Hematological and Biochemical Reference Ranges for the Population with Sickle Cell Disease at Steady State in Tanzania

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and the evaluation of interventions. This study was conducted at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania, to establish laboratory reference ranges among children and adults with SCD at steady state. Patients were grouped into five age groups and according to their sex. Aggregate functions were used to handle repeated measurements within the individual level in each age group. A nonparametric approach was used to smooth the curves, and a parametric approach was used to determine SCD normal ranges. Comparison between males and females and against the general population was documented. Data from 4422 patients collected from 2004–2015 were analyzed. The majority of the patients (35.41%) were children aged between 5–11 years. There were no significant differences (p ≥ 0.05) in mean corpuscular hemoglobin concentration (MCHC), lymphocytes, basophils, and direct bilirubin observed between males and females. Significant differences (p < 0.05) were observed in all selected parameters across age groups except with neutrophils and MCHC in adults, as well as platelets and alkaline phosphatase in infants when the SCD estimates were compared to the general population. The laboratory reference ranges in SCD at steady state were different from those of the general population and varied with sex and age. The established reference ranges for SCD at steady state will be helpful in the management and monitoring of the progress of SCD.

Utility of fetal facial markers on a second trimester genetic sonogram in screening for Down syndrome in a high-risk Thai population

Background To establish the reference ranges and evaluate the efficacy of the fetal facial sonomarkers prenasal thickness (PT), nasal bone length (NBL), PT/NBL ratio and NBL/PT ratio for Down syndrome screening in the second trimester of high-risk pregnancies using two-dimensional (2D) ultrasound. Methods A prospective study was done in Thai pregnant women at high risk for structural and chromosomal abnormalities between May 2018 and May 2019. The main exclusion criteria were any fetal anatomical anomaly detected on ultrasonography or postpartum examination, abnormal chromosome or syndrome other than Down syndrome. Ultrasounds were performed in 375 pregnant women at 14 to 22 weeks’ gestation and the fetal facial parameters were analyzed. Down syndrome results were confirmed by karyotyping. The reference ranges of these facial ultrasound markers were constructed based on the data of our population. The Down syndrome screening performance using these facial ultrasound markers was evaluated. Results In total, 340 euploid fetuses and 11 fetuses with Down syndrome met the inclusion criteria. The PT, NBL, and PT/NBL ratios in the euploid fetuses gradually increased with gestation progression while the NBL/PT ratio gradually decreased between 14–22 weeks’ gestation. The NBL, PT/NBL ratio, and NBL/PT ratio all had 100% sensitivity and PT had 91% sensitivity. These facial markers had 100% negative predictive value for Down syndrome screening in the second trimester. The Bland–Altman analysis showed the intra- and inter-observer variations of PT and NBL had high intraclass correlation coefficients (ICC) in both operators, with ICCs of 0.98 and 0.99 and inter-observer ICCs of 0.99 for both operators. Conclusion The facial ultrasound markers are very useful for second trimester Down syndrome screening in our population. These facial ultrasound markers were easily identifiable and highly consistent either intra- or inter-operator by using widely-available 2D ultrasound. However, the reference ranges for these markers need to be constructed based on individual populations. Trial registration Registration number: REC 61–029-12–3. Date of registration: 18 May 2018.

Hematological and Biochemical Reference Ranges for Population With Sickle Cell Disease at Steady-State in Tanzania

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and evaluation of interventions. This study was conducted at Muhimbili National Hospital (MNH) in Dar es Salaam, to establish laboratory reference ranges in SCD at steady-state. Patients were grouped into five age groups with respects to their sex. Aggregate functions were used to handle repeated measures within the indi-vidual level in each age group. A nonparametric approach was used to smooth the curves and a parametric approach was used to determine SCD normal ranges. Comparison between males and females and against the general population was documented. Data from 4,422 patients collected from 2004-2015 were analyzed. The majority of the patients (35.41%) were children aged between 5-11 years. There were no significant differences (p&ge;0.05) in mean corpuscular hemoglobin concentration (MCHC), lymphocytes, basophils and bilirubin direct observed between males and females. Significant differences (p&lt;0.05) were observed in all selected parameters across age groups except neutrophils and MCHC in adults, as well as platelets and alkaline phosphatase in infants when SCD estimates were compared to the general population. Laboratory reference ranges in SCD at steady-state were different from those of the general population and varied with sex and age. The established reference ranges for SCD at steady-state will be a helpful in the management and monitoring of the progress of SCD.

