Factors influencing false-positive results of rifampicin resistance detected by Xpert MTB/RIF: A retrospective study in Zhejiang, China.

Objective: This study aimed to explore the factors influencing false-positive results for rifampicin resistance (RIF-R) detected using Xpert MTB/RIF (Xpert). Methods: This retrospective analysis included the clinical data of patients from September 2019 to February 2023. The chi-square and rank sum tests were used to compare differences in patient characteristics between the true-positive and false-positive groups. Logistic regression was used to analyze the factors influencing false positives in the detection of RIF-R by Xpert. Results: A total of 384 patients were included. Logistic regression analysis revealed that, with mutation of probe E as the reference, mutations on probe A or C (OR = 72.68, P < 0.001), probe D (OR = 6.44, P < 0.001), and multiple probes (OR = 5.94, P = 0.002) were associated with false-positive results in Xpert detection of RIF-R. Taking probe delay ΔCt <4 as the reference, ΔCt (4-5.9) (OR = 13.54, P < 0.001), ΔCt (6-7.9) (OR = 48.08, P < 0.001) probe delays were associated with false positives in Xpert detection of RIF-R. When very low quantification is accompanied by a probe delay, the probability of false-positive RIF-R detection can reach 80 %. Conclusions: Clinicians should consider factors such as probe mutation type, probe delay, and very low quantification accompanied by probe delay when interpreting Xpert results, which can reduce the misdiagnosis of tuberculosis drug resistance.

Analysis of Influencing Factors of Postoperative Quality of Life in Patients with Renal Cancer under the Continuing Care Model Based on the Omaha System.

BACKGROUND: Scientific nursing is of great significance for improving negative emotions, self-management ability and quality of life of patients after cancer surgery. The Omaha system has been widely used in the field of care in many countries and regions, and although it helps to improve the quality of life of cancer patients after surgery, there are still large differences between different patients. This study examines factors affecting postoperative quality of life in renal cancer patients under the continuous care Omaha system, aiming to refine nursing plans. METHODS: We retrospectively analyzed clinical data from 108 renal cancer patients undergoing radical treatment, all of whom received care via the Omaha system. The score for quality of life and the scores for Strategies Used by People to Promote Health (SUPPH), Social Support Rate Scale (SSRS), and Medical Coping Modes Questionnaire (MCMQ) of patients with different baseline data were compared. RESULTS: Patients with spouses as primary caregivers scored higher across psychological, physical, physiological, and societal dimensions of quality of life than those with children or others as caregivers (p < 0.001). Patients without underlying diseases have higher physiological, societal dimensions, overall satisfaction total score for quality of life (compared to those with underlying diseases, p < 0.001), patients with clinical stage III have lower physiological, societal dimensions, overall satisfaction, and total score for quality of life (compared to stage I/II, p < 0.001). The physiological, societal dimensions, overall satisfaction, and total quality of life score for patients with medical or commercial insurance as the settlement method for medical expenses are higher (compared to self-funded, p < 0.001). In the SUPPH scale, the positive attitude score, stress reduction score, making decisions score, and total score were positively correlated with the total score for quality of life (p < 0.001, p < 0.001, p = 0.008, p < 0.001, respectively). In the SSRS scale, the objective support score, subjective support score, useless support score, and total score were positively correlated with the total score for quality of life (all p < 0.001). In the MCMQ scale, the confrontation score was positively correlated with the total score for quality of life (p < 0.001). The acceptance-resignation and avoidance scores were negatively correlated with the total score for quality of life (p < 0.001). CONCLUSION: The quality of life of patients is not only affected by primary caregivers, underlying diseases, clinical staging, and medical expense settlement methods, but also positively correlated with self-efficacy and social support, and negatively correlated with coping styles.

Evaluation of the Prognostic Role of Neutrophil-Lymphocyte Ratio, C-Reactive Protein-Albumin Ratio, and Platelet-Lymphocyte Ratio in Patients with the Co-Presentation of Coronary Artery Disease and COVID-19.

