Age-specific Reference Values Research Articles

Longitudinal trends in testicular volume z scores from puberty to adulthood, sperm quality, and paternity outcomes after childhood cancer.

Childhood cancer therapy may cause subfertility. This study correlated cancer therapy exposures with testicular volumes from puberty to adulthood, spermatogenesis, and paternity outcomes in adulthood. The study population comprised 255 male childhood cancer survivors (CCS) (survival ≥5 years, diagnosed in 1964-2000 at the Helsinki Children's Hospital) whose testicular volume was measured at ages 12 years (n=38), 14 years (n=57), 16 years (n=63), 18 years (n=105), and in adulthood (n=43; median age, 27 years). Testicular volumes were converted to age-specific z scores. In addition, 92 CCS provided semen sample in adulthood (median age, 25.2 years); and paternity was evaluated through national register data (mean age at assessment, 37.6 years; n=252). Compared with age-specific reference values, CCS generally exhibited low testicular volume z scores at ages 12-18 years. Testicular volume z scores in CCS treated exclusively with chemotherapy returned to the reference range in adulthood. In contrast, patients exposed to testicular radiation ≥1 gray (Gy) (median dose, 12 Gy) showed no late recovery in testicular size. Testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥12 g/m2 were identified as risk factors for azoospermia in adulthood. Patients exposed to testicular radiation ≥1 Gy and a cyclophosphamide equivalent dose ≥4 g/m2 had lower paternity rates. Testicular volume growth after prolonged follow-up suggests a potential late recovery of spermatogenesis in CCS treated exclusively with chemotherapy. However, alkylating agents increased the risk of having prolonged azoospermia and nonpaternity. High-dose testicular radiation causes long-term depletion of spermatogonia and was the strongest risk factor for azoospermia and nonpaternity.

Pediatric reference values of NT-proBNP and Galectin-3 based on a French cohort

BackgroundIn pediatric cardiology, the fact that some new biomarkers have assay-specific normal values has to be considered for correct clinical decisions. The current study aimed to provide age-adjusted normative values for NT-proBNP and Galectin-3 using the Abbott immunoassay system from a prospective French pediatric cohort sera collection and to validate our data for NT-proBNP on a second retrospective cohort. MethodsWe analyzed 283 consecutive samples for NT-proBNP and 140 samples for Galectin-3 collected from apparently healthy children (0–18 years) with outpatient treatment at our institution (Hôpital Necker-Enfants malades, Paris, France) during 24 months. ResultsFor NT-proBNP and Galectin-3, we establish four age partitions, respectively two (<2 years / >2 years) and establish upper reference values and their 90 % CI for each biomarker (Galectin-3 (ng/mL): 56 [44–70] / 26 [23–29]). We evaluated the diagnostic performance of our upper reference values of NT-proBNP on a retrospective cohort (n = 428) with positive predictive value of 0.92. ConclusionsUsing Abbott immunoassay system, we report age-specific reference values for NT-proBNP and for the first time for Galectin-3 in a healthy French pediatric cohort. These data call for larger cohort studies to define more robustly percentiles and diagnostic performance for NT-proBNP.

Age-Dependent Signature of Serum Inflammatory Cytokines in Healthy Children and Young Adults.

The study of sensitive and specific biomarkers, such as blood inflammatory cytokines, could provide an answer to the challenges faced in the differential diagnosis of patients with systemic inflammation. Limited data exist on the impact of age on serum levels of inflammatory cytokines. We collected serum samples of 42 healthy children and young adults (1 month to 21 years). Serum levels of interleukin 1 receptor antagonist (IL-1Ra), IL-1β, IL-6, IL-18, tumor necrosis factor-alpha (TNF-α), CXCL9, and CXCL10 were measured. Data were analyzed for three different age groups (<6, 6-17, and 18-21 years). IL-18, TNF-α, and CXCL9 values varied significantly according to age group. Median values of IL-18 and TNF-α decline with age, whereas CXCL9 and CXCL10 are lowest at 6-17 years. IL-1Ra is stable among age groups. In the majority of cases, IL-1β and IL-6 are not measurable above the lower limit of quantification. A scoping literature review revealed highly variable data on IL-1Ra, IL-18, TNF-α, and CXCL10. For CXCL9, pediatric reference data are scarce. In conclusion, we report an age-dependent signature of multiple inflammatory cytokines measured in the serum of healthy children and young adults, suggesting the need to use age-specific reference values in future pediatric studies.

