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OBJECTIVES: The aims of this study were to suggest patient-adjusted optical spectral transmission (OST) cut-off values for the first time and to develop clinical models that predict the probability of an early rheumatoid arthritis (RA) diagnosis based on OST findings and the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria as a reference standard. METHODS: OST examinations were performed in newly diagnosed RA patients and healthy controls by the HandScan device. Moreover, RA patients underwent a full clinical [tender/swollen joint counts (TJC/SJC), disease activity score-28 (DAS28)] and laboratory evaluation. OST confounding factors were examined via logistic multivariate regression analyses and patient-adjusted OST-cut-offs were subsequently determined. Furthermore, statistical models to calculate the probability of an RA diagnosis, based on the measured OST values and the presence of OST influencing factors, were developed. Finally, correlations of OST with RA activity parameters were assessed. RESULTS: 1.584 joints of 72 early RA patients were examined via OST and compared to 2.200 joints of 100 healthy controls and 1.166 joints of 53 patients with non-inflammatory arthralgia (NIA), respectively. Overall OST diagnostic performance was excellent in the whole cohort between RA- and healthy control-group [Area-Under-the-Curve (AUC): 0.810 (95%CI: 0.746-0.873); p < 0.0001], and further improved in RA-patients with ≥ 1 swollen wrist/finger joint(s) [AUC: 0.841 (95%CI: 0.773-0.908); p < 0.0001]. Comparison between RA patients and patients with non-inflammatory arthralgia showed similar results by an AUC of 0.788 (95%-CI: 0.709-0.867; p < 0.0001), and further improved in RA patients with ≥ 1 swollen wrist/finger joint(s) [AUC: 0.822 (95%CI: 0.74-0.90); p < 0.0001]. For the assessment of an adjusted RA diagnosis probability, two gender-specific statistical models were developed, based on OST values and patient age. OST cut-off values of 11.2 and 18.21 were calculated for female and male patients with active disease (sensitivity 93% and 67%; specificity 71.2% and 90%), respectively. Among RA patients, OST was associated moderately/significantly with DAS28 (r = 0.42,p < 0.001) and swollen joint count (rho = 0.355,p = 0.002). CONCLUSION: The development of patient-adjusted OST cut-off values and the suggested statistical models significantly enhance OST's diagnostic performance, supporting its utility in differentiating between RA and non-inflammatory conditions. Future research should include a broader spectrum of arthritis types to validate OST's comprehensive diagnostic utility also across various inflammatory arthritides. TRIAL REGISTRATION: DRKS00016752 (German Registry of Clinical Trials).

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The Clinical and Laboratory Standards Institute has published epidemiological cut-off values for susceptibility data generated at 22°°C and read after 44-48 h for florfenicol, oxolinic acid and oxytetracycline against Aeromonas salmonicida. The cut-off values for the minimum inhibitory concentration (MIC) and disc diffusion were derived from data obtained by 1 laboratory and 2 laboratories respectively. The present work reports the generation of susceptibility data from additional laboratories and the calculation of provisional cut-off values from aggregations of these data with previously published data. With respect to MIC data, the provisional cut-off values, derived from aggregations of the data from 4 laboratories, were ≤4 µg ml-1 for florfenicol, ≤0.0625 µg ml-1 for oxolinic acid and ≤1 µg ml-1 for oxytetracycline. For disc diffusion data, the provisional cut-off values derived from aggregations of the data from 5 laboratories were ≥30 mm for florfenicol, ≥32 mm for oxolinic acid and ≥25 mm for oxytetracycline. In addition, a cut-off value of ≥29 mm for ampicillin was derived from the aggregation of data from 4 laboratories.

