Percentile Of Population Research Articles

Association between genetic predisposition of AF and the risk of ischemic stroke and thromboembolism

Abstract Background Ischemic stroke and thromboembolism are the major complications of atrial fibrillation (AF), however, its association with genetic background of AF remains unclear. To investigate the association between genetic predisposition of AF underlying common variants and the risk of ischemic stroke and thromboembolism. Methods We included unrelated individuals with non-valvular AF from UK biobank. The polygenic risk scores of AF (PRSAF) was calculated for each individual using the effect weight from a previous study which has been validated in both European and mixed-ancestry population[1, 2]. The SNPs from the original score were lifted over to GRCh38 and 6514708 of 6730541 were available in the UK biobank genotype data. The clinical data was defined by ICD-10 code. The primary endpoint is ischemic stroke or thromboembolism resulting in hospitalization after first AF diagnosis. Results A total of 28810 unrelated patients were included in the study. Among them, 4064 had PRSAF over 90th percentile of the general population, and were considered having high genetic risk. The rest 18746 with per SD increase in PRSAF lower than 90th percentile of the general population were considered having lower genetic risk. Generally, age and sex adjusted model demonstrated that per standard deviation change in PRSAF is associated with 9% increase in the risk of stroke or thromboembolism (HR=1.09, 95%CI: 1.03-1.14), and patients with high genetic risk was associated with 15% increase in the risk of stroke or thromboembolism (HR=1.15, 95%CI: 1.02-1.31).The result remained stable when further adjusted for clinical risk factors (1.09, 95%CI: 1.04-1.15 per SD increase in PRSAF) and competing risk of death (1.10, 95%CI: 1.05-1.16 per SD increase in PRSAF). There was no interaction between CHA2DS2-VASc score risk stratification and the per SD increase in PRSAF (P interaction = 0.751, Figure 1A). However, the association between per SD increase in PRSAF and the event tended to be affected by age at AF onset (HR = 1.02 95%CI: 0.94, 1.11 for early onset AF; HR = 1.12 95%CI: 1.05, 1.19 for non-early onset AF, P for interaction = 0.062, Figure 1B). Multi-variate COX regression including PRSAF, components of CHA2DS2-VASc score, and other AF risk factors revealed that history of stroke/thromboembolism, age over 65 years, hypertension, diabetes and high AF genetic risk were significantly associated with the outcome (Figure 1C). To evaluate the importance of these risk factors, average population attributable fraction for 10-year risk of stroke/thromboembolism in the study population was calculated, indicating that genetic risk of AF is responsible for 3.26% (0.89%-5.63%) of the events (Figure 1D). Conclusion Genetic predisposition of AF underlying common variants is associated with ischemic stroke and thromboembolism independent of clinical risk factors. But its role in different AF populations, like early onset AF, remains further investigation.Figure 1

Pulmonary function using impulse oscillometry system and clinical outcomes at age 4 years in children born extremely preterm with or without bronchopulmonary dysplasia

This study aimed to describe the early assessment of lung function and respiratory morbidity in children born extremely preterm with or without bronchopulmonary dysplasia (BPD). MethodsThis was a prospective study including all the children born at gestational age ≤28 weeks who received treatment in the NICU of the Centre Intercommunal de Créteil in France, from January 2006 to March 2012. Lung function, using the impulse oscillometry system, respiratory morbidity and growth were assessed at age 4 years. Lung function and clinical course of children were compared in children with and without BPD. ResultsWe included 136 extremely premature children; 26 (19 %) had BPD. Children with and without BPD did not significantly differ in resistance measurements at 5 Hz (R5) and 20 Hz (R20) and reactance (X5) measurements at age 4 years. A total of 104 (76 %) pre-term children had respiratory resistance R5 above the 95th percentile for the reference population (z-score >1.64), regardless of BPD status. The mean (SD) R5 z-score for all children was 2.1 (±0.7), whereas the mean (SD) R20 was in the normal range (z-score = 1.1 [±0.3]). After treatment with bronchodilators, all children showed no significant change in resistance. The prevalence of asthma symptoms at age 4 years was common and estimated at 30 % regardless of BPD status. ConclusionEarly assessment of lung function by the impulse oscillometry system revealed that most preschool children who were born extremely preterm had abnormal total airway resistance regardless of BPD status. The system is an essential tool for the early assessment of children born prematurely.

