Wild-type distributions of minimum inhibitory concentrations and epidemiological cut-off values-laboratory and clinical utility.

The characterization of wild-type minimum inhibitory concentration (MIC) and zone diameter distributions with the setting of epidemiological cut-off values (ECOFFs or ECVs) provides a reference for the otherwise relative MIC values in the international system for antimicrobial susceptibility testing. Distributions of MIC values for a species and an agent follow a log-normal distribution, which in the absence of resistance mechanisms is monomodal and designated wild type (WT). The upper end of the WT distribution, the ECOFF, can be identified with statistical methods. In the presence of phenotypically detectable resistance, the distribution has at least one more mode (the non-WT), but despite this, the WT is most often identifiable using the same methods. The ECOFF provides the most sensitive measure of resistance development in a species against an agent. The WT and non-WT modes are independent of the organism´s response to treatment, but when the European Committee on Antimicrobial Susceptibility Testing (EUCAST) determines the clinical breakpoints, the committee avoids breakpoints that split WT distributions of target species. This is to avoid the poorer reproducibility of susceptibility categorization when breakpoints split major populations but also because the EUCAST has failed to identify different clinical outcomes for isolates with different MIC values inside the wild-type distribution. In laboratory practice, the ECOFF is used to screen for and exclude resistance and allows the comparison of resistance between systems with different breakpoints from different breakpoint organizations, breakpoints evolving over time, and different breakpoints between human and animal medicine. The EUCAST actively encourages colleagues to question MIC distributions as presented on the website (https://www.eucast.org/mic_and_zone_distributions_and_ecoffs) and to contribute MIC and inhibition zone diameter data.

The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Serum dithiothreitol-oxidizing capacity (DOC) is a promising biomarker for excluding significant liver fibrosis: a proof-of-concept study.

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study.

BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. METHODS: This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively. CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

Hospital distribution, seasonality, time trends and antifungal susceptibility profiles of all Aspergillus species isolated from clinical samples from 2015 to 2022 in a tertiary care hospital.

BACKGROUND: Aspergillus species cause a variety of serious clinical conditions with increasing trend in antifungal resistance. The present study aimed at evaluating hospital epidemiology and antifungal susceptibility of all isolates recorded in our clinical database since its implementation. METHODS: Data on date of isolation, biological samples, patients' age and sex, clinical settings, and antifungal susceptibility tests for all Aspergillus spp. isolated from 2015 to 2022 were extracted from the clinical database. Score test for trend of odds, non-parametric Mann Kendall trend test and logistic regression analysis were used to analyze prevalence, incidence, and seasonality of Aspergillus spp. isolates. RESULTS: A total of 1126 Aspergillus spp. isolates were evaluated. A. fumigatus was the most prevalent (44.1%) followed by A. niger (22.3%), A. flavus (17.7%) and A. terreus (10.6%). A. niger prevalence increased over time in intensive care units (p-trend = 0.0051). Overall, 16 (1.5%) were not susceptible to one azole compound, and 108 (10.9%) to amphotericin B, with A. niger showing the highest percentage (21.9%). The risk of detecting A. fumigatus was higher in June, (OR = 2.14, 95% CI [1.16; 3.98] p = 0.016) and reduced during September (OR = 0.48, 95% CI [0.27; 0.87] p = 0.015) and October as compared to January (OR = 0.39, 95% CI [0.21; 0.70] p = 0.002. A. niger showed a reduced risk of isolation from all clinical samples in the month of June as compared to January (OR = 0.34, 95% CI [0.14; 0.79] p = 0.012). Seasonal trend for A. flavus showed a higher risk of detection in September (OR = 2.7, 95% CI [1.18; 6.18] p = 0.019), October (OR = 2.32, 95% CI [1.01; 5.35] p = 0.048) and November (OR = 2.42, 95% CI [1.01; 5.79] p = 0.047) as compared to January. CONCLUSIONS: This is the first study to analyze, at once, data regarding prevalence, time trends, seasonality, species distribution and antifungal susceptibility profiles of all Aspergillus spp. isolates over a 8-year period in a tertiary care center. Surprisingly no increase in azole resistance was observed over time.

