Cross-Sectional Study of four Serological Bone Turnover Markers for the Risk Assessment of Medication-Related Osteonecrosis of the Jaw.

BACKGROUND: Despite the benefits related to the use of bisphosphonates and denosumab, medication-related osteonecrosis of the jaw (MRONJ) is a serious complication. The purpose of this study was to investigate the utility of 4 biochemical markers including serum c-terminal telopeptide cross-link of type I collagen (s-CTX), serum osteocalcin (s-OC), serum parathormon (s-PTH), and serum bone-specific alkaline phosphatase (s-BAP) as useful clinical tools to help assess the risk for MRONJ prior to invasive oral surgery. MATERIALS AND METHODS: Twenty patients diagnosed with MRONJ and 20 controls who have been on antiresorptive therapies with no occurrence of MRONJ were included in this 2-arm cross-sectional study. The s-CTX, s-OC, s-PTH, and s-BAP values were measured. Mann-Whitney U test compared the s-CTX, s-OC, s-PTH, and s-BAP values of the MRONJ group and the controls (P < 0.05). RESULTS: Lower values were observed in the MRONJ group compared with the control group for s-CTX (130.00 pg/mL versus 230.0 pg/mL; P = 0.12) and for s-OC (10.6 ng/mL versus 14.80 ng/mL; P = 0.051) both without significance and for s-BAP (0.23 µkat/L versus 0.31 µkat/L; P = 0.002) with significance. By contrast, the median s-PTH value of the MRONJ group was higher (30.65 ng/L versus 25.50 ng/L; P = 0.89), but without significance. CONCLUSIONS: The evaluation of the 4 biochemical markers showed that only the value of s-BAP was significantly decreased in the MRONJ patients compared with the controls. Presently, because of the lack of evidence, a routine check prior to oral surgery for the risk assessment of MRONJ cannot be recommended.

Dwell times and risk of non-elective removal of 1-French peripherally inserted central catheters according to catheter tip position in very preterm infants.

We investigated dwell times and risk of non-elective removal of 975 single-lumen 1-French peripherally inserted central catheters (1FR-PICC) according to tip position in a cohort of very preterm infants with a mean (SD) gestational age of 27+6 (2+1) weeks and a mean (SD) birth weight of 988 (294) g over an eight-year period. Infants with a 1FR-PICC inserted for continuous infusion of intravenous fluids within the first 30 days of life were eligible. Dwell times of PICC with elective versus non-elective removal, risk of non-elective removal of PICC according to tip position, and differences between upper versus lower limb catheter insertion were analysed. 33.8% PICC were removed non-electively. Median (IQR) dwell time was 193 (142-287) versus 154 (102-260) h for elective versus non-elective removal (p < 0.001). Non-elective removal was more common for lower limb insertion sites: 41 versus 31% (p = 0.002). PICC were significantly more likely to be removed non-electively when located in the axillary (odds ratio (OR) 2.08), cephalic (OR 8.93), external iliac (OR 4.99), and femoral (OR 10.31) vein. CONCLUSION: In this cohort, dwell times of 1FR-PICC lines removed non-electively were similar to 1.9- or 2.0FR-PICC. PICC tips positioned in the axillary, cephalic, external iliac, and femoral veins had a higher risk of non-elective removal. What is Known: •Peripherally inserted central catheters (PICC) are widely used in neonatal intensive care. •Previous studies focused on 2-French PICC and newborns of all gestational ages. What is New: •Dwell times of 1-French PICC removed non-electively were similar to 2-French PICC. •1-French PICC tips positioned more peripherally had a higher risk of non-elective removal.

