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World Journal of Urology May 2024To predict the post transurethral prostate resection(TURP) urethral stricture probability by applying different machine learning algorithms using the data obtained from...
PURPOSE
To predict the post transurethral prostate resection(TURP) urethral stricture probability by applying different machine learning algorithms using the data obtained from preoperative blood parameters.
METHODS
A retrospective analysis of data from patients who underwent bipolar-TURP encompassing patient characteristics, preoperative routine blood test outcomes, and post-surgery uroflowmetry were used to develop and educate machine learning models. Various metrics, such as F1 score, model accuracy, negative predictive value, positive predictive value, sensitivity, specificity, Youden Index, ROC AUC value, and confidence interval for each model, were used to assess the predictive performance of machine learning models for urethral stricture development.
RESULTS
A total of 109 patients' data (55 patients without urethral stricture and 54 patients with urethral stricture) were included in the study after implementing strict inclusion and exclusion criteria. The preoperative Platelet Distribution Width, Mean Platelet Volume, Plateletcrit, Activated Partial Thromboplastin Time, and Prothrombin Time values were statistically meaningful between the two cohorts. After applying the data to the machine learning systems, the accuracy prediction scores for the diverse algorithms were as follows: decision trees (0.82), logistic regression (0.82), random forests (0.91), support vector machines (0.86), K-nearest neighbors (0.82), and naïve Bayes (0.77).
CONCLUSION
Our machine learning models' accuracy in predicting the post-TURP urethral stricture probability has demonstrated significant success. Exploring prospective studies that integrate supplementary variables has the potential to enhance the precision and accuracy of machine learning models, consequently progressing their ability to predict post-TURP urethral stricture risk.
Topics: Humans; Male; Urethral Stricture; Machine Learning; Retrospective Studies; Aged; Transurethral Resection of Prostate; Postoperative Complications; Algorithms; Middle Aged; Predictive Value of Tests
PubMed: 38748256
DOI: 10.1007/s00345-024-05017-x -
Blood Research May 2024Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by reduced factor VIII (FVIII) levels. Approximately 10-15% of patients with severe HA (SHA) do not...
BACKGROUND
Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by reduced factor VIII (FVIII) levels. Approximately 10-15% of patients with severe HA (SHA) do not present with the anticipated bleeding pattern. Here, we assessed the phenotypic severity of hemophilia A using rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-clot waveform analysis (APTT-CWA).
METHODS
Patients diagnosed with hemophilia A were enrolled. Clinical phenotype assignment was performed according to the published literature, and patients were classified into four phenotypic subgroups. The whole blood sample was first run on ROTEM in INTEM mode using platelet-poor plasma, APTT was run, and the APTT-CWA graph was simultaneously recorded.
RESULTS
A total of 66 patients were recruited for this study. Statistically significant differences were observed between the four phenotypically categorized groups using ROTEM and APTT-CWA. On comparing patients with mild/moderate-to-severe phenotypes (Group II) with SHA without inhibitors (Group IV), no significant difference was found for all parameters of ROTEM or APTT-CWA. The MCF, MA30, MAXV, and Alpha angle values using ROTEM were found to be the lowest in patients with SHA with inhibitors, which helped differentiate them from those with SHA without inhibitors. However, these two groups could not be differentiated using the APTT-CWA parameters.
CONCLUSION
ROTEM can be used to distinguish patients with SHA with inhibitors from those with SHA without inhibitors using a combination of parameters with high sensitivity and specificity. However, APTT-CWA cannot be used to differentiate these patient groups.
PubMed: 38743166
DOI: 10.1007/s44313-024-00018-6 -
BMC Pregnancy and Childbirth May 2024Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia.
METHODS
This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger's regression test and funnel plot were employed to assess publication bias among the included studies.
RESULTS
A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65-1.29, p < 0.001), 1.05 (95% CI: 0.74-1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant.
CONCLUSIONS
The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Partial Thromboplastin Time; Prothrombin Time; Thrombin Time; Blood Coagulation
PubMed: 38741046
DOI: 10.1186/s12884-024-06543-7 -
Perfusion May 2024Bleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The... (Review)
Review
INTRODUCTION
Bleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The optimal anticoagulation monitoring protocol in these patients is unknown. This study aims to compare the incidence of thrombotic and hemorrhagic complications before and after a protocol change. In addition, the association between hemostatic complications, coagulation tests and risk factors is evaluated.
METHODS
This is a retrospective single center cohort study of adult ECMO patients. We collected demographics, ECMO parameters and coagulation test results. Outcomes of the aPTT guided and multimodal protocol, including aPTT, anti-Xa assay and rotational thromboelastometry were compared and the association between coagulation tests, risk factors and hemostatic complications was determined using a logistic regression analysis for repeated measurements.
