunt after IVH. [ABSTRACT FROM AUTHOR]

Pulmonary congestion (PC) is common in hemodialysis (HD) patients. We explored the association of anemia and pulmonary congestion in HD patients. A prospective pilot observational study included 18 patients on maintenance HD. Individual B-lines scores (BLS; 8-sites method) were obtained by lung ultrasound, before and after the first two consecutive HD sessions of the week (HD1-HD2), with different inter-dialytic intervals (68 vs. 44 h). Bioimpedance spectroscopy body composition (BIS) was performed before each HD session. Hemoglobin (Hb) levels, in addition to circulating markers of chronic inflammation (soluble urokinase Plasminogen Activator Receptor [suPAR], soluble Suppression of Tumorigenicity 2 [sST2]) were obtained. Mean (±SD) BLS values were quite elevated at all time points: Pre-HD1 (16 ± 5.53), post-HD1 (15.3 ± 6.63), pre-HD2 (16.3 ± 5.26) and post-HD2 (13.6 ± 5.83), respectively. No direct significant correlation was found between inflammation markers levels and BLS. However, mean levels (±SD, ng/mL) of suPAR pre-HD1 (7.88 ± 3.07) and pre-HD2 (7.78 ± 3.02) remained significantly above the normal range (<4 ng/mL), and sST2 levels reached 2-fold the upper normal value in most patients (27.4 ± 17.8). Pulmonary congestion reflected by BLS was negatively correlated to Hb levels pre-HD1 (R² = 0.439, p = 0.003), and pre-HD2 (R² = 0.301, p = 0.018). In addition, Hb levels were negatively correlated to global volume status estimated by BIS (R² = 0.351, p = 0.009). Hemoglobin levels were negatively correlated to pulmonary congestion and to the global volume status evaluated by BIS. Chronic inflammation markers were increased in HD patients, suggesting a complex volume- and non-volume-dependent pathophysiology of pulmonary congestion in HD patients. [ABSTRACT FROM AUTHOR]

Endothelial injury indices, such as Endothelial Activation and Stress Index (EASIX), modified EASIX (m-EASIX), and simplified EASIX (s-EASIX) scores, have been previously associated with chimeric antigen receptor-T (CAR-T) cell immunotherapy complications. Soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor-15 (GDF-15), and soluble C5b-9 (sC5b-9) have been described as markers of endothelial injury post-hematopoietic stem cell transplantation. In the current study, we examined whether suPAR, GDF-15, and sC5b-9 levels were associated with endothelial injury indices in adult CAR-T cell recipients. The levels of these markers were measured in patients before CAR-T cell infusion and in healthy individuals with immunoenzymatic methods. We studied 45 CAR-T cell recipients and 20 healthy individuals as the control group. SuPAR, GDF-15, and sC5b-9 levels were significantly higher in the patients' group compared to the healthy control group (p < 0.001, in all comparisons). SuPAR levels at baseline were associated with the m-EASIX scores calculated at the same time point (p = 0.020), while suPAR and GDF-15 concentrations were correlated with EASIX scores at day 14 post-infusion (p < 0.001 in both comparisons). Moreover, sC5b-9 levels were correlated with the s-EASIX scores at infusion (p = 0.008) and the EASIX scores at day 14 (p = 0.005). In our study, sC5b9, suPAR, and GDF-15 levels were found to reflect endothelial injury in CAR-T cell recipients. [ABSTRACT FROM AUTHOR]

Background: Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings. Methods: This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents. Results: Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons. Conclusions: In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations. [ABSTRACT FROM AUTHOR]

Objective • To evaluate the effectiveness of urokinase and heparin in preventing catheter infection and dysfunction in permanent hemodialysis tunneled cuffed catheters. Methods • We randomized 153 cases of maintenance hemodialysis patients with newly implanted permanent hemodialysis tunneled cannula catheters from November 2018 to November 2021 for this single-center prospective randomized controlled trial The eligible patients were given one of two treatment plans: Patients in the control group (73 patients) were given heparin (6260 U/mL)three times a week after hemodialysis. The intervention group (80 cases) was administered urokinase(25000 U/mL) on the basis of heparin. After six months of maintenance hemodialysis with the above sealing protocols, the primary result was the frequency of catheter malfunction, and the secondary outcome was the frequency of catheter-associated infection. Results • In the final analysis of 153 patients, catheter malfunctions occurred in 29 of the 80 patients assigned to heparin alone, with an incidence of 36.3%, and 16 of the 73 subjects assigned to urokinase combined with heparin, with a rate of 21.9%. This represents an almost 2-fold increase in the risk of catheter malfunction among patients treated with heparin alone as compared to those treated with urokinase once weekly (hazard ratio, 1.85; 13 patients (16.3%) allocated to heparin alone experienced catheter- related bacteremia, compared to 4 patients (5.5%) assigned to urokinase (hazard ratio, 2.79; 95%CI, 1.08 to 7.22; P = .03). Baseline levels, and adverse events, including bleeding incidents, did not statistically differ between the two groups. Conclusion • Urokinase can be used as a secondary prevention drug for long-term catheter malfunction and infection based on its cheapness, efficacy, and safety, which can effectively save medical costs, and its sealing protocol is simple and suitable for promotion. [ABSTRACT FROM AUTHOR]

Background/Objectives: The incidence of acute kidney injury (AKI) has been steadily increasing. Despite its high prevalence, there is no pathogenetically rational therapy for AKI. This deficiency stems from the poor understanding of the pathogenesis of AKI. Renal ischemia/hypoxia is one of the leading causes of clinical AKI. This study investigates whether αMUPA mice, overexpressing the urokinase plasminogen activator (uPA) gene are protected against ischemic AKI, thus unraveling a potential renal damage treatment target. Methods: We utilized an in vivo model of I/R-induced AKI in αMUPA mice and in vitro experiments of uPA-treated HEK-293 cells. We evaluated renal injury markers, histological changes, mRNA expression of inflammatory, apoptotic, and autophagy markers, as compared with wild-type animals. Results: the αMUPA mice exhibited less renal injury post-AKI, as was evident by lower SCr, BUN, and renal NGAL and KIM-1 along attenuated adverse histological alterations. Notably, the αMUPA mice exhibited decreased levels pro-inflammatory, fibrotic, apoptotic, and autophagy markers like TGF-β, IL-6, STAT3, IKB, MAPK, Caspase-3, and LC3. By contrast, ACE-2, p-eNOS, and PGC1α were higher in the kidneys of the αMUPA mice. In vitro results of the uPA-treated HEK-293 cells mirrored the in vivo findings. Conclusions: These results indicate that uPA modulates key pathways involved in AKI, offering potential therapeutic targets for mitigating renal damage. [ABSTRACT FROM AUTHOR]