Neurofilament light chain concentration in an aging population

Background Neurofilament light chain (NF-L) concentration is recognized to be modified in neurological diseases and traumatic brain injuries, but studies in the normal aging population are lacking. It is, therefore, urgent to identify influencing factors of NF-L concentration in the aging population. Method We assessed NF-L concentration in sera of a large cohort of 409 community-dwelling adults aged over 65 years. We studied the association between NF-L and various physiological factors but also with self-reported comorbidities or life-style habits. Results We showed that NF-L concentration in serum was tightly associated with cystatin C concentration (r = 0.501, p < 0.0001) and consequently, to the estimated glomerular filtration rate (eGFR) (r = − 0.492; p < 0.0001). Additionally, NF-L concentration was dependent on age and body mass index (BMI) but not sex. Among the self-reported comorbidities, subjects who reported neurological disorders, cardiovascular diseases or history of fracture had higher NF-L concentration in univariate analysis, whereas it was only the case for subjects who reported neurological disorders in the multivariate analysis. NF-L concentration was also increased when Mini-Mental State Examination (MMSE) was decreased (≤ 25 points) but not when geriatric depression score (GDS) was increased (> 5 points) in both univariate and multivariate analysis. Finally, we are providing reference ranges by age categories for subjects with or without altered renal function. Conclusion NF-L concentration in the aging population is not driven by the increasing number of comorbidities or depression. Yet, NF-L blood concentration is dependent on kidney function and NF-L interpretation in patients suffering from renal failure should be taken with caution.

Oxygen saturation and heart rate in healthy term and late preterm infants with delayed cord clamping

Blood oxygen in the fetus is substantially lower than in the newborn infant. In the minutes after birth, arterial oxygen saturation rises from around 50–60% to 90–95%. Initial respiratory efforts generate negative trans-thoracic pressures that drive liquid from the airways into the lung interstitium facilitating lung aeration, blood oxygenation, and pulmonary artery vasodilatation. Consequently, intra- (foramen ovale) and extra-cardiac (ductus arteriosus) shunting changes and the sequential circulation switches to a parallel pulmonary and systemic circulation. Delaying cord clamping preserves blood flow through the ascending vena cava, thus increasing right and left ventricular preload. Recently published reference ranges have suggested that delayed cord clamping positively influenced the fetal-to-neonatal transition. Oxygen saturation in babies with delayed cord clamping plateaus significantly earlier to values of 85–90% than in babies with immediate cord clamping. Delayed cord clamping may also contribute to fewer episodes of brady-or-tachycardia in the first minutes after birth, but data from randomized trials are awaited. Impact Delaying cord clamping during fetal to neonatal transition contributes to a significantly earlier plateauing of oxygen saturation and fewer episodes of brady-and/or-tachycardia in the first minutes after birth. We provide updated information regarding the changes in SpO2 and HR during postnatal adaptation of term and late preterm infants receiving delayed compared with immediate cord clamping. Nomograms in newborn infants with delayed cord clamping will provide valuable reference ranges to establish target SpO2 and HR in the first minutes after birth.

Significance of Levothyroxine Treatment on Serum Lipid in Pregnant Women With Subclinical Hypothyroidism

BackgroundThere is no consensus reference range for serum lipid levels during pregnancy. The benefit of levothyroxine (L-T4) on serum lipid levels are unclear among pregnant women with subclinical hypothyroidism (SCH).ObjectiveTo determine the recommended reference ranges for serum lipid concentrations during pregnancy and effects of L-T4 treatment on serum lipids in pregnant women with SCH. Designcohort study.MethodsA analysis of 20365 women in the first trimester was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University during 2018–2020. After excluding women with adverse pregnancy outcomes, we determined the reference range of serum lipid in the first and third trimesters of pregnancy by using median and quartile to determine appropriate percentiles. Next, we divided into three groups as follows: SCH L-T4 treatment group (n=319), SCH non-intervention group (n=103) and the control group(n=9598).ResultsThe recommended reference range for serum lipids in the first trimester of pregnancy should be: TC < 5.33 mmol/L, TG < 1.73 mmol/L, LDL-C < 3.12 mmol/L and HDL-C> 1.1 mmol/L, and in third trimester of pregnancy should be: TC < 8.47 mmol/L, TG < 4.86 mmol/L, LDL-C < 5.3 mmol/L and HDL-C >1.34 mmol/L.There are significant differences in TC and LDL-C levels between SCH treatment group and SCH non-intervention Group (P=0.043, P=0.046; respectively).ConclusionsWe determine the recommended reference ranges for serum lipid concentrations during pregnancy. TC and LDL-C levels in pregnant women with SCH could improve after L-T4 treatment.