A Pilot Study Using Continuous Glucose Monitoring among Patients with a Low 1-Hour Glucose Challenge Test Result versus Controls to Detect Maternal Hypoglycemia.

A low 1-hour glucose challenge test (GCT) result (<10th percentile for population) has been associated with neonatal morbidity, including small-for-gestational-age birth weight, and it is hypothesized that underlying maternal hypoglycemia may contribute to this neonatal morbidity. We sought to assess whether eligible patients would undergo continuous glucose monitoring to allow comparison of maternal hypoglycemia between those with a low GCT result versus controls. This exploratory study enrolled patients who completed a GCT between 24 and 30 weeks' gestation from June to September 2022. English- or Spanish-speaking participants aged ≥18 years wore a blinded continuous glucose monitor (CGM) for 10 days. There were 10 participants each in the low GCT (<82 mg/dL) and normal GCT group. Proportions were calculated to determine recruitment rates and describe the low versus normal glycemic groups across clinical and sociodemographic characteristics. Maternal hypoglycemia, defined using various proposed thresholds, was analyzed as continuous data (time duration) with Student's t-tests and categorical data (number of episodes) with chi-square tests and bivariate analyses were performed comparing participants with a low versus normal GCT. Primary outcome measures were recruitment, enrollment, and adherence rates, and overall glycemic values for each group. Of 64 eligible patients, 58 (91%) were approached, and of them, 20 (35%) were enrolled. All 20 participants had CGM data to review with 100% adherence. Average glucose values were similar between participants in the low GCT and normal GCT groups (111.7 ± 18.0 vs. 111.6 ± 11.7 mg/dL, p = 0.99), and participants with a low GCT value did not demonstrate more hypoglycemia than those with a normal GCT value across five proposed thresholds on CGM analysis. In this pilot study, participants wore blinded CGMs to collect glycemic data, and those with a low GCT result did not experience more hypoglycemia than those with a normal GCT on CGM analysis. · Study participants wore continuous glucose monitors in blinded mode to gather glycemic data with 100% adherence.. · Participants with a low GCT result (<82 mg/dL) as compared with those with a normal GCT result were not more likely to demonstrate maternal hypoglycemia using several thresholds on CGM analysis.. · In our cohort, there were few participants in either glycemic group who reported food insecurity or lived in a food desert..

Apixaban dosing in hemodialysis - can drug level monitoring mitigate controversies?

BackgroundInconsistent study results and contradictory recommendations from health authorities regarding the use of apixaban in patients on hemodialysis have generated considerable uncertainty among clinicians, making investigations of appropriate dosing an unmet need.MethodsWe analyzed pre-dialysis apixaban drug levels from a tertiary care dialysis unit, comparing 2.5 mg once versus twice daily dosing. We applied mixed-effects models including dialysis modality, adjusted standard Kt/V, ultrafiltration, and dialyzer characteristics. We included an exploratory analysis of bleeding events and compared the drug levels of our dialysis patients to those from non-CKD reference populations taking the standard dose of 5 mg twice daily.ResultsWe analyzed 143 drug levels from 24 patients. Mean (SD) age at first drug level measurement was 64.7 (15.9) years (50 % female), median (IQR) follow-up was 12.5 (5.5 – 21) months. For the apixaban 2.5 mg once and twice daily groups, median (IQR) drug levels were 54.4 (< 40 – 72.1) and 71.3 (48.8 – 104.1) ng/mL respectively (P < 0.001). Levels were below the detection limit in 30 % (with 2.5 mg once daily) and 14 % (with 2.5 mg twice daily) respectively. Only dosing group (twice versus once daily) was independently associated with higher drug levels (P = 0.002). Follow-up did not suggest accumulation. The 95th percentile of drug levels did not exceed those of non-CKD populations taking 5 mg twice daily. Median (IQR) drug levels before a bleeding (8 episodes) were higher than those without a subsequent bleeding: 111.6 (83.1 – 129.3) versus 54.8 (< 40 – 77.1) ng/mL (P < 0.001). Concomitant antiplatelet therapy was used in 86% of those with bleeding events versus 6% without bleeding events (P < 0.001).ConclusionsDrug monitoring may be a contributory tool to increase patient safety. Despite non-existing target ranges, drug levels on both edges of the spectrum (e.g. below detectability or beyond the 95th percentiles of reference populations) may improve decision-making in highly individualized risk-benefit analyses.

Noonan Syndrome Growth Charts and Genotypes: 15-year Longitudinal Single-centre Study.

