Sex-specific Reference Values Research Articles

Creatine kinase serum levels in children revisited: New reference intervals from a large cohort of healthy children and adolescents

BackgroundCreatine Kinase (CK) has become increasingly important in pediatrics as a commonly used laboratory screening parameter for neuromuscular diseases. Recent research suggests that hyperCKemia in children is not always associated with pathology and can occur due to several reasons. Little is known of various clinical factors that may influence CK throughout child development. ObjectiveThis study aimed to establish reliable age- and sex-specific reference ranges for serum CK levels in healthy infants, children, and adolescents. In addition, the effect of puberty, oral contraceptive (OC) use as well as steroid hormones on CK was examined. Materials and methodsThe data was collected from subjects of the longitudinal population-based “LIFE Child”-cohort between 2011 and 2016 in Leipzig, Germany. 5238 blood samples of 2707 healthy children, aged between 0.14 months and 18 years, were analyzed. ResultsSerum CK levels raised during the first year of life, peaking shortly after age one (P50girls = 2.7 µkat/L, P50boys = 2.90 µkat/L). There was a pronounced difference in the 97.5th percentile between boys and girls during adolescence with its maximum at age 18 (P97.5girls = 5.74 µkat/L, P97.5boys14.48 µkat/L). Also, mean CK serum levels were significantly higher in boys (bboys = 0.29, pboys < 0.001). Intake of oral contraceptives (OC), extreme underweight, underweight and obesity revealed a significant inverse correlation with CK serum levels. ConclusionAge, sex, OC intake and weight status affect serum CK levels, particularly during infancy and puberty. We recommend the use of age- and sex-specific reference values for CK serum levels to assess the clinical relevance of measurements.

New Reference Values for Thyroid Volume by Ultrasound in German Children and Adolescents from a Population-Based Study.

Reliable reference values for thyroid ultrasound measurements are essential to effectively guide individual diagnostics and direct health care measures at the population level, such as iodine fortification programs. However, the latest reference values for total thyroid volume (Tvol) provided by the WHO in 2004 only apply to the 6 to 12-year-old age group and are limited to countries with a long history of iodine sufficiency, which does not reflect the situation in most European countries, including Germany. The present aims to derive up to date thyroid volume ultrasound reference values in German children and adolescents. Data from the baseline assessment of a nationwide study in German children and adolescents (KiGGS) conducted between 2003 and 2006 were used to determine sex-specific reference values for Tvol in thyroid-healthy participants aged 6 to 17 years by age and body surface area (BSA) according to the Lambda-Mu-Sigma (LMS) method. Data from 5559 participants were available for reference chart construction (girls: 2509 (45.1%)). On average, the 97th percentile is 33.4% and 28.5% higher than the corresponding WHO's reference values for boys and girls, respectively. These findings are consistent with most other studies in German and European children and adolescents at a similar time of investigation. Notably, the sample used for this study was iodine-sufficient according to WHO criteria. The reference values provided by the WHO are overly conservative for this population and could potentially apply to other European countries with a similar history of iodine supply.

Age- and Sex-Specific MR-Feature Tracking Reference Values of Right Atrial Deformation in Healthy Adults.

Although right atrial (RA) myocardial deformation has important implications for patient diagnosis, prognosis, and risk stratification, its implementation in clinical practice has been hampered by limited normal reference values, especially in Asian populations. To establish age- and sex-specific reference values for RA strain, strain rate (SR), and displacement based on a large sample of healthy Chinese adults using MR-feature tracking (MR-FT). Retrospective. 524 healthy Chinese adults (287 male; mean age 43.7 ± 11.9 years). 1.5T/balanced steady-state free precession. RA deformation parameters, including reservoir, conduit, and booster strain (εs, εe, and εa), peak positive, early negative, and late negative SR (SRs, SRe, and SRa), and total, passive, and active displacement (Ds, De, and Da), were assessed using MR-FT. Student's t-test, one-way ANOVA, coefficients of determination (r2 ), intraclass correlation coefficients (ICC), and Bland-Altman plots. A P value <0.05 was considered significant. Women demonstrated significantly greater magnitudes of RA deformation parameters than men: εs (57.4% ± 15.1% vs. 44.3% ± 12.6%), εe (37.5% ± 13.4% vs. 27.4% ± 10.9%), εa (19.9% ± 5.7% vs. 16.9% ± 5.0%), SRs (2.62 ± 0.88 sec-1 vs. 2.00 ± 0.63 sec-1 ), SRe (-2.98 ± 1.26 sec-1 vs. -2.16 ± 0.92 sec-1 ), SRa (-2.28 ± 0.75 sec-1 vs. -1.84 ± 0.62 sec-1 ), Ds (-7.80 ± 1.90 mm vs. -7.46 ± 1.70 mm), and De (-4.84 ± 1.31 mm vs. -4.49 ± 1.21 mm). For both sexes, aging was significantly associated with decreased RA reservoir and conduit function (εs, SRs, Ds, εe, SRe, and De), and with increased εa and Da. RA deformation measurements had good to excellent intraobserver and interobserver reproducibility, with ICCs ranging from to 0.790 to 0.972. This study provides age- and sex-specific reference values of RA strain, SR, and displacement based on a large cohort of healthy Chinese adults using MR-FT. 3 TECHNICAL EFFICACY: Stage 2.