There are no effective therapies to prevent preeclampsia (PE). Pravastatin shows promise by attenuating processes associated with PE such as decreased cytotrophoblast (CTB) migration, aberrant angiogenesis, and increased oxidative stress. This study assesses the effects of pravastatin on hyperglycemia-induced CTB dysfunction. Methods: Human CTB cells were treated with 100, 150, 200, 300, or 400 mg/dL glucose for 48 h. Some cells were pretreated with pravastatin (1 µg/mL), while others were cotreated with pravastatin and glucose. The expression of urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) mRNA, vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin (sEng) were measured. CTB migration was assayed using a CytoSelect migration assay kit. Statistical comparisons were performed using an analysis of variance with Duncan's post hoc test. Results: The hyperglycemia-induced downregulation of uPA was attenuated in CTB cells pretreated with pravastatin at glucose levels > 200 mg/dL and cotreated at glucose levels > 300 mg/dL (p < 0.05). Hyperglycemia-induced decreases in VEGF and PlGF and increases in sEng and sFlt-1 were attenuated in both the pretreatment and cotreatment samples regardless of glucose dose (p < 0.05). Pravastatin attenuated hyperglycemia-induced dysfunction of CTB migration. Conclusions: Pravastatin mitigates stress signaling responses in hyperglycemic conditions, weakening processes leading to abnormal CTB migration and invasion associated with PE in pregnancy. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of neuronavigation-assisted stereotactic drilling drainage compared with that of craniotomy in the treatment of massive intracerebral haemorrhage (ICH) in elderly patients. This was a randomized, controlled, blind endpoint clinical study. Elderly patients with massive ICH treated at our neurosurgery department, without the formation of brain herniation preoperatively, all underwent neurosurgical intervention. Patients were randomly assigned to two groups: the minimally invasive surgery (MIS) group, which received neuronavigation-assisted stereotactic drilling drainage, and the craniotomy haematoma removal surgery (CHRS) group. Patient characteristics, surgical anaesthesia methods, surgery duration, intraoperative bleeding volume, duration of ICU stay duration of hospital stay, complications, and modified Rankin scale (mRS) scores at 90 days posttreatment were compared between the two groups. Statistical analysis was performed on the collected data. A total of 67 patients were randomly assigned, with 33 (49.25%) in the MIS group and 34 (50.75%) in the CHRS group. Compared with the CHRS group, the MIS group had advantages, including the use of local anaesthesia, shorter surgery duration, less intraoperative bleeding, shorter ICU stay, and fewer complications (P < 0.05). The MIS group had a significantly improved patient prognosis at 90 days (mRS 0–3). However, there were no significant differences in hospital stay or 90-day survival rate between the two groups (P > 0.05). For elderly patients with massive ICH without brain herniation, stereotactic drilling drainage is a simple surgical procedure that can be performed under local anaesthesia. Patients treated with this approach seem to have better outcomes than those treated with craniotomy. In clinical practice, neuronavigation-assisted stereotactic drilling drainage is recommended for surgical treatment in elderly patients with massive ICH without brain herniation. Clinical trial registration number: NCT04686877 [ABSTRACT FROM AUTHOR]

Introduction. Prompt resolution of arteriovenous fistula (AVF) thrombosis is essential to minimize the need for temporary dialysis catheters. Identifying the ideal timing for the management of thrombosed arteriovenous fistula (AVF) is an area that has not been thoroughly explored. Herein, we examined a local infusion of urokinase for thrombolysis followed by ultrasound-guided percutaneous transluminal balloon angioplasty (PTA) in acute and subacute AVF thromboses. Methods. This retrospective cohort research assessed thrombosed AVF in patients referred to the Second Xiangya Hospital. We included patients who underwent local thrombolysis followed by ultrasound-guided PTA treatment between January 1, 2018, and January 1, 2020. Results. We enrolled the records of 86 patients into the present study, including 44 patients with acute AVF thrombosis (group 1: thrombus age, < 72 hours) and 42 patients with subacute AVF thrombosis (group2: thrombus age, 72 hours to seven days). The thrombolytic success rate was 79.5% in group 1 and 42.9% in group 2 (P < .001). All patients underwent ultrasound-guided PTA to dissolve any residual thrombi regardless of thrombolytic success. Technical success after PTA procedures was achieved in 93.2% of patients in group 1 and 88.1% in group 2 (P = .417). Primary patency at six months was comparable between the two groups (67.5% vs. 64.8%, P = .564). We observed that thrombolytic effect does not affect PTA success rate, and six-month patency rate. Conclusion. Direct local infusion of urokinase to the affected area followed by ultrasound-guided PTA constitutes a minimally invasive and effective method for salvaging thrombosed AVF in contrast to abandoning the occluded fistula. [ABSTRACT FROM AUTHOR]

Purpose: To investigate and compare the efficacy of two different types of thrombolysis combined with percutaneous transluminal angioplasty (PTA) for acute thrombosis in arteriovenous fistula (AVF) and graft (AVG). Methods: A total of 128 patients on hemodialysis with acute AVF/AVG occlusion, from May 2021 to May 2023 at Jiangmen Central Hospital, Guangdong, were randomly assigned to study group (catheterdirected thrombolysis) (CDT) comprising of 62 patients and control group (scalp needle thrombolysis) comprising of 66 patients. Patients whose thrombolysis was unsuccessful on the first day, received PTA therapy the next day. Thrombolytic success rates, urokinase dosage, PTA therapy rates, mural thrombus occurrence, and post-thrombolytic complications were evaluated and compared. Result: There was no significant difference in overall thrombolytic success rate, PTA combination rate and incidence of hemorrhage (p > 0.05) between study and control groups. Recanalization rate after urokinase thrombolytic therapy on first day was significantly higher in the study group than in the control group (p < 0.05). Urokinase dosage (first day) of patients whose thrombolytic therapy was successful was significantly lower in the study group than in the control group (p < 0.001). Conclusion: Mechanical fragmentation by angiography catheter combined with urokinase thrombolysis improves efficacy, but shows no advantage when combined with PTA. Additional studies using a larger patient population on anticoagulant therapy and longer investigation time are recommended to enhance the generalizability of this treatment approach. [ABSTRACT FROM AUTHOR]

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated Pseudomonas toxin. Its purpose was to simultaneously target tumors and their vasculature in the tumor microenvironment. In prior studies on mice and dogs, the drug proved efficacious. Here, we report the safety of eBAT in normal wildtype, uPAR knockout, and immunoreplete and immunodeficient tumor-bearing mice, as well as in dogs with spontaneous sarcoma that more closely mirror human cancer onset. In immunocompetent mice, tumor-bearing mice, uPAR knockout mice, and mice receiving species-optimized eBAT, toxicities were mild and self-limiting. Likewise, in dogs with life-threatening sarcoma given dosages found to be biologically active, eBAT was well tolerated. In mice receiving higher doses, eBAT was associated with dose-dependent evidence of liver injury, including portal biliary hyperplasia, oval cell proliferation, lymphoplasmacytic inflammation, periportal hepatocellular microvesicular change, hemorrhage, necrosis, and apoptosis. The results support continuing the clinical development of eBAT as a therapeutic agent for individuals with sarcoma and other cancers. [ABSTRACT FROM AUTHOR]