Barthel Index and Age as Predictors of Discharge Destination in Patients with Glioblastoma.

This study aimed to investigate the predictive factors of transfer of glioblastoma multiforme (GBM) patients who underwent rehabilitation in acute care hospitals. We retrospectively identified 85 patients with GBM who underwent rehabilitation at our hospital. Multivariable logistic regression analysis showed that age and Barthel index (BI) at rehabilitation initiation significantly influenced the discharge destination. Cut-off values for these factors were 76 years of age and 30 BI points. These findings could help predict the discharge destination and the choice of rehabilitation strategies of newly diagnosed patients with GBM admitted to an acute care hospital.

The value of CT shape quantification in predicting pathological classification of lung adenocarcinoma.

OBJECTIVE: To evaluate whether quantification of lung GGN shape is useful in predicting pathological categorization of lung adenocarcinoma and guiding the clinic. METHODS: 98 patients with primary lung adenocarcinoma were pathologically confirmed and CT was performed preoperatively, and all lesions were pathologically ≤ 30 mm in size. On CT images, we measured the maximum area of the lesion's cross-section (MA). The longest diameter of the tumor (LD) was marked with points A and B, and the perpendicular diameter (PD) was marked with points C and D, which was the longest diameter perpendicular to AB. and D, which was the longest diameter perpendicular to AB. We took angles A and B as big angle A (BiA) and small angle A (SmA). We measured the MA, LD, and PD, and for analysis we derived the LD/PD ratio and the BiA/SmA ratio. The data were analysed using the chi-square test, t-test, ROC analysis, and binary logistic regression analysis. RESULTS: Precursor glandular lesions (PGL) and microinvasive adenocarcinoma (MIA) were distinguished from invasive adenocarcinoma (IAC) by the BiA/SmA ratio and LD, two independent factors (p = 0.007, p = 0.018). Lung adenocarcinoma pathological categorization was indicated by the BiA/SmA ratio of 1.35 and the LD of 11.56 mm with sensitivity of 81.36% and 71.79%, respectively; specificity of 71.79% and 74.36%, respectively; and AUC of 0.8357 (95% CI: 0.7558-0.9157, p < 0.001), 0.8666 (95% CI: 0.7866-0.9465, p < 0.001), respectively. In predicting the pathological categorization of lung adenocarcinoma, the area under the ROC curve of the BiA/SmA ratio combined with LD was 0.9231 (95% CI: 0.8700-0.9762, p < 0.001), with a sensitivity of 81.36% and a specificity of 89.74%. CONCLUSIONS: Quantification of lung GGN morphology by the BiA/SmA ratio combined with LD could be helpful in predicting pathological classification of lung adenocarcinoma.

Cutoff estimation and construction of their confidence intervals for continuous biomarkers under ternary umbrella and tree stochastic ordering settings.

Tuberculosis (TB) studies often involve four different states under consideration, namely, "healthy," "latent infection," "pulmonary active disease," and "extra-pulmonary active disease." While highly accurate clinical diagnosis tests do exist, they are expensive and generally not accessible in regions where they are most needed; thus, there is an interest in assessing the accuracy of new and easily obtainable biomarkers. For some such biomarkers, the typical stochastic ordering assumption might not be justified for all disease classes under study, and usual ROC methodologies that involve ROC surfaces and hypersurfaces are inadequate. Different types of orderings may be appropriate depending on the setting, and these may involve a number of ambiguously ordered groups that stochastically exhibit larger (or lower) marker scores than the remaining groups. Recently, there has been scientific interest on ROC methods that can accommodate these so-called "tree" or "umbrella" orderings. However, there is limited work discussing the estimation of cutoffs in such settings. In this article, we discuss the estimation and inference around optimized cutoffs when accounting for such configurations. We explore different cutoff alternatives and provide parametric, flexible parametric, and non-parametric kernel-based approaches for estimation and inference. We evaluate our approaches using simulations and illustrate them through a real data set that involves TB patients.

Intraoperative Glucose and Kidney Injury After On-Pump Cardiac Surgery: A Retrospective Cohort Study.