Adolescent Reference Values for MR-Derived Biventricular Strain Obtained Using Feature-Tracking and Myocardial Tagging.

Myocardial strain is a promising marker for the detection of early left or right ventricular (LV or RV) dysfunction in pediatric populations. The reference standard for MR strain measurement is myocardial tagging (MT); however, MT has limited clinical utility because the additional acquisitions needed are time-consuming. In contrast, MR-feature tracking (FT) allows strain quantification from routinely acquired cine sequences. Studies providing reference values obtained with both FT and MT for adolescents are lacking. To use MR-FT and MT to define sex-specific LV and RV strain reference values for adolescents. Cross-sectional, prospective. One hundred twenty-three adolescents aged 15-18 years (52% girls) without known cardiovascular disease. Balanced steady-state free-precession sequence for FT analysis and a spatial modulation of magnetization hybrid TFE-EPI sequence for MT acquisitions at 3.0-T. Segment Medviso software was used to obtain longitudinal (LS) and circumferential (CS) strain for both ventricles, and radial strain (RS) for LV. The Student t-test was used for between-sex comparisons of continuous variables. Sex-specific percentiles were calculated using the weighted average method. Intraobserver and interobserver agreement was assessed in 30 randomly selected studies using intraclass correlation coefficients (ICC). A P-value <0.05 was considered statistically significant. FT-derived LVLS and LVCS were significantly higher in girls than in boys (-19.8% vs. -17.8% and -22.2% vs. -21.0%, respectively), as they were with MT (LVLS: -18.1% vs. -16.8%; LVCS: -20.8% vs. -19.7%). FT-LVRS was higher in girls than in boys (44.8% vs. 35.1%), while MT-LVRS was the opposite (18.6% vs. 22.7%). FT-RVLS was higher in girls (-23.4% vs. -21.3%), but there were no between-sex differences in MT-derived RVLS or RVCS. ICC values for intraobserver agreement were ≥0.89, whereas for interobserver agreement were <0.80 for MT-LVRS and ≥0.80 for all remaining parameters. This study provides sex-specific reference biventricular strain values obtained with MR-MT and MR-FT for adolescents aged 15-18 years. MR-FT may be a valid method for obtaining strain values in pediatric populations. 1 TECHNICAL EFFICACY: Stage 3.

The Effect of Age, Hypertension, and Overweight on Arterial Stiffness Assessed Using Carotid Wall Echo-Tracking in Childhood and Adolescence.

Arterial stiffness represents an independent predictor of the risk of subsequent cardiovascular events. Early identification of high-risk individuals is necessary for effective prevention and targeted interventions. Carotid wall echo-tracking is a modern method for an accurate evaluation of the structural and functional properties of carotid arteries. This study aimed to assess age and sex-specific reference values of the echo-tracking parameters of carotid stiffness in 400 healthy children and adolescents and to evaluate the potential early effect of elevated blood pressure and overweight in 69 overweight normotensives, 45 white coat hypertensives, and 44 essential hypertensives. Stiffness index β, pressure-strain elastic modulus (Ep), arterial compliance (AC), and pulse wave velocity β (PWV β) were evaluated using Aloka ProSound F75. Both white coat and essential hypertension were associated with impaired carotid wall properties with the greatest effect on Ep, followed by PWV β, index β, and AC. The excess weight showed a weaker effect on Ep and PWV β. This is the first study to compare the effects of white coat and essential hypertension on carotid arterial stiffness assessed using the echo-tracking technique in childhood and adolescence with direct application of pediatric reference values specific to age and sex.