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients' coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA. [ABSTRACT FROM AUTHOR]

Hemodialysis (HD) patients are at high risk of cardiovascular disease and death. Reliable biomarkers for risk stratification and detection of acute myocardial infarction (AMI) are therefore pivotal. Cardiac troponins (cTn) are the preferred biomarkers for AMI. It remains unclear, if cTn concentrations changes as a consequence of HD treatment itself during dialysis. In this study, cTn was compared with soluble urokinase plasminogen activator receptor (suPAR) and Beta-2-microglobulin (B2M). We performed a prospective study including 17 HD patients measuring high-sensitive cardiac troponin t (hs-cTnT), suPAR and B2M before and after a dialysis session and verified the results in a random subgroup of eight patients from the group by repeating their measurements before and after a dialysis session 15 weeks later. Biomarker concentrations after dialysis were adjusted according to hemodilution or concentration according to the hemoglobin concentration. The average hs-cTnT concentration decreased significantly by −9.9% after dialysis (95% CI: −13.6% to −6.2%). The average (paired) difference were − 6.7 ng/L (p = 0.0104) after dialysis comparing 25 HD treatment occasions. SuPAR was not significantly influenced by dialysis. B2M decreased by −58% after HD as an expected result from the molecular size of the biomarker. The hs-cTnT in average decreased by −9.9% after dialysis. This is a diagnostic challenge since the current guidelines suggest a 20% change in hs-cTnT in patients with acute myocardial infarction. Larger prospective studies investigating the different factors influencing hs-cTnT after HD are warranted. Adjusting biomarker concentrations according to hemodilution or concentration using the hemoglobin concentration, should be considered in future studies to determine more exact changes in concentrations of cTnT and other relevant biomarkers. [ABSTRACT FROM AUTHOR]

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry‐based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75.4 years), higher medication use (7.0; 71.3% with polypharmacy) and more blood tests outside reference intervals (5.0) (including C‐reactive protein, neutrophils and albumin), and the most common diagnoses were chronic pulmonary disease (27.6%), cerebrovascular disease (18.4%) and dementia (11.5%). Patients with low suPAR were more morbid than what was reflected by suPAR alone. Future studies must determine which factors that contribute the most to potential algorithms when stratifying patients based on their risk of adverse clinical outcomes. These data indicate that inclusion of medication data could be relevant. [ABSTRACT FROM AUTHOR]

Purpose of the study. Is to determine the features in the content and activity of some components of the plasminogen activation system in the blood of patients of different ages with leiomyomas (LM) and uterine corpus endometrial cancer (UCEC).Patients and methods. The study was carried out in patients with LM (n = 35) and UCEC T1a-2N0M0 (n = 56) of reproductive, perimenopausal and postmenopausal ages. Using ELISA methods, the content and activity of urokinase (u-PA), tissue plasminogen activator (t-PA), their inhibitor PAI-1, as well as the content of the soluble form of the u-PA receptor (su-PAR) were determined in the blood of patients. The Student´s test was used for statistical processing.Results. Regardless of the nature of the uterus tumor, it has been noted a significant increase in the activity and blood level of PAI-1 (up to 8 times, p < 0.01), especially pronounced in patients with UCEC of reproductive age. It was combined with the absence of changes or with a decreasing in blood level of su-PAR by more than 40 % (p < 0.05). We observed a rise of u-PA blood level without changes in one´s activity in patients with LM of perimenopausal age. And in patients with LM and UCEC of postmenopausal age an increase in u-PA blood level as well as elevation of u-PA activity (up to 3.9 times, p < 0.01–0.05) were noted. There was an increase in the calculated t-PA index (activity per unit mass) by 1.4–2.8 times (p < 0.05) in the most patients. The indicators of LM patients were characterized by the minimum value of the ratio “t-PA activity/u-PA activity in the blood” among all studied subgroups of patients. Age-related features of the researched parameters were observed more often in the cases of LM than in the cases of UCEC. The most pronounced differences between LM and UCEC were observed in patients of reproductive and postmenopausal age, characterized by stable hormonal levels.Conclusion. The participation of the plasminogen activation system in the pathogenesis of tumor lesions of the uterine body has been shown. The system’s “response” to the development of tumors in the uterus has both general characteristics and features that depend on the nature of the tumors and on the age-specific hormonal regulation of the body, which are most pronounced in postmenopausal women. The results obtained can be used in research aimed at clarifying the targets of targeted therapy for LM and UCEC in accordance with the age of patients.

Objective: The present study compared interleukin 1-beta (IL-1β) and soluble urokinase plasminogen activation factor receptor (suPAR) levels in peri-implant sulcular fluid of patients with cement-retained and screw-retained implants. Method and materials: Patients with cement-retained and screw-retained implants were included. Demographic data were collected, and implant-related characteristics (geometry, insertion torque, loading and retention protocol, arch location, duration in function, and depth of insertion) were retrieved from records. Modified Plaque Index, crestal bone loss, probing depth, and modified Bleeding Index were measured. suPAR and IL-1β levels were assessed in peri-implant sulcular fluid. Statistical comparisons were done and correlation between clinicoradiographic parameters and peri-implant sulcular fluid IL-1β and suPAR were assessed. Statistical significance was judged at P < .05. Results: Clinical and radiographic parameters showed no difference among screw-retained and cement-retained implants. There was no difference peri-implant sulcular fluid volume among patients with cement-retained (0.22 ± 0.00 μL) and screw-retained (0.19 ± 0.005 μL) implants. Levels of IL-1β and suPAR in patients with cement-retained and screw-retained implants were 50.08 ± 0.6 ng/mL and 44.6 ± 0.08 ng/mL, and 0.28 ± 0.05 ng/mL and 0.22 ± 0.006 ng/mL, respectively. Conclusion: Implants with cement-retained or screw-retained restorations are comparable to one another in terms of clinicoradiographic status and demonstrate IL-1β and suPAR levels within the normal range in the peri-implant sulcular fluid provided oral hygiene is stringently maintained. [ABSTRACT FROM AUTHOR]

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients’ coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA.

Background Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-to-head controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. Methods A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. Results A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean± standard deviation changes in pleural opacity was –33.0%±9.9% in the UK group and –41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. Conclusion IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.