Utility of fractional excretion of magnesium in diagnosing renal magnesium wasting in pediatric nephrology practice

BackgroundFractional excretion of magnesium (FEMg) is commonly used to diagnose of renal magnesium (Mg) wasting, but it can be affected by serum Mg (SMg) and serum creatinine concentration (SCr). We investigated the sensitivity and specificity of FEMg to diagnose Mg wasting in subgroups with different SMg and eGFR (estimated glomerular filtration rate) in pediatric nephrology practice. MethodsOne hundred and nineteen patients (59 males and 60 females, median 15 years) seen in our pediatric clinic were investigated for FEMg, SMg, eGFR, and urine Mg-to-creatinine ratio (Mg/Cr). Normal eGFR was defined as ≥ 90 ml/min/1.73 m2 or for infants SCr < chronic kidney disease stage 2. Urine Mg/Cr was compared with age-specific reference values. ResultsSixteen of all patients (13 %) had hypomagnesemia. All had FEMg greater than the cut-off value of 2 %. Only 4 patients had elevated urine Mg/Cr. Of 65 patients with normal SMg and eGFR, 19 had FEMg above the cut-off value of 4 %. Of these, 13 patients had elevated urine Mg/Cr i.e. Mg wasting (sensitivity and specificity of FEMg, 93 % and 88 %, respectively). Among 38 patients with normal SMg and low eGFR, 30 had FEMg > 4 %, but only 6 had elevated urine Mg/Cr (sensitivity 100 % and specificity 25 %). Overall, hypomagnesemic patients and normomagnesemic patients with elevated urine Mg/Cr were diagnosed with Mg wasting (36/119, 30 %). ConclusionsFEMg has variable sensitivity and specificity depending on SMg and eGFR in the diagnosis of Mg wasting. Mg wasting is not uncommon in pediatric nephrology practice.

Quantitative study of the ossification centers of the body of sphenoid bone in the human fetus

The aim of the present study was to examine the growth dynamics of the two ossification centers of the body of sphenoid bone in the human fetus, based on their linear, planar and volumetric parameters. The examinations were carried out on 37 human fetuses of both sexes aged 18–30 weeks of gestation, which had been preserved in 10% neutral formalin solution. Using CT, digital image analysis software, 3D reconstruction and statistical methods, we evaluated the size of the presphenoid and postsphenoid ossification centers. The presphenoid ossification center grew proportionately in sagittal diameter, projection surface area and volume, and logarithmically in transverse diameter. The postsphenoid ossification center increased logarithmically in sagittal diameter, transverse diameter and projection surface area, while its volumetric growth followed proportionately. The numerical findings of the presphenoid and postsphenoid ossification centers may be considered age-specific reference values of potential relevance in monitoring the normal fetal growth and screening for congenital disorders in the fetus. The obtained results may contribute to a better understanding of the growing fetal skeleton, bringing new numerical information regarding its diagnosis and development.

#745 Age and gender specific reference values for renal volume and association with risk factors for chronic kidney disease in a general population

Abstract Background and Aims Renal volume (RV) is associated with renal function and with a variety of cardiovascular risk factors (CVRF). We analyzed RV by magnetic resonance imaging (MRI) in a large population-based study (Study of Health in Pomerania; SHIP-TREND) and tested the influence of age, sex, smoking status, BSA, systolic and diastolic blood pressure, type 2 diabetes, HDL-C, LDL-C, estimated glomerular filtration rate (eGFR) and uric acid on RV. Method 1,815 participants without kidney disease (930 women) aged 21-81 years were included in our study. Right and left RV with and without body surface area (BSA) indexation were compared among three age groups (22-39 years, 40-59 years, 60-81 years) by median and interquartile range and tested separately in women and men. Results eGFR, uric acid, right and left RV were higher in men compared to women (all p &amp;lt; 0.001). Left kidney were larger than right kidneys (both sexes). With age, RV showed a continuously decreasing trend in women and an upside down U-shape relation in men. In multivariable linear regression models, current smoking (β = 14.96, 95% CI 12.12; 17.79), BSA (β = 97.66, 95% CI 90.4; 104.93), diastolic blood pressure (β = 0.17, 95% CI 0.01; 0.32), and eGFR (β = 0.57, 95% CI 0.50; 0.65) were positively associated with both left and right renal volume whereas uric acid (β = −0.03, 95% CI −0.05; −0.01) showed an inverse association with RV. Interestingly, the same eGFR correlated with higher RV in men compared to women. Conclusion Reference values for RV are different for age-groups and sex. For any given age, female kidneys are smaller than male kidneys. RV associates positively with eGFR, but for any chosen eGFR, renal volume in females is lower compared to males. RV decreases with age, but in men, RV first increases in the age group 40-59 years before finally decreasing with a faster decline after 60 years. This may reflect hyperfiltration and glomerular hypertrophy associated with the presence of CVRF.