BNP, troponin I, and YKL-40 as screening markers in extremely preterm infants at risk for pulmonary hypertension associated with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is often complicated by pulmonary hypertension (PH). We investigated three biomarkers potentially suitable as screening markers for extremely preterm infants at risk of BPD-associated PH. In this prospective observational cohort study conducted in a tertiary neonatal intensive care unit, 83 preterm infants with BPD born <28-wk gestation and still inpatients at 36-wk corrected age received an echocardiogram and blood tests of B-type natriuretic peptide (BNP), troponin I, and YKL-40. Infants were analyzed according to echocardiographic evidence of tricuspid regurgitation (TR). Thirty infants had evidence of TR on echocardiogram at 36-wk corrected age. Infants with or without TR had similar baseline demographics: mean ± SD gestational age 261 ± 12 vs. 261 ± 11 wk and birth weight 830 ± 206 vs. 815 ± 187 g, respectively. There was no difference in duration of respiratory support. The right ventricular systolic pressure of infants with evidence of TR was 40 ± 16 mmHg. BNP was the only biomarker that proved to be significantly higher in infants with evidence of TR: median (interquartile range) serum level 54.5 (35-105) vs. 41.5 (30-59) pg/ml, P = 0.043. Subgroup analysis of infants with severe BPD requiring discharge on home oxygen or BPD-related mortality revealed similar results. There was no difference between groups for troponin I and YKL-40. In conclusion, increased serum levels of BNP were associated with evidence of TR at 36-wk corrected gestational age in extremely preterm infants, suggesting a potential role as a screening biomarker for BPD-associated PH.

Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: a prospective cohort study.

BACKGROUND: Molybdenum cofactor deficiency (MoCD) is characterised by early, rapidly progressive postnatal encephalopathy and intractable seizures, leading to severe disability and early death. Previous treatment attempts have been unsuccessful. After a pioneering single treatment we now report the outcome of the complete first cohort of patients receiving substitution treatment with cyclic pyranopterin monophosphate (cPMP), a biosynthetic precursor of the cofactor. METHODS: In this observational prospective cohort study, newborn babies with clinical and biochemical evidence of MoCD were admitted to a compassionate-use programme at the request of their treating physicians. Intravenous cPMP (80-320 µg/kg per day) was started in neonates diagnosed with MoCD (type A and type B) following a standardised protocol. We prospectively monitored safety and efficacy in all patients exposed to cPMP. FINDINGS: Between June 6, 2008, and Jan 9, 2013, intravenous cPMP was started in 16 neonates diagnosed with MoCD (11 type A and five type B) and continued in eight type A patients for up to 5 years. We observed no drug-related serious adverse events after more than 6000 doses. The disease biomarkers urinary S-sulphocysteine, xanthine, and urate returned to almost normal concentrations in all type A patients within 2 days, and remained normal for up to 5 years on continued cPMP substitution. Eight patients with type A disease rapidly improved under treatment and convulsions were either completely suppressed or substantially reduced. Three patients treated early remain seizure free and show near-normal long-term development. We detected no biochemical or clinical response in patients with type B disease. INTERPRETATION: cPMP substitution is the first effective therapy for patients with MoCD type A and has a favourable safety profile. Restoration of molybdenum cofactor-dependent enzyme activities results in a greatly improved neurodevelopmental outcome when started sufficiently early. The possibility of MoCD type A needs to be urgently explored in every encephalopathic neonate to avoid any delay in appropriate cPMP substitution, and to maximise treatment benefit. FUNDING: German Ministry of Education and Research; Orphatec/Colbourne Pharmaceuticals.

Gentamicin trough levels using a simplified extended-interval dosing regimen in preterm and term newborns.

UNLABELLED: To evaluate a simplified gentamicin extended-interval dosing regimen in a large cohort of preterm and term newborns, we conducted a retrospective cohort study over a 4-year period. All inborn newborns who received gentamicin for the first episode of suspected or proven sepsis were eligible. Newborns received 4 mg/kg gentamicin intravenously 24-hourly, except for those at <28 weeks of gestation who received gentamicin 36-hourly. Trough levels were taken before the third dose and considered non-toxic if ≤2 µg/mL. Infants were analysed in gestational age subgroups: <28 weeks, 28-31 weeks, 32-35 weeks, 36-39 weeks and ≥40 weeks. Newborns who received indomethacin co-medication were analysed separately. Nine hundred ninety-three newborns, gestational age range 23(+2)-42(+1) weeks, birth weight range 397-5936 g, were included. The median (interquartile range (IQR)) gentamicin trough level for all newborns was 1.3 µg/mL (0.8-1.7). Ninety per cent of newborns had non-toxic trough levels. The incidence of trough levels >2 µg/mL was between 2.2 and 9.7 % in all subgroups except for infants born at 28-31 weeks of gestation, where 21.7 % of trough levels were >2 µg/mL. Indomethacin co-medication significantly increased the median gentamicin trough level in preterm infants at <32 weeks of gestation. CONCLUSION: This study demonstrates that simplified gentamicin dosage regimens are feasible. Prospective evaluations are required to establish safety profiles.

