Resultados de la ventilación asistida ajustada neuronalmente no invasiva y la presión positiva continua nasal en recién nacidos prematuros: revisión sistemática y metanálisis / Outcomes of noninvasive neurally adjusted ventilatory assist and nasal continuous positive airway pressure in preterm infants: a systematic review and meta-analysis

Introducción: los beneficios de la ventilación asistida ajustada neuronalmente (NAVA) en los recién nacidos prematuros son inciertos. El objetivo de este estudio fue explorar si la NAVA no invasiva (NIV) era más beneficiosa para los recién nacidos prematuros que la presión positiva continua nasal (NCPAP). Diseño del estudio: metanálisis de tres ensayos clínicos: dos ensayos controlados aleatorizados y un estudio de grupos cruzados. Se comparó la NAVA-NIV con la NCPAP y se informó sobre el fracaso del tratamiento, la mortalidad y los eventos adversos como resultados principales. Resultados: tres estudios con 173 pacientes (89 recibieron NAVA-NIV) cumplieron los criterios de inclusión en este metanálisis. No se observaron diferencias en el fracaso del tratamiento entre la NAVA-NIV y la NCPAP (razón de riesgos [RR] = 1,09; intervalo de confianza [IC] del 95 % = 0,65-1,84; diferencia de riesgos = 0,02; IC95% = -0,10-0,14; I2 = 33 %; P = 0,23). De manera similar, no hubo diferencias en la mortalidad (RR = 1,52; IC95% = 0,51-4,52; no aplica heterogeneidad). En comparación con la NCPAP, la NAVA-NIV redujo significativamente el uso de cafeína (RR = 0,85; IC 95% = 0,74-0,98; I2 = 71 %; P = 0,03). Conclusiones: en comparación con la NCPAP, no hay evidencia suficiente para sacar una conclusión sobre los beneficios o daños de la NAVA-NIV en los recién nacidos prematuros. Los hallazgos de esta revisión deben confirmarse en ensayos clínicos con una metodología rigurosa y potencia adecuada

Introduction: The benefits of neurally adjusted ventilatory assist (NAVA) in preterm infants are unclear. This study aimed to explore if noninvasive NAVA is more beneficial for preterm infants than nasal continuous positive airway pressure (NCPAP). Study design: Meta-analysis was performed in three clinical trials comprising two randomized controlled trials and one crossover study. We compared NIV-NAVA and NCPAP and reported treatment failure, mortality, and adverse events as the primary outcomes. Results: Three studies including 173 patients (89 of whom underwent NIV-NAVA) were eligible for this meta-analysis. This review found no difference in treatment failure between NIV-NAVA and NCPAP (RR 1.09, 95% CI 0.65 to 1.84; RD 0.02, 95% CI -0.10-0.14; I2=33%, P=0.23). Similarly, there was no difference in mortality (RR 1.52, 95% CI 0.51-4.52, heterogeneity not applicable). Compared with NCPAP, NIV-NAVA significantly reduced the use of caffeine (RR 0.85, 95% CI 0.74-0.98, I2=71%, P=0.03). Conclusions: Compared with NCPAP, there is insufficient evidence to conclude on the benefits or harm of NIV-NAVA therapy for preterm infants. The findings of this review should be confirmed using methodologically rigorous and adequately powered clinical trials.

Outcomes of noninvasive neurally adjusted ventilatory assist and nasal continuous positive airway pressure in preterm infants: a systematic review and meta-analysis. / Resultados de la ventilación asistida ajustada neuronalmente no invasiva y la presión positiva continua nasal en recién nacidos prematuros: revisión sistemática y metanálisis.

INTRODUCTION: The benefits of neurally adjusted ventilatory assist (NAVA) in preterm infants are unclear. This study aimed to explore if noninvasive NAVA is more beneficial for preterm infants than nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: Meta-analysis was performed in three clinical trials comprising two randomized controlled trials and one crossover study. We compared NIV-NAVA and NCPAP and reported treatment failure, mortality, and adverse events as the primary outcomes. RESULTS: Three studies including 173 patients (89 of whom underwent NIV-NAVA) were eligible for this meta-analysis. This review found no difference in treatment failure between NIVNAVA and NCPAP (RR 1.09, 95% CI 0.65 to 1.84; RD 0.02, 95% CI -0.10-0.14; I2=33%, P=0.23). Similarly, there was no difference in mortality (RR 1.52, 95% CI 0.51-4.52, heterogeneity not applicable). Compared with NCPAP, NIVNAVA significantly reduced the use of caffeine (RR 0.85, 95% CI 0.74-0.98, I2=71%, P=0.03). CONCLUSIONS: Compared with NCPAP, there is insufficient evidence to conclude on the benefits or harm of NIV-NAVA therapy for preterm infants. The findings of this review should be confirmed using methodologically rigorous and adequately powered clinical trials.