Polytrauma in Children.

Inadequate clinical experience still causes uncertainty in the acute diagnostic evaluation and treatment of polytrauma in children (with or without coagulopathy). This review deals with the main aspects of the acute care of severely injured children in the light of current guidelines and other relevant literature, in particular airway control, volume and coagulation management, acute diagnostic imaging, and blood coagulation studies in the shock room. This review is based on literature retrieved by a selective search in PubMed, Medline (OVIDSP), the Cochrane Central Register of Controlled Trials, and Epistemonikos covering the period January 2001 to August 2023. Review articles and the updated S2k clinical practice guideline on polytrauma management in childhood were considered. Most accidents in childhood occur at home and in the child's free time, with varying mechanisms and patterns of injury depending on age. The outcome of treatment depends largely on the presence or absence or traumatic brain injury, which affects 66% of children with polytrauma and is thus the most common type of injury in this group, and of hemorrhagic shock with or without coagulopathy. Acute care follows the ABCDE algorithms with attention to special features in children, including age-specific reference values. According to a registry study, coagulopathy and hypovolemic shock are associated with 22% and 17% mortality, respec - tively. Treatment in a pediatric trauma reference center of the trauma network is recommended. Computed tomography (CT) should be carried out in children in accordance with defined criteria (PECARN), as a team decision and with the use of age-specific low-dose CT protocols. In children as in adults, viscoelasticity-based point-of-care tests enable the prompt diagnosis of relevant coagulopathies and their treatment in consideration of age-specific target values. The administration of tranexamic acid remains controversial. 4% of polytrauma patients are children. Because children differ from adults both anatomically and physiologically, the diagnostic evaluation and management of polytrauma in children presents a special challenge. The evidence base for pediatric polytrauma management is still inadequate; current recommendations are based on consensus, in consideration of the special features of children compared to adults.

Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study

IntroductionIn light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their...

Normative values of motor performance and their relationship with BMI status in Hong Kong preschoolers

This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3–5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P50 and P95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese.

Heart rate in newborns is associated with age, sex and maternal levothyroxine therapy.

To evaluate the definition and causes of neonatal bradycardias. This retrospective study included 135 term-born newborns referred for 24-hour Holter monitoring due to bradycardia. Bradycardia was defined as either a heart rate below 80 beats per minute (standard definition) or a heart rate below our recently published age-specific reference values for neonatal heart rate. The mean (SD) age was 6.1 (1.3) days. With standard definition, 107 newborns (79%) had bradycardia, whereas only 20 (15%) had a minimum heart rate lower than the age-specific reference. Younger newborns had lower heart rates. Each day increased the minimum, mean and maximum heart rate by 1.8 (95% CI: 1.0, 2.6), 4.2 (95% CI: 3.0, 5.3) and 2.1 beats per minute (95% CI: 0.3, 3.8), respectively. Male sex and maternal levothyroxine medication were negatively associated with the mean and maximum heart rate. None of the newborns had a cardiac cause for low heart rate. Among term newborns with bradycardias, younger age, male sex and maternal levothyroxine medication were associated with a lower heart rate on Holter monitoring. Given the age-related increase in heart rate, the 80 beats per minute limit as a universal threshold for abnormal heart rate in newborns appears inappropriate.

Relation Between Endothelial Dysfunction and Exercise Training-Mediated Adaptation in Cardiovascular Risk Factors, Cardiorespiratory Fitness, and Vascular Health in Humans: A secondary analysis

