Efficacy of Lung Ultrasound vs Chest X-Ray in Detecting Lung Consolidation and Edema in Premature Infants in the NICU.

BACKGROUND The incidence of lung diseases in premature newborns is significantly higher than in full-term newborns due to their underdeveloped lungs. Ultrasound and X-ray are commonly-used bedside examinations in neonatology. This study primarily compares the efficacy of chest X-ray (CXR) and lung ultrasound (LUS) images in evaluating lung consolidation and edema in premature newborns at Neonatal Intensive Care Units (NICU). MATERIAL AND METHODS A retrospective analysis was conducted on LUS and CXR examination results, along with clinical records of premature newborns admitted to our hospital's NICU from November 1, 2019, to December 31, 2021. CXR and LUS scans were performed on the same newborn within a day. We evaluated the consolidations and edema by interpreting the CXR and LUS images, then compared the findings. RESULTS Out of 75 cases, 34 showed lung consolidations on LUS (45%), while only 14 exhibited consolidations on CXR (19%). The detection rate of consolidations by LUS was significantly higher compared to CXR (34/75 vs 14/75, P<0.001). Differences were observed between the 2 bedside examinations in identifying consolidations, with some cases seen only on LUS. CXR struggled to accurately assess the severity of lung edema visible on LUS, showing significant disparity in detecting interstitial edema (53/75 vs 21/75, P<0.001). CONCLUSIONS LUS outperforms chest CXR for bedside assessment of lung consolidation and edema in premature newborns.

A case of early-onset congenital syphilitic osteomyelitis of the calcaneus and literature review.

BACKGROUND: Congenital syphilis (CS) is a sexually transmitted disease caused by Treponema pallidum (TP). When the skeletal system is involved, it often results in multiple, symmetrical bone destruction at the epiphyses of long tubular bones such as the humerus and radius, rarely involving the calcaneus. This article reports a case of calcaneal osteomyelitis caused by TP in a child with no other bone damage and subtle clinical manifestations, No similar cases have been reported. CASE PRESENTATION: A 4-month-old male infant presented with right foot swelling without any obvious cause and no history of trauma. X-ray and CT scans showed bone loss in the calcaneus and surrounding soft tissue swelling. Review of past medical records revealed that the infant had been diagnosed with CS infection during a hospital stay for "pneumonia" at one month old. The parents refused surgery, opting for conservative treatment at an external hospital for three weeks, during which the symptoms of the affected foot showed no significant improvement. Subsequently, the child was treated at our hospital with surgery, including lesion removal and cast fixation, followed by oral antibiotic treatment. The last follow-up showed no swelling or tenderness in the affected foot, with good mobility, and X-rays indicated that the bone had essentially returned to normal. CONCLUSIONS: Early CS rarely involves the calcaneus. When diagnosing unexplained calcaneal osteomyelitis in infants, this rare cause should be considered. A thorough medical history should be taken and a careful physical examination conducted. Once diagnosed, timely surgical debridement and appropriate antibiotic therapy targeting TP infection are required. Early identification and intervention can result in a good prognosis without related complications.

Development and validation of a nomogram for predicting the prognosis in children with spinal cord injuries.

AIMS: This research aims to construct and verify an accurate nomogram for forecasting the 3-, 5-, and 7-year outcomes in pediatric patients afflicted with spinal cord injury (SCI). METHODS: Pediatric patients with SCI from multiple hospitals in China, diagnosed between Jan 2005 and Jan 2020, were incorporated into this research. Half of these patients were arbitrarily chosen for training sets, and the other half were designated for external validation sets. The Cox hazard model was employed to pinpoint potential prognosis determinants related to the American Spinal Injury Association (ASIA) and Functional Independence Assessment (FIM) index. These determinants were then employed to formulate the prognostic nomogram. Subsequently, the bootstrap technique was applied to validate the derived model internally. RESULTS: In total, 224 children with SCI were considered for the final evaluation, having a median monitoring duration of 68.0 months. The predictive nomogram showcased superior differentiation capabilities, yielding a refined C-index of 0.924 (95% CI: 0.883-0.965) for the training cohort and a C-index of 0.863 (95% CI: 0.735-0.933) for the external verification group. Additionally, when applying the aforementioned model to prognostic predictions as classified by the FIM, it demonstrated a high predictive value with a C-index of 0.908 (95% CI: 0.863-0.953). Moreover, the calibration diagrams indicated a consistent match between the projected and genuine ASIA outcomes across both sets. CONCLUSION: The crafted and verified prognostic nomogram emerges as a dependable instrument to foresee the 3-, 5-, and 7-year ASIA and FIM outcomes for children suffering from SCI.

Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis.

BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear. METHODS: We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary evaluation period (Weeks 24-36). RESULTS: Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups [hazard ratio 1.10; 95% confidence interval (CI) 0.62, 1.93]. In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was -0.10 g/dL (95% CI -0.33, 0.12) in the primary evaluation period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively. CONCLUSIONS: In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.

The combined effects of overweight/obesity and dietary antioxidant quality score on hypertension in children and adolescents.

BACKGROUND: This study was to evaluate the combined effects of overweight/obesity and DAQS on the risk of hypertension in children and adolescents. METHODS: In this cross-sectional study, the data of 14,316 subjects were extracted from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression analysis was used to explore the associations of obesity and DAQS with the risk of hypertension. The combined effect of overweight/obesity and DAQS on the risk of hypertension was evaluated. RESULTS: Body mass index (BMI)-for-age < 85th percentile was associated with reduced risk of hypertension in children and adolescents [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.41-0.62]. No significant association between DAQS ≥ 3 and the risk of hypertension before and after the adjustment of confounders (P > 0.05). Subjects with BMI-for-age of < 85th percentile and DAQS < 3 was associated with decreased risk of hypertension (OR = 0.53, 95%CI: 0.35-0.79). People with BMI-for-age of < 85th percentile and DAQS ≥ 3 was correlated with decreased risk of hypertension (OR = 0.52, 95%CI: 0.36-0.74). Subgroup analysis revealed that in subjects aged ≥ 12 years, decreased risk of hypertension was observed in BMI-for-age < 85th percentile and DAQS < 3 group (OR = 0.48, 95%CI: 0.31-0.73) as well as BMI-for-age < 85th percentile and DAQS ≥ 3 group (OR = 0.47, 95%CI: 0.32-0.67). In boys, BMI-for-age < 85th percentile and DAQS < 3 group (OR = 0.45, 95%CI: 0.25-0.81) as well as BMI-for-age < 85th percentile and DAQS ≥ 3 group (OR = 0.40, 95%CI: 0.25-0.65) were correlated with decreased risk of hypertension. CONCLUSION: Overweight/obesity and DAQS had combined effects on the risk of hypertension in children and adolescents, which implied that for children and adolescents with normal weight, to keep normal weight combined with high quality of diet might be recommended.

Visualizing the Anomalous Catalysis in Two-Dimensional Confined Space.

Confined nanospaces provide a new platform to promote catalytic reactions. However, the mechanism of catalytic enhancement in the nanospace still requires insightful exploration due to the lack of direct visualization. Here, we report operando investigations on the etching and growth of graphene in a two-dimensional (2D) confined space between graphene and a Cu substrate. We observed that the graphene layer between the Cu and top graphene layer was surprisingly very active in etching (more than 10 times faster than the etching of the top graphene layer). More strikingly, at a relatively low temperature (∼530 °C), the etched carbon radicals dissociated from the bottom layer, in turn feeding the growth of the top graphene layer with a very high efficiency. Our findings reveal the in situ dynamics of the anomalous confined catalytic processes in 2D confined spaces and thus pave the way for the design of high-efficiency catalysts.

Intrauterine growth restriction neonates present with increased angiogenesis through the Notch1 signaling pathway.

