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Clinica Chimica Acta; International... Jun 2024The viral load (VL) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals is critical for improving clinical treatment strategies, care,...
BACKGROUND
The viral load (VL) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals is critical for improving clinical treatment strategies, care, and decisions. Several studies have reported that the initial SARS-CoV-2 VL is associated with disease severity and mortality. Cycle threshold (Ct) values and/or copies/mL are often used to quantify VL. However, a multitude of platforms, primer/probe sets of different SARS-CoV-2 target genes, and reference material manufacturers may cause inconsistent interlaboratory interpretations. The first International Standard for SARS-CoV-2 RNA quantitative assays has allowed diagnostic laboratories to transition SARS-CoV-2 VL results into international units per milliliter (IU/mL). The Cobas SARS-CoV-2 Duo quantitative assay provides VL results expressed in IU/mL.
MATERIALS AND METHODS
We enrolled 145 and 50 SARS-CoV-2-positive, hospitalized and 50-negative individuals at the Tri-Service General Hospital, Taiwan from January to May 2022. Each participant's electronic medical record was reviewed to determine asymptomatic, mild, moderate, and severe cases. Nasopharyngeal swabs were collected using universal transport medium. We investigated the association of SARS-CoV-2 VL with disease severity using the Cobas SARS-CoV-2 Duo quantitative assay and its functionality in clinical assessment and decision making to further improve clinical treatment strategies. Limit of detection (LOD) was assessed.
RESULTS
All 50 SARS-CoV-2-negative samples confirmed negative for SARS-CoV-2, demonstrating 100 % specificity of the Cobas SARS-CoV-2 Duo assay. Patients with severe symptoms had longer hospital stays, and the length of hospital stay (30.56 days on average) positively correlated with the VL (8.22 ± 1.21 log IU/mL). Asymptomatic patients had the lowest VL (5.54 ± 2.06 log IU/mL) at admission and the shortest hospital stay (14.1 days on average).
CONCLUSIONS
VL is associated with disease severity and duration of hospitalization; therefore, its quantification should be considered when making clinical care decisions and treatment strategies. The Cobas SARS-CoV-2 Duo assay provides a commutable unitage IU/mL for interlaboratory interpretations.
Topics: Humans; Viral Load; COVID-19; SARS-CoV-2; Disease Progression; Male; Female; Middle Aged; Adult; Aged; RNA, Viral
PubMed: 38754576
DOI: 10.1016/j.cca.2024.119731 -
PloS One 2024Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus...
BACKGROUND
Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus (HIV). The burden of hepatitis among HIV-positive individuals has not been studied in the Afar region. Therefore, this study aimed to determine the prevalence of HBV and HCV coinfection and associated factors among HIV-positive patients in Afar Regional State, northeast Ethiopia.
METHODS
A cross-sectional study was conducted on 477 HIV-positive patients between February 2019 and May 2019. A structured and pretested questionnaire was used to collect socio-demographic data and associated factors. Five milliliters of blood was collected, and Hepatitis B surface antigen (HBsAg) and HCV antibodies were detected using rapid test kits. Positive samples were confirmed using enzyme-linked immunosorbent assay (ELISA). Binary and multivariable logistic regression analyses were performed to identify associated factors. Statistical significance was set at P <0.05.
RESULTS
Among the 477 study participants, 320/477(67.1%) of them were females and 157(32.9%) males. The overall prevalence of HIV-HBV and HIV-HCV coinfection was 25(5.2%) and 7(1.5%), respectively. Multi-sexual practice was significantly associated with HIV-HBV coinfection (AOR = 5.3; 95% CI: 1.2-24.4, P = 0.032).
CONCLUSION
The prevalence of both HIV-HBV and HIV-HCV coinfection was intermediate. Multi-sexual practice was significantly associated with HIV-HBV coinfection. Screening of all HIV-positive patients for HBV and HCV and health education regarding the transmission modes should be considered.
Topics: Humans; Ethiopia; Female; Male; Adult; Hepatitis B; Coinfection; Hepatitis C; HIV Infections; Cross-Sectional Studies; Middle Aged; Prevalence; Young Adult; Adolescent; Hepatitis B Surface Antigens; Hepacivirus; Risk Factors; Hepatitis B virus
PubMed: 38753600
DOI: 10.1371/journal.pone.0302453 -
Drug Testing and Analysis May 2024Accurate determination of carboxy-hemoglobin (COHb%) is essential for the assessment of hemoglobin mass (Hbmass) by CO-rebreathing. To analyze blood samples for a...