Association Between Socio-Affective Symptoms and Glutathione and CD4 and CD8 Lymphocytes in College Students

Background: The prevalence of anxiety and depression in young students is associated with biosocial factors and scholastic stress. However, few studies have evaluated emotional-affective symptoms that are related to the immune system and antioxidant parameters in young individuals without diagnoses of affective disorders.Aim: This study aims to assess the relationship between emotional-affective symptoms and glutathione concentrations and CD4 and CD8 lymphocyte counts in college students.Methods: College students (n = 177) completed standardized psychometric instruments, including the Perceived Stress Scale, Hamilton Anxiety Scale, Beck Depression Inventory, Familiar Social and Friends Support Scale, and Rosenberg Scale. Blood samples were biochemically analyzed. Analyses of variance were conducted between four groups according to symptom severity.Results: A considerable prevalence of stress, anxiety, and depression symptoms was observed and negatively correlated with self-esteem and socio-familiar support. Perceived stress was sexually dimorphic. Although biochemical parameters were within reference ranges, glutathione, CD4, and CD8 tended to be lower in participants with anxiety and depression symptoms, which may be of predictive value.Conclusion: The relationship between antioxidant/immune parameters and socio-affective scores is latent in undiagnosed college students who might develop affective disorders. The findings suggest that during the initial development of affective disorders, stress management strategies should be implemented to help college students cope with the academic load and monitor negative changes in their physiological state.

Age- and sex-specific pediatric LMS-Percentiles for Laboratory Parameters enabled by Data mining

Background:Various laboratory parameters routinely measured in pediatric practice covariate with sex and age. Conventional reference intervals are not suitable to account for this variation. Here we demonstrate construction of continuous LMS percentile curves from routine laboratory data. This allows adequate adjustment for both sex- and age-dependent covariation in childhood.Material and Methods:Anonymized routine blood test results requested by primary health care physicians were collected, outliers excluded and LMS-models generated in R.Results:Percentiles for several biomarkers derived from a regional population were established in the 'LMS' framework and provided here for comparison with etablished reference ranges, discussion and, potentially, clinical use.Conclusion: The reference framework 'LMS' is well-known from pediatric growth charts and can also be used in laboratory medicine.

Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

According to current guidelines, growth hormone (GH) therapy is strongly recommended in children and adolescents with GH deficiency (GHD) in order to accelerate growth rate and attain normal adult height. The diagnosis of GHD requires demonstration of decreased GH secretion in stimulation tests, below the established threshold value. Currently, GHD in children is classified as secondary insulin-like growth factor-1 (IGF-1) deficiency. Most of children diagnosed with isolated GHD presents with normal GH secretion at the attainment of near-final height or even in mid-puberty. The most important clinical problems, related to the diagnosis of isolated GHD in children and to optimal duration of rhGH therapy include: arbitrary definition of subnormal GH peak in stimulation tests, disregarding factors influencing GH secretion, insufficient diagnostic accuracy and poor reproducibility of GH stimulation tests, discrepancies between spontaneous and stimulated GH secretion, clinical entity of neurosecretory dysfunction, discrepancies between IGF-1 concentrations and results of GH stimulation tests, significance of IGF-1 deficiency for the diagnosis of GHD, a need for validation IGF-1 reference ranges. Many of these issues have remained unresolved for 25 years or even longer. It seems that finding solutions to them should optimize diagnostics and therapy of children with short stature.

Challenges in the Management of Atrial Fibrillation With Subclinical Hyperthyroidism

Subclinical thyroid disorders have a high prevalence among older individuals and women. Subclinical hypothyroidism is diagnosed by elevated serum levels of thyroid-stimulating hormone (TSH) with thyroxine levels within the reference range, and subclinical hyperthyroidism is diagnosed by low TSH in conjunction with thyroxine and triiodothyronine levels within reference ranges. Atrial fibrillation is the most commonly diagnosed cardiac arrhythmia and has been associated with an increased risk of mortality, heart failure, stroke, and depression. Mechanistic data from animal and human physiology studies as well as observational data in humans support an association of subclinical hyperthyroidism with atrial fibrillation. Guidelines recommend the measurement of TSH in the evaluation of new-onset atrial fibrillation. All patients with overt hyperthyroidism should be treated, and treatment of subclinical hyperthyroidism should be considered in patients older than 65 years with TSH &lt; 0.4 mlU/L, or in younger patients with TSH &lt; 0.1 mlU/L. Guidelines also recommend screening for AF in patients with known hyperthyroidism. Wearable devices that measure the heart electrical activity continuously may be a novel strategy to detect atrial fibrillation in patients at risk. In this review, we explore the interplay between thyroid hormones and atrial fibrillation, management controversies in subclinical hyperthyroidism, and potential strategies to improve the management of atrial fibrillation in patients with subclinical hyperthyroidism.