Intrauterine growth restriction (IUGR) is associated with increased perinatal mortality and morbidity, and plays an important role in the development of adult cardiovascular diseases. This study brings forward a hypothesis that Human umbilical vein endothelial cells (HUVECs) from IUGR newborns present dysfunctions and varying changes of signaling pathways as compared to the Control group. Similar pathways may also be present in pulmonary or systemic vasculatures. HUVECs were derived from newborns. There were three groups according to the different fetal origins: normal newborns (Control), IUGR from poor maternal nutrition (IUGR1), and pregnancy-induced hypertension (IUGR2). We found that IUGR-derived HUVECs showed a proliferative phenotype compared to those from normal subjects. Interestingly, two types IUGR could cause varying degrees of cellular dysfunction. Meanwhile, the Notch1 signaling pathway showed enhanced activation in the two IUGR-induced HUVECs, with subsequent activation of Akt or extracellular signal regulated protein kinases1/2 (ERK1/2). Pharmacological inhibition or gene silencing of Notch1 impeded the proliferative phenotype of IUGR-induced HUVECs and reduced the activation of ERK1/2 and AKT. In summary, elevated Notch1 levels might play a crucial role in IUGR-induced HUVECs disorders through the activation of ERK1/2 and AKT. These pathways could be potential therapeutic targets for prevention of the progression of IUGR associated diseases later in life.

Performance of Tönnis triple osteotomy in older children with developmental dysplasia of the hip (DDH) assisted by a 3D printing navigation template.

BACKGROUND: The objective of this study is to investigate the preparation of a navigation template via a computer-aided design (CAD) and 3D printing (3DP) in order to improve the effectiveness of Tönnis triple osteotomy in older children with developmental dysplasia of the hip (DDH). METHOD: Thirty-eight older children who received Tönnis triple osteotomy were included in this study. Among them, 20 were categorized as the 3DP navigation template group (3DP group), and the remaining 18 were categorized as the conventional surgery group (CS group). Data, including preoperative and postoperative pelvic sharp angle (SA), lateral center-edge angle (LCEA), acetabular roof angle (ARA), acetabular head index (AHI), crossover sign (COS), ischial spine sign (ISS), operation time (OT), intraoperative blood loss (IBL), and number of radiation exposures (NORE) were recorded for both groups. In addition, the therapeutic effect was evaluated at the last follow-up, according to the McKay criteria and Severin's criteria. RESULTS: In the 3DP and CS groups, the mean OT was 126.6 ± 17.6 min and 156.0 ± 18.6 min, respectively; the mean IBL was 115.0 ± 16.9 ml and 135.7 ± 26.5 ml, respectively; the NORE were 3.3 ± 0.8 times and 8.6 ± 1.3 times, respectively. There were significant differences in the OT, IBL, and NORE between the two groups (P = 0.03, 0.05, < 0.001, respectively). At the last follow-up, the 3DP and CS groups displayed SA of 41.8 ± 2.3° and 42.6 ± 3.1°, respectively; LCEA of 35.6 ± 4.2° and 37.1 ± 2.8°, respectively; ARA of 6.9 ± 1.8° and 9.8 ± 2.6°, respectively; and AHI of 86.6 ± 4.1% and 84.3 ± 2.8%, respectively; COS(+) of 5 hips and 4 hips, respectively; ISS(+) of 6 hips and 7 hips. We observed no statistical differences in the SA, LCEA, ARA, AHI, COS and ISS between the two groups (P = 0.918, 0.846, 0.643, 0.891, 0.841, 0.564, respectively). According to the McKay criteria, the 3DP group had 10 excellent, 6 good, and 4 general hips, whereas, the CS group had 12 excellent, 4 good, and 2 general hip. There was no statistical difference between the two groups (P = 0.698). In 3DP group the postoperative Severin's grading included 13 hips in grade I, 4 in grade II, 3 in grade III. Alternately, in the CS group, the postoperative Severin's grading included 11 hips in grade I, 5 in grade II, 2 in grade III. The Severin 's criteria also showed no statistical difference between the two groups (P = 0.945). CONCLUSIONS: Base on our analysis, our CAD-3DP-fabricated navigation template assisted Tönnis triple osteotomy in older DDH children, it reduced operation time and number of radiation exposures. However, no significant differences in radiological assessment and functional outcomes were observed when an experienced surgeon performs the surgery. Therefore, Surgeons who have less experience in triple osteotomy profit more from the application of this technology.

