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JMIR Bioinformatics and Biotechnology May 2024The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with...
BACKGROUND
The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms.
OBJECTIVE
We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors.
METHODS
We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models.
RESULTS
We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively.
CONCLUSIONS
The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (P<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.
PubMed: 38935968
DOI: 10.2196/56884 -
Pharmaceuticals (Basel, Switzerland) May 2024The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population...
AIMS
The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile.
METHODS
Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges.
RESULTS
A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CL), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM.
CONCLUSIONS
We found that qCRP, CRRT, CL, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.
PubMed: 38931333
DOI: 10.3390/ph17060665 -
Materials (Basel, Switzerland) Jun 2024The paper presents the study concerning the preparation and physio-chemical and biological properties of wool-copper (WO-Cu) materials obtained by the sputter deposition...
The paper presents the study concerning the preparation and physio-chemical and biological properties of wool-copper (WO-Cu) materials obtained by the sputter deposition of copper onto the wool fibers. The WO-Cu material was subjected to physio-chemical and biological investigations. The physio-chemical investigations included the elemental analysis of materials (C, N, O, S, and Cu), their microscopic analysis, and surface properties analysis (specific surface area and total pore volume). The biological investigations consisted of the antimicrobial activity tests of the WO-Cu materials against colonies of Gram-positive () bacteria, Gram-negative () bacteria, and fungal mold species (). Biochemical-hematological tests included the evaluation of the activated partial thromboplastin time and pro-thrombin time. The tested wool-copper demonstrated the ability to interact with the DNA in a time-dependent manner. These interactions led to the DNA's breaking and degradation. The antimicrobial and antifungal activities of the WO-Cu materials suggest a potential application as an antibacterial/antifungal material. Wool-copper materials may be also used as customized materials where the blood coagulation process could be well controlled through the appropriate copper content.
PubMed: 38930247
DOI: 10.3390/ma17122878 -
Animals : An Open Access Journal From... Jun 2024This study explored the effects of hyperbaric oxygen therapy (HBOT) on hemogram, serum biochemistry and hemostatic variables in female dogs undergoing...
BACKGROUND
This study explored the effects of hyperbaric oxygen therapy (HBOT) on hemogram, serum biochemistry and hemostatic variables in female dogs undergoing laparoscopic-assisted ovariohysterectomy (OVH).
MATERIALS
Thirty adult, mixed-breed, healthy female dogs were randomly divided into the following three groups: HBOT + SURG (exposed to two absolute atmospheres (ATAs) for 45 min followed by laparoscopic-assisted OVH), HBOT (exposed to two ATAs for 45 min) and SURG (laparoscopic-assisted OVH). Blood samples were collected at T0 (at the admission), at T1, 24 h after T0 (immediately after HBOT in the HBOT + SURG and HBOT groups, and immediately before anesthetic premedication in the SURG group), and at T2, 48 h after T0 (24 h after HBOT and anesthetic premedication).
METHODS
Assessments included erythrogram, leukogram, thrombogram, renal and hepatic serum biochemistry, prothrombin time (PT), activated partial thromboplastin time (APTT), buccal mucosal bleeding time (BMBT) and bloodstain area (BA) on hygroscopic paper collected at the BMBT.
RESULTS
Both the HBOT + SURG and SURG groups presented neutrophilia ( ≤ 0.0039) at T2 and an increase of ALP at T2 ( ≤ 0.0493), the SURG group presented an increase in leukocyte count at T2 ( = 0.0238) and the HBOT + SURG group presented a reduction in lymphocyte count at T2 ( = 0.0115). In the HBOT + SURG group, there was a reduction in PT and APTT in relation to the baseline value ( ≤ 0.0412).
CONCLUSIONS
A session of HBOT at two ATAs for 45 min did not cause changes in the BMBT or BA in healthy female dogs. Some blood parameters investigated (neutrophil and lymphocyte count, ALP, PT and APTT) were affected by the use of HBOT.
PubMed: 38929404
DOI: 10.3390/ani14121785 -
Children (Basel, Switzerland) Jun 2024Prior guidelines recommended maintaining normothermia following traumatic brain injury (TBI), but recent studies suggest therapeutic hypothermia as a viable option in... (Review)
Review
BACKGROUND
Prior guidelines recommended maintaining normothermia following traumatic brain injury (TBI), but recent studies suggest therapeutic hypothermia as a viable option in pediatric cases. However, some others demonstrated a higher mortality rate. Hence, the impact of hypothermia on neurological symptoms and overall survival remains contentious.