B-type and N-terminal pro-B-type natriuretic peptides are equally useful in assessing patent ductus arteriosus in very preterm infants.

AIM: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) have been shown to correlate with the size of the patent ductus arteriosus (PDA) in preterm infants. We investigated whether BNP or NTproBNP was more closely correlated with PDA size. METHODS: This prospective observational study included preterm infants born <32 weeks' gestation who had an echocardiogram performed within the first four days of life. Blood samples were taken simultaneously for BNP and NTproBNP measurements prior to echocardiographic examination. RESULTS: Of the 60 infants recruited, 58 had complete data sets. The cohort's mean and standard deviation (SD) gestational age was 27(+3) (2(+2)) weeks, the mean (SD) birthweight was 1032 (315) grams, and 46 (79.3%) infants had a PDA with a mean (SD) diameter of 3.2 (0.9) mm. Median and interquartile range (IQR) BNP levels were 486.5 (219-1316) pg/mL for infants with a PDA and 190 (95.5-514.5) pg/mL for infants without a PDA. Median (IQR) NTproBNP levels were 10 858.5 (6319-42 108) pg/mL for infants with a PDA and 7488 (3363-14 227.5) pg/mL for infants without a PDA. Both BNP (R = 0.35, p = 0.0066) and NTproBNP (R = 0.31, p = 0.018) were significantly correlated with PDA size. CONCLUSION: BNP and NTproBNP are similarly useful for assessing PDA size in preterm infants.

Unplanned extubation and subsequent trial of noninvasive ventilation in the neonatal intensive care unit.

OBJECTIVE: Unplanned extubation (UE) occurs as an infrequent complication of mechanical ventilation in the neonatal intensive care unit (NICU). Following UE, a trial of noninvasive ventilation (NIV) may be considered if a neonate is showing adequate respiratory effort. This study investigated the success and failure rate of NIV management of neonates experiencing UE. STUDY DESIGN: Retrospective single-center study of neonates experiencing UE in the NICU over a 9-year period. Reintubation within 12 hours of a trial of NIV following UE was defined as treatment failure. Short-term respiratory outcomes were analyzed for all infants plus the incidence of bronchopulmonary dysplasia for preterm infants born less than 32 weeks' gestation. RESULTS: A total of 43 patients were included. Of those, 30 infants were trialed on NIV following UE. Baseline demographics were similar between both the groups except for the oxygen requirement before UE. The NIV was successful in 20 and failed in 10 infants. Infants who failed a trial of the NIV were reintubated between 0.45 and 5.25 hours following UE. Respiratory outcomes in very preterm infants did not differ between groups. CONCLUSION: A trial of NIV may be considered as a treatment option in preterm and term newborns experiencing UE in the NICU.

Accuracy of infrared thermometers in very low birth weight infants and impact on newborn behavioural states.

AIM: To study the impact on newborn behavioural states and accuracy of three infrared thermometers compared with digital axillary thermometer measurements in very low birth weight infants. METHODS: Single-centre prospective observational study. Preterm infants born <1500-g birth weight were eligible. Infants were observed for pre-measurement behaviour state using a five-point neonatal behaviour observation tool. One infrared temperature was taken from each of the devices, followed by an axillary measurement. Further behaviour-state observations were recorded following infrared and axillary measurements. RESULTS: One hundred measurements were collected from each infrared device among a cohort of 42 very low birth weight infants. Only one infrared device showed satisfactory agreement with bias -0.071 (95% limits of agreement -0.68 to 0.54). The other two devices demonstrated poor agreement: bias -1.34; 95% limits of agreement -2.62 to -0.5 and bias -0.56; 95% limits of agreement -1.38 to 0.25. Neonatal behavioural scores showed only minimal changes when infrared measurements were performed but increased significantly following axillary measurements. The difference between the two modalities was statistically significant with a mean increase of 1.44 points following axillary measurements (95% confidence interval 1.21 to 1.67, P < 0.001). CONCLUSIONS: Temperature measurements taken with infrared thermometers demonstrated less disruption to preterm infants' behavioural state, however accuracy of devices varied.