MicroRNA-214 promotes alveolarization in neonatal rat models of bronchopulmonary dysplasia via the PlGF-dependent STAT3 pathway.

BACKGROUND: Recently, the role of several microRNAs (miRNAs or miRs) in pulmonary diseases has been described. The molecular mechanisms by which miR-214 is possibly implicated in bronchopulmonary dysplasia (BPD) have not yet been addressed. Hence, this study aimed to investigate a putative role of miR-214 in alveolarization among preterm neonates with BPD. METHODS: Microarray-based gene expression profiling data from BPD was employed to identify differentially expressed genes. A BPD neonatal rat model was induced by hyperoxia. Pulmonary epithelial cells were isolated from rats and exposed to hyperoxia to establish cell injury models. Gain- and loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were measured using RT-qPCR and Western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene and RIP assays. IL-1ß, TNF-a, IL-6, ICAM-1 and Flt-1 expression in the rat models was measured using ELISA. RESULTS: The lung tissues of neonatal rats with BPD showed decreased miR-214 expression with elevated PlGF expression. PlGF was found to be a target of miR-214, whereby miR-214 downregulated PlGF to inactivate the STAT3 pathway. miR-214 overexpression or PlGF silencing decreased the apoptosis of hyperoxic pulmonary epithelial cells in vitro and restored alveolarization in BPD neonatal rats. CONCLUSION: Overall, the results demonstrated that miR-214 could facilitate alveolarization in preterm neonates with BPD by suppressing the PlGF-dependent STAT3 pathway.

Prevalence of congenital scoliosis in infants based on chest-abdomen X-ray films detected in the emergency department.

PURPOSE: To investigate the prevalence of congenital scoliosis (CS) in infants based on chest-abdomen radiographs. METHODS: A retrospective review was conducted on infants in the emergency department (ED) of a tertiary children's hospital between February 2008 and September 2019. Patients who had undergone chest-abdomen X-rays were included. All films from the enrolled patients were screened for CS. Their demographic characteristics, type, and location of the vertebral and rib anomalies, and concomitant defects of other systems were analyzed. RESULTS: In total, 50,426 infants were enrolled; 89 (1.8‰) were diagnosed with CS, including 56 males and 33 females. There was no gender difference in CS prevalence. The visiting age of the CS patients (70 ± 98days) was significantly younger than that of the non-CS group (P < 0.05), with CS patients mainly visiting for digestive (53.9%) and respiratory symptoms (41.6%). Sixty-eight (76.4%) CS patients had main thoracic (T6-T11) vertebral malformations. Rib anomalies were documented in 27 (30.3%) patients, of which 14 had complex rib anomalies. Forty (44.9%) patients had concomitant defects of other organs, of which eight patients had two systemic abnormalities mixed. The most common extraspinal defects were imperforate anus (21, 23.6%) and congenital cardiac defects (17, 19.1%). CONCLUSION: The prevalence of CS in infants based on chest-abdomen X-rays in the ED was 1.8‰. Both the vertebral and rib anomalies mainly affected the main thoracic region. The spine deformities in infants with concomitant defects of other organs could be identified earlier because of early-onset symptoms, which also bring out a selection bias in our analysis.

Application of 3-Dimensional Printing Technology in Rotational Osteotomy of Congenital Radioulnar Synostosis.

PURPOSE: To investigate whether computer-aided design (CAD) and 3-dimensional printing technology can assist in accurate completion of ulna-radius proximal rotational osteotomy in congenital radioulnar synostosis (CRUS). METHODS: We treated 1 right arm and 4 left arms of 4 boys with a mean age of 5.2 years (range, 4.3-6.0 years) between July 2018 and April 2019. Computed tomography (CT) scans of the forearm were performed on the children before surgery. Using the CT data, the pronation angle of the forearm was measured. An individualized dial with a matching forearm diameter was designed before surgery to control the angle of the rotational osteotomy. Ulna and radius models, and individualized dials, were prepared for each patient using 3-dimensional printing technology. Preoperative simulated surgery was performed using the 3-dimensional printed models. During the surgery, 2 Kirschner wires were used as operating levers for rotation, and rotational angle correction was precisely controlled using the dial. The cast and internal fixation were removed after x-ray examination showed that the osteotomy had healed, about 5 weeks after surgery. RESULTS: The rotational osteotomies were completed in a single operation, and the correction angle was 60°. No complications occurred after the operation. All patients showed functional improvements in activities of daily living. CONCLUSIONS: For CRUS patients, models and dials made with CAD and 3-dimensional printing technology can assist in precise rotational osteotomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Involvement of Hdac3-mediated inhibition of microRNA cluster 17-92 in bronchopulmonary dysplasia development.