Comparison of body mass index and fat mass index to classify body composition in adolescents—The EVA4YOU study

The objectives of this study were to develop age- and sex-specific reference percentiles for fat mass index (FMI) and fat-free mass index (FFMI) in adolescents aged 14 to 19 years and to determine differences in overweight/obesity classification by FMI and body mass index (BMI). The EVA4YOU study is a single-center cross-sectional study conducted in western Austria. Cardiovascular risks including anthropometric measurements and bioelectrical impedance analysis were assessed in adolescents (mean age 17 years). FMI and FFMI were calculated as the ratio of fat mass (FM) and fat-free mass (FFM) to the square of height and compared to study population–specific BMI percentiles. One thousand four hundred twenty-two adolescents were included in the analysis. Girls had a significantly higher mean FM and FMI and a significantly lower mean FFM, FFMI (p < 0.001, each), and mean BMI (p = 0.020) than boys. Body composition classification by FMI and BMI percentiles shows a concordance for the < 75th and > 97th percentile, but a significant difference in percentile rank classifications between these two cut-off values (all p < 0.05). Based on FMI, 15.5% (221/1422) of the whole population and 29.4% (92/313) of those between the 75th and 97th percentiles are classified one category higher or lower than those assigned by BMI. Conclusion: Classification of normal or pathologic body composition based on BMI and FMI shows good accordance in the clearly normal or pathologic range. In an intermediate range, FMI reclassifies categories based on BMI in more than a quarter of adolescents. Cut-off values to differentiate normal from pathologic FMI values on a biological basis are needed.Trial registration: The study is registered at www.clinicaltrials.gov (Identifier: NCT04598685; Date of registration: October 22, 2020).What is Known:• Chronic non-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally, with major risk factors including unhealthy diets, harmful behaviors, and obesity. Obesity in children and adolescents is a key risk factor for later NCDs, which is commonly measured by Body Mass Index (BMI).• BMI can be misleading as it doesn't distinguish between fat mass (FM) and fat-free mass (FFM), leading to potential misclassification of obesity in children. Previous studies have already suggested the use of the Fat Mass Index (FMI) and Fat-Free Mass Index (FFMI) as a more accurate measures of body composition.What is New:• This study adds the first age- and sex-specific reference values for FMI and FFMI in Austrian adolescents using bioelectrical impedance analysis (BIA) as a safe and secure measurement method of a large representative cohort.• We found percentile misclassification between BMI and FMI when categorizing for obesity, especially in intermediate categories of body composition. Furthermore, when comparing the new reference values for FMI and FFMI to existing ones from the US, UK, and Germany we could show a good alignment within the European cohorts and major differences with American values, indicating and confirming the difference of FMI and FFMI for different populations of different ethnical background, living on different continents.

Digital neuropsychological measures by defense automated neurocognitive assessment: reference values and clinical correlates.

Although the growth of digital tools for cognitive health assessment, there's a lack of known reference values and clinical implications for these digital methods. This study aims to establish reference values for digital neuropsychological measures obtained through the smartphone-based cognitive assessment application, Defense Automated Neurocognitive Assessment (DANA), and to identify clinical risk factors associated with these measures. The sample included 932 cognitively intact participants from the Framingham Heart Study, who completed at least one DANA task. Participants were stratified into subgroups based on sex and three age groups. Reference values were established for digital cognitive assessments within each age group, divided by sex, at the 2.5th, 25th, 50th, 75th, and 97.5th percentile thresholds. To validate these values, 57 cognitively intact participants from Boston University Alzheimer's Disease Research Center were included. Associations between 19 clinical risk factors and these digital neuropsychological measures were examined by a backward elimination strategy. Age- and sex-specific reference values were generated for three DANA tasks. Participants below 60 had median response times for the Go-No-Go task of 796 ms (men) and 823 ms (women), with age-related increases in both sexes. Validation cohort results mostly aligned with these references. Different tasks showed unique clinical correlations. For instance, response time in the Code Substitution task correlated positively with total cholesterol and diabetes, but negatively with high-density lipoprotein and low-density lipoprotein cholesterol levels, and triglycerides. This study established and validated reference values for digital neuropsychological measures of DANA in cognitively intact white participants, potentially improving their use in future clinical studies and practice.

Reference intervals for cardiometabolic risk factors in China: a national multicenter cross-sectional study on an adult population sample.