INTRODUCTION: Acute kidney injury (AKI) is a common complication after on-pump cardiac surgery, and previous studies have suggested that blood glucose is associated with postoperative AKI. However, limited evidence is available regarding intraoperative glycemic thresholds in cardiac surgery. The aim of this study was to explore the association between peak intraoperative blood glucose and postoperative AKI, and determine the cut-off values for intraoperative glucose concentration associated with an increased risk of AKI. METHODS: The study was retrospective and single-centered. Adult patients in West China Hospital of Sichuan University who underwent on-pump cardiac surgery (n = 3375) were included. The primary outcome was the incidence of AKI. Multivariable logistic analysis using restricted cubic spline was performed to explore the association between intraoperative blood glucose and postoperative AKI. RESULTS: The incidence of AKI in the study population was 18.0% (607 of 3375). Patients who developed AKI had a significantly higher peak intraoperative glucose during the surgery compared to those without AKI. After adjustment for confounders, the incidence of AKI increased with peak intraoperative blood glucose (adjusted odds ratio, 1.08, 95% confidence interval 1.03, 1.12). Furthermore, it was demonstrated that the possibility of AKI was relatively flat till 127.8 mg/dL (7.1 mmol/L) glucose levels which started to rapidly increase afterward. CONCLUSIONS: Increased intraoperative blood glucose was associated with an increased risk of AKI. Among patients undergoing on-pump cardiac surgery, avoiding a high glucose peak (i.e., below 127.8 mg/dL [7.1 mmol/L]) may reduce the risk of postoperative AKI.

Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy.

BACKGROUND: The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. OBJECTIVES: We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). METHODS: We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. CONCLUSIONS: The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.

Influence of cutoff radius and tip atomic structure on energy barriers encountered during AFM tip sliding on 2D monolayers.

In computational studies using the Lennard-Jones (LJ) potential, the widely adopted 2.5σcutoff radius effectively truncates pairwise interactions across diverse systems (Santraet al2008J. Chem. Phys.129234704, Chen and Gao 2021Friction9502-12, Bolintineanuet al2014Part. Mech.1321-56, Takahiro and Kazuhiro 2010J. Phys.: Conf. Ser.215012123, Zhouet al2016Fuel180718-26, Toxvaerd and Dyre 2011J. Chem. Phys.134081102, Toxvaerd and Dyre 2011J. Chem. Phys.134081102). Here, we assess its adequacy in determining energy barriers encountered by a Si monoatomic tip sliding on various two-dimensional (2D) monolayers, which is crucial for understanding nanoscale friction. Our findings emphasize the necessity of a cutoff radius of at least 3.5σto achieve energy barrier values exceeding 95% accuracy across all studied 2D monolayers. Specifically, 3.5σcorresponds to 12.70 Å in graphene, 12.99 Å in MoS2and 13.25 Å in MoSe2. The barrier values calculated using this cutoff support previous experiments comparing friction between different orientations of graphene and between graphene and MoS2(Almeidaet al2016Sci. Rep.631569, Zhanget al2014Sci. China57663-7). Furthermore, we demonstrate the applicability of the 3.5σcutoff for graphene on an Au substrate and bilayer graphene. Additionally, we investigate how the atomic configuration of the tip influences the energy barrier, finding a nearly threefold increase in the barrier along the zigzag direction of graphene when using a Si(001) tip composed of seven Si atoms compared to a monoatomic Si tip.

Insight into antiphospholipid syndrome: the role and clinical utility of neutrophils extracellular traps formation.