RESULTS
In total, 250 patients were included, 138 in the aPTT protocol and 112 in the multimodal protocol. The incidence of thrombosis (aPTT: 14%; multimodal: 12%) and bleeding (aPTT: 36%; multimodal: 40%), did not significantly differ between protocols. In the aPTT guided protocol, the aPTT was associated with thrombosis (Odds Ratio [OR] 1.015; 95% confidence interval [CI] 1.004-1.027). In both protocols, surgical interventions were risk factors for bleeding and thrombotic complications (aPTT: OR 93.2, CI 39.9-217.6; multimodal OR 17.5, CI 6.5-46.9).
DISCUSSION
The incidence of hemostatic complications was similar between both protocols and surgical interventions were a risk factor for hemostatic complications. Results from this study help to elucidate the role of coagulation tests and risk factors in predicting hemostatic complications in patients undergoing ECMO support.
PubMed: 38739366
DOI: 10.1177/02676591241253474 -
Translational Lung Cancer Research Apr 2024Epidermal growth factor receptor () T790M mutation is the standard predictive biomarker for third-generation epidermal growth factor receptor tyrosine kinase inhibitor...
Development and validation of a deep learning-based model to predict response and survival of T790M mutant non-small cell lung cancer patients in early clinical phase trials using electronic medical record and pharmacokinetic data.
BACKGROUND
Epidermal growth factor receptor () T790M mutation is the standard predictive biomarker for third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. While not all T790M-positive patients respond to third-generation EGFR-TKIs and have a good prognosis, it necessitates novel tools to supplement genotype detection for predicting efficacy and stratifying -mutant patients with various prognoses. Mixture-of-experts (MoE) is designed to disassemble a large model into many small models. Meanwhile, it is also a model ensembling method that can better capture multiple patterns of intrinsic subgroups of enrolled patients. Therefore, the combination of MoE and Cox algorithm has the potential to predict efficacy and stratify survival in non-small cell lung cancer (NSCLC) patients with mutations.
METHODS
We utilized the electronic medical record (EMR) and pharmacokinetic parameters of 326 T790M-mutated NSCLC patients, including 283 patients treated with Abivertinib in phase I (n=177, for training) and II (n=106, for validation) clinical trials and an additional validation cohort 2 comprising 43 patients treated with BPI-7711. Furthermore, 18 patients underwent whole-exome sequencing for biological interpretation of CoxMoE. We evaluated the predictive performance for therapeutic response using the area under the curve (AUC) and the Concordance index (C-index) for progression-free survival (PFS).
RESULTS
CoxMoE exhibited AUCs of 0.73-0.83 for predicting efficacy defined by best overall response (BoR) and achieved C-index values of 0.64-0.65 for PFS prediction in training and validating cohorts. The PFS of 198 patients with a low risk [median, 6.0 (range, 1.0-23.3) months in the abivertinib treated cohort; median 16.5 (range, 1.4-27.4) months in BPI-7711 treated cohort] of being non-responder increased by 43% [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.40-0.78; P=0.0013] and 50% (HR, 0; 95% CI, 0-0; P=0.01) compared to those at high-risk [median, 4.2 (range, 1.0-35) months in the abivertinib treated cohort; median, 11.0 (range, 1.4-25.1) months in BPI-7711 treated cohort]. Additionally, activated partial thromboplastin time (APTT), creatinine clearance (Ccr), monocyte, and steady-state plasma trough concentration utilited to construct model were found significantly associated with drug resistance and aggressive tumor pathways. A robust correlation was observed between APTT and Ccr with PFS (log-rank test; P<0.01) and treatment response (Wilcoxon test; P<0.05), respectively.
CONCLUSIONS
CoxMoE offers a valuable approach for patient selection by forecasting therapeutic response and PFS utilizing laboratory tests and pharmacokinetic parameters in the setting of early-phase clinical trials. Simultaneously, CoxMoE could predict the efficacy of third-generation EGFR-TKI non-invasively for T790M-positive NSCLC patients, thereby complementing existing EGFR genotype detection.
PubMed: 38736496
DOI: 10.21037/tlcr-23-737 -
Foods (Basel, Switzerland) Apr 2024A novel fibrinolytic enzyme was produced by the liquid fermentation of . The enzyme was purified from the culture supernatant by hydrophobic interactions, gel...
A novel fibrinolytic enzyme was produced by the liquid fermentation of . The enzyme was purified from the culture supernatant by hydrophobic interactions, gel filtration, and ion exchange chromatographies. It was purified by 241.02-fold, with a specific activity of 3619 U/mg and a final yield of 10.02%. SDS-PAGE analysis confirmed the purity of the enzyme, showing a single band with a molecular weight of 19.5 kDa. The first nine amino acids of the N-terminal of the purified enzyme were A-T-Y-T-G-G-S-Q-T. The enzyme exhibited optimal activity at a temperature of 42 °C and pH 7.6. Its activity was significantly improved by Zn, K, Ca, Mn, and Mg while being inhibited by Fe, Fe, Al, and Ba. The activity of the enzyme was completely inhibited by ethylenediamine tetraacetic acid (EDTA), and it was also dose-dependently inhibited by phenylmethylsulfonyl fluoride (PMSF) and soy trypsin inhibitor (SBTI). However, inhibitors such as N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK), aprotinin, and pepstatin did not significantly affect its activity, suggesting that the enzyme was a serine-like metalloproteinase. The enzyme acted as both a plasmin-like fibrinolytic enzyme and a plasminogen activator, and it also exhibited the capability to hydrolyze fibrinogen and fibrin. In vitro, it demonstrated the ability to dissolve blood clots and exhibit anticoagulant properties. Furthermore, it was found that the enzyme prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), and reduced the levels of fibrinogen (FIB) and prothrombin activity (PA). Based on these studies, the enzyme has great potential to be developed as a natural agent for the prevention and treatment of thrombotic diseases.