The reference intervals (RIs) of adult blood lipid parameters currently used in China are not derived from the results of research in local populations and have not been adjusted for age and sex. In this study, we aimed to determine accurate RIs for blood lipid parameters and blood glucose (GluG) for Chinese adults using a national multicenter study. A total of 11,333 adults between 18 and 90 years of age were recruited in seven representative regions in China between June 2020 and December 2020. Hospitals participating in the study were regrouped into two geographical regions, southern China (Changsha, Chengdu, Hangzhou, and Nanning) and northern China (Beijing, Shenyang, and Ningxia), according to their geographical and administrative location. All samples were freshly collected and measured collectively in one laboratory on the Mindray full Automatic biochemical analyzer chemistry BS2000 analytical systems. Outliers were removed using the Tukey test. Three-level nested analysis of variance and scatter plot were used to explore the variations in sex, age, and region. Percentile curves of each indicator were plotted using the least mean square (LMS) method. The lower limit (2.5th percentile) and the upper limit (97.5th percentile) of the RI were determined by using nonparametric statistical methods. We also calculated the 90% confidence interval (CI) for the lower and upper limits. A total of 8,283 participants were enrolled in the final analysis, with 3,593 (43.4%) men and 4,690 (56.6%) women. Regionality was observed in three analytes [small dense low density lipoprotein cholesterol (sd-LDLC), GluG, and apolipoprotein A1 (ApoA1)]. In northern China, the sd-LDLC and GluG levels in Shenyang were significantly higher than those in Ningxia and Beijing (P<0.05). In southern China, the sd-LDLC and GluG levels in Nanning were significantly higher than those in the three other cities (P<0.05), whereas the sd-LDLC and GluG levels in Chengdu were significantly lower than those in the three other cities (P<0.05). The level of ApoA1 in Chengdu was significantly higher than that in the three other cities. The homocysteine (HCY) level in male participants was clearly higher than that in female participants [ratio of standard deviation (SDR)sex =0.56], whereas the levels of high density lipoprotein cholesterol (HDLC) (SDRsex =0.40) and ApoA1 (SDRsex =0.27) in males were lower. The GluG and HCY level increased gradually with age. In females aged 45-55 years, there was an interesting change in scatter charts, where triglyceride (TG) and total cholesterol (TC) increased rapidly. We also found that for the age group of >55 years, the levels of TG and TC in females gradually surpassed those in males. The findings of this study may help establish age- and sex-specific reference values for the blood lipids of Chinese adults and serve as a valuable guide for the screening, diagnosis, treatment, prevention, and monitoring of cardiovascular disease (CVD).

Age- and Sex-Specific Reference Values for Renal Volume and Association with Risk Factors for Chronic Kidney Disease in a General Population—An MRI-Based Study

Age- and Sex-Specific Reference Values for Renal Volume and Association with Risk Factors for Chronic Kidney Disease in a General Population—An MRI-Based Study

SARCOPENIA AT INITIAL DIAGNOSIS OF PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Inflammatory bowel disease (IBD) can impact patients’ nutritional status. Poor oral intake, poor nutrient absorption, stool protein loss, and increased energy requirement all contribute. Poor nutritional status can manifest as inadequate growth, reduced weight gain, and sarcopenia, defined as decreased muscle mass and strength. Studies demonstrate decreased muscle mass in pediatric IBD patients leads to higher rates of therapy escalation, surgery, and post-operative complications. We sought to obtain the muscle mass at IBD diagnosis via cross-sectional imaging, compare to pediatric age- and sex-specific psoas muscle reference values for pediatric norms, and analyze muscle mass comparison between IBD subtypes and correlations with anthropometrics at diagnosis. METHODS Patients with new diagnosis of IBD [Crohn’s disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC)] aged 6-16 at diagnosis during 1/01/2016 through 12/31/2019 at our tertiary care facility were included in this retrospective study. Those with chronic medical conditions and lack of cross-sectional imaging within 3 months of diagnosis were excluded. Demographic and anthropometric data at diagnosis of IBD were obtained. The psoas muscle area in mm2 was measured on cross-sectional imaging at lumbar level 3-4 (L3-4) and 4-5 (L4-5) bilaterally to obtain total psoas muscle area (TPMA) at each level and compared to pediatric reference values. Statistical analysis included analysis of variance and Spearman correlations, performed using SAS v9.4. RESULTS Cross-sectional imaging from 162 patients with newly diagnosed IBD were reviewed. Average age was 12.1 years, with male predominance of 93 patients (57.4%). Most patients were diagnosed with CD (n=119, 73.5%), followed by UC (n=39, 24.1%), and IC (n=4, 2.5%) (Table 1). Measures of sarcopenia at both lumbar levels for TPMA and both lumbar levels z-score showed significant difference across IBD subtypes (Table 2). CONCLUSIONS Negative mean TPMA z-score &amp;lt; -1 was noted in all patients at both L3-4 and L4-5 levels, with a statistically significant difference between IBD types and mean TPMA at L3-4, TPMA at L4-5, mean z-score at L3-4, and mean z-score at L4-5. In a subgroup analysis, UC patients were significantly different from CD patients on all four measures, suggesting a higher rate of sarcopenia in CD patients at diagnosis. We plan to expand analysis to compare sarcopenia with disease location, medical therapy, hospitalization rate, need for surgical intervention, and anthropometrics over time. We hope to underscore importance of sarcopenia as measure of nutritional status at diagnosis, particularly when patients present with normal anthropometrics. Table 1 Table 2 SUBGROUP COMPARISONS Ulcerative Colitis patients were significantly different from Crohn’s Disease patients on all 4 measures. Indeterminate Colitis patients were significantly different from Ulcerative Colitis patient on the 2 Total Psoas Muscle Area Measures.

Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors: The iBoneFIT project

BackgroundPediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density (aBMD). However, the prevalence of muscle strength deficits is not well documented, and the associations of muscle strength with aBMD are unknown in this population. Therefore, this study aimed to investigate the prevalence of upper- and lower-body muscle strength deficits and to examine the associations of upper- and lower-body muscle strength with age-, sex, and race-specific aBMD Z-scores at the total body, total hip, femoral neck, and lumbar spine. MethodsThis cross-sectional study included 116 pediatric cancer survivors (12.1 ± 3.3 years old, mean ± SD; 42.2% female). Upper- and lower-body muscle strength were assessed by handgrip and standing long jump test, respectively. Dual‑energy X‑ray absorptiometry was used to measure aBMD (g/cm2). Associations between muscle strength and aBMD were evaluated in multivariable linear regression models. Logistic regression was used to evaluate the contribution of muscle strength (1-decile lower) to the odds of having low aBMD (Z-score ≤ 1.0). All analyses were adjusted for time from treatment completion, radiotherapy exposure, and body mass index. ResultsMore than one-half of survivors were within the 2 lowest deciles for upper- (56.9%) and lower- body muscle strength (60.0%) in comparison to age- and sex-specific reference values. Muscle strength deficits were associated with lower aBMD Z-scores at all sites (B = 0.133–0.258, p = 0.001–0.032). Each 1-decile lower in upper-body muscle strength was associated with 30%–95% higher odds of having low aBMD Z-scores at all sites. Each 1-decile lower in lower-body muscle strength was associated with 35%–70% higher odds of having low aBMD Z-scores at total body, total hip, and femoral neck. ConclusionMuscle strength deficits are prevalent in young pediatric cancer survivors, and such deficits are associated with lower aBMD Z-scores at all sites. These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.

Reference values for the 1-minute sit-to-stand and 5 times sit-to-stand tests to assess functional capacity: a cross-sectional study

ObjectivesTo establish age-specific and sex-specific reference values and equations for the 1-minute sit-to-stand (1MSTS) and 5 times sit-to-stand (5TSTS) tests for Portuguese adults. DesignCross-sectional study. Descriptive statistics were explored to compute reference values and reference equations were established with a forward stepwise multiple regression. SettingCommunity. ParticipantsIn total, 546 adult volunteers without disabilities [age range 18 to 95 years; 58% female] were recruited. Main outcome measuresData on age, sex, height, weight, body mass index (BMI), smoking status and physical activity were collected using a structured questionnaire developed specifically for this study. Participantsperformed three repetitions of the 1MSTS and 5TSTS and the best repetition was used for analysis. ResultsNormative values were provided by sex for each age decade. Reference equations were: 1MSTS= 61.53 – (0.34 x age) – (3.57 x sex) – (0.33 x BMI), r2 = 26%; and 5TSTS= 3.89 + (0.10 x age) - (0.96 x physical activity), r2 = 27%. ConclusionsThe proposed reference values and equations will help to interpret the results of functional capacity obtained from healthy or diseased adult populations. Contribution of the paper•Sit-to-stand tests are accessible options to assess functional capacity.•Reference equation for the Portuguese population was developed for the 1-minute sit-to-stand [61.53 – (0.34 x age) – (3.57 x sex) – (0.33 x body mass index)].•Reference equation for the Portuguese population was developed for the 5-times sit-to-stand [3.89 + (0.10 x age) – (0.96 x physical activity)].