Aim: The purpose of this study was to investigate the role of neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) in the prognosis of patients with coronary artery disease (CAD) complicated with coronavirus disease 2019 (COVID-19). Methods: This study included 265 patients. A receiver operating characteristic (ROC) curve analysis was performed to preliminarily evaluate the predictive ability of NLR, CAR, and PLR for all-cause death. The primary outcome was all-cause death during hospitalization, while the secondary outcomes were cardiovascular death and respiratory failure death. The Cox proportional hazard model with adjusted covariates was used to analyze the cumulative risk of outcomes. We also conducted subgroup analyses based on the acute and chronic characteristics of CAD. Propensity score matching (PSM) was used to further evaluate the robustness of the primary outcome. Results: The ROC curve analysis results showed that the area under curve (AUC) values were 0.686 (95% CI 0.592-0.781, P<0.001) for NLR, 0.749 (95% CI 0.667-0.832, P<0.001) for CAR, and 0.571 (95% CI 0.455-0.687, P=0.232) for PLR. The Cox proportional hazard model showed that trends in NLR and PLR did not affect the risk of all-cause death (P=0.096 and P=0.544 for trend, respectively), but a higher CAR level corresponded to a higher risk of all-cause death (P<0.001 for trend). Similarly, The trends of NLR and PLR did not affect the risk of cardiovascular death and respiratory failure death, while a higher CAR level corresponded to a higher risk of cardiovascular death and respiratory failure death. The results of subgroup analyses and PSM were consistent with the total cohort. Conclusion: In patients with CAD complicated with COVID-19, a higher CAR level corresponded to a higher risk of all-cause death, cardiovascular death, and respiratory failure death, while trends in NLR and PLR did not.

Inflammatory risk of albumin combined with C-reactive protein predicts long-term cardiovascular risk in patients with diabetes.

AIMS: The purpose of this study was to evaluate the predictive value of inflammatory risk as defined by the Glasgow Prognostic Score (GPS) for cardiovascular death in patients with diabetes. METHODS: This study included 4956 patients (≥18 years old) with diabetes in the National Health and Nutrition Survey from 1999 to 2010. The mortality rate was determined by the correlation with the national death index on December 31, 2019. The GPS was composed of the serum C-reactive protein and the albumin. The primary outcome was cardiovascular death and the secondary outcome was all-cause death. The Cox proportional risk model adjusted for demographic factors and traditional cardiovascular risk factors was used to analyze the cumulative risk of outcomes. RESULTS: Among 4956 diabetes patients with a median follow-up of 10.9 years, 601 cardiovascular deaths and 2187 all-cause deaths were recorded. After adequate model adjustment, compared with the low GPS group, the high GPS group (HR, 1.257 (1.007-1.570), P = 0.043) had a higher cardiovascular mortality. Compared with the low GPS group, the all-cause mortality of the high GPS group (HR, 1.394 (1.245-1.560), P < 0.001) was higher. The results of subgroup analyses were similar with that of the overall cohort. CONCLUSIONS: The inflammatory risk as defined by the GPS was closely related to the increased risk of cardiovascular and all-cause death in patients with diabetes. It may be a convenient and efficient clinical practical risk assessment tool for patients with diabetes.

The impact of urinary albumin-creatinine ratio and glomerular filtration rate on long-term mortality in patients with heart failure: The National Health and Nutrition Examination Survey 1999-2018.