Comparison of the pharyngeal pressure provided by two heated, humidified high-flow nasal cannulae devices in premature infants.

AIMS: This study aims to determine if there is a difference in the pharyngeal pressure, measured as a surrogate for continuous positive distending airway pressure, delivered to premature infants between two commonly used heated, humidified high-flow nasal cannulae (HHHFNC) devices: Fisher & Paykel Healthcare HHHFNC and Vapotherm 2000i. METHODS: Pharyngeal pressure measurements were taken from stable premature infants receiving HHHFNC for respiratory support. Flow rates of 2-8 L/min were studied. RESULTS: Nine infants had pharyngeal pressure measurements recorded with both HHHFNC devices at flow rates of 2-8 L/min. There was no difference in pharyngeal pressures recorded between devices at flow rates of 2-6 L/min; measured pressure was linearly associated with flow (R(2) = 0.9). At flow rates of 7 L/min, Vapotherm delivered a mean (standard deviation) pharyngeal pressure of 4.7 (2.2) cmH2 O compared with 4.23 (2.2) cmH2 O by the Fisher & Paykel device (P = 0.04). At a flow of 8 L/min, the mean pharyngeal pressure via Vapotherm was 4.9 (2.2) cmH2 O compared with 4.1 (2.3) cmH2 O with the Fisher & Paykel device (P = 0.05). CONCLUSIONS: Both HHHFNC delivered similar pharyngeal pressures at flow rates of 2-6 L/min. The pressure limiter valve of the Fisher & Paykel device attenuated the pharyngeal pressures at flows of 7 and 8 L/min. Vapotherm trended towards higher delivered pharyngeal pressure at flow rates 7 and 8 L/min, but the clinical significance of the difference remains unclear.

The diagnostic value of a single measurement of superior vena cava flow in the first 24 h of life in very preterm infants.

Low superior vena cava (SVC) flow has been associated with intraventricular haemorrhage (IVH) in very preterm infants. We studied the diagnostic value of a single measurement of SVC flow within the first 24 h of life in very preterm infants and its association with occurrence or extension of IVH in a setting of limited availability of neonatal echocardiography. Preterm infants who were born at less than 30 weeks gestation and who had an echocardiogram within 24 h after birth were eligible. Baseline, clinical and ultrasound data were collected. A total of 165 preterm infants were included. Low SVC flow (<41 ml/kg/min) occurred in six infants and was associated with severe IVH and extension of IVH, although this was not significant after adjusting for confounders. The only independently associated variable with low SVC flow was admission temperature (odds ratio 0.27, p = 0.001). A review of SVC flow values shows that these are higher now than initially reported. This study does not show an association of low SVC flow and severe IVH or extension of IVH after adjusting for confounders as a single measurement of SVC flow did not add any diagnostic value in this cohort. Thus, the exact role of SVC flow measurements in the circulatory assessment of preterm infants remains to be elucidated. However, admission temperature may have an effect on systemic blood flow in very preterm infants.

Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants.

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3+CD4+ T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1ß and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.

Systematic review of the safety of regular preventive asthma medications during pregnancy.

OBJECTIVE: To review the safety of regular preventive asthma medications during pregnancy. DATA SOURCES: The following databases were searched from inception to February 2011: Ovid MEDLINE, PubMed, Cochrane Library, EMBASE and CINAHL Plus. STUDY SELECTION AND DATA EXTRACTION: The search was limited to human studies published in the English language. Titles of all articles were screened for relevance. Abstracts of relevant articles were scrutinized to confirm relevance before obtaining full text. DATA SYNTHESIS: Selected articles were read by 2 authors and the accuracy of the data extracted was confirmed. RESULTS: Thirty-three articles were included in the final review. Small sample size, missing data, inadequate control for confounding factors, and poor documentation of dosage range were common limitations of the studies reviewed. The use of inhaled corticosteroids, cromolyns, and long-acting ß(2) agonists during pregnancy was not associated with any particular adverse event, although the fluticasone/salmeterol combination has been associated with poor outcomes in postmarketing studies. Congenital malformations have been reported with leukotriene receptor antagonist exposure during pregnancy, but those women also had exposure to other medications, including oral corticosteroids. CONCLUSIONS: Some negative outcomes of preventive asthma medications have been reported, although their direct link with medication use is inconclusive. Selection of preventive medications for asthma management during pregnancy should be based on an assessment of the risks and benefits of medication use versus the risks of poorly controlled asthma.

Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure.

OBJECTIVE: To investigate the applicability, efficacy, and safety of single-pass albumin dialysis in children. DESIGN: Retrospective data review of uncontrolled clinical data. SETTING: University-based pediatric intensive care unit collaborating with a local center for liver transplantation. PATIENTS: Nine children, aged 2 to 15 yrs, who were treated with single-pass albumin dialysis for acute liver failure of various origins under a compassionate-use protocol between 2000 and 2006. All patients met high-urgency liver transplantation criteria. INTERVENTIONS: Single-pass albumin dialysis was performed as rescue therapy for children with acute liver failure. MEASUREMENTS AND MAIN RESULTS: The decrease in hepatic encephalopathy (grades 1-4) and the serum levels of bilirubin, bile acids, and ammonium were measured to assess the efficacy of detoxification. As a measure of liver synthesis function, thromboplastin time and fibrinogen were analyzed. The safety of the procedure was assessed by documenting adverse effects on mean arterial blood pressure, platelet count, and clinical course. Seven out of nine patients were bridged successfully to either native organ recovery (n = 1) or liver transplantation (n = 6), one of them twice. Six out of nine patients undergoing single-pass albumin dialysis (ten treatments) survived. In six patients, hepatic encephalopathy could be reduced at least by one degree. Ammonium, bilirubin, and bile acid levels decreased in all patients. One patient had an allergic reaction to albumin. CONCLUSIONS: In childhood acute liver failure, treatment with single-pass albumin dialysis was generally well tolerated and seems to be effective in detoxification and in improving blood pressure, thus stabilizing the critical condition of children before liver transplantation and facilitating bridging to liver transplantation. It may be beneficial in avoiding severe neurologic sequelae after acute liver failure and thereby improve survival. Single-pass albumin dialysis is an inexpensive albumin-based detoxification system that is easy to set up and requires little training. Whether and to what extent single-pass albumin dialysis can support children with acute liver failure until native liver recovery remains unclear.

Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities.

Necrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/TH17 polarization. In murine NEC, pro-inflammatory type 3 NKp46-RORγt+Tbet+ innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46+RORγt+ ILC3 are obliterated. Both species exhibit dysregulation of intestinal TLR repertoires, with TLR4 and TLR8 increased, but TLR5-7 and TLR9-12 reduced. Transgenic IL-37 effectively protects mice from intestinal injury and mortality, whilst exogenous IL-37 is only modestly efficacious. Mechanistically, IL-37 favorably modulates immune homeostasis, TLR repertoires and microbial diversity. Moreover, IL-37 and its receptor IL-1R8 are reduced in human NEC epithelia, and IL-37 is lower in blood monocytes from infants with NEC and/or lower birthweight. Our results on NEC pathomechanisms thus implicate type 3 cytokines, TLRs and IL-37 as potential targets for novel NEC therapies.

Precise selective deposition of microparticles on electrodes of microelectronic chips.

We examined the high precision deposition of toner and polymer microparticles with a typical size of approximately 10 microm on electrode arrays with electrodes of 100 microm and below using custom-made microelectronic chips. Selective desorption of redundant particles was employed to obtain a given particle pattern from preadsorbed particle layers. Microparticle desorption was regulated by dielectrophoretic attracting forces generated by individual pixel electrodes, tangential detaching forces of an air flow, and adhesion forces on the microchip surface. A theoretical consideration of the acting forces showed that without pixel voltage, the tangential force applied for particle detachment exceeded the particle adhesion force. When the pixel voltage was switched on, however, the sum of attracting forces was larger than the tangential detaching force, which was crucial for desorption efficiency. In our experiments, appropriately large dielectrophoretic forces were achieved by applying high voltages of up to 100 V on the pixel electrodes. In addition, electrode geometries on the chip's surface as well as particle size influenced the desorption quality. We further demonstrated the compatibility of this procedure to complementary metal oxide semiconductor chip technology, which should allow for an easy technical implementation with respect to high-resolution microparticle deposition.

