Monofilament assessment of neuropathy in a community diabetes clinic

Objective. To compare the detection of diabetic neuropathy using monofilament, cotton wool, pinprick, vibration sense and symptom evaluation.Setting. The diabetes clinic of a community hospital.Methods. Two examiners evaluated 89 women with diabetes mellitus (DM) using a 10 g monofilament, cotton wool, pinprick and a 128 Hz tuning fork after completion of a University of Texas subjective peripheral neuropathy verbal questionnaire.Results. Vibration sense was abnormal in either foot in 8% of subjects. Neuropathy as defined by monofilament, cotton wool and pinprick was present in 26%, 3% and 6% of patients respectively. The respective kappa values (κ) for the comparison between monofilament neuropathy and cotton wool neuropathy, pinprick neuropathy and symptomdefined neuropathy were 0.18, 0.21 and 0.06. The κ-value comparing monofilament and tuning fork-defined neuropathy was 0.24. There was fair agreement between 10 versus 3 sites (κ= 0.60).Conclusion. More abnormalities were detected using the monofilament compared with cotton wool or pinprick. There was poor concordance between symptoms and clinically detected neuropathy. The ideal number of sites that need to be evaluated is still contentious

Insights in a restricted temporary pacemaker strategy in a lean transcatheter aortic valve implantation program

OBJECTIVES: To study the safety and feasibility of a restrictive temporary‐RV‐pacemaker use and to evaluate the need for temporary pacemaker insertion for failed left ventricular (LV) pacing ability (no ventricular capture) or occurrence of high‐degree AV‐blocks mandating continuous pacing. BACKGROUND: Ventricular pacing remains an essential part of contemporary transcatheter aortic valve implantation (TAVI). A temporary‐right‐ventricle (RV)‐pacemaker lead is the standard approach for transient pacing during TAVI but requires central venous access. METHODS: An observational registry including 672 patients who underwent TAVI between June 2018 and December 2020. Patients received pacing on the wire when necessary, unless there was a high‐anticipated risk for conduction disturbances post‐TAVI, based on the baseline‐ECG. The follow‐up period was 30 days. RESULTS: A temporary‐RV‐pacemaker lead (RVP‐cohort) was inserted in 45 patients, pacing on the wire (LVP‐cohort) in 488 patients, and no pacing (NoP‐cohort) in 139 patients. A bailout temporary pacemaker was implanted in 14 patients (10.1%) in the NoP‐cohort and in 24 patients (4.9%) in the LVP‐cohort. One patient in the LVP‐cohort needed an RV‐pacemaker for incomplete ventricular capture. Procedure time was significantly longer in the RVP‐cohort (68 min [IQR 52–88.] vs. 55 min [IQR 44–72] in NoP‐cohort and 55 min [IQR 43–71] in the LVP‐cohort [p < 0.005]). Procedural high‐degree AV‐block occurred most often in the RVP‐cohort (45% vs. 14% in the LVP and 16% in the NoP‐cohort [p ≤ 0.001]). Need for new PPI occurred in 47% in the RVP‐cohort, versus 20% in the NoP‐cohort and 11% in the LVP‐cohort (p ≤ 0.001). CONCLUSION: A restricted RV‐pacemaker strategy is safe and shortens procedure time. The majority of TAVI‐procedures do not require a temporary‐RV‐pacemaker

Children of Low Socioeconomic Status Show Accelerated Linear Growth in Early Childhood; Results from the Generation R Study

Objectives: People of low socioeconomic status are shorter than those of high socioeconomic status. The first two years of life being critical for height development, we hypothesized that a low socioeconomic status is associated with a slower linear growth in early childhood. We studied maternal educational level (high, mid-high, mid-low, and low) as a measure of socioeconomic status and its association with repeatedly measured height in children aged 0-2 years, and also examined to what extent known determinants of postnatal growth contribute to this association. Methods: This study was based on data from 2972 mothers with a Dutch ethnicity, and their children participating in The Generation R Study, a population-based cohort study in Rotterdam, the Netherlands (participation rate 61%). All children were born between April 2002 and January 2006. Height was measured at 2 months (mid-90% range 1.0-3.9), 6 months (mid-90% range 5.6-11.4), 14 months (mid-90% range 13.7-17.9) and 25 months of age (mid-90% range 23.6-29.6). Results: At 2 months, children in the lowest educational subgroup were shorter than those in the highest (difference: -0.87 cm; 95% CI: -1.16, -0.58). Between 1 and 18 months, they grew faster than their counterparts. By 14 months, children in the lowest educational subgroup were taller than those in the highest (difference at 14 months: 0.40 cm; 95% CI: 0.08,0.72). Adjustment for other determinants of postnatal growth did not explain the taller height. On the contrary, the differences became even larger (difference at 14 months: 0.61 cm; 95% CI: 0.26,0.95; and at 25 months: 1.00 cm; 95% CI: 0.57,1.43) Conclusions: Compared with children of high socioeconomic status, those of low socioeconomic status show an accelerated linear growth until the18th month of life, leading to an overcompensation of their initial height deficit. The long-term consequences of these findings remain unclear and require further study

Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis

Objective: Corticosteroids are used in sepsis treatment to benefit outcome. However, discussion remains on which patients will benefit from treatment. Inter-individual variations in cortisol sensitivity, mediated through the glucocorticoid receptor, might play a role in the observed differences. Our aim was to study changes in mRNA levels of three glucocorticoid receptor splice variants in neutrophils of children with sepsis. Patients and design: Twenty-three children admitted to the pediatric intensive care unit with sepsis or septic shock were included. Neutrophils were isolated at days 0, 3 and 7, and after recovery (>3 months). mRNA levels of the glucocorticoid receptor splice variants GR-α (determining most of the cortisol effect), GR-P (increasing GR-α effect) and GR-β (inhibitor of GR-α) were measured quantitatively. Main results: Neutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-α and GR-P splice variants on day 0 compared to after recovery. GR-α and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-β mRNA levels did not change significantly during sepsis. GR expression was negatively correlated to interleukin-6 (a measure of disease severity, r = -0.60, P = 0.009). Conclusions: Children with sepsis or septic shock showed a transient depression of glucocorticoid receptor mRNA in their neutrophils. This feature may represent a tissue-specific adaptation during sepsis leading to increased cortisol resistance of neutrophils. Our study adds to understanding the mechanism of cortisol sensitivity in immune cells. Future treatment strategies, aiming at timing and tissue specific regulation of glucocorticoids, might benefit patients with sepsis or septic shock

Maternal smoking during pregnancy and subcutaneous fat mass in early childhood. The Generation R Study

Maternal smoking during pregnancy increases the risk of obesity in the offspring. Not much is known about the associations with other measures of body composition. We assessed the associations of maternal smoking during pregnancy with the development of subcutaneous fat mass measured as peripheral and central skinfold thickness measurements in early childhood, in a population-based prospective cohort study from early fetal life onward in the city of Rotterdam, The Netherlands. The study was performed in 907 mothers and their children at the ages of 1.5, 6 and 24 months. As compared to non-smoking mothers, mothers who continued smoking during pregnancy were more likely to have a younger age and a lower educational level. Their children had a lower birth weight, higher risk of small size for gestational age and were breastfed for a shorter duration (P-values <0.01). We did not observe differences in peripheral, central and total subcutaneous fat mass between the offspring of non-smoking mothers, mothers who smoked in first trimester only and mothers who continued smoking during pregnancy (P > 0.05). Also, the reported number of cigarettes smoked by mothers in both first and third trimester of pregnancy were not associated with peripheral, central and total subcutaneous fat mass in the offspring at the ages of 1.5, 6 and 24 months. Our findings suggest that fetal exposure to cigarette smoke during pregnancy does not influence subcutaneous fat mass in early childhood. Follow-up studies are needed in children at older ages and to identify associations of maternal smoking during pregnancy with other measures of body composition

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

CKD-MBD after kidney transplantation

Successful kidney transplantation corrects many of the metabolic abnormalities associated with chronic kidney disease (CKD); however, skeletal and cardiovascular morbidity remain prevalent in pediatric kidney transplant recipients and current recommendations from the Kidney Disease Improving Global Outcomes (KDIGO) working group suggest that bone disease—including turnover, mineralization, volume, linear growth, and strength—as well as cardiovascular disease be evaluated in all patients with CKD. Although few studies have examined bone histology after renal transplantation, current data suggest that bone turnover and mineralization are altered in the majority of patients and that biochemical parameters are poor predictors of bone histology in this population. Dual energy X-ray absorptiometry (DXA) scanning, although widely performed, has significant limitations in the pediatric transplant population and values have not been shown to correlate with fracture risk; thus, DXA is not recommended as a tool for the assessment of bone density. Newer imaging techniques, including computed tomography (quantitative CT (QCT), peripheral QCT (pQCT), high resolution pQCT (HR-pQCT) and magnetic resonance imaging (MRI)), which provide volumetric assessments of bone density and are able to discriminate bone microarchitecture, show promise in the assessment of bone strength; however, future studies are needed to define the value of these techniques in the diagnosis and treatment of renal osteodystrophy in pediatric renal transplant recipients

Influence of birth size and body composition on bone mineral density in early adulthood:the PROGRAM study

Background/objectives Low bone mineral density (BMD) may lead to osteoporosis and is associated with increased fracture risk. Associations between BMD and various factors have been reported. Our objective was to investigate whether birth size, lean body mass (LBM) and fat mass (FM) are determinants of BMD of the total body (BMDTB) and the lumbar spine (BMDLS). Methods In the PROgramming factors for GRowth And Metabolism (PROGRAM) study of a cohort of 312 young adults aged 18-24 years, BMDTB and BMDLS were determined by dual-energy X-ray absorptiometry (DXA). Subsequently, differences in BMDTB and BMDLS were analysed in four subgroups: young adults born small for gestational age with short stature (SGA-S) or with catch-up growth (SGA-CU), or born appropriate for gestational age (AGA) with idiopathic short stature (ISS) or with normal stature (controls). Results Adult weight, LBM, FM and weight gain during childhood were the main positive determinants for BMDTB in early adulthood, whereas birth size had no influence (adjusted R-2 = 0.50). Gender, adult weight, LBM, FM and weight gain were the significant determinants of BMDLS. In the subgroups, after correction for age, gender and adult body size, the ISS group had a significantly lower BMDTB than controls but there was no difference in BMDLS between the subgroups. Conclusions Prenatal growth has no significant influence on BMDTB and BMDLS in early adulthood. Gender and postnatal growth, particularly weight gain, are the main positive determinants. To achieve a normal BMD in adulthood, healthcare workers should aim for a normal weight gain in children