Abstract Purpose A priori cardiovascular (CV) health status may impact reductions in risk factors and CV mortality and morbidity following exercise training, although this is not fully understood. Therefore, the purpose of the study was to examine if endothelial function (assessed via flow mediated dilation; FMD%), predicts the magnitude of change in CV risk factors or fitness following exercise training. Methods We pooled data from 338 individuals who underwent supervised exercise training (8–26 weeks). Using recent sex- and age-specific reference values for flow-mediated dilation (FMD%), we categorised participants as having preserved endothelial function (P-EF) (&gt; 50th percentile of reference value, 56 females, 67 males, 46 ± 17 years) or reduced endothelial function (R-EF) (&lt; 50th percentile of reference value, 67 females, 148 males, 48 ± 17 years). The effects of exercise training on cardiovascular risk factors (BMI, cholesterol, glucose and triglycerides), cardiorespiratory fitness (VO2peak) and vascular function (FMD%) were examined using a two-way mixed design general linear model. Results Exercise training significantly improved physical fitness (P &lt; 0.001), with no difference in the magnitude of improvement between P-EF and R-EF. Modest but significant reductions were present in BMI, blood pressure and total cholesterol (all P &lt; 0.005), with no difference between P-EF and R-EF groups in the magnitude of changes in these variables with training. Exercise training did not significantly alter glucose, triglycerides, high density lipoprotein (HDL) and low-density lipoprotein (LDL) (all P &gt; 0.05). Conclusion Individuals with reduced and preserved a priori endothelial function status can obtain benefits from exercise in terms of risk factor modification and fitness change. Therefore, exercise has the potential to be beneficial in all clinical groups.

Reference values for estimated VO2max by two submaximal cycle tests: the Åstrand-test and the Ekblom-Baktest.

Submaximal tests estimating VO2max have inherent biases; hence, using VO2max estimations from the same test is essential for reducing this bias.This study aimed to establish sex- and age-specific reference values for estimated VO2max using the Åstrand-test (Å-test) and the Ekblom-Bak test (EB-test). We also assessed the effects of age, exercise level, and BMI on VO2max estimations. We included men and women (20-69years) from the Swedish working population participating in Health Profile Assessments between 2010 and 2020. Excluding those on heart rate-affecting medicines and smokers, n = 263,374 for the Å-test and n = 95,043 for the EB-test were included. VO2max reference values were based on percentiles 10, 25, 40, 60, 75, and 90 for both sexes across 5-year age groups. Estimated absolute and relative VO2max were for men 3.11L/min and 36.9mL/min/kg using the Å-test, and 3.58 L/min and 42.4mL/min/kg using the EB-test. For women, estimated absolute and relative VO2max were 2.48L/min and 36.6mL/min/kg using the Å-test, and 2.41L/min and 35.5mL/min/kg using the EB-test. Higher age (negative), higher exercise level (positive), and higher BMI (negative) were associated with estimated VO2max using both tests. However, explained variance by exercise on estimated VO2max was low, 10% for the Å-test and 8% for the EB-test, and moderate for BMI, 23% and 29%. We present reference values for estimated VO2max from two submaximal cycle tests. Age, exercise, and BMI influenced estimated VO2max. These references can be valuablein clinical evaluations using the same submaximal tests.

Reference Values in the 6-Minute Walk Test in Chilean Children Aged 3-10Years and Relationship With Cardiometabolic Risk.

The aim of this study was to evaluate the performance of healthy Chilean children aged 3-10years in the 6-minute walking test (6MWT) and cardiometabolic risk variables and to determine sex- and age-specific reference values. This study involved 1165 healthy children (age = 6.36 [1.70]y old). The 6MWT was used to evaluate exercise performance. Furthermore, anthropometric measures were collected, like weight, height, body mass index, waist circumference, and skin folds. Resting heart rate and blood pressure (BP) were also evaluated. The prevalence of overweight and obesity was 35.0% and 25.4% in preschoolers and 29.0% and 36.2% in school-age children, respectively, showing significant differences (P < .05) between age groups. The distance walked (6-min walk distance) increased significantly year on year at ages from 3 to 10years. According to the regression analysis, 6MWT performance was positively related to age, systolic BP, and height, whereas it was negatively related to ∑4 skinfold fat, resting heart rate, diastolic BP, and waist circumference. This study provides a reference equation and an age- and sex-adjusted percentile curve to assess the predicted 6MWT performance in a cohort of prepubertal Chilean children. The 6-minute walk distance depends mainly on age; however, other variables, such as resting heart rate, BP, skinfold fat, and waist circumference, add significant information and should be taken into account.

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. Participants546 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. ProcedureParticipants performed 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)].