METHODS
We conducted a systematic review and meta-analysis to evaluate the effects of hypothermia on neurological outcomes in pediatric TBI patients. The PubMed/Medline, Scopus, and Web of Science databases were searched until 1 January 2024 and data were analyzed using appropriate statistical methods.
RESULTS
A total of eight studies, comprising nine reports, were included in this analysis. Our meta-analysis did not reveal significant differences in mortality (RR = 1.58; 95% CI = 0.89-2.82, = 0.055), infection (RR = 0.95: 95% CI = 0.79-1.1, = 0.6), arrhythmia (RR = 2.85: 95% CI = 0.88-9.2, = 0.08), hypotension (RR = 1.54: 95% CI = 0.91-2.6, = 0.10), intracranial pressure (SMD = 5.07: 95% CI = -4.6-14.8, = 0.30), hospital length of stay (SMD = 0.10; 95% CI = -0.13-0.3, = 0.39), pediatric intensive care unit length of stay (SMD = 0.04; 95% CI = -0.19-0.28, = 0.71), hemorrhage (RR = 0.86; 95% CI = 0.34-2.13, = 0.75), cerebral perfusion pressure (SMD = 0.158: 95% CI = 0.11-0.13, = 0.172), prothrombin time (SMD = 0.425; 95% CI = -0.037-0.886, = 0.07), and partial thromboplastin time (SMD = 0.386; 95% CI = -0.074-0.847, = 0.10) between the hypothermic and non-hypothermic groups. However, the heart rate was significantly lower in the hypothermic group (-1.523 SMD = -1.523: 95% CI = -1.81--1.22 < 0.001).
CONCLUSIONS
Our findings challenge the effectiveness of therapeutic hypothermia in pediatric TBI cases. Despite expectations, it did not significantly improve key clinical outcomes. This prompts a critical re-evaluation of hypothermia's role as a standard intervention in pediatric TBI treatment.
PubMed: 38929280
DOI: 10.3390/children11060701 -
International Journal of Molecular... Jun 2024Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients...
Acute kidney injury (AKI) is a significant complication in burn patients, impacting outcomes substantially. This study explores the heterogeneity of AKI in burn patients by analyzing creatinine time-series data to identify distinct AKI clusters and evaluating routine biomarkers' predictive values. A retrospective cohort analysis was performed on 2608 adult burn patients admitted to Hangang Sacred Heart Hospital's Burn Intensive Care Unit (BICU) from July 2010 to December 2022. Patients were divided into four clusters based on creatinine trajectories, ranging from high-risk, severe cases to lower-risk, short-term care cases. Cluster A, characterized by high-risk, severe cases, showed the highest mortality and severity, with significant predictors being PT and TB. Cluster B, representing intermediate recovery cases, highlighted PT and albumin as useful predictors. Cluster C, a low-risk, high-resilience group, demonstrated predictive values for cystatin C and eGFR cys. Cluster D, comprising lower-risk, short-term care patients, indicated the importance of PT and lactate. Key biomarkers, including albumin, prothrombin time (PT), cystatin C, eGFR cys, and total bilirubin (TB), were identified as significant predictors of AKI development, varying across clusters. Diagnostic accuracy was assessed using area under the curve (AUC) metrics, reclassification metrics (NRI and IDI), and decision curve analysis. Cystatin C and eGFR cys consistently provided significant predictive value over creatinine, with AUC values significantly higher ( < 0.05) in each cluster. This study highlights the need for a tailored, biomarker-driven approach to AKI management in burn patients, advocating for the integration of diverse biomarkers in clinical practice to facilitate personalized treatment strategies. Future research should validate these biomarkers prospectively to confirm their clinical utility.
Topics: Humans; Biomarkers; Burns; Acute Kidney Injury; Male; Female; Middle Aged; Adult; Retrospective Studies; Creatinine; Cystatin C; Aged; Glomerular Filtration Rate
PubMed: 38928473
DOI: 10.3390/ijms25126769 -
Biomedicines Jun 2024Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and...
Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; = 0.002) and use of meropenem (B = 1237.220; = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; = 0.040) and longer prothrombin times (B = 0.412; = 0.043), and higher IL-6 (B = 0.137; = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; = 0.017) were predictive of higher aPTT values. Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.
PubMed: 38927488
DOI: 10.3390/biomedicines12061281 -
Biomolecules May 2024We recently reported the potential application of recombinant prothrombin activator ecarin (RAPClot™) in blood diagnostics. In a new study, we describe RAPClot™ as...