Fluorescence molecular imaging plays a vital role in image‐guided surgery. In this context, the urokinase plasminogen activator receptor (uPAR) is an interesting biomarker enabling the detection and delineation of various tumor types due to its elevated expression on both tumor cells and the tumor microenvironment. In this study, anti‐uPAR Nanobodies (Nbs) are generated through llama immunization with human and murine uPAR protein. Extensive in vitro characterization and in vivo testing with radiolabeled variants are conducted to assess their pharmacokinetics and select lead compounds. Subsequently, the selected Nbs are converted into fluorescent agents, and their application for fluorescence‐guided surgery is evaluated in various subcutaneous and orthotopic tumor models. The study yields a panel of high‐affinity anti‐uPAR Nbs, showing specific binding across multiple types of cancer cells in vitro and in vivo. Lead fluorescently‐labeled compounds exhibit high tumor uptake with high contrast at 1 h after intravenous injection across all assessed uPAR‐expressing tumor models, outperforming a non‐targeting control Nb. Additionally, rapid and accurate tumor localization and demarcation are demonstrated in an orthotopic human glioma model. Utilizing these Nbs can potentially enhance the precision of surgical tumor resection and, consequently, improve survival rates in the clinic. [ABSTRACT FROM AUTHOR]

Pleural effusion is the most common manifestation of pleural disease, and chest ultrasound is crucial for diagnostic workup and post-treatment monitoring. Ultrasound helps distinguish the various types of pleural effusion and enables the detection of typical manifestations of empyema, which presents as a complicated, septated effusion. This may benefit from drainage and the use of intrapleural enzyme therapy or may require more invasive approaches, such as medical or surgical thoracoscopy. The mechanism of action of intrapleural enzymatic therapy (IPET) is the activation of plasminogen to plasmin, which breaks down fibrin clots that form septa or the loculation of effusions and promotes their removal. In addition, IPET has anti-inflammatory properties and can modulate the immune response in the pleural space, resulting in reduced pleural inflammation and improved fluid reabsorption. In this article, we briefly review the literature on the efficacy of IPET and describe a case series in which most practical applications of IPET are demonstrated, i.e., as a curative treatment but also as an alternative, propaedeutic, or subsequent treatment to surgery. [ABSTRACT FROM AUTHOR]

• First systematic review looking at suPAR as a biomarker in a psychiatric population. • Primary analyses showed elevated suPAR levels in those with depressive disorder. • Secondary analysis showed elevated plasma suPAR levels in those with schizophrenia. • Two studies found no difference in serum suPAR levels between groups. • Chronic inflammatory dysregulation may contribute to the pathogenesis of these disorders. There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants. Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately. The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [−0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [−0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [−1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of minimally invasive thoracic catheterization assisted with urokinase combined with dexamethasone on serum T lymphocyte related cytokines and fibrinolytic activity in patients with tuberculous pleurisy. METHODS: A total of 90 patients with tuberculous pleurisy admitted into the hospital from Apr. 2019 to Apr. 2023 were extracted to be divided into the dexamethasone group and combined group via the random number table method, with 45 cases in each group. Patients in the dexamethasone group were treated with minimally invasive thoracic catheterization assisted with dexamethasone, while the combined group received minimally invasive thoracic catheterization assisted with urokinase combined with dexamethasone. The improvement of clinical symptoms and pleural thickness of two groups were compared. Levels of lung function [ maximum expiratory flow (MEF), forced vital capacity ( FVC) and forced expiratory volume in one second ( FEV1 )], hypersensitive C-reactive protein ( hs-CRP ) and tumor necrosis factor ( TNF-α), T lymphocyte CD4+ and CD3+, tissue type plasminogen activator (t-PA) / plasminogen activator inhibitor 1 (PAI-1) and type Ⅲ procollagen (PC-Ⅲ) levels of two groups were detected, the therapeutic effects of two groups were compared. RESULTS: The disappearance time of chest tightness, pleural effusion and fever in combination group was shorter than that in dexamethasone group, and the pleural thickness was lower than that in dexamethasone group, with statistically significant differences (P < 0. 05). After treatment, the levels of MEF, FVC and FEV1 in combined group were higher than those in dexamethasone group, the levels of hs-CRP, TNF-α and PC-Ⅲ were lower than those in dexamethasone group, and the levels of CD4+, CD3+ and t-PA/ PAI-1 were higher than those in dexamethasone group, with statistically significant differences (P< 0. 05). The total effective rate of combined group was 95. 56% (43 / 45), higher than 80. 00% (36 / 45) of dexamethasone group, the difference was statistically significant ( P < 0. 05 ). CONCLUSIONS: The efficacy of minimally invasive thoracic catheterization assisted with urokinase combined with dexamethasone in the treatment of patients with tuberculous pleurisy is significant, which can effectively reduce the clinical symptoms, improve lung function, reduce inflammation, and improve immune function and fibrinolytic activity. [ABSTRACT FROM AUTHOR]

Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through intensive research. The urokinase plasminogen activator receptor (uPAR) is part of the plasminogen activator system and possesses inflammatory, angiogenetic, and fibrinolytic capabilities. As a first, this study aims to identify uPAR in the hematoma fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH and, if present, to investigate if the uPAR level at the time of surgery may be a predictor for later developing recurrent CSDH. uPAR expression in the hematoma membrane and dura mater was analyzed using immunohistochemistry and presented as the H-score of the positive immunostaining. The uPAR levels in the hematoma fluid and systemic blood were determined using a multiplex antibody bead kit (Luminex). Samples were collected at the time of the first CSDH surgery, and in the case of recurrent CSDH within 90 days, the samples were again collected at reoperation. A comparison of uPAR expression between the hematoma membrane and dura mater, as well as uPAR levels in systemic blood and hematoma fluid, was performed using the Wilcoxon rank sum test. We included 112 patients, 26 of whom had recurrent CSDH. The median hematoma uPAR level was 22,125 (14,845–33,237) and significantly higher than the median systemic blood level of 789 pg/L (465–2,088) (p < 0.001). Similarly, the uPAR level of the hematoma membrane was 14.3 (7.54–44.8) and significantly higher than the dural uPAR level of 0.81 (0.3–1.98) (p < 0.001). For the first time, we identified uPAR in the subdural fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH. The high expression of uPAR in the subdural fluid and hematoma membrane indicates that the mechanisms of CSDH are predominantly in the subdural fluid collection and surrounding hematoma membrane. [ABSTRACT FROM AUTHOR]