Growth patterns in Noonan syndrome (NS) remain relatively unknown. The objective of this study was to provide growth reference curves for patients with NS and identify correlations between their growth, genotype, and clinical features. This was a 15-year-long, monocentric, observational, retrospective, non-interventional study. Children with NS followed up between 2005 and 2022 at 'Bambino Gesù' Children's Hospital, Italy, were included, and excluded if they had received growth hormone treatment. Comparison of growth curves of participants with NS versus the general Italian population and further genotypic analyses were performed. Overall, 190 eligible participants with NS were identified, with median (interquartile range) age of 14.01 (9.05-19.25) years, (55.8% male). Cardiovascular anomalies were present in 85.3% of participants, most commonly pulmonary stenosis (52.6%) and atrial septal defects (36.8%); 48.1% of male participants had cryptorchidism. The most frequently detected mutations were in PTPN11 (66.3%) and SOS1 (13.9%). NS-sex-specific centile curves for height, weight, body mass index, and height velocity were produced. For both sexes, the 50th percentile of height and weight for participants with NS overlapped with the 3rd percentile for the general Italian population. Both sexes with a PTPN11 mutation had a significantly lower height and weight than those with 'other mutations' at 5 years old. No significant associations were observed between cardiac anomalies and PTPN11 mutation status. We present longitudinal data describing growth curves and trends, the natural history, and genotypes of the NS population, which provide a useful tool for clinicians in the management of NS.

Glaucomatous Focal Perfusion Loss in the Macula Measured by Optical Coherence Tomographic Angiography

Purpose: To measure low perfusion area (LPA) and focal perfusion loss (FPL) in the macula using OCT angiography (OCTA) for glaucoma. DesignProspective, cross-sectional “case-control” comparison study. Methods: A total of 60 patients with primary open-angle glaucoma (POAG) and 37 normal participants were analyzed. AngioVue 6 × 6-mm high-definition (400 × 400 transverse pixels) macular OCTA scans were performed on one eye of each participant. Flow signal was calculated using the split-spectrum amplitude-decorrelation angiography algorithm. En face ganglion cell layer plexus (GCLP) and superficial vascular complex (SVC) images were generated. Using custom software, vessel density (VD) maps were obtained by computing the fraction of area occupied by flow pixels after low-pass filtering by local averaging 41 × 41 pixels. LPA was defined by local VD below 0.5 percentile over a contiguous area above 98.5 percentile of the normal reference population. The FPL was the percent VD loss (relative to normal mean) integrated over the LPA. Results: Among patients with POAG, 30 had perimetric and 30 had pre-perimetric glaucoma. The LPAGCLP-VD was 0.16±0.38 mm2 in normal and 5.78±6.30 mm2 in glaucoma subjects (P<0.001). The FPLGCLP-VD was 0.20%±0.47% in normal and 7.52%±8.84% in glaucoma subjects (P<0.001). The perimetric glaucoma diagnostic accuracy, measured by the area under the receiver operating curve, was 0.993 for LPAGCLP-VD and 0.990 for FPLGCLP-VD. The sensitivities were 96.7% and 93.3% at 95% specificity, respectively. The LPAGCLP-VD and FPLGCLP-VD had good repeatability (0.957 and 0.952 by intraclass correlation coefficient). Diagnostic accuracy was better than GCLP VD (AROC 0.950, sensitivity 83.3%) and OCT ganglion cell complex (GCC) thickness (AROC 0.927, sensitivity 80.0%), GCC focal loss volume (AROC 0.957, sensitivity 80.0%). The LPAGCLP-VD and FPLGCLP-VD correlated well with central VF mean deviations (Pearson's r=-0.716 and -0.705 respectively, both P<0.001). Conclusion: Assessment of macular focal perfusion loss using OCTA is useful in evaluating glaucomatous damage.

Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice.

Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic cardiovascular disease risk, apoB measurement has not become widely adopted into routine clinical practice. One barrier for use of apoB measurement is lack of consistent guidance for clinicians on how to interpret and apply apoB results in clinical context. Whereas guidelines have often provided clear low-density lipoprotein cholesterol targets or triggers to initiate treatment change, consistent targets for apoB are lacking. In this review, we synthesize existing data regarding the epidemiology of apoB by comparing guideline recommendations regarding use of apoB measurement, describing population percentiles of apoB relative to low-density lipoprotein cholesterol levels, summarizing studies of discordance between low-density lipoprotein cholesterol and apoB levels, and evaluating apoB levels in clinical trials of lipid-lowering therapy to guide potential treatment targets. We propose evidence-guided apoB thresholds for use in cholesterol management and clinical care.