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This experiment was motivated by the need to understand the impacts of delaying the first colostrum collection on immunoglobulin G (IgG) concentrations in goat colostrum, addressing a gap in caprine-specific research, despite its significance in dairy farming. Concurrently, we examined the relationship between colostral IgG, total protein (TP) and Brix values. Two colostrum samples were collected from 56 Saanen goats, one from each udder half. The first sample was collected from the right teat immediately postbirth, and the second sample was collected from the left teat at one of the predetermined postpartum intervals: 0, 4-6, 8-10, or 12-14 h postpartum, each time interval comprising 14 goats. Colostral IgG was determined by ELISA, Brix was determined by digital refractometry, and TP was determined by the Bradford protein method. Sperman's correlations and Lin's concordance correlation coefficient were used to determine the direction and strength of the association and to assess agreement (prediction accuracy) between methods, respectively. Receiver operator characteristic analysis was used to determine Brix and TP thresholds for predicting good-quality colostrum using several cut-offs (20, 30, 40, and 50 g/L IgG). Mean (± SD) for colostral IgG, Brix, and TP were 54 ± 22.6 g/L, 22 ± 5.0%, and 12 ± 2.8 g/dL, respectively. The statistical analysis did not provide evidence of a significant impact of time of first collection (up to 14 h postpartum), on IgG, Brix, and TP. Brix and IgG values exhibited both a high degree of correlation (r = 0.89-90) and concordance (ρc = 0.89-90), indicating a strong and reliable relationship between the two measurements. The prevalence of samples ≥ 20, 30, 40, and 50 g of IgG/L were 96, 88, 71, and 54%, respectively. Optimal Brix and TP thresholds predicting IgG ≥ 20, 30, 40, and 50 g/L IgG were 13.8, 17.5, 20.1, and 22.5%, and 6.8, 9.3, 10.8, and 11.1 g/dL, respectively. Increasing the IgG threshold resulted in lower sensitivity but higher specificity for estimating colostral IgG using Brix or TP values. The present findings indicate that delaying the first colostrum collection up to 14 h postpartum did not result in conclusive changes in colostral IgG concentration, Brix values, or total protein levels. Our results also confirm the reliability of Brix refractometry as an on-farm tool for estimating IgG concentrations in goat colostrum. These results are particularly relevant to intensive dairy systems, offering insights to enhance colostrum management and task prioritisation, especially during the bustling kidding periods.

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PURPOSE: To evaluate the responsiveness of the original low back pain specific Oswestry Disability Index (ODI) and the spinal stenosis specific Zürich Claudication Questionnaire (ZCQ), and to investigate cut-off values for clinical "success" for ODI and ZCQ in surgically treated patients with lumbar spinal stenosis (LSS). METHODS: We included 601 LSS patients (218 with, 383 without degenerative spondylolisthesis) from the NORDSTEN trials. Outcome measures included ODI and ZCQ (symptom severity and physical function scales) with three alternative response parameters: scores at follow-up, absolute and relative changes from baseline to two-year follow-up. Effect size and standardised response mean evaluated internal responsiveness. External responsiveness was assessed by the Spearman rank correlation between patient-reported global perceived effect scale (GPE) and ODI and ZCQ, and receiver operating characteristics (ROC). We evaluated which cut-off values could maximise the percentage of correctly classified patients according to the GPE-anchor "completely recovered" / "much improved" for each parameter. RESULTS: Internal and external responsiveness were high for all three indices with effect sizes, standardized response means, ROC and corresponding area under the curve > 0.8. Correlations with GPE responses were moderate (> 0.50) for absolute change and strong (> 0.67) for relative change and follow-up scores. The 30% ODI relative change cut-off correctly classified 81% of patients to "success", within a range of accurate cut-offs according to the GPE-anchor. CONCLUSION: ODI and ZCQ demonstrate comparable responsiveness in evaluating outcomes for surgically treated LSS patients. The 30% ODI threshold was consistent with treatment "success" in NORDSTEN trials. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02007083 10/12/2013, NCT02051374 31/01/2014 and NCT03562936 20/06/2018.

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BACKGROUND: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. METHODS: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. RESULTS: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. CONCLUSIONS: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.

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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.

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Heterozygous carriers of the survival of motor neuron 1 (SMN1) gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland China remains suboptimal, mainly attributed to the limitations of the existing carrier screening methods. Herein, we aimed to develop a low-cost, accessible, and accurate carrier screening method based on duplex droplet digital PCR (ddPCR), to cover a wider population in developing countries, including China. The receiver operating characteristic curve was used to determine the cut-off value of SMN1 copy numbers. Performance validation was conducted for linearity, precision, and accuracy. In total, 482 cases were considered to validate the concordance between the developed ddPCR assay and multiplex ligation-dependent probe amplification. Linear correlations were excellent between the expected concentration of the reference gene and the observed values (R2 > 0.99). Both the intra- and inter-assay precision of our ddPCR assays were less than 6.0%. The multiplex ligation-dependent probe amplification and ddPCR results were consistent in 480 of the 482 cases (99.6%). Two cases with multiplex ligation-dependent probe amplification, suggestive of two copies of SMN1 exon 7, were classified into three copies by ddPCR analysis. The overall correct classification of the samples included in our ddPCR assay was 100%. This study demonstrates that an appropriate cut-off value is an important prerequisite for establishing a semi-quantitative method to determine the SMN1 copy numbers. Compared to conventional methods, our ddPCR assay is low-cost, highly accurate, and has full potential for application in population spinal muscular atrophy carriers screening.