Objective To investigate and compare the efficacy of endoscopic-assisted hematoma evacuation and burr hole hematoma drainage combined with urokinase in the treatment of septated chronic subdural hematoma (CSDH). Methods A total of 38 patients with septated CSDH who were admitted in Peking Union Medical College Hospital and received endoscopic-assisted hematoma evacuation (endoscopy group, n = 19) or burr hole drainage combined with urokinase (burr hole group, n = 19) from January 2022 to December 2023. The change rate of the hematoma cavity was calculated, the modified Rankin Scale (mRS) and Barthel Index (BI) were used to evaluate neurological function prognosis and abilities of daily living. In addition, postoperative drainage time, postoperative hospitalization time, total hospitalization cost and incidence of cerebrospinal fluid leakage were recorded. Results The two treatment modalities did not show differences in the change rate of the hematoma cavity (t = 0.858, P = 0.396). Both endoscopy group (Z = -4.116, P = 0.000) and burr hole group (Z = -4.195, P = 0.000) had lower mRS scores on discharge than on admission, while the difference between the 2 groups on discharge was not significant (Z = -0.502, P = 0.616). The endoscopy group (Z = -1.557, P = 0.119) and burr hole group (Z = -0.091, P = 0.928) had no significant difference in BI scores on discharge versus on admission, and the difference in BI scores between the 2 groups on discharge was also not statistically significant (Z = -0.853, P = 0.394). Postoperative drainage time was longer in the endoscopy group (t = -2.488, P = 0.018), but postoperative hospitalization time was longer in the burr hole group (t = -3.894, P = 0.000). Total hospitalization cost in both 2 groups (t = 1.175, P = 0.248) and the incidence of cerebrospinal fluid leakage (Fisher's exact probability: P = 0.313) were not statistically significant. Conclusions Both neuroendoscopic surgery and burr hole drainage combined with urokinase treatment are safe and effective in treating septated CSDH. They can clear the hematoma and improve neurological function; neuroendoscopic surgery can faster improve the neurological function and shorter postoperative hospitalization time. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to introduce a cost-effective and less invasive method for the evacuation of intraparenchymal hemorrhage (IPH).

Objective To investigate the treatment methods and efficacy of acute pulmonary embolism. Methods The diagnosis and treatment information of 8 patients with APE secondary to pelvic vein thrombosis admitted by the Changsha First Hospital from 2020 to 2021 were recorded and analyzed. All patients treated with temporary inferior vena cava filter combined with catheter contact thrombolysis. The prognosis was analyzed after the 3-month follow-up. Results After treatment, Arterial partial pressure of oxygen increased from （52.83±4.18） mmHg to （92.34±6.12） mmHg （t=33.221, P＜0.01）, and blood oxygen saturation increased from (80.83±5.34)% to (96.12±4.11)% （t=13.853, P＜0.01）. The shock index and Miller's score significantly decreased. All patients recovered and were discharged, with an average hospital stay of 17.5 days. The recovery rate of the temporary inferior vena cava filter was 100%, with an average recovery time of 3.38 weeks. After 3 months, pulmonary artery CTA showed a 100% patency rate of the pulmonary artery tunk. Conclusion The combination of temporary inferior vena cava filter and catheter contact thrombolysis is a safe and effective treatment for acute pulmonary embolism secondary to pelvic vein thrombosis.

Objective: Minimally invasive surgery for spontaneous intracerebral hemorrhage is impeded by inadequate lysis of the target blood clot. Ultrasound is thought to expedite intravascular thrombolysis, thereby facilitating vascular recanalization. However, the impact of ultrasound on intracerebral blood clot lysis remains uncertain. This study aimed to explore the feasibility of combining ultrasound with urokinase to enhance blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage. Methods: The blood clots were divided into four groups: control group, ultrasound group, urokinase group, and ultrasound + urokinase group. Using our experimental setup, which included a key-shaped bone window, we simulated a minimally invasive puncture and drainage procedure for spontaneous intracerebral hemorrhage. The blood clot was then irradiated using ultrasound. Blood clot lysis was assessed by weighing the blood clot before and after the experiment. Potential adverse effects were evaluated by measuring the temperature variation around the blood clot in the ultrasound + urokinase group. Results: A total of 40 blood clots were observed, with 10 in each experimental group. The blood clot lysis rate in the ultrasound group, urokinase group, and ultrasound + urokinase group (24.83 ± 4.67%, 47.85 ± 7.09%, 61.13 ± 4.06%) was significantly higher than that in the control group (16.11 ± 3.42%) (p = 0.02, p < 0.001, p < 0.001). The blood clot lysis rate in the ultrasound + urokinase group (61.13 ± 4.06%) was significantly higher than that in the ultrasound group (24.83 ± 4.67%) (p < 0.001) or urokinase group (47.85 ± 7.09%) (p < 0.001). In the ultrasound + urokinase group, the mean increase in temperature around the blood clot was 0.26 ± 0.15°C, with a maximum increase of 0.38 ± 0.09°C. There was no significant difference in the increase in temperature regarding the main effect of time interval (F = 0.705, p = 0.620), the main effect of distance (F = 0.788, p = 0.563), or the multiplication interaction between time interval and distance (F = 1.100, p = 0.342). Conclusions: Our study provides evidence supporting the enhancement of blood clot lysis in an in vitro model of spontaneous intracerebral hemorrhage through the combined use of ultrasound and urokinase. Further animal experiments are necessary to validate the experimental methods and results. [ABSTRACT FROM AUTHOR]

Background: The role of the innate immune system has long been associated with Alzheimer's disease (AD). There is now accumulating evidence that the soluble Urokinase Plasminogen Activator Receptor pathway, and its genes, PLAU and PLAUR may be important in AD, and yet there have been few genetic association studies to explore this. Objective: This study utilizes the DNA bank of the Brains for Dementia Research cohort to investigate the genetic association of common polymorphisms across the PLAU and PLAUR genes with AD. Methods: TaqMan genotyping assays were used with standard procedures followed by association analysis in PLINK. Results: No association was observed between the PLAU gene and AD; however, two SNPs located in the PLAUR gene were indicative of a trend towards association but did not surpass multiple testing significance thresholds. Conclusions: Further genotyping studies and exploration of the consequences of these SNPs on gene expression and alternative splicing are warranted to fully uncover the role this system may have in AD. [ABSTRACT FROM AUTHOR]