BACKGROUND: The incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns, has been paradoxically rising despite medical advances. Histone deacetylase 3 (Hdac3) has been reported to be a crucial regulator in alveologenesis. Hence, this study aims to investigate the mechanism of Hdac3 in the abnormal pulmonary angiogenesis and alveolarization of BPD. METHODS: A hyperoxia-induced BPD model of was developed in newborn mice, and primary lung fibroblasts were isolated from adult mice. Hdac3 was knocked out in vivo and knocked down in vitro, while microRNA (miR)-17 was downregulated in vivo and in vitro to clarify their roles in abnormal pulmonary angiogenesis and alveolarization. Mechanistic investigations were performed on the interplay of Hdac3, miR-17-92 cluster, enhancer of zeste homolog 1 (EZH1), p65 and placental growth factor (Pgf). RESULTS: Hdac3 was involved in abnormal alveolarization and angiogenesis in BPD mice. Further, the expression of the miR-17-92 cluster in BPD mice was downregulated by Hdac3. miR-17 was found to target EZH1, and Hdac3 rescued the inhibited EZH1 expression by miR-17 in lung fibroblasts. Additionally, EZH1 augmented Pgf expression by recruiting p65 thus enhancing the progression of BPD. Hdac3 augmented the recruitment of p65 in the Pgf promoter region through the miR-17/EZH1 axis, thus enhancing the transcription and expression of Pgf, which elicited abnormal angiogenesis and alveolarization of BPD mice. CONCLUSIONS: Altogether, the present study revealed that Hdac3 activated the EZH1-p65-Pgf axis through inhibiting miR-17 in the miR-17-92 cluster, leading to accelerated abnormal pulmonary angiogenesis and alveolarization of BPD mice.

Lung Ultrasound Score Predicts the Extravascular Lung Water Content in Low-Birth-Weight Neonates with Patent Ductus Arteriosus.

BACKGROUND Patent ductus arteriosus (PDA) is a common congenital cardiac abnormality in premature infants. In low-birth-weight infants weighing less than 2500 g, if the PDA continues to open, abnormal circulation hemodynamics and pulmonary edema may occur. This study aimed to investigate the role of lung ultrasound score in the assessment of pulmonary edema in low-weight neonates with PDA. MATERIAL AND METHODS Two hundred and twenty-one neonates with low birth weight were selected as the subjects, children with PDA as the observation group, and children with closed ductus arteriosus as the control group. On the fourth postnatal day, lung ultrasound examination and 6-segment lung ultrasound scoring were performed. RESULTS All 221 infants (94 in the observation group, 127 controls) underwent ultrasound examinations of the lungs. Intergroup differences in gestational age, birth weight, length of hospital stay, and left ventricular ejection fraction were not statistically significant. There was a significant difference in lung ultrasound score (t=0.005, P=0.000) and aortic root ratio to left atrial (t=0.085, P=0.000), which was negatively correlated with gestational age (r=-0.235, P=0.000) and positively correlated with PDA diameter (r=0.261, P=0.011). CONCLUSIONS Low-birth-weight children often have PDA. Its continued opening changes the circulation hemodynamics in children. Lung ultrasound score can semi-quantitatively evaluate the extravascular lung water content, identifying the need to intervene and follow up the hemodynamic significance of PDA over time.

Noninvasive high-frequency oscillatory ventilation as respiratory support in preterm infants: a meta-analysis of randomized controlled trials.