Age-Specific Reference Values for Amino Acid Content in Dried Blood Spots in Children in Western Kazakhstan, Measured by Tandem Mass Spectrometry

Measuring the level of amino acids in the blood is one of the stages in the early diagnosis of inborn errors of metabolism (IEM), implying timely initiation of therapeutic measures. Tandem mass spectrometry (MS/MS) is now replacing traditional IEM screening methods. Dried blood spot amino acid reference values developed for the pediatric population are crucial for interpreting test results and diagnosing aminoacidopathies. The study aims to establish reference values for amino acid (AAs) concentrations in samples of dried blood spots from newborns in Western Kazakhstan using LC-MS/MS (liquid chromatography-tandem mass spectrometry) technology. Methods: The cross-sectional study included 250 healthy newborns of Western Kazakhstan aged 1-3 days, born at term and breastfed, 49.2% male and 50.2% female. To establish the age-specific reference values for AAs, newborns were divided into three groups: (1) 1 day, (2) 2 days, and (3) 3 days. Blood samples on Guthrie cards were collected on days 1–3 of life and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nonparametric statistical approaches were used to generate the 2.5th–97.5th percentile distributions for newborns. Results: 3 of the 15 DBS amino acid distributions were dependent on gender. There was a statistically significant difference in the mean level of alanine, citrulline, and glutamic acid in males and females. The highest values were determined in the female group. Age-related differences in glutamic acid, leucine, ornithine, tyrosine, and valine concentration levels were observed. No significant correlations were found between the concentrations of 15 amino acids in dried blood spots and the body weight of newborns. Conclusion: The present study established amino acid concentrations that can be utilized as reference standards in Kazakhstan's newborn screening program for inherited metabolic diseases.

Establishing Body Mass Index growth charts for Pakistani children and adolescents using the lambda-mu-sigma (LMS) and quantile regression method.

Assessment of growth and nutritional status is an essential part of clinical evaluation and care in pediatrics. Therefore, we aimed to establish age and gender specific smoothed BMI growth reference charts of Pakistani children and adolescents aged 2-18 years and to compare our LMS median percentile values with WHO 2007 international references and with references from other foreign studies. A representative cross-sectional sample of 10,668 healthy Pakistani subjects aged 2 to 18 years was studied. For calculation of BMI (kg/m2), height (cm) and weight (kg) were measured using standard procedures. Age and gender specific smoothed BMI growth reference values and associated charts were obtained using lambda-mu-sigma (LMS) as well as quantile regression (QR) statistical methods. In the sample studied, the mean (±SD) BMI of all subjects was 16.50 (±2.83 kg/m2). Smoothed BMI percentile curves (5th, 10th, 25th, 50th, 75th, 90th and 95th) obtained by using LMS and QR methods, showed that BMI increased with age in both sexes. During pubertal age, girls had larger percentiles than boys. Centile values estimated by the LMS and QR procedure had small variability from the empirical centiles. Comparison of LMS BMI 50th percentile with references from WHO 2007 and data from other countries demonstrated that Pakistani children had substantially lower BMI percentiles than their counterparts in the reference population. This comprehensive study suggests that WHO 2007 references are not suitable for Pakistani children. The QR method should be considered as an alternative method to develop growth charts.

Reference values for body composition in healthy urban Mexican children and adolescents.

Given the increasing incidence of chronic degenerative diseases related to changes in tissues, the availability of diagnostic tools with greater accuracy in the estimation of body composition (BC) has become necessary. Interpreting the BC values of individuals requires reference data obtained from a healthy population with the same ethnicity, to identify individuals at risk for the development of negative health outcomes. Generate reference values (RV) of body composition (BC) for Mexican children and adolescents. This was an urban-population-based cross-sectional study of healthy Mexican children and adolescents. BC estimations by anthropometry, multifrequency bioimpedance analysis (MF-BIA) and dual-energy X-ray absorptiometry (DXA) where used to create sex- and age-specific RV by means of generalized additive models for location, scale and shape (GAMLSS). We assessed 2104 subjects, and after confirming a clinically and metabolically healthy status, we measured 1659 subjects aged 5-20 years, [806 females (49%) and 853 males (51%)] by anthropometry, MF-BIA and DXA to create sex- and age- smoothed reference centiles, lambda (L), mu (M), and sigma (S) values. We also built sex- and age-smoothed graphic curves for each variable of interest. We present valid RV and curves for BC variables estimated by anthropometry, MF-BIA and DXA from clinically and metabolically healthy urban Mexican children and adolescents. These RV are different from those reported for other populations, and therefore, should be used for clinical and research purposes involving urban Mexican children and adolescents.

A Systematic Review of the Clinical Diagnosis of Transient Hypogammaglobulinemia of Infancy.