The relation between synovitis of individual finger joints and grip force over the first 5 years in early rheumatoid arthritis — a cohort study

Objective The objective of this study was to investigate the relation between swelling and tenderness of individual finger joints and grip force in patients with early rheumatoid arthritis (RA).Methods In an inception cohort of patients with early RA (symptom duration < 12 months), all patients were examined by the same rheumatologist, and grip force was measured using the Grippit instrument at inclusion, 1 and 5 years. The average grip force values of each hand were evaluated and expressed as % of expected values, based on age- and sex-specific reference values. Linear regression analyses were used to assess the cross-sectional relation between the involvement of individual finger joints and grip force. In generalized estimating equations, the impact of time-varying synovitis/tenderness on grip force over time was estimated. Analyses were adjusted for wrist involvement, erythrocyte sedimentation rate, and patient-reported pain.ResultsIn 215 patients with early RA, grip force was 39% of expected at diagnosis, and increased to 56% after 5 years. Synovitis of the first metacarpophalangeal (MCP) joint (60% and 69% at baseline in the right and left hand) was associated with reduced grip force at inclusion (adjusted ß − 9.2 percentage unit of expected grip force; 95% CI − 13.6 to − 4.8 for both hands combined) and at all follow-up evaluations. Synovitis of MCP I and MCP IV (12% at baseline) was significantly associated with reduced grip force over time in both hands. Proximal interphalangeal (PIP) joint swelling, and tenderness of MCP or PIP joints, had less impact on grip force.ConclusionMCP I synovitis is the major contributor to reduced grip force in patients with early RA. This underlines the importance of the involvement of the thumb for impaired hand function in RA. MCP IV synovitis, but not PIP involvement or finger joint tenderness, also has a substantial impact on grip force.

Sex-Specific Total Testosterone and Dehydroepiandrosterone Sulfate Status in Noncritically Ill Hospitalized Patients with Coronavirus Disease 2019: A Cross-Sectional Study.

In individuals with coronavirus disease 2019 (COVID-19), male subjects have consistently been linked to poor severity and prognosis. Data on sex hormones in non-critical COVID-19-infected patients are scarce. The aim of this study was to assess the status of total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS) among noncritical patients with COVID-19 according to sex and their associations with clinical and biochemical features. This cross-sectional observational study was done in the COVID-19 unit of a University hospital during the period of September 2021 to February 2022 among 91 adults (18-65 years) with reverse transcriptase- polymerase chain reaction confirmed noncritical COVID-19 patients. Blood was drawn by venipuncture before receiving steroids between 07:00 to 09:00 a.m. in a fasting state to measure serum TT and DHEAS by chemiluminescent microparticle immunoassay. Diagnosis and classification of COVID-19 were done according to World Health Organization's interim guidance. Age- and sex-specific laboratory reference values were used to classify the TT and DHEAS status of the patients. Only three males (8.1%) had low TT and the rest had normal TT. On the other hand, 15 (27.8%) of the females had high TT with normal levels in the rest. Similarly, 11 (29.7%) males had low DHEAS. Females had low, normal, and high DHEAS in four (7.4%), 48 (88.9%), and two (3.7%) cases respectively. Males with moderate severity of COVID-19 had significantly lower DHEAS (post hoc P=0.038) than the mild group. Both TT (P=0.008) and DHEAS (P=0.023) significantly correlated with neutrophils/lymphocytes ratio and only DHEAS with platelets/lymphocytes ratio (P=0.044) in males. In females, TT significantly correlated with serum sodium (P=0.034). In noncritical COVID-19 patients, substantial gender variations in TT and DHEAS were detected and correlated with severity markers in males.

Hypothyroidism, comorbidity and health-related quality of life: a population-based study.

Hypothyroidism is associated with a decreased health-related quality of life (HRQoL). We hypothesized that individuals with hypothyroidism (defined as use of thyroid hormone (TH)) and especially those having an impaired HRQoL are characterized by a high prevalence of comorbid disorders and that the impact of hypothyroidism and comorbidity on HRQoL is synergistic. Presence of comorbidity was based on data obtained using structured questionnaires, physical examination, biochemical measurements and verified medication use. Single morbidities were clustered into 14 different disease domains. HRQoL was measured using the RAND-36. Logistic regression analyses were used to determine the effect of TH use on the odds of having an affected disease domain and a lower score than an age- and sex-specific reference value for HRQoL. TH was used by 4537/14,7201 participants of the population-based Lifelines cohort with a mean (± s.d.) age of 51.0 ± 12.8 years (88% females). Eighty-five percent of the TH users had ≥1 affected disease domain in contrast to 71% of nonusers. TH use was associated with a higher odds of 13 out of 14 affected disease domains independent of age and sex. In a multivariable model, TH use was associated with a decreased HRQoL across six out of eight dimensions. No significant interactions between TH use and affected disease domains were observed. TH users with an impaired HRQoL had significantly more comorbidity than those not having an impaired HRQoL. In this large, population-based study, we demonstrated that TH users had more comorbidity than individuals not using TH. The coexistence of other chronic medical conditions in subjects with TH use led to further lowering of HRQoL in an additive manner.