Pediatric obesity and type 1 diabetes mellitus (T1DM) represent two common chronic diseases associated with chronic inflammation, endothelial dysfunction and long-term complications. The aim of the present study was to assess the possible diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation and impaired endothelial function, in children with the diseases. In this cross-sectional study, children and adolescents with T1DM (N = 41) or obesity (N = 37), aged < 18 years old, and without proteinuria were included, together with children of similar age and without evident morbidity that served as controls (N = 42). Serum samples were obtained during standard outpatient follow up and the urokinase-type plasminogen activator receptor (suPAR) concentrations were measured using a commercially available sandwich ELISA kit (DUP00, R&D systems). Clinical and biochemical indices that were also assessed include body mass index (BMI) z-score, Tanner stages, glycosylated haemoglobin (HbA1c), fasting lipid profile and serum creatinine. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls. Also, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359, p < 0.001) and serum creatinine levels (Spearman rho −0.334, p = 0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p = 0.009) in the whole cohort. Conclusion: Serum suPAR may be a useful predictive marker of inflammation or endothelial dysfunction for children with obesity and T1DM, as well as a promising therapeutic target. Further studies are needed in order to clarify whether the reported differences in suPAR levels could reflect a greater impairment of the inflammation status and endothelial function in children with obesity compared to children with T1DM. What is Known: • Paediatric obesity and type 1 diabetes are characterised by chronic inflammation and metabolic dysregulation. • Urokinase plasminogen activator receptor (uPAR) has been proposed as a useful biomarker for chronic inflammation and cardiovascular risk in adults. What is New: • Serum suPAR levels were increased in children and adolescents with obesity compared to those with T1DM and healthy controls; thus, obesity may affect the inflammatory status and endothelial function to a higher degree than T1DM during childhood. • Serum suPAR may serve as a diagnostic and predictive marker of inflammation and endothelial dysfunction for children and adolescents with obesity and T1DM. [ABSTRACT FROM AUTHOR]

Background: Although the precise pathogenetic mechanisms remain incompletely elucidated, hypertension is characterized by endothelial damage and infammation. The soluble urokinase plasminogen activator receptor (suPAR) is an infammatory biomarker that increases in parallel with disease activity in conditions such as systemic infammation, infection, cancer, and atherosclerosis. The objective of this study was to assess infammation by means of serum suPAR levels in hypertensive patients and those with resistant hypertension. Methods: Eighty-six adults, 29 newly diagnosed hypertensive patients (HT group) and 23 resistant hypertensive patients (RHT group) and 34 healthy controls, were included in this cross-sectional, observational study. Ambulatory blood pressure monitoring results were included in the analysis. Serum suPAR levels were measured using Enzyme-Linked ImmonuSorbent Assay (ELISA). Patients were divided into 2 groups as “high suPAR” and “low suPAR.” Results: The serum suPAR level was lower in the control group than that of the HT and RHT groups (P = .001). Systolic and diastolic blood pressure values were positively correlated with the serum suPAR level (r = 0.254, P = .018; r = 0.239, P = .027, respectively). Being in the high-suPAR group was found to increase the risk of RHT by 19.5 times. Other risk factors for RHT were found to be lower urinary sodium excretion and higher urinary albumin excretion [odds ratio (OR) = 0.98; OR = 1.09, respectively]. Conclusion: In our study, suPAR levels were found associated with RHT. To our best knowledge, this study is the frst to evaluate the relationship between serum suPAR levels and RHT [ABSTRACT FROM AUTHOR]

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dosedependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression. IMPORTANCE The role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines. [ABSTRACT FROM AUTHOR]

Osteosarcoma, the most common primary bone cancer that affects adolescents worldwide, has the early metastatic potential to be responsible for high mortality rates. Morin has a multipurpose role in numerous cancers, whereas little is known about its role in osteosarcoma migration and invasion. Therefore, we hypothesized that morin suppresses the invasive activities and the migratory potential of human osteosarcoma cells. Our results showed that morin reduced migration and invasion capabilities in human osteosarcoma U2OS and HOS cells. Moreover, morin inhibited the urokinase plasminogen activator (uPA) expression through a signal transducer and an activator of transcription‐3 (STAT3) phosphorylation. After STAT3 overexpression, the decrease of the migratory potential and uPA expression caused by 100 μM of morin in U2OS cells was countered, indicating that STAT3 contributes to the antimetastatic property of morin in human osteosarcoma cells by reducing uPA. In conclusion, morin may be a potential candidate for the antimetastatic treatment of human osteosarcoma. [ABSTRACT FROM AUTHOR]

Background Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population. Methods We prospectively enrolled 99 adults with dengue—40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients. Results The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P <.001), critical (P <.001), and recovery (P =.005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P =.04) There were no significant differences in chymase and tryptase levels between dengue patients and controls. Conclusions In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Deviations in haemostasis are found in about 50 % of patients with cancer and up to 90% of those with metastatic disease. Many studies investigate the dynamics of the processes of coagulation and fibrinolysis and their role as a predictor of therapeutic response, early relapse, or metastasis risk. BACKGROUND: To investigate the serum levels of urokinase plasminogen activator (uPA) in patients with brain metastases treated with robotic stereotactic radiosurgery (SRS) with CyberKnife. MATERIAL AND METHODS: Serum levels of urokinase plasminogen activator (uPA) were measured in 66 patients with solid tumours, divided into two groups, with oligometastatic disease and brain metastases. In this prospective longitudinal study, the serum levels of uPA were measured before starting the therapy and at the first, third, and sixth months after patients were irradiated with the CyberKnife system. RESULTS: Analysis of serum uPA levels in the post-treatment period showed a statistically significant decrease between the baseline and the 6 months post-treatment time point in both patient groups. The baseline value of serum uPA in the group with lung cancer decreased by 62.7 %, and in the group with other types of cancer - by 60 %. Despite the significant reduction of serum uPA levels 6 months after the treatment, the levels remained significantly higher in both groups than in healthy controls. CONCLUSION: Ongoing research on uPA and cancer will enrich our knowledge and expand the possibilities for clinical utilization of the marker in the oncology setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholangiocarcinoma (CCA) accounts for approximately 15% of primary liver cancers. CCA has a poor prognosis and, thus, more effective systemic treatments are needed. We tested opaganib and upamostat, drugs that target sphingosine kinase 2 and multiple serine proteases, primarily trypsins, which are highly expressed in CCA tumors. This study demonstrates the results of inhibiting these novel targets with these drugs individually and in combination in a patient-derived CCA xenograft mouse model. Upamostat is an orally available small-molecule serine protease inhibitor that is a highly potent inhibitor of trypsin 1, trypsin 2, trypsin 3 (PRSS1/2/3), and the urokinase-type plasminogen activator (uPA). These enzymes are expressed in many cancers, especially during tissue remodeling and subsequent tumor cell invasion. Opaganib (ABC294640), a novel, orally available small molecule is a selective inhibitor of the phosphorylation of sphingosine to sphingosine-1-phosphate (S-1-P) by sphingosine kinase 2 (SPHK2). Both sphingosine kinase 1 (SPHK1) and SPHK2 are known to regulate the proliferation-inducing compound S-1-P. However, SPHK2 is more critical in cancer pathogenesis. The goal of this project was to investigate the potential antitumor effects of upamostat and opaganib, individually and in combination, on cholangiocarcinoma (CCA) xenografts in nude mice. PAX165, a patient-derived xenograft (PDX) from a surgically resected CCA, expresses substantial levels of SPHK2, PRSS1, PRSS2, and PRSS3. Four groups of 18 mice each were treated with upamostat, opaganib, both, or vehicle. Mouse weights and PAX165 tumor volumes were measured. Tumor volumes in the upamostat, opaganib, and upamostat plus opaganib groups were significantly decreased compared to the control group. [ABSTRACT FROM AUTHOR]