Transient hypogammaglobulinemia of infancy (THI) is a primary immunodeficiency caused by a temporary decline in serum immunoglobulin G (IgG) levels greater than two standard deviations below the mean age-specific reference values in infants between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as IgG is only transferred across the placenta from mother to infant during the third trimester of pregnancy. This study aimed to conduct a systematic review of the diagnostic criteria for transient hypogammaglobulinemia of infancy. Systematic review: Three electronic databases (PubMed, MEDLINE, and Google Scholar) were manually searched from September 2021 to April 2022. Abstracts were screened to assess their fit to the inclusion criteria. Data were extracted from the selected studies using an adapted extraction tool (Cochrane). The studies were then assessed for bias using an assessment tool adapted from Cochrane. Of the 215 identified articles, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in the six domains. A total of five studies (31%) had a low risk of bias, while four studies (25%) had a high risk of bias, and bias in the case of seven studies (44%) was unclear. We conclude that THI is only definitively diagnosed after abnormal IgG levels normalise. Hence, THI is not a benign condition, and monitoring for subsequent recurrent infections must be conducted. The diagnostic criteria should also include vaccine and isohaemagglutinin responses to differentiate THI from other immunological disorders in infants.

Left-to-right ventricular volume ratio and outcome in heart failure with preserved ejection fraction.

Age-specific and gender-specific reference values for left ventricular (LV) and right ventricle volumes are available. The prognostic implications of the ratio between these volumes in heart failure and preserved ejection fraction (HFpEF) have never been evaluated. We examined all HFpEF outpatients undergoing a cardiac magnetic resonance from 2011 to 2021. The left-to-right ventricular volume ratio (LRVR) was defined as the ratio between the LV and right ventricle end-diastolic volume indexes (LVEDVi/RVEDVi). Among 159 patients [median age 58 years (interquartile range 49-69), 64% men, LV ejection fraction 60% (54-70%)] the median LRVR was 1.21 (1.07-1.40). Over 3.5 years (1.5-5.0), 23 patients (15%) experienced all-cause death or heart failure hospitalization, and 22 (14%) cardiovascular death or heart failure hospitalization. The risk of all-cause death or heart failure hospitalization increased with an LRVR less than 1.0 or at least 1.4. An LRVR less than 1.0 was associated with a higher risk of all-cause death or heart failure hospitalization [hazard ratio 5.95, 95% confidence interval (CI) 1.67-21.28; P = 0.006] and cardiovascular death or heart failure hospitalization (hazard ratio 5.68, 95% CI 1.58-20.35; P = 0.008) as compared with LRVR 1.0-1.3. Furthermore, an LRVR at least 1.4 was associated with a higher risk of all-cause death or heart failure hospitalization (hazard ratio 4.10, 95% CI 1.58-10.61; P = 0.004) and cardiovascular death or heart failure hospitalization (hazard ratio 3.71, 95% CI 1.41-9.79; P = 0.008) as compared with LRVR 1.0-1.3. These results were confirmed in patients without dilation of either ventricle. LRVR values less than 1.0 or at least 1.4 are associated with worse outcomes in HFpEF. LRVR may become a valuable tool for risk prediction in HFpEF.

Health Risk and Underweight.

We used routinely collected laboratory parameters from a total of 4087 patients. The risk score was calculated on the basis of electrolytes, blood count, transaminases and LDH. The nine parameters used were summed as zlog-transformed values. Where appropriate, the scales were inverted so that high values represented higher risk. For statistical prediction of the risk score, weight/height and age reference values from the WHO, the CDC (Center of Disease Control) and representative studies of German children and adults (KIGGS and NNS) were used. The score calculated from nine laboratory parameters already shows a convincing relationship with BMI. Among the weight measures used for height and age, the z-score from the CDC reference population emerged as the best estimate, explaining 34% of the variance in health risk measured by the laboratory score. The percentile rank for each age-specific median weight from the KIGGS/NNS still explained more than 31% of the variance. In contrast, percentiles explained less variance than BMI without age correction. The score we used from routine laboratory parameters appears to be an appropriate measure for assessing the health risk associated with underweight, as measured by the quality of the association with BMI. For estimating health risk based on weight, height and age alone, z-scores and percentages of age-specific median weight, as opposed to percentiles, are appropriate parameters. However, the study also shows that existing age-specific BMI reference values do not represent risk optimally. Improved statistical estimation methods would be desirable.