Ultrasound Cut-Off Values for Rectus Femoris for Detecting Sarcopenia in Patients with Nutritional Risk.

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.

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.

Development of a low-cost and accurate carrier screening method for spinal muscular atrophy in developing countries.

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.

Cut-off values of preoperative knee extensor strength and hip abductor strength for predicting good walking ability after total knee arthroplasty.

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.

Epidemiological cut-off values for non-O1/ non-O139 Vibrio cholerae disc diffusion data generated by standardised methods.

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.

Shear wave elastography as a non-invasive tool for staging liver fibrosis in children: A study in Algerian pediatric patients.

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.

Back to basics: likelihood ratios for olive and grass pollen specific IgE in seasonal allergic rhinitis.

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.

The optimal cut-off values of screening tools for dynapenia: a cross-sectional study.

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.

Evaluation of plasma immunoglobulin G and BW thresholds for predicting preweaning mortality in commercially raised dairy goat kids.

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.

Assessment of the Performance of Obesity Measures in the Screening of Hypertension in a South African Adolescent Population.

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.

Prognostic cardiovascular cut-off values of dietary caffeine in a cohort of unselected men and women from general population.

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.

Evaluation of MIC distribution and establishment of epidemiological cut-off values for Streptococcus parauberis isolated from aquatic animals.

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.

Application of machine learning tools and integrated OMICS for screening and diagnosis of inborn errors of metabolism.

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.

Lupus anticoagulant laboratory diagnosis by applying the 2020 ISTH-SSC guidelines.

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.

Handgrip strength is associated with 12-month survival in male patients suffering with advanced chronic liver disease.

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.

Gradient concentration strip-specific epidemiological cut-off values of antifungal drugs in various yeast species and five prevalent Aspergillus species complexes.

OBJECTIVES: To determine the epidemiological cut-off values (ECVs) of ten antifungal agents in a wide range of yeasts and Aspergillus spp. using gradient concentration strips. METHODS: The minimum inhibitory concentrations for amphotericin B, anidulafungin, caspofungin, micafungin, flucytosine, fluconazole, itraconazole, isavuconazole, posaconazole, and voriconazole, determined with gradient concentration strips at 35 French microbiology laboratories between 2002 and 2020, were retrospectively collected. Then, the ECVs were calculated using the iterative method and a cut-off value of 97.5%. RESULTS: Minimum inhibitory concentrations were available for 17 653 clinical isolates. In total, 48 ECVs (including 32 new ECVs) were determined: 29 ECVs for frequent yeast species (e.g. Candida albicans and itraconazole/flucytosine, and Candida glabrata species complex [SC] and flucytosine) and rare yeast species (e.g. Candida dubliniensis, Candida inconspicua, Saccharomyces cerevisiae, and Cryptococcus neoformans) and 19 ECVs for Aspergillusflavus SC, Aspergillusfumigatus SC, Aspergillusnidulans SC, Aspergillusniger SC, and Aspergillusterreus SC. CONCLUSIONS: These ECVs can be added to the already available gradient concentration strip-specific ECVs to facilitate minimum inhibitory concentration interpretation and streamline the identification of nonwild type isolates.

Variability among commercial batches of normal pooled plasma in lupus anticoagulant testing.

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.

The establishment and validation of reference intervals for plasma Pentraxin-3 in healthy volunteers and patients with Takayasu's arteritis.

BACKGROUND AND AIMS: To establish reference intervals (RIs) for PTX-3 and to validate the performance of these RIs in a population including healthy volunteers and Takayasu's arteritis (TAK) patients. MATERIALS AND METHODS: Plasma PTX-3 levels were determined in 166 healthy volunteers and 63 TAK patients. RIs were established in healthy volunteers according to guidelines from the Clinical and Laboratory Standards Institute (CLSI, C28-A3). Global assessment was used to quantitatively diagnose active/non-active TAK patients. Screening and monitoring performances were validated by identifying active TAK patients from the whole population or diagnosed TAK patients. RESULTS: The PTX-3 RI was calculated to be 0.87-2.78 ng/mL. For screening purposes, 1.55 ng/mL had a high sensitivity of 90.32 % and the RI upper limit (2.78 ng/mL) had a high specificity of 97.94 %. For monitoring purposes, the sensitivity/specificity of the cut-off value (1.55 ng/mL) and RI median were 90.32 %/90.63 % and 80.85 %/90.63 %, respectively. These screening and monitoring performances of PTX-3 were superior to those of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). CONCLUSION: The distribution of serum PTX-3 levels was stable and uniform across the population. The screening and monitoring performances of the cut-off value and RI-derived values of PTX-3 were higher than CRP and ESR.

Corrigendum: Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China.

[This corrects the article DOI: 10.3389/fmicb.2022.924709.].

Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China.

Legionnaires' disease (LD), caused by Legionella, including the most prevalent Legionella pneumophila, has been treated primarily with antibiotics. Environmental water and soil are the reservoirs for L. pneumophila. Studying antimicrobial susceptibility using a large number of isolates from various environmental sources and regions could provide an unbiased result. In the present study, antimicrobial susceptibility of 1464 environmental L. pneumophila isolates that were derived from various environmental water and soil sources of 12 cities in China to rifampin (RIF), erythromycin (ERY), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP), moxifloxacin (MOX), levofloxacin (LEV), and doxycycline (DOX) was investigated, and minimum inhibitory concentration (MIC) data were obtained. We show that regarding macrolides, ERY was least active (MIC90 = 0.5 mg/L), while CLA was most active (MIC90 = 0.063 mg/L). A total of three fluoroquinolones have similar MICs on L. pneumophila. Among these antimicrobials, RIF was the most active agent, while DOX was the most inactive one. We observed different susceptibility profiles between serogroup 1 (sg1) and sg2-15 or between water and soil isolates from different regions. The ECOFFs were ERY and AZI (0.5 mg/L), RIF (0.002 mg/L), CIP, CLA and MOX (0.125 mg/L), LEV (0.063 mg/), and DOX (32 mg/L). Overall, two fluoroquinolone-resistant environmental isolates (0.14%) were first documented based on the wild-type MIC distribution. Not all azithromycin-resistant isolates (44/46, 95.65%) harbored the lpeAB efflux pump. The MICs of the ERY and CLA on the lpeAB + isolates were not elevated. These results suggested that the lpeAB efflux pump might be only responsible for AZI resistance, and undiscovered AZI-specific resistant mechanisms exist in L. pneumophila. Based on the big MIC data obtained in the present study, the same defense strategies, particularly against both CLA and RIF, may exist in L. pneumophila. The results determined in our study will guide further research on antimicrobial resistance mechanisms of L. pneumophila and could be used as a reference for setting clinical breakpoints and discovering antimicrobial-resistant isolates in the clinic, contributing to the antibiotic choice in the treatment of LD.