Reference Values for Cardiorespiratory Fitness in Patients Aged 6 to 18 Years

To develop reference values for cardiorespiratory fitness, as quantified by peak oxygen uptake (VO2peak) and treadmill time, in patients aged 6 through 18 years referred for cardiopulmonary exercise testing (CPET). We reviewed a clinical pediatric CPET database for fitness data in children aged 6-18 years with no underlying heart disease. CPET was obtained via the Bruce protocol utilizing objectively confirmed maximal effort via respiratory exchange ratio. Fitness data (VO2peak and treadmill test duration) were analyzed to determine age- and sex-specific reference values for this pediatric cohort. Data from 2,025 pediatric CPETs (53.2% female) were included in the analyses. VO2peak increased with age in males, but not females. Treadmill test duration increased with age in both males and females. Fitness was generally higher in males when compared with females in the same age groups. Our study provides extensive reference values to date for both VO2peak and total treadmill test time via the Bruce protocol for a pediatric population without known cardiac disease. Furthermore, the inclusion of objectively confirmed maximal exercise effort increases confidence in these findings compared with prior studies in this area. Clinicians performing CPET in pediatric populations can utilize these reference values to characterize test results according to representative peer data.

Muscle Reference Values From Thoracic and Abdominal CT for Sarcopenia Assessment: The Framingham Heart Study.

Loss of muscle mass is a known feature of sarcopenia and predicts poor clinical outcomes. Although muscle metrics can be derived from routine computed tomography (CT) images, sex-specific reference values at multiple vertebral levels over a wide age range are lacking. The aim of this study was to provide reference values for skeletal muscle mass and attenuation on thoracic and abdominal CT scans in the community-based Framingham Heart Study cohort to aid in the identification of sarcopenia. This secondary analysis of a prospective trial describes muscle metrics by age and sex for participants from the Framingham Heart Study without prior history of cancer who underwent at least 1 CT scan between 2002 and 2011. Using 2 previously validated machine learning algorithms followed by human quality assurance, skeletal muscle was analyzed on a single axial CT image per level at the 5th, 8th, 10th thoracic, and 3rd lumbar vertebral body (T5, T8, T10, L3). Cross-sectional muscle area (cm 2 ), mean skeletal muscle radioattenuation (SMRA, in Hounsfield units), skeletal muscle index (SMI, in cm 2 /m 2 ), and skeletal muscle gauge (SMRA·SMI) were calculated. Measurements were summarized by age group (<45, 45-54, 55-64, 65-74, ≥75 years), sex, and vertebral level. Models enabling the calculation of age-, sex-, and vertebral-level-specific reference values were created and embedded into an open access online Web application. The cohort consisted of 3804 participants (1917 [50.4%] males; mean age, 55.6 ± 11.8 years; range, 33-92 years) and 7162 CT scans. Muscle metrics qualitatively decreased with increasing age and female sex. This study established age- and sex-specific reference values for CT-based muscle metrics at thoracic and lumbar vertebral levels. These values may be used in future research investigating the role of muscle mass and attenuation in health and disease, and to identify sarcopenia.

Accelerometer Metrics: Healthy Adult Reference Values, Associations with Cardiorespiratory Fitness, and Clinical Implications.