Under Nutrition in Less than Six Months Needs More Attention

Under nutrition in infants is a critical public health concern with far-reaching consequences on child growth and development, particularly during the crucial first six months of life(1). This formative period lays the foundation for future health outcomes and any disruption in adequate nutrition can lead to a host of long-term issues, including stunted growth, compromised immune function, and impaired cognitive development(2). According to the Black et al. (2008) study, these factors are responsible for approximately 2.2 million deaths annually and contribute to 21% of disability-adjusted life-years in this age group(3). The 2011 United Nation Children's Fund (UNICEF) Global Nutrition report indicated that more than 311 million children (32% of all children) were undernourished. Globally, more than four million children died within a year of their birth due to inadequate nutrition.In addition, poor infant nutrition has been shown to be responsible for more than 40% of deaths in children younger than 5 years, particularly during their first month of life(4). The adverse effects of infant undernutrition include physical disabilities, poor school attendance, diabetes, hypertension and cardiovascular disease which may affect the subsequent generation(5).Therefore, undernutrition may have negative long-term consequences for a country’s economic growth and development. The impact of undernutrition on child growth and development starts in utero. Maternal undernutrition has been associated with poor foetal growth which may result in low birth weight (LBW, weight at birth less than 2500 g), small for gestational age (SGA, newborns weighing less than the 10th percentile of a sex-specific reference population) and preterm birth (PTB, children born before 37 gestational weeks(6). In 2016, UNICEF reported that 15% (20 million) of newborns worldwide had LBW and 10% (15 million) PTB. In 2010, 32.4 million newborns worldwide were SGA. The prevalence of SGA was 27% in LMICs, with SSA having one of the highest prevalence(7). The first six months of life are characterized by rapid growth and development, as well as a heightened vulnerability to nutrition-related risks(8).

Gut microbiota and its relationship with early vascular ageing in a Spanish population (MIVAS study).

Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA). A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited. EVA was defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), cardio-ankle vascular index (CAVI) or brachial-ankle pulse wave velocity (ba-PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA). cf-PWV was measured by SphygmoCor® System; CAVI and ba-PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing. Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p < .01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray-Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12-2.6, p = .013) remained significant. In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity.

Incongruence between Cardiorespiratory Fitness and Subjective Reports of Physical Activity in Multiple Sclerosis: A Focus on Sex Differences.

The link between moderate- to vigorous-intensity physical activity (MVPA) and cardiorespiratory fitness in individuals with multiple sclerosis (MS) remains unclear. This study examined the relationship between self-reported MVPA and objectively assessed cardiorespiratory fitness, emphasizing sex differences. 107 adults with MS (77 females), aged (mean ± standard deviation) 47.2 ± 10.2 years, were recruited from a local MS clinic. Fitness was measured as maximal oxygen uptake (V̇O2max) during a graded maximal exercise test using a recumbent stepper. MVPA (24-hour recall) was estimated as the duration of activities ≥ 3 MET (metabolic equivalent of task). MET-minutes were calculated by multiplying MET by duration. We explored sex differences in self-reported MVPA, cardiorespiratory fitness, and disability; examined sex differences in associations between these variables; and investigated whether MET-minutes of MVPA predicted V̇O2max in females and males. Mean V̇O2max was 24.79 mL·kg-1·min-1, indicating poor cardiorespiratory fitness levels, despite high levels of self-reported MVPA (mean = 412.5 MET-minutes). Fifty-three percent of males and 40% of females had V̇O2max levels below the 20th age- and sex-standardized population percentile, indicating poor cardiorespiratory fitness. There were statistically significant associations between MVPA and V̇O2max (Rho = 0.27, p = .01), as well as disability and V̇O2max (Rho = -0.35, p = .02), in females but not males. A regression model using sex, age, body mass, disability, and MVPA to estimate V̇O2max was valid in predicting V̇O2max values that were statistically equivalent to those measured in the laboratory in females but not males. However, the inclusion of MVPA did not add to the predictive value of this equation. Despite reporting high levels of MVPA, people with MS had poor cardiorespiratory fitness. MVPA, fitness, and disability were associated in females only, indicating that sex differences should be considered in fitness appraisal. Self-reported MVPA did not predict fitness, suggesting 24-hour recall may not be representative of true activity or fitness levels in persons with MS. Future work should examine sex differences in associations between MVPA and fitness using objective measures such as accelerometry.