BACKGROUND AND AIMS: The urinary albumin‒creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are important markers of renal dysfunction, but few studies have simultaneously examined their impact on long-term mortality in patients with heart failure (HF). METHODS AND RESULTS: This study included patients with HF from the National Health and Nutrition Survey from 1999 to 2018. The fully adjusted Cox proportional risk model was adopted, and propensity score matching (PSM) was also used for risk adjustment. Among 988 patients, a median follow-up of 7.75 years was recorded. A higher UACR corresponded to a higher risk of cardiovascular death (P < 0.001 for trend). No statistically significant difference was found in the trend of eGFR risk stratification on the risk of cardiovascular death (P = 0.09 for trend). After PSM, the results showed that when grouped by UACR, the high-risk group had a higher risk of cardiovascular death regardless of a cutoff value of 30 or 300 mg/g (all P < 0.05). When grouped by eGFR, regardless of a cutoff value of 45 or 30 mL/min/1.73 m2, compared to the low-risk group, the high-risk group did not have a statistically significant increase in cardiovascular death (P = 0.086 and P = 0.093, respectively). The subgroup analysis of the main outcome showed an interaction between the UACR and eGFR (P = 0.044). CONCLUSIONS: Both the UACR and eGFR are markers for predicting the progression of HF, but the UACR may be a more important indicator than the eGFR, and they synergistically and complementarily reflect the long-term cardiovascular risk of HF patients.

Smoking is a Factor in Discordance Between QuantiFERONTB Gold Assay and Tuberculosis Etiology: Especially in Older Patients.

Purpose: Exploring whether smoking is an influencing factor for the inconsistency between QuantiFERONTB Gold assay (QFT-GIT) and tuberculosis etiology. Patients and Methods: The clinical data of patients who were confirmed positive for Mycobacterium tuberculosis (MTB) after undergoing QFT-GIT testing from September 2017 to August 2021 were retrospectively analyzed. Chi-square and rank-sum tests were used to compare the differences in characteristics between smokers and non-smokers. Logistic regression was used to adjust for confounding factors affecting smoking. Propensity score matching (PSM) was used to verify the above conclusions again. Results: Positive results of tuberculosis etiology were adopted as the standard, the incidence of inconsistent results between QFT-GIT and tuberculosis etiology was 8.90% (108/1213), of which the false negative rate was 6.27% (76/1213) and the indeterminate rate was 2.64% (32/1213). In the overall population, the smokers had a lower level of basal IFN-γ (Z=-2.079, P=0.038). Among 382 elderly (≥65 years old) patients, the smokers had lower levels of antigen-stimulated IFN-γ (Z=-2.838, P=0.005). After performing BOX-COX transformation on all non-normally distributed data, logistic stepwise regression was used to adjust confounding factors. The results showed that smoking was an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiology results (OR=1.69, P=0.020). Using PSM for 1:2 matching, the results showed that smoking was still an independent risk factor for the inconsistent results of QFT-GIT and tuberculosis etiology (OR= 1.95, P=0.019). Age-stratified analysis showed that smoking was an independent risk factor in discordance between QFT-GIT and tuberculosis etiology in patients aged ≥65 years (OR=2.40, P=0.005), but not in patients aged <65 years (P > 0.05). Conclusion: Smoking can reduce the body's IFN-γ release ability, and smoking (especially the elderly) is an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiological results.

Development of a novel forensic age estimation strategy for aged blood samples by combining piRNA and miRNA markers.

In forensic investigations, age estimation is vital for determining whether a suspect is under or over the legally defined adult age. With breakthroughs in RNA sequencing technology, small noncoding RNAs have provided new ways to solve problems related to the age estimation of trace or aged samples, owing to their small molecular weight and better stability. In our previous study, we had applied miRNAs for the age estimation of bloodstains; however, further improvement of the existing model is needed. PIWI-interacting RNAs (PiRNAs), which are 24-32 nt noncoding small RNA molecules involved in the PIWI-piRNA pathway, play an important role in the aging process. In this study, we explored the possibility of simultaneously analyzing piRNAs and miRNAs for better age estimation purpose. Through massively parallel sequencing, five age-related piRNAs were identified in blood samples that had been stored for eight years. Further real-time PCR analysis revealed that two piRNAs (piR-000753 and piR-020548) showed relatively higher efficiency in age estimation. Additionally, two age-related miRNAs (miR-324-3p and miR-330-5p) were used to build the estimation model. Among all algorithms tested, gradient boosting showed the lowest mean absolute error (MAE) and root mean square error (RMSE) values (3.171 and 4.403 years, respectively) for the validation dataset (n = 110). The errors of the model were less than 5 years and 10 years for 81.82% and 96.36% of the samples, respectively. The results suggest that the combined use of piRNA and miRNA markers may increase the accuracy of age estimation, and our new model has great potential for application in forensic casework.