Noncontact charge measurement of moving microparticles contacting dielectric surfaces.

In this study examples for a noncontact procedure that allow the description of instant electric charging of moving microparticles that contact dielectric surfaces, for instance, of a flow hose are presented. The described principle is based on the measurement of induced currents in grounded metal wire probes, as moving particles pass close to the probe. The feasibility of the approach was tested with laser printer toner particles of a given size for different basic particle flow and charging conditions. An analytic description for the induced currents was developed and compared to observed effects in order to interpret the results qualitatively. The implementation of the presented procedure can be applied to transparent and nontransparent particle containers and flow lines of complex geometry which can be composed from the presented basic flow stream configurations.

Association of BNP, NTproBNP, and early postnatal pulmonary hypertension in very preterm infants.

OBJECTIVE: B-type natriuretic peptide (BNP) has been shown to correlate with pulmonary hypertension (PH) in term neonates with persistent pulmonary hypertension of the newborn or congenital diaphragmatic hernia, and in very preterm infants with bronchopulmonary dysplasia. This study investigated the potential association of BNP and N-terminal-pro-BNP (NTproBNP) and PH within the first 72 hr of life in very preterm infants. METHODS: Preterm infants <32 weeks gestational age who received an echocardiogram within the first 72 hr of life were eligible. BNP and NTproBNP were sampled at the time of the echocardiogram. Right ventricular systolic pressure (RVSP) was calculated as a surrogate marker of PH. Simple and multiple linear regression analysis was performed to examine associations and potential confounding factors. RESULTS: Sixty-one infants were included with a median (IQR) birth weight of 983 g (826-1,167) and a median (IQR) gestational age of 27(2) weeks (26(2) -28(6) ). There was no difference between BNP or NTproBNP levels for infants with or without measurable RVSP. There was no significant correlation of BNP and RVSP in multiple linear regression analysis (regression coefficient -0.0035 (95%CI: -0.020 to 0.013), P = 0.67). Also, NTproBNP and RVSP were not significantly correlated in multiple linear regression analysis (regression coefficient 0.0071 (95%CI: -0.019 to 0.033), P = 0.58). CONCLUSION: B-type natriuretic peptides did not correlate with RVSP in the early postnatal period of very preterm infants. Pediatr Pulmonol. 2016;51:820-824. © 2016 Wiley Periodicals, Inc.

Systemic cardiovascular disease in uremic rats induced by 1,25(OH)2D3.

OBJECTIVE: Vitamin D may contribute to cardiovascular disease in the absence of hypercalcemia in patients with chronic kidney disease. METHODS: We investigated the effects of long-term (6-week) treatment with 1,25(OH)2D3, at a non-hypercalcemic dosage (0.25 microg/kg per day per orally) in 5/6 nephrectomized rats: (i) vehicle-treated, sham-operated rats; (ii) 1,25(OH)2D3-treated, sham-operated rats; (iii) vehicle-treated, 5/6 nephrectomized rats; and (iv) 1,25(OH)2D3-treated, 5/6 nephrectomized rats. RESULTS: Creatinine clearance after 6 weeks was significantly lower and parathyroid hormone levels were significantly higher in 1,25(OH)2D3-treated uremic rats, compared with uremic controls (P < 0.01). Serum calcium levels, as well as the calcium-phosphorus product, did not differ between both groups. Mean systolic blood pressure in 1,25(OH)2D3-treated animals was significantly increased, compared with vehicle (each P < 0.01). In addition, 1,25(OH)2D3-treated uremic animals showed left ventricular hypertrophy. Diffuse aortic calcification involving the intima and media layer occurred in 1,25(OH)2D3-treated uremic animals, but not in other groups. The mean aortic wall area and lumen area were increased two-fold in 1,25(OH)2D3-treated uremic animals compared with vehicle (P < 0.01), whereas the wall/lumen ratio remained unchanged, indicating fusiform aneurysm formation. CONCLUSIONS: Hypertension, left ventricular hypertrophy, aortic calcification, and aneurysm, without hypercalcemia, occurred in 1,25(OH)2D3-treated, 5/6 nephrectomized rats. These data indicate a permissive effect of uremia for cardiovascular damage induced by non-hypercalcemic doses of 1,25(OH)2D3.