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INTRODUCTION: Total knee arthroplasty (TKA) reduces pain and improves physical function; however, not all patients have successful outcomes after surgery. To identify these patients would be critical information for improving rehabilitation programs. The purpose of this study was to clarify the cut-off values of lower extremity muscle strength for predicting postoperative good walking ability. MATERIALS AND METHODS: Timed Up and Go test of 105 patients was measured at 6 months postoperatively, and participants were divided into good (< 9.1 s) and poor (≥ 9.1 s) walking ability. Both sides of knee extensor strength (KES) and hip abductor strength (HAS) were measured using hand-held dynamometer preoperatively. Receiver operating characteristic (ROC) curve analysis was used to identify cut-off values for classifying the participants into the two groups. RESULTS: Of the 105 patients, 54 were allocated in the poor walking ability group, whereas 51 were allocated in the good walking ability group. KES and HAS were significantly greater in the good walking ability group than in the poor walking ability group. ROC curve analysis revealed that the cut-off value for KES was 0.79 Nm/kg (area under the curve (AUC) 0.68; sensitivity 64.7%; specificity 68.5%) on the involved side and 0.86 Nm/kg (AUC 0.73; sensitivity 84.6%; specificity 55.6%) on the uninvolved side, and for HAS was 0.57 Nm/kg (AUC 0.71; sensitivity 60.8%; specificity 71.7%) on the involved side and 0.61 Nm/kg (AUC 0.76; sensitivity 66.7%; specificity 77.4%) on the uninvolved side. CONCLUSION: The cut-off values of preoperative KES and HAS for predicting good walking ability after TKA are 0.79 Nm/kg on the involved side and 0.86 Nm/kg on the uninvolved side, and 0.57 Nm/kg on the involved side and 0.61 Nm/kg on the uninvolved side, respectively. We should provide enhanced pre- and post-operative rehabilitation programs for patients with muscle strength lower than these values.

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This work generates the data needed to set epidemiological cut-off values for disc-diffusion zone measurements of Vibrio cholerae. The susceptibility of 147 European isolates of non-O1/non-O139 V. cholerae to 19 antibiotics was established using a standardised disc diffusion method which specified incubation of Mueller Hinton agar plates at 35°C. Epidemiological cut-off values were calculated by analysis of the zone size data with the statistically based normalised resistance interpretation method. Cut-off values for 17 agents were calculated by analysis of the aggregated data from all 4 laboratories participating in this study. The cut-off values calculated were ≥18 mm for amoxicillin/clavulanate, ≥18 mm for amikacin, ≥19 mm for ampicillin, ≥27 mm for cefepime, ≥31 mm for cefotaxime, ≥24 mm for ceftazidime, ≥24 mm for chloramphenicol, ≥31 mm for ciprofloxacin, ≥16 mm for erythromycin, ≥ 27 mm for florfenicol, ≥16 mm for gentamicin, ≥23 mm for imipenem, ≥25 mm for meropenem, ≥29 mm for nalidixic acid, ≥28 mm for norfloxacin, ≥13 mm for streptomycin and ≥23 mm for tetracycline. For the other 2 agents the data from 1 laboratory was excluded from the censored aggregation because the data from that laboratory was considered excessively imprecise. The cut-off values for these 2 agents calculated for the aggregation of the data from 3 laboratories were ≥23 mm for trimethoprim and ≥24 mm for trimethoprim/sulfamethoxazole. These zone size data will be submitted to the Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) for their consideration in setting international consensus epidemiological cut-off values for non O1/non-O139 V. cholerae.