PubMed: 38731663
DOI: 10.3390/foods13091292 -
Molecules (Basel, Switzerland) Apr 2024This current article was dedicated to the determination of the composition of phenolic compounds in extracts of four species of the genus in order to establish a...
This current article was dedicated to the determination of the composition of phenolic compounds in extracts of four species of the genus in order to establish a connection between the composition of polyphenols and biological effects. A chemical analysis revealed that the composition of the extracts studied depended both on the plant species and its part (leaf or flower) and on the extractant used. All four species of were rich sources of phenolic compounds and contained hydrolyzable tannins, condensed tannins, phenolic acids and their derivatives, and flavonoids. The activities included data on those that are most important for creating functional foods with plant components: the influence on blood coagulation measured by prothrombin and activated partial thromboplastin time, and on the activity of the digestive enzymes (pancreatic amylase and lipase). It was established that plant species, their parts, and extraction methods contribute meaningfully to biological activity. The most prominent result is as follows: the plant organ determines the selective inhibition of either amylase or lipase; thus, the anticoagulant activities of and hold promise for health-promoting food formulations associated with general metabolic disorders.
Topics: Plant Extracts; Phenols; Lipase; Flavonoids; Polyphenols; Amylases; Blood Coagulation; Humans; Anticoagulants; Plant Leaves
PubMed: 38731503
DOI: 10.3390/molecules29092013 -
Thrombosis Research Jun 2024Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII...
BACKGROUND
Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques.
AIMS
We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits.
METHODS AND RESULTS
We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5'-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group.
CONCLUSIONS
Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.
Topics: Rabbits; Animals; Factor VIII; Neointima; Thrombosis; Male; Myocytes, Smooth Muscle; Tunica Intima; Humans; Platelet Aggregation; Femoral Artery
PubMed: 38729030
DOI: 10.1016/j.thromres.2024.04.025 -
Frontiers in Molecular Biosciences 2024Traditional Chinese medicine (TCM) has a long history and particular advantages in the diagnosis and treatment of diabetic foot gangrene (DFG). Patients with DFG are...
Traditional Chinese medicine (TCM) has a long history and particular advantages in the diagnosis and treatment of diabetic foot gangrene (DFG). Patients with DFG are mainly divided into two subtypes, tendon lesion with edema (GT) and ischemic lesion without edema (GI), which are suitable for different medical strategies. Metabolomics has special significance in unravelling the complexities of multifactorial and multisystemic disorders. This study acquired the serum metabolomic profiles of two traditional Chinese medicine subtypes of DFG to explore potential molecular evidence for subtype characterization, which may contribute to the personalized treatment of DFG. A total of 70 participants were recruited, including 20 with DM and 50 with DFG (20 with GI and 30 with GT). Conventional gas chromatography-mass spectrometry (GC-MS) followed by orthogonal partial least-squares discriminant analysis (OPLS-DA) were used as untargeted metabolomics approaches to explore the serum metabolomic profiles. Kyoto encyclopedia of genes and genomes (KEGG) and MetaboAnalyst were used to identify the related metabolic pathways. Compared with DM patients, the levels of 14 metabolites were altered in the DFG group, which were also belonged to the differential metabolites of GI (13) and GT (7) subtypes, respectively. Among these, urea, α-D-mannose, cadaverine, glutamine, L-asparagine, D-gluconic acid, and indole could be regarded as specific potential metabolic markers for GI, as well as L-leucine for GT. In the GI subtype, D-gluconic acid and L-asparagine are positively correlated with activated partial thromboplastin time (APTT) and fibrinogen (FIB). In the GT subtype, L-leucine is positively correlated with the inflammatory marker C-reactive protein (CRP). Arginine and proline metabolism, glycine, serine and threonine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis are the most important metabolic pathways associated with GI. The main metabolic pathways related to GT include pyrimidine metabolism, glutathione metabolism, biosynthesis of valine, leucine, and isoleucine, as well as valine, serine, and isoleucine with metabolites. The results of this study indicate that patients with different DFG subtypes have distinct metabolic profiles, which reflect the pathological characteristics of each subtype respectively. These findings will help us explore therapeutic targets for DFG and develop precise treatment strategies.
PubMed: 38725871
DOI: 10.3389/fmolb.2024.1384307 -
ESC Heart Failure May 2024It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support...
AIMS
It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.
METHODS AND RESULTS
aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti-Xa than temporary MCS devices.
CONCLUSIONS
aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.
PubMed: 38725133
DOI: 10.1002/ehf2.14816