Impact of cardiac size on diagnostic performance of single-photon emission computed tomography myocardial perfusion imaging: insights from the REgistry of Fast Myocardial Perfusion Imaging with NExt generation single-photon emission computed tomography.

Variation in diagnostic performance of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been observed, yet the impact of cardiac size has not been well characterized. We assessed whether low left ventricular volume influences SPECT MPI's ability to detect obstructive coronary artery disease (CAD) and its interaction with age and sex. A total of 2066 patients without known CAD (67% male, 64.7 ± 11.2 years) across nine institutions underwent SPECT MPI with solid-state scanners followed by coronary angiography as part of the REgistry of Fast Myocardial Perfusion Imaging with NExt Generation SPECT. Area under receiver-operating characteristic curve (AUC) analyses evaluated the performance of quantitative and visual assessments according to cardiac size [end-diastolic volume (EDV); <20th vs. ≥20th population or sex-specific percentiles], age (<75 vs. ≥75 years), and sex. Significantly decreased performance was observed in patients with low EDV compared with those without (AUC: population 0.72 vs. 0.78, P = 0.03; sex-specific 0.72 vs. 0.79, P = 0.01) and elderly patients compared with younger patients (AUC 0.72 vs. 0.78, P = 0.03), whereas males and females demonstrated similar AUC (0.77 vs. 0.76, P = 0.67). The reduction in accuracy attributed to lower volumes was primarily observed in males (sex-specific threshold: EDV 0.69 vs. 0.79, P = 0.01). Accordingly, a significant decrease in AUC, sensitivity, specificity, and negative predictive value for quantitative and visual assessments was noted in patients with at least two characteristics of low EDV, elderly age, or male sex. Detection of CAD with SPECT MPI is negatively impacted by small cardiac size, most notably in elderly and male patients.

Association between BMI z-score and body composition indexes with blood pressure and grip strength in school-age children: a cross-sectional study

Childhood obesity is linked to diverse health outcomes, including elevated blood pressure (EBP). Emerging evidence showed that excess fat mass (FM) may have a deleterious impact on blood pressure even in normal-weight children. The primary objective of this study was to assess the association between body weight status by BMI z-score and body composition parameters by conventional bioelectrical impedance analysis (BIA) and bioelectrical impedance vector analysis (BIVA). Also, we aimed to explore the performance of BMI z-score, %FM, and FM index (FMI) in discriminating EBP in a sample of school-age Mexican children. Children were classified as having normal weight, overweight or obesity according to WHO criteria for BMI z-score. FMI was considered high when above 75th percentile, and fat free mass index (FFMI) was considered low when below 25th percentile of the reference population. Body composition was also classified according to the BIVA method and EBP was determined when systolic and/or diastolic blood pressure ≥ 90th percentile. BMI z-score groups were compared by Student´s t-test or the Mann–Whitney U test, or by the chi-square test or Fisher exact test. Receiving operating characteristic (ROC) analysis was performed. 61 children were included (52.5% boys, median age 9.8 (25th, 75th percentiles: 8.5, 11.0)) years. High FMI was observed in 32.3% of children with normal weight. Low FFMI was present in 93.5% of children with normal weight and 53.3% of those with overweight/obesity. According to BIVA, 58.1% and 43.3% of children with normal weight and overweight/obesity were classified as having cachexia. All the three adiposity indicators showed significant areas under the ROC curve (AURC) greater than 0.775 for EBP, with the largest one displayed for FM% (0.794). Hight FMI and low FFMI are common in children with normal weight. Identifying deficiency of FFM might be limited by using solely BMI indicators. Cachexia by BIVA was present in a high proportion of children with either normal weight or overweight/obesity. Both BMI z-score and FM (% and FMI) performed well at discriminating EBP, with a numerically greater AURC observed for FM%. Body composition in pediatric population is relevant for identifying body composition abnormalities at early age.