Distinguishing between monozygotic twins' blood samples through immune repertoire sequencing.

Monozygotic (MZ) twins with highly similar genomic DNA sequences can not be distinguished by conventional forensic DNA testing. The immune repertoire (IR) reflects an individual's immune history, which is unique between individuals, has been applied to individualized treatment in precision medicine. However, the application of IR in forensic genetics has not been reported to date. In this study, the diversity in the complementary determining region 3 (CDR3) of both the T-cell receptor ß chain (TCRß) and B-cell receptor heavy chain (also known as immunoglobulin heavy chain, IGH) in four pairs of MZ twins were analyzed. The results showed that the amino acid sequences length distribution frequency of TCRß CDR3 had 4-10 differences, and the nucleic acid sequences length distribution frequency of TCRß CDR3 had 2-7 differences between MZ twins. The shared difference of four pairs of MZ twins focused on the length distribution frequency of 34 bp nucleotide sequences in TCRß. By analyzing the usage frequency of V and J genes in TCRß and IGH CDR3 DNA sequence rearrangements, we also found that there were biases between each pair of MZ twins, and the usage frequency of TRBJ2-3 showed common differences between each pair of MZ twins. Furthermore, each pair of MZ twins had its own unique V-J genes combination mode in TCRß and IGH CDR3 DNA sequences. This study, for the first time, suggested that IR can be used as a potential biological marker to distinguish MZ twins.

The Importance of Integrated Regulation Mechanism of Coronary Microvascular Function for Maintaining the Stability of Coronary Microcirculation: An Easily Overlooked Perspective.

Coronary microvascular dysfunction (CMD) refers to a group of disorders affecting the structure and function of coronary microcirculation and is associated with an increased risk of major adverse cardiovascular events. At present, great progress has been made in the diagnosis of CMD, but there is no specific treatment for it because of the complexity of CMD pathogenesis. Vascular dysfunction is one of the important causes of CMD, but previous reviews mostly considered microvascular dysfunction as a whole abnormality so the obtained conclusions are skewed. The coronary microvascular function is co-regulated by multiple mechanisms, and the mechanisms by which microvessels of different luminal diameters are regulated vary. The main purpose of this review is to revisit the mechanisms by which coronary microvessels at different diameters regulate coronary microcirculation through integrated sequential activation and briefly discuss the pathogenesis, diagnosis, and treatment progress of CMD from this perspective.

Malnutrition is Associated with an Increased Risk of Death in Hospitalized Patients with Active Pulmonary Tuberculosis: A Propensity Score Matched Retrospective Cohort Study.

Background: This study aimed to investigate whether nutrition levels in patients with active pulmonary tuberculosis (TB) affect their risk of all-cause mortality during hospitalization and to further evaluate the predictive ability of Geriatric Nutritional Risk Index (GNRI) and Body Mass Index (BMI) for risk of all-cause mortality. Methods: Patients from January 1, 2020 to December 31, 2021 were retrieved, and a total of 1847 were included. The primary outcome was all-cause mortality. Propensity score matching (PSM) was performed for risk adjustment, and receiver operating characteristic (ROC) curve analysis was performed to assess the predictive ability of GNRI and BMI for all-cause mortality. Results: Malnourished TB patients were older, had more congestive heart failure, and had more chronic obstructive pulmonary disease or asthma. Under the nutrition level grouping defined by GNRI, the all-cause mortality in the malnourished group did not appear to reach a statistical difference compared with the nonmalnourished group (P = 0.078). When grouped by level of nutrition as defined by BMI, the all-cause mortality was higher in the malnourished group (P = 0.009), and multivariate logistic regression analysis revealed that malnutrition was an independent risk factor for all-cause mortality. After propensity score matching, the results showed that the all-cause mortality was higher in the malnutrition group, regardless of BMI or GNRI defined nutrition level grouping, compared with the control group (both P < 0.001). The ROC curve analysis revealed that the area under the curve (AUC) was 0.811 ([95% confidence interval (CI) 0.701-0.922], P < 0.001) for GNRI and 0.728 ([95% CI 0.588-0.869], P = 0.001) for BMI. Conclusion: In the clinical treatment of patients with active TB, more attention should be paid to the management of nutritional risk. GNRI may be a highly effective and easy method for predicting short-term outcomes in patients with active pulmonary TB.