We recently reported the potential application of recombinant prothrombin activator ecarin (RAPClot™) in blood diagnostics. In a new study, we describe RAPClot™ as an additive to develop a novel blood collection prototype tube that produces the highest quality serum for accurate biochemical analyte determination. The drying process of the RAPClot™ tube generated minimal effect on the enzymatic activity of the prothrombin activator. According to the bioassays of thrombin activity and plasma clotting, γ-radiation (>25 kGy) resulted in a 30-40% loss of the enzymatic activity of the RAPClot™ tubes. However, a visual blood clotting assay revealed that the γ-radiation-sterilized RAPClot™ tubes showed a high capacity for clotting high-dose heparinized blood (8 U/mL) within 5 min. This was confirmed using Thrombelastography (TEG), indicating full clotting efficiency under anticoagulant conditions. The storage of the RAPClot™ tubes at room temperature (RT) for greater than 12 months resulted in the retention of efficient and effective clotting activity for heparinized blood in 342 s. Furthermore, the enzymatic activity of the RAPClot™ tubes sterilized with an electron-beam (EB) was significantly greater than that with γ-radiation. The EB-sterilized RAPClot™ tubes stored at RT for 251 days retained over 70% enzyme activity and clotted the heparinized blood in 340 s after 682 days. Preliminary clinical studies revealed in the two trials that 5 common analytes (K, Glu, lactate dehydrogenase (LD), Fe, and Phos) or 33 analytes determined in the second study in the γ-sterilized RAPClot™ tubes were similar to those in commercial tubes. In conclusion, the findings indicate that the novel RAPClot™ blood collection prototype tube has a significant advantage over current serum or lithium heparin plasma tubes for routine use in measuring biochemical analytes, confirming a promising application of RAPClot™ in clinical medicine.
Topics: Humans; Recombinant Proteins; Blood Coagulation; Serum; Thromboplastin; Blood Specimen Collection; Thrombelastography; Gamma Rays; Anticoagulants
PubMed: 38927049
DOI: 10.3390/biom14060645 -
BMC Pulmonary Medicine Jun 2024This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission.
BACKGROUND
This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission.
METHODS
This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell's C-index, calibration plots, DCA, and K-M curve.
RESULT
Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836-0.881), 0.773 (0.746-0.799), 0.736 (0.701-0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723-0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model's good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P < 0.0001).
CONCLUSION
The nomogram can provide valuable guidance for clinical practitioners to early predict the probability of RF occurrence in AECOPD patients, take relevant measures, prevent RF, and improve patient outcomes.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Intensive Care Units; Middle Aged; Databases, Factual; ROC Curve; Risk Assessment; Aged, 80 and over; Nomograms; Risk Factors; Pulmonary Disease, Chronic Obstructive
PubMed: 38926685
DOI: 10.1186/s12890-024-03099-2 -
Anais Da Academia Brasileira de Ciencias 2024The need for the identification of risk factors associated to COVID-19 disease severity remains urgent. Patients' care and resource allocation can be potentially...
The need for the identification of risk factors associated to COVID-19 disease severity remains urgent. Patients' care and resource allocation can be potentially different and are defined based on the current classification of disease severity. This classification is based on the analysis of clinical parameters and routine blood tests, which are not standardized across the globe. Some laboratory test alterations have been associated to COVID-19 severity, although these data are conflicting partly due to the different methodologies used across different studies. This study aimed to construct and validate a disease severity prediction model using machine learning (ML). Seventy-two patients admitted to a Brazilian hospital and diagnosed with COVID-19 through RT-PCR and/or ELISA, and with varying degrees of disease severity, were included in the study. Their electronic medical records and the results from daily blood tests were used to develop a ML model to predict disease severity. Using the above data set, a combination of five laboratorial biomarkers was identified as accurate predictors of COVID-19 severe disease with a ROC-AUC of 0.80 ± 0.13. Those biomarkers included prothrombin activity, ferritin, serum iron, ATTP and monocytes. The application of the devised ML model may help rationalize clinical decision and care.
Topics: Humans; COVID-19; Machine Learning; Severity of Illness Index; Female; Male; Biomarkers; Middle Aged; Prognosis; SARS-CoV-2; Adult; Ferritins; Aged; Brazil; Hematologic Tests; ROC Curve; Risk Factors
PubMed: 38922277
DOI: 10.1590/0001-376520242023089