Health-related quality of life and cognitive function after out-of-hospital cardiac arrest; a comparison of prehospital return-of-spontaneous circulation and refractory arrest managed with extracorporeal cardiopulmonary resuscitation

BackgroundExtracorporeal cardiopulmonary resuscitation (ECPR) for selected refractory out-of-hospital cardiac arrest (OHCA) is increasingly used. Detailed knowledge of health-related quality of life (HRQoL) and long-term cognitive function is limited. HRQoL and cognitive function were assessed in ECPR-survivors and OHCA-survivors with prehospital return of spontaneous circulation after standard advanced cardiac life support (sACLS). MethodsFifteen ECPR-survivors and 22 age-matched sACLS-survivors agreed to participate in this follow-up study. Participants were examined with echocardiography, 6-minute walk test, and neuropsychological testing, and answered HRQoL (EQ-5D-5L and Short Form 36 (SF-36)), and mental health questionnaires. ResultsMost patients were male (73 % and 82 %) and median age at follow-up was similar between groups (55 years and 60 years). Low flow time was significantly longer for ECPR-survivors (86 min vs. 15 min) and lactate levels were significantly higher (14.1 mmol/l vs. 3.9 mmol/l). No between-group difference was found in physical function nor in cognitive function with scores corresponding to the 23rd worst percentile of the general population. SACLS-survivors had HRQoL on level with the Danish general population while ECPR-survivors scored lower in both EQ-5D-5L (index score 0.73 vs. 0.86, p = 0.03, visual analog scale: 70 vs. 84, p = 0.04) and in multiple SF-36 health domains (role physical, bodily pain, general health, and mental health). ConclusionsDespite substantially longer low flow times with thrice as high lactate levels, ECPR-survivors were similar in cognitive and physical function compared to sACLS-survivors. Nonetheless, ECPR-survivors reported lower HRQoL overall and related to mental health, pain management, and the perception of limitations in physical role.

Long-term Catch-up Growth and Risk Factors for Short Adult Height After Pediatric Liver Transplantation: A Retrospective Study.

Children requiring liver transplantation generally have severe growth retardation. Recipients experience posttransplantation catch-up growth, although some show short adult heights. We aimed to determine decades-long catch-up growth trends and risk factors for short adult height following liver transplantation. We analyzed long-term height Z scores and risk factors for short adult height in a single-center retrospective cohort of 117 pediatric liver transplantation recipients who survived >5 y, with 75 of them reaching adult height. Median age at transplantation was 1.3 y, and the most common primary diagnosis was biliary atresia (76.9%). Mean height Z scores pretransplantation and 1, 3, and 8 y after transplantation were -2.26, -1.59, -0.91, and -0.59, respectively. The data then plateaued until 20 y posttransplantation when mean adult height Z score became -0.88, with a median follow-up of 18.6 y. Nineteen recipients did not show any catch-up growth, and one quarter of recipients had short adult height (<5th percentile of the healthy population). Multivariate analysis identified old age (odds ratio, 1.22 by 1 y; P = 0.002), low height Z scores at transplantation (odds ratio, 0.46 by 1 point; P < 0.001), and posttransplantation hospital stay ≥60 d (odds ratio, 4.95; P = 0.015) as risk factors for short adult height. In contrast, prolonged steroid use after transplantation was not considered a significant risk factor. Although tremendous posttransplantation catch-up growth was observed, final adult height remained inadequate. For healthy physical growth, liver transplantation should be performed as early as possible, before growth retardation becomes severe.

Comparison of Quantile Regression and Gaussian (Z-scores) Percentiles to BSA in Growth Charts With a Pakistani Population.

Introduction: In the current study, we construct growth charts of body surface area (BSA) for adults using the quantile regression (QR) approach and growth charts of different Gaussian Percentiles (Z-scores) against age. Methods: A cross-sectional data consisting of 3,473 individuals aged 5 or more, both males and females were taken from Multan city. Quantile regression (QR) was used to construct BSA growth charts. Growth charts for different Z-scores were also constructed. Results: For our data set, the mean BSA is 0.48750. The BSA percentiles show a trending higher after the age of 5 until the age of 22, then decrease between age 22 and 35, and then finally increase after age 35. The Z-score curve increases slightly after age 5 and then proceeds higher until age 22. After age 22 and before 35 it plateaus and then increases slightly after age 35. Conclusion: Since the use of empirical BSA percentiles and Z-scores with grouped age provides a discrete approximation for the population percentiles and Z-scores, it is more accurate to use continuous BSA percentile and Z-score, curves against given ages while using quantile regression and Z-score approach. Furthermore, this approach can also be adopted to construct many other growth charts for physiological and medical sciences.

How to enhance the applicability of a risk prediction model for term small-for-gestational-age neonates in clinical settings?