Risk Assessment of Major Adverse Cardiovascular and Cerebrovascular Events and Bleeding for Acute Myocardial Infarction With or Without Active Tuberculosis.

PURPOSE: The underlying ischemic and bleeding risks of acute myocardial infarction (AMI) with active tuberculosis (TB) are unknown. The goal of this study was to explore the ischemic and bleeding risks, as well as treatment strategies during hospitalization, in patients with AMI with or without active TB. METHODS: Patients were recruited from a tuberculosis hospital from 2014 to 2021. The primary outcomes were major cardiovascular and cerebrovascular events (MACE) and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding. Multivariate logistic regression and propensity score matching were performed for risk adjustment. Subgroups were defined according to AMI with active pulmonary TB and AMI with active TB undergoing percutaneous coronary intervention (PCI). FINDINGS: A total of 242 patients were enrolled. Compared with AMI without active TB, AMI with active TB had a higher risk of MACE and BARC type 3 or 5 bleeding (P < 0.001 and P = 0.002, respectively). Multivariate logistic regression analysis showed that, compared with AMI without active TB, the odds ratio (OR) was 6.513 (95% CI, 2.195-19.331) for MACE in patients with AMI with active TB, and the OR was 16.074 (95% CI 3.337-77.436) for BARC type 3 or 5 bleeding in patients with AMI with active TB. After propensity score matching, AMI with active TB tended to increase the risk of MACE, although not statistically significantly (P = 0.189), and increased BARC type 3 or 5 bleeding (P < 0.001), compared with AMI without active TB. Results of subgroup analyses showed that active TB had outcomes consistent with those of the total cohort. AMI patients with active pulmonary TB who underwent PCI had a lower risk of MACE without an increase in the risk of bleeding compared with those not undergoing PCI. IMPLICATIONS: Patients with AMI with active TB have a higher risk of MACE (or severe MACE) and bleeding than patients with AMI without active TB. However, AMI patients with active TB are still advised to undergo PCI for a high net clinical benefit.

An Application of ITO Analysis in Secondary Kinship Identification.

Objective: As the methods of the paternity and kinship testing have been developed, the second-degree and more distant relationships remain challenging in forensic science. Currently, the ITO method is the mainstream method to clarify the kinship between two individuals. Methods: In this study, the ITO algorithm was used to calculate the uncle-nephew index based on 55 autosomal short tandem repeats (STRs) loci that were universally used for forensic identification. 19 STRs loci in Y chromosome were used for verification of the kinship. Results: The cumulative uncle-nephew index between A and B was calculated to 0.993 by the analysis of the genotyping results of 21 STRs. When genotyping results of the other 34 STRs were added to the calculation algorithm, the cumulative uncle-nephew index between A and B was promoted to 227.928. Meanwhile, genotyping results of 17 Y-STRs loci showed that A and B shared the same Y-STRs haplotype that was in accord with the paternal inheritance law. Conclusion: The biological uncle-nephew relationship between A and B are identified by applying the statistical principles and genetic technologies.

Secondary prevention of antithrombotic therapy in patients with stable cardiovascular disease at high ischemic risk: A network meta-analysis of randomized controlled trials.