Accurate determination of carboxy-hemoglobin (COHb%) is essential for the assessment of hemoglobin mass (Hbmass) by CO-rebreathing. To analyze blood samples for a certain period of time after blood collection, it is necessary to know the stability of the COHb% during storage. The aim of the study was to determine the stability of COHb% at different storage temperatures over a period of up to 3 months. Twenty-five milliliters of cubital venous blood was taken from five volunteers (three females and two males) before and after inhalation of 0.8/1.0 mL/kg carbon monoxide and stored at +20°C and +4°C for 6 days and at -70°C for 12 weeks. Within the first 6 days, the blood was analyzed daily, then weekly for 12 weeks. Additionally, Hbmass was determined in 13 endurance athletes immediately after blood collection and after storage for 3 days (eight cyclists) and 7 days (five swimmers) at +20°C or +4°C. COHb% before and after CO inhalation was 1.56 ± 0.48 and 5.86 ± 1.12%, respectively, and remained unchanged over 6 days, with no difference between storage at different temperatures. The standard deviation (STD) over time was between 0.07% and 0.12%. Similarly, storage at -70°C for 12 weeks did not change COHb%, whereas STD was 0.07%. Hbmass determined immediately and, after 3 or 7 days of storage, differed by 10 ± 7 g and 15 ± 11 g corresponding to a typical error of 0.8% and 1.1%. Blood storage at +20°C and +4°C for 6 days and at -70°C for 12 weeks does not affect COHb% and has, therefore, no influence on Hbmass assessment.
PubMed: 38747126
DOI: 10.1002/dta.3710 -
Emergency Medicine International 2024Fixed, large volume resuscitation with intravenous fluids (IVFs) in septic shock can cause inadvertent hypervolemia, increased medical interventions, and death when...
BACKGROUND
Fixed, large volume resuscitation with intravenous fluids (IVFs) in septic shock can cause inadvertent hypervolemia, increased medical interventions, and death when unguided by point-of-care ultrasound (POCUS). The primary study objective was to evaluate whether total IVF volume differs for emergency department (ED) septic shock patients receiving POCUS versus no POCUS.
METHODS
We conducted a retrospective observational cohort study from 7/1/2018 to 8/31/2021 of atraumatic adult ED patients with septic shock. We agreed upon variables and defined septic shock as lactate ≥4 and hypotension (SBP <90 or MAP <65). A sample size of 300 patients would provide 85% power to detect an IVF difference of 500 milliliters between POCUS and non-POCUS cohorts. Data are reported as frequencies, median (IQR), and associations from bivariate logistic models.
RESULTS
304 patients met criteria and 26% (78/304) underwent POCUS. Cardiac POCUS demonstrated reduced ejection fraction in 15.4% of patients. Lung ultrasound showed normal findings in 53% of patients. The POCUS vs. non-POCUS cohorts had statistically significant differences for the following variables: higher median lactate (6.7 [IQR 5.2-8.7] vs. 5.6], = 0.003), lower systolic blood pressure (77.5 [IQR 61-86] vs. 85.0, < 0.001), more vasopressor use (51% vs. 34%, = 0.006), and more positive pressure ventilation (38% vs. 24%, = 0.017). However, there were no statistically significant differences between POCUS and non-POCUS cohorts in total IVF volume ml/kg (33.02 vs. 32.1, = 0.47), new oxygen requirement (68% vs. 59%, = 0.16), ED death (3% vs. 4%, = 0.15), or hospital death (31% vs. 27%, = 0.48). There were similar distributions of lactate, total fluids, and vasopressors in patients with CHF and severe renal failure.
CONCLUSIONS
Among ED patients with septic shock, POCUS was more likely to be used in sicker patients. Patients who had POCUS were given similar volume of crystalloids although these patients were more critically ill. There were no differences in new oxygen requirement or mortality in the POCUS group compared to the non-POCUS group.