To construct a simple term small-for-gestational-age (SGA) neonate prediction model that is clinically practical. This analysis was based on the Born in Guangzhou Cohort Study (BIGCS). Mothers who had a singleton pregnancy, delivered a term neonate, and had an ultrasonography within 30 + 0 to 32 + 6 weeks of gestation were included. Term SGA was defined with customized population percentiles. Prediction models were constructed with backward selection logistic regression in a four-step approach, where model 1 contained fetal biometrics only, models 2 and 3 included maternal features and a time factor (weeks between ultrasonography and delivery), respectively; and model 4 contained all features mentioned. The prediction performance of individual models was evaluated based on area under the curve (AUC) and a calibration test was performed. The prevalence of SGA in the study population of 21 346 women was 11.5%. With a complete-case analysis approach, data of 19 954 women were used for model construction and validation. The AUC of the four models were 0.781, 0.793, 0.823, and 0.834, respectively, and all were well-calibrated. Model 3 consisted of fetal biometrics and corrected for time to delivery was chosen as the final model to build risk prediction graphs for clinical use. A prediction model derived from fetal biometrics in early third trimester is satisfactory to predict SGA.

Remnant cholesterol and risk of premature mortality: an analysis from a nationwide prospective cohort study.

To explore the relationship between remnant cholesterol (RC) and the risk of premature mortality as well as life expectancy in the general population. We included a total of 428 804 participants from the UK Biobank for analyses. Equivalent population percentiles approach based on the low-density lipoprotein cholesterol cut-off points was performed to categorize participants into three RC groups: low (with a mean RC of 0.34mmol/L), moderate (0.53mmol/L), and high (1.02mmol/L). We used multivariable Cox proportional hazards models to evaluate the relationship between RC groups and the risk of premature mortality (defined as death before age 75 years). Life table methods were used to estimate life expectancy by RC groups. During a median follow-up of 12.1 years (Q1-Q3 11.0-13.0), there were 23 693 all-cause premature deaths documented, with an incidence of 4.83 events per 1000 person-years [95% confidence interval (CI): 4.77-4.89]. Compared with the low RC group, the moderate RC group was associated with a 9% increased risk of all-cause premature mortality [hazard ratio (HR) = 1.09, 95% CI: 1.05-1.14], while the high RC group had an 11% higher risk (HR=1.11, 95% CI: 1.07-1.16). At the age of 50 years, high RC group was associated with an average 2.2 lower years of life expectancy for females, and an average 0.1 lower years of life expectancy for males when compared with their counterparts in the low RC group. Elevated RC was significantly related to an increased risk of premature mortality and a reduced life expectancy. Premature death in the general population would benefit from measurement to aid risk stratification and proactive management of RC to improve cardiovascular risk prevention efforts.

Exaggerated Systolic Blood Pressure Increase with Exercise and Myocardial Ischemia on Exercise Stress Echocardiography.

Central Illustration : Exaggerated Systolic Blood Pressure Increase with Exercise and Myocardial Ischemia on Exercise Stress Echocardiography ESBPRE: exaggerated systolic blood pressure response to exercise; HR: heart rate; SBP: systolic blood pressure. The association between exaggerated systolic blood pressure response to exercise (ESBPRE) and myocardial ischemia is controversial and little studied in patients with established or suspected chronic coronary syndrome. To verify the relationship between myocardial ischemia and ESBPRE in patients undergoing exercise stress echocardiography (ESE). This is a cross-sectional study with 14,367 patients undergoing ESE, from January 2000 to January 2022, divided into the following 2 groups: G1, composed of patients whose peak systolic pressure increased ≥ 90 mmHg (value corresponding to the 95th percentile of the study population), and G2, patients who did not demonstrate an exaggerated hypertensive response. The groups were compared using Student's t and chi-square tests. P values < 0.05 were considered significant. Logistic regression was also performed to identify independent risk factors for myocardial ischemia, ESBPRE, complaints of typical chest pain prior to the exam, and angina during the test. Of the 14,367 patients, 1,500 (10.4%) developed ESBPRE, and 7,471 (52.0%) were female. The percentages of previous complaints of typical chest pain, angina during the test, and myocardial ischemia in patients with ESBPRE were 5.8%, 2.4% and 18.1%, compared to 7.4%, 3.9%, and 24.2%, in patients without ESBPRE, respectively (p = 0.021,p = 0.004, p < 0.001). In multivariate analysis, ESBPRE was independently associated with a lower probability of myocardial ischemia (odds ratio: 0.73; 95% confidence interval: 0.58 to 0.93; p = 0.009). Exaggerated increase in systolic blood pressure during ESE may be a marker for excluding myocardial ischemia.