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BACKGROUND: Traditionally, liver biopsy has been the gold standard for fibrosis staging. However, it is an invasive, expensive and uncomfortable procedure that is associated with the risk of complications. Thus, non-invasive methods such as shear wave elastography (SWE) have been developed as potential alternatives to liver biopsy. The aim of this study is to evaluate the diagnostic performance of SWE in pediatric patients with liver fibrosis, specifically in a group of Algerian children and to determine whether this method can be a reliable alternative to liver biopsy. METHODS: This prospective, descriptive, monocentric study evaluated the non-invasive diagnostic performance of 2D-SWE in assessing liver fibrosis in pediatric patients. The assessment was carried out using various statistical methods, including Spearman's correlation coefficient, Kappa concordance coefficients, regression analysis, as well as the calculation of area under the receiver operating characteristic (AUROC) values and corresponding cut-off points based on the receiver operating characteristic (ROC) curve. RESULTS: Our study found that 2D-SWE is strongly correlated with liver biopsy in estimating liver fibrosis in children, with a correlation coefficient greater than 0.8. Furthermore, the Kappa correlation coefficients exceeded 0.8, indicating a strong agreement between 2D-SWE and liver biopsy results. The AUROC value was not less than 0.9 for significant fibrosis and above (≥ F2), indicating that it has satisfactory diagnostic performance in detecting liver fibrosis in children. CONCLUSION: 2D-SWE shows promise as a non-invasive method for evaluating liver fibrosis in children, offering a potential alternative to liver biopsy. Larger studies are needed to substantiate the findings of this study and to confirm the accuracy and reliability of 2D-SWE for assessing liver fibrosis in children.

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PURPOSE: This study evaluated whether anthropometric measurements and the five times sit-to-stand test could be used to identify dynapenia. The cut-off values of accurate screening tools for identifying dynapenia were also established. MATERIALS AND METHODS: This was a cross-sectional study conducted on individuals ≥ 60 years old (N = 529). All participants underwent handgrip strength measurement, anthropometric measurements and the five times sit-to-stand test. The participants whose handgrip strength was < 28 kg for men and < 18 kg for women were considered to have dynapenia. The association between the recorded variables and dynapenia was determined using logistic regression, and cut-off values were established by performing the Receiver Operating Characteristic curve analysis. RESULTS: The prevalence of dynapenia was 35.42% in men and 25.61% in women. For males, both calf circumference (≤ 35.2 cm) and the five times sit-to-stand test (≥ 14.6 s) could be used as accurate tools for dynapenia. For females, only the five times sit-to-stand test (≥ 11.8 s) had sufficient accuracy to be used as a screening tool for dynapenia. CONCLUSIONS: The five times sit-to-stand test was an accurate screening tool for identifying dynapenia. The calf circumference could be only used as a screening tool in males.

Calf circumference and the five times a sit-to-stand test can be used as accurate screening tools in males with dynapenia.Only the five times sit-to-stand test had sufficient accuracy in females with dynapenia.The optimal cut-off values established for older males and females are only applicable to the Asian population.

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The high preweaning mortality rate is a concerning issue for the commercial dairy industry. In this context, early identification of at-risk individuals can be instrumental. To address this, we conducted a prospective cohort study with the objective of evaluating plasma immunoglobulin G concentration (pIgG-24 h) and initial BW (IBW) measured at 1d old in 363 male dairy kids (Saanen) for predicting preweaning mortality under commercial conditions. Receiver operator characteristic (ROC) analysis was used to determine critical thresholds for pIgG-24 h and IBW. Subsequently, areas under the curve (AUC), sensitivity (Se), and specificity (Sp) were examined to assess the accuracy of these thresholds. Multivariable regressions were used to model odds ratios (OR) for mortality, controlling for confounding effects between IBW and pIgG-24 h. The mean (±SD) pIgG-24 h and IBW were 16.4 ± 9.37 g/L and 4.0 ± 0.61 kg. Overall mortality ≤ 14d and ≤42d old was 12% and 21%, respectively. Critical pIgG-24 h thresholds predicting mortality ≤ 14 d and ≤42 d old were < 10.1 g/L (AUC = 0.74, Se = 59%, and Sp = 82%) and <11.4 g/L (AUC 0.70, Se = 53%, and Sp = 77%), respectively. Kids with pIgG-24 h < 10.1 g/L were six times more likely to die ≤ 14 d old [OR; 95% CI (6; 3-12)], and kids with pIgG-24 h < 11.4 g/L were four times more likely to die ≤ 42 d old (4; 2-6). The IBW threshold most linked to mortality ≤ 14 d was <3.95 kg (AUC 0.60, Se = 59%, and Sp = 61%). However, this association became inconclusive after adjusting for pIgG-24 h differences. Conversely, an IBW of <3.0 kg was associated with notably higher mortality odds within both 14 and 42 d, irrespective of pIgG-24 h levels (10; 3-37, and 4; 1-20, respectively), suggesting that kids with an IBW < 3.0 kg face an increased likelihood of dying before 42 d, irrespectively of their IgG levels. While our findings suggest pIgG-24 h < 11.4 g/L and IBW < 3.0 kg as strong indicators of early mortality risks in male dairy kids, these results require further validation for other systems.