To provide an overview of the available literature data on clinical applications of positron emission tomography (PET) targeting the urokinase-type plasminogen activator receptor in oncology. A literature search was conducted in PubMed, Web of Science and Scopus databases up to June 2023. The results were presented according to the PRISMA guidelines. The quality of the studies was assessed using the Critical Appraisal Skill Program checklist. Seven papers were selected for final analysis, involving 266 patients with solid tumors who underwent PET with uPAR-ligands. Thematic areas identified include feasibility studies (n = 2) on the safety, pharmacokinetics, and dosimetry of uPAR-targeting radiopharmaceuticals; uPAR-directed imaging in head and neck cancer (n = 2); uPAR PET in prostate cancer (n = 2); and the investigation of uPAR in neuroendocrine neoplasms (n = 1). Six of the seven studies used the radiopharmaceutical [68Ga]Ga-NOTA-AE105 while one study used [64Cu]Cu-DOTA-AE105. The studies showed protocol homogeneity, with static PET imaging at 20 minutes. The quality assessment revealed limitations such as small cohorts and the fact that all studies were performed by a single research group. uPAR-PET appears to be a promising imaging tool in well-selected oncological settings, but it needs to be validated by multicentre collaboration. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). Methods We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias. Results Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (− 7.77, − 3.87); P

Abstract Objective To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome. Methods A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children’s Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded. Results A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group. Conclusion The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Objective The aim of this study was to introduce a cost-effective and less invasive method for the evacuation of intraparenchymal hemorrhage (IPH). Background IPH in the presence or absence of intraventricular hemorrhage has severe morbidity and has almost 50% mortality whether the patient is managed surgically or medically. Development of minimally invasive surgical techniques offers better outcomes but requires the use of special instruments and a unique skill set that is costly and requires special training. Method We inserted infant feeding tube within the hematoma via the left Kocher's burr hole. We instilled 40,000 IU of urokinase serially at an 8 hours interval for 3 days to evacuate the left gangliocapsular hematoma. Result We have treated a 50 years old hypertensive male patient with left gangliocapsular IPH and right hemiparesis (power: ⅖ on admission). After a month, on follow-up, the patient was conscious and oriented with improved right hemiparesis (power: ⅘). Conclusion This technique of evacuating hematoma is instrumental in peripheral centers in developing as well as under-developed countries where there are limited resources and a better outcome is expected with minimal morbidity. [ABSTRACT FROM AUTHOR]

Background: Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings. Methods: This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents. Results: Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons. Conclusions: In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations.

Objective: To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome. Methods: A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children's Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded. Results: A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group. Conclusion: The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). Methods: We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias. Results: Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (− 7.77, − 3.87); P<0.00001] and the residual pleural thickness [MD-1.31, 95%CI (− 1.70, − 0.91); P<0.00001], pleural effusion drainage volume [MD 822.81, 95%CI (666.46,977.96); P<0.00001], FVC%pred [MD 7.95, 95%CI (4.51,11.40); P<0.00001], FEV1%pred [MD 12.67, 95%CI (10.09,15.24); P<0.00001] were significantly different. Conclusion: The clinical effect of urokinase is better than that of antituberculous therapy alone: it can increase total pleural effusion, decrease residual pleural thickness, improve the pulmonary function, and shorten the time of pleural effusion absorption. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionTo compare the efficacy of urokinase and alteplase intravenous thrombolysis in the treatment of acute phase cerebral infarction and investigate their impact on serum S-100β and nerve growth factor (NGF) levels.Parameters assessed included NIHSS score reduction, vascular recanalization rates, mRS, Barthel Index, and adverse reactions. Post-treatment blood samples were also collected for further analysis.The clinical treatment effectiveness and Vascular recanalization rate in Group A was higher than in Group B, with p < 0.05. After treatment, the NIHSS score in Group A was lower than in Group B (p < 0.05), and the mRS score was slightly lower, but the difference was not significant (p > 0.05). After treatment, the levels of IL-6, TNF-α, and CRP in Group A were lower than in the control group (p < 0.05). The S-100β level in Group A was lower than in Group B, and NGF level was higher than in Group B (p < 0.05). Group A had better prognosis.The efficacy and safety of both urokinase and alteplase intravenous thrombolysis for acute phase cerebral infarction have been demonstrated, yet disparities exist in neurological function recovery and regulation of biochemical indicators. Alteplase intravenous thrombolysis emerges as the superior option, displaying greater effectiveness and safety, alongside improved regulation of serum S-100β and NGF levels. Tailoring treatment plans to individual patient characteristics and drug mechanisms is essential. Given these findings, the promotion of alteplase intravenous thrombolysis in the management of acute phase cerebral infarction is justified. [ABSTRACT FROM AUTHOR]

Urokinase plasminogen activator receptor (uPAR) encoded by the PLAUR gene is known as a clinical marker for cell invasiveness in glioblastoma multiforme (GBM). It is additionally implicated in various processes, including angiogenesis and inflammation within the tumor microenvironment. However, there has not been a comprehensive study that depicts the overall functions and molecular cooperators of PLAUR with respect to intra-tumoral subtypes of GBM. Using single-cell RNA sequencing data from 37 GBM patients, we identified PLAUR as a marker gene for two distinct subtypes in GBM. One subtype is featured by inflammatory activities and the other subtype is marked by ECM remodeling processes. Using the whole-transcriptome data from single cells, we are able to uncover the molecular cooperators of PLAUR for both subtypes without presuming biological pathways. Two protein networks comprise the molecular context of PLAUR, with each of the two subtypes characterized by a different dominant network. We concluded that targeting PLAUR directly influences the mechanisms represented by these two protein networks, regardless of the subtype of the targeted cell. [ABSTRACT FROM AUTHOR]