Accelerometer-assessed physical activity (PA) can be summarized using cut-point-free or population-specific cut-point-based outcomes. We aimed to 1) examine the interrelationship between cut-point-free (intensity gradient (IG) and average acceleration (AvAcc)) and cut-point-based accelerometer metrics, 2) compare the association between cardiorespiratory fitness (CRF) and cut-point-free metrics to that with cut-point-based metrics in healthy adults aged 20 to 89 yr and patients with heart failure, and 3) provide age-, sex-, and CRF-related reference values for healthy adults. In the COmPLETE study, 463 healthy adults and 67 patients with heart failure wore GENEActiv accelerometers on their nondominant wrist and underwent cardiopulmonary exercise testing. Cut-point-free (IG: distribution of intensity of activity across the day; AvAcc: proxy of volume of activity) and traditional (moderate-to-vigorous and vigorous activity) metrics were generated. The "interpretablePA" R-package was developed to translate findings into clinical practice. IG and AvAcc yield complementary information on PA with both IG ( P = 0.009) and AvAcc ( P < 0.001) independently associated with CRF in healthy individuals (adjusted R2 = 73.9%). Only IG was independently associated with CRF in patients with heart failure ( P = 0.043, adjusted R2 = 38.4%). The best cut-point-free and cut-point-based model had similar predictive value for CRF in both cohorts. We produced age- and sex-specific reference values and percentile curves for IG, AvAcc, moderate-to-vigorous PA, and vigorous PA for healthy adults. IG and AvAcc are strongly associated with CRF and thus indirectly with the risk of noncommunicable diseases and mortality, in healthy adults and patients with heart failure. However, unlike cut-point-based metrics, IG and AvAcc are comparable across populations. Our reference values provide a healthy age- and sex-specific comparison that may enhance the translation and utility of cut-point-free metrics in clinical practice.

Association Between Fat Depletion and Prognosis of Amyotrophic Lateral Sclerosis: CT-Based Body Composition Analysis.

The purpose of this study was to present the results of our investigation of the prognostic value of adipopenia and sarcopenia in patients with amyotrophic lateral sclerosis (ALS). Consecutive patients with ALS with abdominal computed tomography (CT) were retrospectively identified at a single tertiary hospital between January 2010 and July 2021. Deep learning-based volumetric CT body composition analysis software was used to obtain abdominal waist fat volume, fat attenuation, and skeletal muscle area at the L3 level, then normalized to the fat volume index (FVI) and skeletal muscle index (SMI). Adipopenia and sarcopenia were defined as the sex-specific lowest quartile and SMI reference values, respectively. The associations of CT-derived body composition parameters with clinical variables, such as body mass index (BMI) and creatinine, were evaluated by Pearson correlation analyses, and associations with survival were assessed using the multivariable Cox regression analysis. Eighty subjects (40 men, 65.5 ± 9.4 years of age) were investigated (median interval between disease onset and CT examination = 25 months). The mean BMI at the CT examination was 20.3 ± 4.3 kg/m2 . The BMI showed a positive correlation with both FVI (R = 0.70, p < 0.001) and SMI (R = 0.63, p < 0.001), and the serum creatinine level was associated with SMI (R = 0.68, p < 0.001). After adjusting for sex, age, King's stage, BMI, creatinine, progression rate, and sarcopenia, adipopenia was associated with shorter survival (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 1.01, 35.0, p = 0.049). In a subgroup analysis for subjects with nutritional failure (stage 4a), the HR of adipopenia was 15.1 (95% CI = 2.45, 93.4, p = 0.003). Deep learning-based CT-derived adipopenia in patients with ALS is an independent poor prognostic factor for survival. ANN NEUROL 2023;94:1116-1125.

Knee injury and osteoarthritis outcome score (KOOS) – National record-based reference values

BackgroundKnee Injury and Osteoarthritis Outcome Score (KOOS) and the short form KOOS-12 are commonly used in clinical practice and research but there are no national record-based reference values to aid interpretation. The aim of this study was to establish national record-based reference values for the KOOS and its short form KOOS-12. Patients and methodsA national record-based representative sample of 9996 adult citizens were derived from the Danish Civil Registration System. The selection of citizens was based on seven predefined age groups with an equal sex distribution across each age strata. The KOOS questionnaire was sent to all participants, together with two supplemental questions regarding previous knee problems and body mass index (BMI). ResultsA total of 2842 participants completed the KOOS, 1463 women (51.4%) and 1379 men (48.6%). The mean KOOS subscale scores were: pain 85.3 (95% confidence interval (CI): 84.6–85.9), symptoms 85.1 (95% CI: 84.5–85.8), activities of daily living (ADL) 86.7 (95% CI: 86.0–87.3), sport and recreation function 70.9 (95% CI: 69.8–72.0), quality of life (QOL) 74.9 (95% CI: 73.9–75.8).Age- and sex-specific reference values showed small differences in mean scores between the five KOOS subscales and all were below the threshold for clinically relevant improvement (10 points).Knee problems were associated with worse KOOS scores across all subscales. The difference in the mean subscale scores between the lowest (<24.9) and highest (>40) BMI groups ranged from 12.9 to 24.1. Comparable results were observed for KOOS-12. ConclusionKOOS and KOOS-12 reference values can, in most situations, be used without stratification for age and sex. Sport/recreation reference values stratified for age and BMI may be of importance.