Introducción: los beneficios de la ventilación asistida ajustada neuronalmente (NAVA) en los recién nacidos prematuros son inciertos. El objetivo de este estudio fue explorar si la NAVA no invasiva (NIV) era más beneficiosa para los recién nacidos prematuros que la presión positiva continua nasal (NCPAP). Diseño del estudio: metanálisis de tres ensayos clínicos: dos ensayos controlados aleatorizados y un estudio de grupos cruzados. Se comparó la NAVA-NIV con la NCPAP y se informó sobre el fracaso del tratamiento, la mortalidad y los eventos adversos como resultados principales. Resultados: tres estudios con 173 pacientes (89 recibieron NAVA-NIV) cumplieron los criterios de inclusión en este metanálisis. No se observaron diferencias en el fracaso del tratamiento entre la NAVA-NIV y la NCPAP (razón de riesgos [RR] = 1,09; intervalo de confianza [IC] del 95 % = 0,65-1,84; diferencia de riesgos = 0,02; IC95% = -0,10-0,14; I2 = 33 %; P = 0,23). De manera similar, no hubo diferencias en la mortalidad (RR = 1,52; IC95% = 0,51-4,52; no aplica heterogeneidad). En comparación con la NCPAP, la NAVA-NIV redujo significativamente el uso de cafeína (RR = 0,85; IC 95% = 0,74-0,98; I2 = 71 %; P = 0,03). Conclusiones: en comparación con la NCPAP, no hay evidencia suficiente para sacar una conclusión sobre los beneficios o daños de la NAVA-NIV en los recién nacidos prematuros. Los hallazgos de esta revisión deben confirmarse en ensayos clínicos con una metodología rigurosa y potencia adecuada.

Early post-operative PV-ACO2/CA-VO2 predicts subsequent acute kidney injury after complete repair of tetralogy of Fallot.

BACKGROUND: Acute kidney injury is a severe complication following complete repair of tetralogy of Fallot. Anaerobic metabolism is believed to contribute to the development of acute kidney injury. The ratio of central venous to arterial carbon dioxide tension to arterio-venous oxygen content (PV-ACO2/CA-VO2) has been proposed as a surrogate for respiratory quotient and an indicator of tissue oxygenation. We hypothesised that a small increase of PV-ACO2/CA-VO2 might have superior discrimination ability in subsequent acute kidney injury prediction. METHODS: This study is retrospective and single-centre design study. The study population consisted of 61 children with tetralogy of Fallot that underwent a complete surgical repair between July 2017 and January 2021. Baseline characteristics and intra-operative parameters were collected through a retrospective chart review. PV-ACO2/CA-VO2 was collected within 12 hours of surgical completion. Acute kidney injury was defined according to the criteria established by the Kidney Disease: Improving Global Outcomes group. Univariate and logistic regression analyses were performed to determine risk factors for acute kidney injury. RESULTS: Of the 61 patients, 20 (32.8%) developed acute kidney injury. Multivariate logistic analyses showed that age, height, haematocrit, and Pv-aCO2/Ca-vO2 were independently associated with the development of acute kidney injury. The addition of Pv-aCO2/Ca-vO2 to the model significantly increased model discrimination [AUROC 0.939 (95% CI 0.894-0.984) and AUROC 0.922 (95% CI 0.869-0.975), respectively]. CONCLUSIONS: The increase of PV-ACO2/CA-VO2 could improve the predictive ability for subsequent development of acute kidney injury in children with tetralogy of Fallot.

Methodological comparison of the allele refractory mutation system and direct sequencing for detecting EGFR mutations in NSCLC, and the association of EGFR mutations with patient characteristics.