PubMed: 38742136
DOI: 10.1155/2024/5675066 -
Journal of Clinical Medicine May 2024Early perihematomal edema (PHE) growth is associated with worse functional outcomes at 90 days. Remote Ischemic conditioning (RIC) may reduce perihematomal inflammation...
Early perihematomal edema (PHE) growth is associated with worse functional outcomes at 90 days. Remote Ischemic conditioning (RIC) may reduce perihematomal inflammation if applied early to patients with intracerebral hemorrhage (ICH). We hypothesize that early RIC, delivered for seven days in patients with spontaneous ICH, may reduce PHE growth. ICH patients presenting within 6 h of symptom onset and hematoma volume < 60 milliliters (mL) were randomized to an RIC + standard care or standard care (SC) group. The primary outcome measure was calculated edema extension distance (EED), with the cm assessed on day seven. Sixty patients were randomized with a mean ± SD age of 57.5 ± 10.8 years, and twenty-two (36.7%) were female. The relative baseline median PHE were similar (RIC group 0.75 (0.5-0.9) mL vs. SC group 0.91 (0.5-1.2) mL, = 0.30). The median EEDs at baseline were similar (RIC group 0.58 (0.3-0.8) cm vs. SC group 0.51 (0.3-0.8) cm, = 0.76). There was no difference in the median day 7 EED (RIC group 1.1 (0.6-1.2) cm vs. SC group 1 (0.9-1.2) cm, = 0.75). Early RIC therapy delivered daily for seven days was feasible. However, no decrease in EED was noted with the intervention.
PubMed: 38731225
DOI: 10.3390/jcm13092696 -
Clinica Chimica Acta; International... Jun 2024To integrate an enhanced molecular diagnostic technique to develop and validate a machine-learning model for diagnosing sepsis.
OBJECTIVE
To integrate an enhanced molecular diagnostic technique to develop and validate a machine-learning model for diagnosing sepsis.
METHODS
We prospectively enrolled patients suspected of sepsis from August 2021 to August 2023. Various feature selection algorithms and machine learning models were used to develop the model. The best classifier was selected using 5-fold cross validation set and then was applied to assess the performance of the model in the testing set. Additionally, we employed the Shapley Additive exPlanations (SHAP) method to illustrate the effects of the features.
RESULTS
We established an optimized mNGS assay and proposed using the copies of microbe-specific cell-free DNA per milliliter of plasma (CPM) as the detection signal to evaluate the real burden, with strong precision and high accuracy. In total, 237 patients were eligible for participation, which were randomly assigned to either the training set (70 %, n = 165) or the testing set (30 %, n = 72). The random forest classifier achieved accuracy, AUC and F1 scores of 0.830, 0.918 and 0.856, respectively, outperforming other machine learning models in the training set. Our model demonstrated clinical interpretability and achieved good prediction performance in differentiating between bacterial sepsis and non-sepsis, with an AUC value of 0.85 and an average precision of 0.91 in the testing set. Based on the SHAP value, the top nine features of the model were PCT, CPM, CRP, ALB, SBP, RR, CREA, PLT and HR.
CONCLUSION
We demonstrated the potential of machine-learning approaches for predicting bacterial sepsis based on optimized mcfDNA sequencing assay accurately.
Topics: Machine Learning; Humans; Sepsis; Male; Female; Middle Aged; Cell-Free Nucleic Acids; Aged; Sequence Analysis, DNA; Prospective Studies
PubMed: 38710402
DOI: 10.1016/j.cca.2024.119716 -
Cell Biochemistry and Function Jun 2024This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and...
This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and anti-inflammatory cytokine and protecting against lung and liver injuries. Male Swiss albino mice were exposed to 0.2 Gy gamma radiation/week for four consecutive weeks then injected intraperitoneally (i.p) with a single dose of 8.3 × 10 CFU Escherichia coli/g b.w. then injected i.p. with 1.0 mg/kg cholecalciferol (Vit D for 7 days starting 4 h after E. coli injection. The results revealed that Cholecalciferol and low dose gamma radiation caused significant depletion in the severity of E. coli infection (colony forming unit per milliliter), log of E. coli, Tumor necrosis factor alpha, Interleukin 6, VEGF, alanine aminotransferase, and aspartate aminotransferase levels and significant elevation in IL-10, IL-4, and HO-1. Immunohistochemical analysis of caspase-3 expression in lung tissue section showed low caspase-3 expression in cholecalciferol and low dose gamma radiation treated group. Histopathological examinations were performed in both lung and liver tissues which also emphasis the biochemical findings. Our results exhibit the importance of cholecalciferol and low dose gamma radiation in improving liver function and providing anti-inflammatory response in diseases causing cytokine storm.