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Introduction: Specific IgE (sIgE) is merely a sensitization marker that cannot be used for allergy diagnosis if there are no associated clinical symptoms. As of 2023, there is still no evidence regarding the quantity of sIgE necessary to confirm or exclude clinical disease. Therefore, this study aimed to calculate cut-offs for sIgE, allowing us to effectively diagnose olive or grass pollen allergy and select allergenic immunotherapy (AIT) candidate patients in a region under high olive and grass allergenic pressure. Methods: An observational retrospective study consisting of the review of electronic medical records from 1,172 patients diagnosed with seasonal rhino-conjunctivitis and suspected allergy to olive or grass pollen. Symptoms correlated with sIgE to Poaceae and Oleaceae whole extracts and sIgE to genuine allergenic components were evaluated. Optimal cut-off values were calculated using receiver operating characteristic curves. Relevant clinical symptoms and AIT indications were taken into consideration when determining the clinical allergy diagnosis. Results: sIgE to Lolium showed the best area under the curve (AUC) for both diagnosis (0.957) and an indication of AIT (0.872). The optimal cut-off values for grass diagnosis and AIT indication were 1.79 kUA/L and 8.83 kUA/L, respectively. A value of 5.62 kUA/L was associated with a positive likelihood ratio (LR) of 10.08 set for grass allergy. Olea sIgE showed the best AUC for the diagnosis (0.950). The optimal cut-off for diagnosis was 2.41 kUA/L. A value of 6.49 kUA/L was associated with a positive LR of 9.98 to confirm olive pollen allergy. In regard to immunotherapy, Ole e 1 sIgE showed the best AUC (0.860). The optimal cut-off was 14.05 kUA/L. Ole e 1 sIgE value of 4.8 kUA/L was associated with a 0.09 negative LR to exclude olive AIT indication. Conclusions: The sIgE cut-offs found in this population under high olive and grass allergenic pressure reduce the gap between sensitization and clinical allergy, providing a new tool for the diagnosis of seasonal allergic rhinitis/asthma and helping to discriminate patients who will benefit from AIT.

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Obesity is known to be one of the most significant risk factors for essential hypertension in childhood. However, whether obesity cut-offs may predict hypertension screening in adolescents remains controversial. This study investigated the performance of obesity cut-off values for the screening of hypertension in a South African adolescent population. In this cross-sectional study, 1144 adolescents aged between 11 and 17 years were recruited from the Eastern Cape Province of South Africa. Anthropometric and blood pressure (BP) parameters including diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) were measured. Assessment of the sensitivity and specific of obesity cut-off values in predicting hypertension was performed using receiver operating characteristic (ROC) analysis. Obesity was positively associated (p < 0.01) with hypertension. Obese individuals, based on the predicted obesity using BMI percentile cut-off (pBMI85.2%), were more likely to develop hypertension (odds ratio: 2.070; p < 0.001) than their counterparts based on the observed obesity cut-off (pBMI95%) (Odd ratio: 1.748 p = 0.004). The area under the curve (AUC) of BMI percentile and WHtR for screening SBP percentile, and DBP percentile and HR as per ROC analysis, was low (<0.65). Equally, the sensitivity and specificity were low (<0.6) for all BP measures (SBP, DBP, and HR). Furthermore, the cut-off values for blood pressure measures, as established by ROC analysis using anthropometric measures, were far below the recommended cut-off values for hypertension screening. The obesity cut-offs for BMI percentile and WHtR established in this populations showed poor performance in diagnosing hypertension even though they were strong predictors of hypertension.