Simple Summary: Neurotropic oncolytic viruses have shown promise for the treatment of brain tumors, as they are naturally capable of entering the brain and selectively killing cancer cells. In this study, the safety, immunologic responses, and anti-tumor effects of intravenous administration of a genetically modified strain of neurotropic oncolytic Newcastle disease virus (NDV) to 20 dogs with spontaneously occurring brain cancers are characterized. Viral treatment was safe, with common side effects limited to transient low-grade fever, chills, and diarrhea. Anti-tumor responses, defined by a post-treatment reduction in tumor size as measured with brain MRI scans, were observed in two dogs. NDV genetic material was detectable in canine tumor tissue after treatment, confirming the ability of NDV to infect tumors. All dogs rapidly developed antibodies to NDV, suggesting that the viral dosing schedule may require modification to improve anti-tumor effects. Neurotropic oncolytic viruses are appealing agents to treat brain tumors as they penetrate the blood–brain barrier and induce preferential cytolysis of neoplastic cells. The pathobiological similarities between human and canine brain tumors make immunocompetent dogs with naturally occurring tumors attractive models for the study of oncolytic virotherapies. In this dose-escalation/expansion study, an engineered Lasota NDV strain targeting the urokinase plasminogen activator system (rLAS-uPA) was administered by repetitive intravenous infusions to 20 dogs with intracranial tumors with the objectives of characterizing toxicities, immunologic responses, and neuroradiological anti-tumor effects of the virus for up to 6 months following treatment. Dose-limiting toxicities manifested as fever, hematologic, and neurological adverse events, and the maximum tolerated dose (MTD) of rLAS-uPA was 2 × 107 pfu/mL. Mild adverse events, including transient infusion reactions, diarrhea, and fever were observed in 16/18 of dogs treated at or below MTD. No infectious virus was recoverable from body fluids. Neutralizing antibodies to rLAS-uPA were present in all dogs by 2 weeks post-treatment, and viral genetic material was detected in post-treatment tumors from six dogs. Tumor volumetric reductions occurred in 2/11 dogs receiving the MTD. Systemically administered rLAS-uPA NDV was safe and induced anti-tumor effects in canine brain tumors, although modifications to evade host anti-viral immunity are needed to optimize this novel therapy. [ABSTRACT FROM AUTHOR]

Soluble urokinase plasminogen activator receptors (suPARs) are a biomarker for inflammatory diseases. This study aims to investigate its diagnostic properties regarding periprosthetic joint infections (PJI). This retrospective cohort study included adult patients who underwent joint puncture for suspected PJI. The presence of PJI was determined according to the criteria of the European Bone and Joint Infection Society (EBJIS). Laboratory study analyses included the determination of white blood cells (WBC) in whole blood, C-reactive protein (CRP) in blood plasma, and suPAR in both blood plasma and synovial fluid. Appropriate diagnostic cut-off values were identified utilizing Youden's J, and their diagnostic performance was determined by calculating the positive (PPV) and negative predictive value (NPV) for each marker. Sixty-seven cases were included in the final analysis. Forty-three samples (64%) were identified as periprosthetic joint infection (PJI) and twenty-four specimen (36%) were PJI negative cases. The PPV and NPV were 0.80 and 0.70 for synovial suPAR, 0.86 and 0.55 for CRP, 0.84 and 0.31 for WBC and 1.00 and 0.31 for plasma suPAR. Synovial suPAR showed a solid diagnostic performance in this study and has the potential to be an alternative or complementary biomarker for PJI. Further investigations in larger patient collectives are indicated. [ABSTRACT FROM AUTHOR]

Introduction: Soluble urokinase plasminogen activator receptor (suPAR) is a biologically active protein and increased levels are associated with worse outcomes in critically ill patients. suPAR in bronchoalveolar fluid (BALF) may be helpful to differentiate between types of acute respiratory distress syndrome (ARDS) and may have potential for early detection of fungal infection. Methods: We prospectively investigated levels of suPAR in BALF and serum in critically ill patients who underwent bronchoscopy for any reason at the ICU of the Department of Internal Medicine, Medical University of Graz, Graz, Austria. Results: Seventy-five patients were available for analyses. Median age was 60 [25th–75th percentile: 50–69] years, 27% were female, and median SOFA score was 12 [11–14] points. Serum suPAR levels were significantly associated with ICU mortality in univariable logistic regression analysis. There was no correlation between BALF and serum suPAR. Serum suPAR was higher in ARDS patients at 11.2 [8.0–17.2] ng/mL compared to those without ARDS at 7.1 [3.7–10.1] (p < 0.001). BALF-suPAR was significantly higher in patients with evidence of fungal lung infection compared to patients without fungal infection both in the general cohort (7.6 [3.2–9.4] vs 2.5 [1.1–5.3], p = 0.013) and in the subgroup of ARDS (7.2 [3.1–39.2] vs 2.5 [1.0–5.2], p = 0.022). All patients were classified as putative/probable invasive aspergillosis. Conclusion: We found significant higher levels of serum suPAR in ARDS patients compared to those not fulfilling ARDS criteria. Serum and BALF-suPAR were significantly higher in those patients with evidence for invasive pulmonary aspergillosis. These findings may suggest testing this biomarker for early diagnosis of fungal infection in a greater cohort. [ABSTRACT FROM AUTHOR]

Copyright of Firat Universitesi Saglik Bilimleri Veteriner Dergisi is the property of Firat Universitesiu, Saglik Bilimleri Enstitusu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Improving noninvasive antenatal diagnosis of fetal inflammatory response syndrome (FIRS) can assist in the evaluation of prenatal risk and reduce perinatal outcomes. This study aimed to determine whether soluble urokinase-type plasminogen activator receptor (suPAR) in vaginally collected amniotic fluid is significant in identifying FIRS after preterm premature rupture of membranes before 34 weeks of gestation. Methods: This was a prospective cohort study of 114 pregnant women and their newborns after preterm premature rupture of membranes at 22–34+6 weeks of gestation. SuPAR was evaluated using an enzyme-linked immunosorbent assay in vaginally collected amniotic fluid. Patients were classified according to the presence or absence of FIRS. FIRS was defined by umbilical cord blood interleukin-6 level > 11 pg/mL or histological funisitis. The data were analyzed using the R package (R–4.0.5). Results: SuPAR was detected in all amniotic fluid samples with a median of 26.23 ng/mL (interquartile range (IQR), 15.19–51.14). The median level of suPAR was higher in the FIRS group than in the non-FIRS group, 32.36 ng/mL (IQR, 17.27–84.16) vs. 20.46 ng/mL (IQR, 11.49–36.63) (P = 0.01), respectively. The presence of histological chorioamnionitis significantly increased the suPAR concentration in the FIRS group (P < 0.001). The areas under the curve for FIRS and FIRS with histological chorioamnionitis were 0.65 and 0.74, respectively, with an optimum cutoff value of 27.60 ng/mL. Controlling for gestational age, the cutoff of suPAR more than 27.60 ng/mL predicted threefold higher odds for FIRS and sixfold higher odds for FIRS with histologic chorioamnionitis. Conclusion: Soluble urokinase-type plasminogen activator receptor in vaginally obtained amniotic fluid may assist in evaluating prenatal risk of FIRS in patients after preterm premature rupture of membranes before 34 weeks of gestation. [ABSTRACT FROM AUTHOR]