Topics: Animals; Mice; Cholecalciferol; Male; Gamma Rays; Escherichia coli Infections; Escherichia coli; Liver; Lung; Cytokines; Cytokine Release Syndrome; Aspartate Aminotransferases
PubMed: 38693631
DOI: 10.1002/cbf.4026 -
Circulation. Cardiovascular... Apr 2024Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives...
BACKGROUND
Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety.
METHODS
Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion.
RESULTS
Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; =0.0165), lower coronary flow reserve (1.82 versus 3.21; ≤0.0001), and higher coronary resistance (655 versus 422 woods units; =0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; =0.8292), coronary flow reserve (2.77 versus 3.21; =0.1107), and coronary resistance (415 versus 422 woods units; =0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates.
CONCLUSIONS
Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.
PubMed: 38682331
DOI: 10.1161/CIRCINTERVENTIONS.123.013860 -
Asian Pacific Journal of Cancer... Apr 2024aim of this study was to examine the synergistic effect between the antibacterial drug ciprofloxacin and the natural compound laetrile on esophageal cancer cells,...
OBJECTIVE
aim of this study was to examine the synergistic effect between the antibacterial drug ciprofloxacin and the natural compound laetrile on esophageal cancer cells, specifically focusing on their combined cytotoxic effect.
METHODS
The combined cytotoxic effects of two alternative incubation durations (24 and 72 hours) were studied using an esophageal cancer cell line. Ciprofloxacin, laetrile, and their combinations were tested at concentrations ranging from 1 to 1000 micrograms/milliliter, to enhance the safety of the combination, the concentrations of the combination constituents were reduced by half compared to when they are used individually, the combination index was then calculated to estimate the components' possible synergistic effects.
RESULT
The results indicate that the combined cytotoxicity of ciprofloxacin and laetrile was greater than the cytotoxicity of either ciprofloxacin or laetrile alone, the combination cytotoxicity increased with higher concentrations and longer incubation periods, in other words, the cytotoxicity pattern of the combination was time-dependent (cell-cycle specific), and concentration dependent, (cell-cycle non-specific).
CONCLUSION
The study found that the combination of ciprofloxacin and laetrile had a greater inhibitory effect on the growth of esophageal cancer cells compared to ciprofloxacin or laetrile alone. This suggests a synergistic effect between the components of the mixture, which can be attributed to a complementary mechanism between the ingredients in the combination.
Topics: Humans; Ciprofloxacin; Esophageal Neoplasms; Drug Synergism; Cell Proliferation; Cell Cycle; Tumor Cells, Cultured; Apoptosis; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38680005
DOI: 10.31557/APJCP.2024.25.4.1433 -
The Journal of Molecular Diagnostics :... Jul 2024The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This...
The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube. The detection limitation of the test was approximately two genome copies of methylated PENK per milliliter of urine. In the retrospective training set (n = 105), an optimal cutoff value was determined to distinguish BC from non-BC, resulting in a sensitivity of 87.3% and a specificity of 95.2%. In the prospective validation set (n = 210, 122 Korean and 88 American patients), the overall sensitivity for detecting all stages of BC was 81.0%, with a specificity of 91.5% and an area under the curve value of 0.889. There was no significant difference between the two groups. The test achieved a sensitivity of 100% in detecting high-grade Ta and higher stages of BC. The negative predictive value of the test was 97.7%, and the positive predictive value was 51.5%. The findings of this study demonstrate that EarlyTect BCD is a highly effective noninvasive diagnostic tool for identifying BC among patients with hematuria.
Topics: Humans; Urinary Bladder Neoplasms; Hematuria; DNA Methylation; Male; Female; Middle Aged; Aged; Sensitivity and Specificity; Biomarkers, Tumor; Retrospective Studies; ROC Curve; Aged, 80 and over; Early Detection of Cancer; Adult
PubMed: 38677548
DOI: 10.1016/j.jmoldx.2024.04.001