Antiphospholipid syndrome (APLS) is a systemic immune dysregulation distinguished by repetitive complications and pregnancy loss in the absence of definite etiology. Most research focuses on the laboratory detection and clinical features of APLS, but its precise etiology remains to be deeply explored. NETosis is a newly developed theory in the pathophysiology of APLS which may serve as the missing bridge between coagulation and inflammation reaching the disease progression and severity. We aimed in this study to navigate the prognostic role of NETosis in thrombotic APLS. Our study included 49 newly diagnosed APLS patients (both 1ry and 2ry) who met clinical and laboratory criteria as per the international consensus statement on the update of the classification criteria for definite APLS and were sub-classified according to the occurrence of thrombotic events in thrombotic and non-thrombotic types. In addition, 20 sex and age-matched reactive subjects and 20 sex and age-matched healthy volunteer controls were enrolled. NETosis formation was assessed by measuring serum Myeloperoxidase (MPO) and Histones level using the enzyme-linked immunosorbent assay (ELISA) technique. Both MPO and Histones levels were able to discriminate among APLS cases from normal controls, showing significant cutoffs of > 2.09 ng/ml for MPO and > 1.45 ng/ml for Histones (AUC values were 0.987and 1.000, respectively). These values can be used as predictors for NETosis pathophysiology in APLS patients. Additionally, these markers demonstrated a significant association with several prognostic indicators, including thrombosis, higher PT and INR, and lower hemoglobin (Hb) levels which are supposed to be ameliorated by using NETs inhibitors. In conclusion, we suggest that measuring NETosis markers, MPO, and Histones, in the early course of APLS using proposed cutoff values will facilitate the timely initiation of anti-NETosis therapy and improve the overall prognosis, particularly for patients with thrombotic APLS.

Determination of a cut-off COmprehensive Score for financial Toxicity (COST) for identifying cost-related treatment nonadherence and impaired health-related quality of life among Chinese patients with cancer.

PURPOSE: This study aimed to determine a cut-off for the simplified Chinese version of the COmprehensive Score for financial Toxicity (COST) that could identify cost-related treatment nonadherence among Chinese patients with cancer. The study also sought to validate this cut-off score by using it to assess impaired health-related quality of life (HRQoL) in the same population. METHODS: A secondary analysis was conducted using data from a cross-sectional survey of 1208 Chinese patients with cancer who were recruited from 12 hospitals in six cities across three provinces of the Chinese mainland. Sociodemographic information and data on financial toxicity (FT), cost-related treatment nonadherence, and HRQoL were used in the analysis. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off for the simplified Chinese version of the COST. RESULTS: The ROC analysis identified a COST cut-off of 18.5 for identifying cost-related treatment nonadherence, yielding a sensitivity of 76.5% and specificity of 71.4%. In the validation study, this cut-off score yielded a sensitivity of 64.2% and a specificity of 67.1% for identifying impaired HRQoL. CONCLUSION: Early and dynamic assessment of cancer-related FT in routine clinical practice may play a crucial role in the early identification and management of FT. Accordingly, a COST cut-off of 18.5 was identified to indicate cost-related treatment nonadherence and impaired HRQoL in a population of patients with cancer from the Chinese mainland. This finding may facilitate the implementation of universal FT screening among patients with cancer in specific settings such as the Chinese mainland.

Study on hydraulic conductivity of dredged sediment-attapulgite vertical cutoff walls under confining pressure.

Landfills require effective containment systems to prevent the leakage of leachate into the underground environment. Cutoff walls are commonly employed for this purpose, with options including rigid and flexible designs. In areas where structural strength is not a primary concern, flexible cutoff walls offer lower permeability and environmental benefits due to their lack of cement content, thereby reducing CO2 emissions. This study investigates the use of dredged sediment and attapulgite as materials for flexible cutoff walls. Through analyses of bound water content, free water content, hydraulic conductivity, and scanning electron microscopy, we explore the impact of confining pressures on cutoff wall permeability. Our findings reveal that the consolidation induced by confining pressure does not significantly alter the bound water content within the cutoff wall. Instead, changes in water content are predominantly attributed to variations in free water content. Under identical confining pressures, we observe a positive correlation between permeability and hydraulic gradient, with permeability increasing as the hydraulic gradient rises, and anti-permeability decreasing accordingly. Additionally, when holding the hydraulic gradient constant, increasing confining pressure leads to a continuous decrease in permeability. Microscopic analyses highlight that high confining pressure not only compresses pore diameter but also alters pore morphology, thereby influencing permeability. This study contributes to the understanding of cutoff wall behavior under different conditions. Our results demonstrate that increasing confining pressure during soil consolidation effectively reduces cutoff wall permeability to meet design standards. However, the influence of high leachate head on permeability should also be considered. These findings provide a more environmentally friendly and lower permeability option for landfill sites, which is significant for the design and enhancement of containment systems in landfill sites.