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BACKGROUND AND AIMS: Among an unselected cohort of men and women from general population (n = 1.668), the prognostic effects of being over the cut-off of all-source dietary caffeine intake were studied. METHODS AND RESULTS: Prognostic cut-off values for coronary events, incident heart failure (HF), cerebrovascular events (CBV) and arrhythmic events (ARR) were found by means of the receiver-operating-characteristic curves method. Those for HF (>230 mg/day), for CBV (>280 mg/day) and for ARR (>280 mg/day) were confirmed in multivariate Cox analysis adjusted for age, body mass index, circulating thyroid hormone, diabetes mellitus, arterial hypertension, smoking, dietary intake of ethanol, basal heart rate, low-density-lipoprotein cholesterol, forced expiratory volume in 1 s and ß-blocking therapy. Being over these cut-off values was associated to a reduced hazard ratio during the follow-up in the whole cohort (HR 0.678, 95%CI 0.567-0.908, p = 0.009 for HF; 0.651, 95%CI 0.428-0.994, p = 0.018 for CBV; 0.395, 95%CI 0.395-0.933, p = 0.022 for ARR) and in men (0.652, 0.442-0.961, p = 0.029; 0.432, 0.201-0.927, p = 0.03; 0.553, 0.302-1.000, p = 0.05, respectively) but not in women. The caffeine-induced risk decrease observed in the whole cohort is therefore entirely attributable to men. In the case of HF, heart rate entered the risk equation in a positive manner without rejecting caffeine. The -163C>A polymorphism of the CYP1A2 gene, codifying for ability to metabolize caffeine, introduced in sensitivity analysis, did not alter the prognostic models. CONCLUSION: Men introducing >230 mg/day caffeine show a reduced risk of HF, and those introducing >280 mg/day a reduced risk of CBV and ARR independent of genetic pattern.

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AIMS: Streptococcus parauberis is responsible for the development of streptococcosis in marine fish. The aim of the current study was to determine the antimicrobial susceptibility of aquatic Strep. parauberis strains, thus establishing laboratory-specific epidemiological cut-off (COWT) values to distinguish wild-type (WT) and nonwild-type (NWT) strains. METHODS AND RESULTS: Using 220 Strep. parauberis isolates obtained from diseased Paralichthys olivaceus, Platichthys stellatus, and Sebastes schlegelii over 6 years from seven different locations in Korea, we established COWT values for eight common antimicrobial agents using the standard broth microdilution method. The COWT values calculated using MIC distribution with the NRI and ECOFFinder methods were the same or within one dilution step for the eight antimicrobials tested. Nine NWT isolates with decreased susceptibility to at least two antimicrobials and one of these isolates exhibited decreased susceptibility to six antimicrobial agents were identified using COWT values based on NRI. CONCLUSIONS: Interpretive criteria for Strep. parauberis have not yet been established, and the findings of this study provide putative COWT values for eight antimicrobial agents frequently used in aquaculture in Korea.

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INTRODUCTION: Tandem mass spectrometry (TMS) has emerged an important screening tool for various metabolic disorders in newborns. However, there is inherent risk of false positive outcomes. Objective To establish analyte-specific cutoffs in TMS by integrating metabolomics and genomics data to avoid false positivity and false negativity and improve its clinical utility. METHODS: TMS was performed on 572 healthy and 3000 referred newborns. Urine organic acid analysis identified 23 types of inborn errors in 99 referred newborns. Whole exome sequencing was performed in 30 positive cases. The impact of physiological changes such as age, gender, and birthweight on various analytes was explored in healthy newborns. Machine learning tools were used to integrate demographic data with metabolomics and genomics data to establish disease-specific cut-offs; identify primary and secondary markers; build classification and regression trees (CART) for better differential diagnosis; for pathway modeling. RESULTS: This integration helped in differentiating B12 deficiency from methylmalonic acidemia (MMA) and propionic acidemia (Phi coefficient=0.93); differentiating transient tyrosinemia from tyrosinemia type 1 (Phi coefficient=1.00); getting clues about the possible molecular defect in MMA to initiate appropriate intervention (Phi coefficient=1.00); to link pathogenicity scores with metabolomics profile in tyrosinemia (r2=0.92). CART model helped in establishing differential diagnosis of urea cycle disorders (Phi coefficient=1.00). CONCLUSION: Calibrated cut-offs of different analytes in TMS and machine learning-based establishment of disease-specific thresholds of these markers through integrated OMICS have helped in improved differential diagnosis with significant reduction of the false positivity and false negativity rates.