Aims: Antithrombotic secondary prevention in stable cardiovascular disease (SCVD) patients at high ischemic risk remains unclear. We compared the efficacy and safety of aspirin monotherapy, clopidogrel monotherapy, ticagrelor monotherapy, rivaroxaban monotherapy, clopidogrel plus aspirin, ticagrelor plus aspirin, and rivaroxaban plus aspirin in the high-risk ischemic cohorts. Methods and results: Eleven randomized controlled trials were included (n = 111737). The primary outcomes were major cardiovascular and cerebrovascular events (MACEs) and major bleeding. A random effects model was used for frequentist network meta-analysis. Odds ratio (OR) and 95% credible intervals (CI) were reported as a summary statistic. Compared with aspirin monotherapy, rivaroxaban plus aspirin [OR 0.79 (95% CI, 0.69, 0.89)], ticagrelor plus aspirin [0.88 (0.80, 0.98)], clopidogrel plus aspirin [0.56 (0.41, 0.77)] were associated with a reduced risk of MACEs, but rivaroxaban monotherapy [0.92 (0.79, 1.07)], ticagrelor monotherapy [0.68 (0.45, 1.05)], and clopidogrel monotherapy [0.67 (0.43, 1.05)] showed no statistically significant difference. However, rivaroxaban monotherapy and all dual antithrombotic strategies increased the risk of major bleeding to varying degrees, with ticagrelor plus aspirin associated with the highest risk of major bleeding. The net clinical benefit favored clopidogrel or ticagrelor monotherapy, which have a mild anti-ischemic effect without an increase in bleeding risk. Conclusion: The present network meta-analysis suggests that clopidogrel or ticagrelor monotherapy may be recommended first in this cohort of SCVD at high ischemic risk. But clopidogrel plus aspirin or rivaroxaban plus aspirin can still be considered for use in patients with recurrent MACEs.

Predictive value of inflammation-based Glasgow prognostic score, platelet-lymphocyte ratio, and global registry of acute coronary events score for major cardiovascular and cerebrovascular events during hospitalization in patients with acute myocardial infarction.

PURPOSE: The goal of this study was to evaluate the predictive ability of the inflammation-based Glasgow Prognostic Score (GPS), platelet-lymphocyte ratio (PLR), Global Registry of Acute Coronary Events (GRACE) score and combined diagnostic models for the occurrence of major adverse cardiovascular and cerebrovascular events (MACEs) in patients with acute myocardial infarction (AMI). METHODS: In this retrospective cohort study, eligible patients were required to meet the third global definition of myocardial infarction. The primary outcome of this study was the occurrence of MACEs during hospitalization. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive ability of the GPS, PLR, GRACE scores, and joint diagnostic models for primary outcomes; univariate and multivariate logistic regression analyses were performed. FINDINGS: A total of 175 patients were enrolled. The results of the univariate ROC curve analysis for the incidence of MACEs during hospitalization showed that the area under the curve (AUC) was 0.780 (95% confidence interval (CI) 0.696-0.864) for the GPS, 0.766 (95% CI 0.682-0.850) for the redefined GPS (RGPS), 0.561 (95% CI 0.458-0.664) for the PLR score (PLRS), and 0.793 (95% CI 0.706-0.880) for GRACE. Multivariate ROC curve analysis showed that the AUC value was 0.809 (95% CI 0.726-0.893) for the GPS combined with GRACE, 0.783 (95% CI 0.701-0.864) for the GPS combined with the PLRS, 0.794 (95% CI 0.707-0.880) for GRACE combined with the PLRS, and 0.841 (95% CI 0.761-0.921) for the GPS combined with GRACE and the PLRS. The combined diagnostic model including the GPS plus GRACE and the PLRS had a higher AUC value than the GPS, RGPS and GRACE models (P = 0.014, P = 0.004, and P = 0.038, respectively). The multivariate logistic regression model showed that the odds ratio for hospitalized MACEs was 5.573 (95% CI 1.588-19.554) for GPS scores of 2 versus 0, and the GRACE score was also an independent risk factor for MACEs, with an odds ratio of 1.023 (95% CI 1.009-1.036). IMPLICATIONS: The diagnostic model combining the GPS plus GRACE and the PLRS has better predictive ability for the occurrence of MACEs during hospitalization than each single score. Thus, the use of a combined GPS plus GRACE and PLRS model will be of clinical benefit in a broad group of individuals with AMI.