Current principles for the establishment of the virological "cutoff points" in transfusion science and medicine: A short concise overview.

Establishing the virological cutoff point, during epidemics, such as the COVID-19 Pandemic, is crucially important as inadequate standardization and the false qualitative results, have enormous clinical and economic consequences when screening for SARS-CoV-2. Moreover, a cutoff point is a crucial step in ensuring a minimal risk of clinical misclassification. Therefore complying with such statutory requirements is an essential part of obligatory good laboratory and clinical practices. In this concise report, we propose a novel methodology for establishing cutoff points for all samples exhibiting detectable levels of the measured parameter, even those from the disease-free group. Based on target specificity and sensitivity levels of 100 % and 95 %, a value of 1209 A is identified as the "best cutoff". In fact, the ROC decision matrixes play a crucial role in determining optimal cutoff points. The most effective discriminators are those that meet specified accuracy criteria. The selection process is influenced by finding the right clinical sensitivity/specificity trade-off.

Diagnostic performance of Mycoplasmopsis bovis antibody ELISA tests on bulk tank milk from dairy herds.

BACKGROUND: Testing of bulk tank milk (BTM) for Mycoplasmopsis bovis (previously Mycoplasma bovis) antibodies is increasingly popular. However the performance of some commercially available tests is unknown, and cutoff values possibly need to be adjusted in light of the purpose. Therefore, the aim of this study was to compare the diagnostic performance of three commercially available M. bovis antibody ELISAs on BTM, and to explore optimal cutoff values for screening purposes. A prospective diagnostic test accuracy study was performed on 156 BTM samples from Belgian and Swiss dairy farms using Bayesian Latent Class Analysis. Samples were initially classified using manufacturer cutoff values, followed by generated values. RESULTS: Following the manufacturer's guidelines, sensitivity of 91.4%, 25.6%, 69.2%, and specificity of 67.2%, 96.8%, 85.8% were observed for ID-screen, Bio K432, and Bio K302, respectively. Optimization of cutoffs resulted in a sensitivity of 89.0%, 82.0%, and 85.5%, and a specificity of 83.4%, 75.1%, 77.2%, respectively. CONCLUSIONS: The ID-screen showed the highest diagnostic performance after optimization of cutoff values, and could be useful for screening. Both Bio-X tests may be of value for diagnostic or confirmation purposes due to their high specificity.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Predictive markers of metabolically healthy obesity in children and adolescents: can AST/ALT ratio serve as a simple and reliable diagnostic indicator?

This study aimed to estimate the prevalence of metabolically healthy obesity (MHO) according to two different consensus-based criteria and to investigate simple, measurable predictive markers for the diagnosis of MHO. Five hundred and ninety-three obese children and adolescents aged 6-18 years were included in the study. The frequency of MHO was calculated. ROC analysis was used to estimate the predictive value of AST/ALT ratio, waist/hip ratio, MPV, TSH, and Ft4 cut-off value for the diagnosis of MHO. The prevalence of MHO was 21.9% and 10.2% according to 2018 and 2023 consensus-based MHO criteria, respectively. AST/ALT ratio cut-off value for the diagnosis of MHO was calculated as ≥ 1 with 77% sensitivity and 52% specificity using Damanhoury et al.'s criteria (AUC = 0.61, p = 0.02), and 90% sensitivity and 51% specificity using Abiri et al.'s criteria (AUC = 0.70, p = 0.01). Additionally, using binomial regression analysis, only the AST/ALT ratio is independently and significantly associated with the diagnosis of MHO (p = 0.03 for 2018 criteria and p = 0.04 for 2023 criteria). CONCLUSION: The ALT/AST ratio may be a useful indicator of MHO in children and adolescents. WHAT IS KNOWN: • Metabolically healthy obesity refers to people who are obese but do not have any of the standard cardio-metabolic risk factors. • Metabolically healthy obesity is not entirely harmless; the metabolic characteristics of individuals with this phenotype are less favorable than those of healthy lean groups. Moreover, it is not a constant state, and there may be a transition to metabolically unhealthy phenotypes over time. WHAT IS NEW: • The prevalence of MHO is 21.9% and 10.2% according to 2018 and 2023 consensus-based metabolically healthy obesity criteria, respectively. • The ALT/AST ratio may be a useful indicator of metabolically healthy obesity in children and adolescents.