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BACKGROUND: The ISTH-SSC guidelines for lupus anticoagulant (LA) testing recommend using in-house determined cut-off values, pooled normal plasma (PNP) for ratio normalization, and a ratio for the mixing test interpretation. They strongly support the mixing step role in the diagnostic process. OBJECTIVES: To investigate and compare the LA testing results and interpretations obtained following the ISTH-SSC guidelines or the available alternatives. PATIENTS/METHODS: Blood samples for LA testing from 462 consecutive patients were evaluated for screening, mixing and confirmatory tests. The analysis focused on the interpretation differences between using (1) the in-house cut-off values versus the manufacturer's cut-off values, (2) a normalized ratio calculated using PNP at each run versus the mean of the reference interval, (3) a normalized ratio versus the index of circulating anticoagulant to interpret the mixing step, and (4) a two-step versus three-step procedure. RESULTS: LA testing outcomes were comparable when using the in-house and manufacturer's cut-off values. More positive dilute Russell's viper venom (DRVV) time results were obtained with the normalized ratio based on PNP than with the mean of the reference interval. Overall, the mixing test results obtained with the normalized ratio and the index of circulating anticoagulant showed a good agreement. Among the 97 DRVV Screen test-positive samples, 33 and 89 were classified as LA-positive with the 3-step and the 2-step procedure, respectively. CONCLUSIONS: The cut-off value used and the way to normalize ratios had a limited impact. Conversely, it is important to understand the mixing test characteristics to maximize its diagnostic potential.

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BACKGROUND: Advanced chronic liver disease (ACLD) patients are usually malnourished, and both conditions in combination increase the likelihood of unfavourable clinical outcomes. Handgrip strength (HGS) has been suggested as a relevant parameter for nutritional assessment and predictor of adverse clinical outcomes in ACLD. However, the HGS cut-off values for ACLD patients have not yet been reliably established. The aims of this study were to preliminarily identify HGS reference values in a sample population of ACLD male patients and to assess their association with survival over a 12-month follow-up period. METHODS: This was a prospective observational study with preliminary analysis of outpatients and inpatients. A total of 185 male patients with a medical diagnosis of ACLD met the inclusion criteria and were invited to participate in the study. The physiological variation in muscle strength related to the age of the individuals included in the study was considered to obtain cut-off values. RESULTS: After categorising HGS by age group (adults: 18-60 years; elderly: ≥60 years), the reference values obtained were 32.5 kg for the adults and 16.5 kg for the elderly. During the 12-month follow-up, 20.5% of the patients died, and 76.3% of those had been identified with reduced HGS. CONCLUSIONS: Patients with adequate HGS showed significantly higher 12-month survival than those with reduced HGS within the same period. Our findings show that HGS is an important predictive parameter for clinical and nutritional follow-up in ACLD male patients.

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INTRODUCTION: Lupus anticoagulant (LA) testing requires normal pooled plasma (NPP) in performing mixing studies and can be used for normalized ratios of clotting times (CTs). The aims were to demonstrate whether significant differences in clotting times between two batches of a same commercial NPP (CRYOcheck™) directly affect NPP-based cut-off values. METHODS: Diluted Russell Viper venom time (DRVVT) and activated partial thromboplastin time (aPTT) were used for LA testing. Screening, mixing and confirm tests were performed with Stago® instruments and reagents. Two batches of commercial NPP (A1291 and A1301 from CRYOcheck™; frozen) were compared in the determination of cut-off values. Cut-off values were defined as 99th percentile values of 60 healthy donors and compared with Mann-Whitney U test. RESULTS: Cut-off values obtained with the two NPP batches were significantly different for DRVVT (screen normalized ratio: 1.09 vs. 1.24, screen mix: 41.9 s vs. 38.9 s; index of circulating anticoagulant: 5.0 vs. 8.4; all had p-value <.001). On the contrary, no significant differences were observed for aPTT (screen normalized ratio: 1.32 vs. 1.34; p-value = .4068, screen mix: 37.8 s vs. 38.1 s; p-value = .1153) except for index of circulating anticoagulant: 9.6 versus 10.4 (p-value <.05). CONCLUSION: This study demonstrates that differences between two commercial NPP batches produced by a same manufacturer influenced LA cut-off values used for mixing studies and normalized ratios. Adequate cut-off setting, taking into account NPP CTs, is important to provide accurate conclusion about the presence or absence of a LA and avoid potential clinical impact.

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