A randomized clinical trial of sex and population-specific troponin cutoffs for ruling out acute MI - the danish study of sex and population-specific cutoffs of troponin (DANSPOT)

Abstract Background Measurements of high-sensitivity cardiac troponin (cTn) T/I are used as the gold standard and are the preferred biomarkers to diagnose acute myocardial infarction (MI) in conjugation with symptoms and changes in the ECG. The URL is based on the 99th percentile of troponin concentrations in a healthy reference population. Currently, a sex-uniform manufacturer provided 99th percentile URL of troponin is utilized at Danish hospitals as a diagnostic cutoff for acute MI for both men and women. Reportedly, healthy men have twofold the troponin level compared to healthy women, suggesting that the use of a uniform URL for troponins may lead to the under-diagnostication of acute MI in women and potentially over-diagnostication in men. Purpose The purpose of the DANSPOT study is to evaluate the clinical effect on diagnosis, treatment and outcomes in men and women presenting with acute MI of implementing international guidelines recommended sex-specific 99th percentile URLs for troponin into clinical practice. Methods First, to determine the sex-specific 99th percentile URLs of troponins (table) based on a healthy Danish reference population, blood samples from Danish blood donors, were analyzed using five high-sensitivity (hs) cTn assays (Siemens Atellica and Vista hs-cTnI, Roche hs-cTnT, Abbott Alinity hs-cTnI and Orthos VITROS hs-cTnI). Second, the DANSPOT study is a nationwide cluster-randomized trial with "stepped-wedge" design (figure) with participation of 22 Danish hospital center. With one-month intervals, each of the 22 centers have been randomized to shift from the presently applied sex-uniform 99th percentile URL of troponin to the population and sex-specific 99th percentiles URLs. First center started implementing the new 99th percentiles URLs on April 1, 2022, and the last center is planned to enroll on January 1, 2024. Patients are followed up in Danish registries for 12 months after index admission. The primary endpoint is a composite of myocardial infarction, unplanned revascularization (after index admission) and all-cause mortality and is calculated for the cohort of women and men with ≥2 measurements of troponin within the first 24 hours of admission with maximal troponin level between the new sex-specific 99th percentile URLs and the old sex-uniform 99th percentile URL. Perspective The clinical significance of sex-specific 99th percentile URLs of troponin is poorly investigated and for the same reason not yet implemented in Denmark or many other countries. With the implementation of population and sex-specific 99th URLs of troponin, we expect to detect significantly more women with acute MI, theoretically resulting in a more accurate diagnosis and treatment of women and men with acute MI. This would be guideline-defining for implementing sex-specific cutoffs for troponin in Denmark as well as internationally as recommended in guidelines by professional cardiological societies.Schematic presentation of study designTable of the new 99th percentiles of cTn

Cardiac Autonomic Dysfunction and Risk of Silent Myocardial Infarction Among Adults With Type 2 Diabetes.

Background There is a paucity of large-scale epidemiological studies on the link between cardiac autonomic neuropathy (CAN) and the risk of silent myocardial infarction (SMI) in type 2 diabetes. We evaluated the association between CAN and the risk of SMI in a large sample of adults with type 2 diabetes. Methods and Results Participants with type 2 diabetes from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without atherosclerotic cardiovascular disease at baseline were included. CAN was ascertained using heart rate variability indices calculated from 10-s resting electrocardiograms. The heart rate variability indices included standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals. CAN was defined as both the standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals less than the fifth percentile of the general population. We used Cox proportional hazards regression to generate hazard ratios (HRs) for incident SMI in relation to CAN measures. Among 4842 participants (mean age, 62.5 years; 46.6% women; 60.2% White), there were 73 incident SMI cases over a median follow-up of 4.9 years (incidence rate 3.1 out of 1000 person-years [95% CI, 2.5-3.9]). After adjusting for confounders, low heart rate variability was associated with a higher risk of SMI (HR, 1.67 [95% CI, 1.02-2.72] and HR, 1.56 [95% CI, 0.94-2.58] for low standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals, respectively). Participants with CAN had a 1.9-fold greater risk of SMI (HR, 1.91 [95% CI, 1.14-3.20]). Conclusions In a large cohort of adults with type 2 diabetes, CAN was significantly associated with an increased risk of incident SMI.