BACKGROUND: Noninvasive high-frequency oscillatory ventilation (nHFOV), a relatively new modality, is gaining popularity despite scarce evidence. This meta-analysis was designed to evaluate the efficacy and safety of nHFOV as respiratory support in premature infants. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from inception of the database to January 2019. All published randomized controlled trials (RCTs) evaluating the effect of nHFOV therapy with nasal continuous positive airway pressure (nCPAP) or biphasic nCPAP (BP-CPAP) in newborns for respiratory support were included. All meta-analyses were performed using Review Manager 5.3. RESULTS: A total of 8 RCTs involving 463 patients were included. The meta-analysis estimated a lower risk of intubation (relative risk = 0.50, 95% confidence interval of 0.36 to 0.70) and more effective clearance of carbon dioxide (weighted mean difference = - 4.61, 95% confidence interval of - 7.94 to - 1.28) in the nHFOV group than in the nCPAP/BP-CPAP group. CONCLUSIONS: Our meta-analysis of RCTs suggests that nHFOV, as respiratory support in preterm infants, significantly remove carbon dioxide and reduce the risk of intubation compared with nCPAP/BP-CPAP. The appropriate parameter settings for different types of noninvasive high-frequency ventilators, the effect of nHFOV in extremely preterm infants, and the long-term safety of nHFOV need to be assessed in large trials.

Airway administration of corticosteroids for prevention of bronchopulmonary dysplasia in premature infants: a meta-analysis with trial sequential analysis.

BACKGROUND: Uncertainly prevails with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. The meta-analysis with sequential analysis was designed to evaluate the efficacy and safety of airway administration (inhalation or instillation) of corticosteroids for preventing bronchopulmonary dysplasia (BPD) in premature infants. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to February 2017. All published randomized controlled trials (RCTs) evaluating the effect of airway administration of corticosteroids (AACs) vs placebo or systemic corticosteroid in prematurity were included. All meta-analyses were performed using Review Manager 5.3. RESULTS: Twenty five RCTs retrieved (n = 3249) were eligible for further analysis. Meta-analysis and trial sequential analysis corrected the 95% confidence intervals estimated a lower risk of the primary outcome of BPD (relative risk 0.71, adjusted 95% confidence interval 0.57-0.87) and death or BPD (relative risk 0.81, adjusted 95% confidence interval 0.71-0.97) in AACs group than placebo and it is equivalent for preventing BPD than systemic corticosteroids. Moreover, AACs fail to increasing risk of death compared with placebo (relative risk 0.90, adjusted 95% confidence interval 0.40-2.03) or systemic corticosteroids (relative risk 0.81, 95% confidence interval 0.62-1.06). CONCLUSIONS: Our findings suggests that AACs (especially instillation of budesonide using surfactant as a vehicle) are an effective and safe option for preventing BPD in preterm infants. Furthermore, the appropriate dose and duration, inhalation or instillation with surfactant as a vehicle and the long-term safety of airway administration of corticosteroids needs to be assessed in large trials.

Whole genome sequencing identifies ANXA3 and MTHFR mutations in a large family with an unknown equinus deformity associated genetic disorder.

The aim of this study was to characterize a previously uncharacterized genetic disorder associated with equinus deformity in a large Chinese family at the genetic level. Blood samples were obtained and whole genome sequencing was performed. Differential gene variants were identified and potential impacts on protein structure were predicted. Based on the control sample, several diseases associated variants were identified and selected for further validation. One of the potential variants identified was a ANXA3 gene [chr4, c.C820T(p.R274*)] variant. Further bioinformatic analysis showed that the observed mutation could lead to a three-dimensional conformational change. Moreover, a MTHFR variant that is different from variants associated with clubfoot was also identified. Bioinformatic analysis showed that this mutation could alter the protein binding region. These findings imply that this uncharacterized genetic disorder is not clubfoot, despite sharing some similar symptoms. Furthermore, specific CNV profiles were identified in association with the diseased samples, thus further speaking to the complexity of this multigenerational disorder. This study examined a previously uncharacterized genetic disorder appearing similar to clubfoot and yet having distinct features. Following whole genome sequencing and comparative analysis, several differential gene variants were identified to enable a further distinction from clubfoot. It is hoped that these findings will provide further insight into this disorder and other similar disorders.

Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is usually diagnosed in preterm infants at least 28 days after birth. Great interest lies in the potential to identify biomarkers that predict development of the disease and future neurodevelopmental outcomes. We have reviewed the existing literature on early biomarkers as predictors for BPD in preterm infants. METHODS: Two reviewers independently searched the databases of PubMed, EMBASE, and Google Scholar for studies pertaining to biomarkers for BPD. Studies were assessed using Quality Assessment of Diagnostic Accuracy Studies criteria. RESULTS: We identified 46 relevant articles that are summarized in the review. These studies assessed over 30 potential biomarkers. Sensitivity and specificity of biomarkers were reported or could be calculated for only 16 articles, and ranged from 0 to 100 %. Based on the nine highest quality studies, serum KL-6, CC16, neutrophil gelatinase-associated lipocalin, and end-tidal carbon monoxide (etCO) perform extremely well in predicting the early diagnosis of established BPD, highlighting these biomarkers as promising candidates for future research. CONCLUSIONS: Published data from studies on serum biomarkers and etCO suggest that biomarkers may have great potential to predict the subsequent BPD and neurodevelopmental outcomes. These biomarkers need validation in larger studies, and the generalizability of biomarkers for predicting BPD, as well as the neurodevelopmental outcomes, needs to be further explored.

A rare case of congenital distal renal tubular acidosis combined with medullary sponge kidney.

Distal renal tubular acidosis combined with medullary sponge kidney (MSK) is not uncommon in adults, but is rare in infants. We report a 13-month-old boy with MSK who had features of distal renal tubular acidosis (nephrocalcinosis, hypercalciuria, hypocitraturia) and failed to thrive. Renal ultrasound revealed bilateral increased medullary echogenicity and nephrocalcinosis. Bilateral medullary nephrocalcinosis in the ultrasound was the first sign that alerted our pediatrician to the presence of MSK in infants. Earlier treatment may increase efficacy.

Safety and Efficacy of Vadadustat Once-Daily and 3-Times-Weekly in Dialysis-Dependent Chronic Kidney Disease Patients with Anemia.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). This study investigated safety and efficacy of once-daily and 3-times-weekly dosing in patients with dialysis-dependent (DD)-CKD compared with darbepoetin alfa (DA). METHODS: This phase 3b, randomized (1:1:1; vadadustat once-daily [starting dose: 300 or 450 mg], vadadustat 3-times-weekly [starting dose: 600 or 750 mg], DA), open-label, active-controlled, noninferiority trial included conversion (weeks 0-20) and maintenance (weeks 20-52) periods. Primary and secondary efficacy endpoints were mean change in hemoglobin from baseline during the primary (PEP, weeks 20-26) and secondary (SEP, weeks 46-52) evaluation periods. Other endpoints included proportion of patients requiring ESA rescue (hemoglobin <9.5 g/dL or with increases in dose ≥50% or ≥100% in DA group). Safety endpoints included treatment-emergent adverse events (TEAEs) and serious AEs (SAEs). RESULTS: Least squares (LS) mean treatment difference between vadadustat once-daily and DA from baseline to PEP was -0.27 g/dL (95% CI, -0.55 to 0.01); the lower bound met the noninferiority threshold (-0.75 g/dL). The LS mean treatment difference between vadadustat 3-times-weekly and DA from baseline to PEP was -0.53 g/dL (95% CI, -0.80 to -0.25), which did not meet the lower bound noninferiority threshold. The LS mean change from baseline to the SEP between DA and vadadustat once-daily was -0.40 (95% CI, -0.79 to -0.02), and for vadadustat 3-times-weekly was -0.42 (95% CI, -0.81 to -0.02). Proportion of patients who received ESA rescue during weeks 2-52 was higher in the DA group than vadadustat groups. Similar TEAEs and treatment-emergent SAEs were observed across groups. CONCLUSIONS: Vadadustat once-daily, but not 3-times-weekly, was noninferior to DA in the correction and maintenance of hemoglobin in patients with DD-CKD converted from an ESA; safety profiles were similar across groups. TRIAL REGISTRATION: EudraCT 2019-004851-36/ClinicalTrials.gov identifier: NCT04313153.