NT-proBNP course during MIS-C post-COVID-19: an observational study.

Multisystem inflammatory syndrome in children (MIS-C or PIMS-TS) is a severe disease. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. However, contrasting cut-offs have been suggested. The aims of the present study were to compare NT-proBNP values depending on the time of measurement and to describe the NT-proBNP course during the MIS-C episode. The data from a single-centre cohort observational study on the impact of time to diagnosis, defined as the time from first symptom to diagnosis of MIS-C, were used for the purpose of this study, with an extended period of inclusion from May 2020 to April 2023. The timing and level of all NT-proBNP samples available for each patient were retrospectively collected. Thirty-seven children (18 (49%) females, median age 8.8 years, 14 (38%) with shock) were included. Until diagnosis, NT-proBNP increased with time and was significantly higher at 6 days from first symptoms than at 3 days (median (interquartile range) 32,933 (7773-61,592) versus 1994 (1291-4190) pg/mL, respectively, p = 0.031). From diagnosis, NT-proBNP decreased by at least 50% after 3.0 (2.1-5.3) days (n = 12) when NT-proBNP at diagnosis was low ≤ 11,000 pg/mL versus 1.8 (0.7-3.4) days (n = 16) when NT-proBNP at diagnosis was high (p = 0.040), and after 3.6 (2.4-5.9) days (n = 7) when fever persisted after 48 h versus 1.8 (0.8-3.0) days (n = 21) when fever resolved before 48 h (p = 0.004).  Conclusions: During the MIS-C episode, NT-proBNP increased over time until diagnosis and treatment. It dropped faster thereafter in children with high NT-proBNP at diagnosis > 11,000 pg/mL and slower in case of persistent fever. What is Known: • NT-proBNP is useful in MIS-C for positive and differential diagnosis, diagnosis of complications and severity, and cardiogenic shock prediction. • Contrasting cut-offs for differential diagnosis and severity assessment have been suggested. What is New: • Before diagnosis, NT-proBNP increases with time and is significantly higher at 6 days from first symptoms than at 3 days suggesting different cut-offs depending on the timing of measurement. • From diagnosis and treatment initiation, the 50% NT-proBNP drop occurs earlier in children with high NT-proBNP at diagnosis > 11,000 pg/mL and later in children with persistent fever.

'Old is gold' does conventional test tube method still reign supreme? An immuno-haematological survey of anti-D detection and titration in ante-natal cases among major hospitals across India.

INTRODUCTION: Anti-D detection and titration plays a major role in RhD negative antenatal cases both, for monitoring maternal as well as fetal status as well as initiation of early therapeutic interventions, such as intra-uterine transfusions (IUT) to improve maternal as well as fetal morbidity and mortality and reduce the adverse effects of haemolytic disease of fetus and newborn (HDFN). We conducted a survey focusing on the policies and procedures of anti-D detection and titration among major tertiary care centres across India. METHODOLOGY: The survey was drafted by a working group of transfusion medicine and immunohematology specialists from six different centres in India. Data were obtained via the use of an online questionnaire. RESULTS: Results were categorised into four categories, Hospital information, immuno-haematological testing methodology, clinical significance of anti-D testing and the role of transfusion medicine specialists. The survey highlighted the modalities as well as the methodologies of anti-D detection and titration in antenatal women across different major tertiary care centres in India. CONCLUSION: This survey provided a unique snapshot of the prevalent methodologies being employed by major tertiary care centres across the country for detection and titration of anti-D levels as well as the important role it plays in the therapy of affected antenatal women to minimise adverse effects on the fetus.