Gefitinib is effective for patients with non-small cell lung cancer (NSCLC) with a mutation in the epidermal growth factor receptor (EGFR) gene, which makes the detection of EGFR mutations a critical step prior to determining a treatment schedule. Therefore, the present study determined the EGFR mutation status in patients with NSCLC using an allele refractory mutation system (ARMS) and analyzed the detection ratio for different specimen types. A total of 1,596 NSCLS samples were collected and EGFR gene mutations were detected on exons 18-21 using ARMS and direct sequencing. The concordance of two methods reached 89.21%, with a total mutation rate of 45.55% (727/1,596), in which the mutation rate in lung adenocarcinoma samples was markedly increased compared with squamous cell carcinoma (51.77 vs. 8.68%). In patients with lung adenocarcinoma, EGFR mutations were more frequent in female patients than male patients (65.53 vs. 39.80%, P<0.01); there was no observable difference depending on age. Similar results were obtained for squamous cell carcinoma. In the present study, certain rare mutations were also identified; these may be subjects for further study. The impact of different sample types on the consistency between the methods was determined to be insignificant. ARMS is a more applicable approach for large-scale clinical detection than direct sequencing, and we hypothesize that ARMS may replace direct sequencing if the drawbacks of ARMS, including its narrow detection range, can be amended.

Altered bulbocavernosus reflex in patients with multiple system atrophy.

OBJECTIVES: Multiple system atrophy (MSA) is characterized by a combination of symptoms including autonomic dysfunction, parkinsonism, cerebellar ataxia, and cortico-spinal disorders. The disease can have either predominant parkinsonism or cerebellar features (MSA-P and MSA-C, respectively). The measurement of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potentials (PSEPs) was originally developed to diagnose diabetic cystopathy and other neuropathologic diseases that share similar symptoms with MSA. We investigated the relationship between abnormalities of neurophysiological parameters and MSA, and estimated the potential value of BCR. METHODS: Fifty-one MSA patients (28 and 23 MSA-P and 23 MSA-C patients, respectively) and 30 healthy controls who were seen at the Department of Neurology were included in the study. A Keypoint EMG/EP system was used to test BCR and PSEPs, and the latencies and amplitudes were recorded for statistical analyses. RESULTS: The BCR was elicited in 78.4% patients with MSA (22/28 MSA-P, 18/23 MSA-C). Prolonged BCR latencies were found in patients with MSA compared with healthy controls (p < 0.001). BCR amplitudes were significantly lower in the MSA group than the control group (p < 0.001). PSEP P41 amplitudes were not significantly different between the MSA and control groups in males (p = 0.608) or females (p = 0.897). There were no significant differences in PSEP latencies among the MSA-P, MSA-C, and control groups (p = 1.0, p = 0.263, and p = 0.060, respectively). DISCUSSION: MSA patients exhibit prolonged BCR latencies and lower amplitudes, which provides a rough anatomical localization of nervous system lesions in MSA patients.

α-Solanine inhibits vascular endothelial growth factor expression by down-regulating the ERK1/2-HIF-1α and STAT3 signaling pathways.

In tumors, vascular endothelial growth factor (VEGF) contributes to angiogenesis, vascular permeability, and tumorigenesis. In our previous study, we found that α-solanine, which is widespread in solanaceae, has a strong anti-cancer effect under normoxia. However, it is unknown whether α-solanine has a similar effect under hypoxia. We used cobalt chloride (CoCl2) to mimic hypoxia in vitro. HIF-1α, which is almost undetectable under normoxia, was significantly increased. Simultaneously, another regulator of VEGF, STAT3, was also significantly activated by CoCl2. We utilized α-solanine in co-culture with CoCl2. α-solanine decreased the expression of VEGF and loss of E-cadherin. α-solanine also suppressed the activation of phospho-ERK1/2 (p-ERK1/2), HIF-1α, and STAT3 signaling. The results provide new evidence that α-solanine has a strong anti-cancer effect via the ERK1/2-HIF-1α and STAT3 signaling pathways and suggest that it may be a potential new drug.

Roles of iron acquisition systems in virulence of extraintestinal pathogenic Escherichia coli: salmochelin and aerobactin contribute more to virulence than heme in a chicken infection model.

BACKGROUND: Avian pathogenic Escherichia coli (APEC) and uropathogenic E. coli (UPEC) are the two main subsets of extraintestinal pathogenic E. coli (ExPEC). Both types have multiple iron acquisition systems, including heme and siderophores. Although iron transport systems involved in the pathogenesis of APEC or UPEC have been documented individually in corresponding animal models, the contribution of these systems during simultaneous APEC and UPEC infection is not well described. To determine the contribution of each individual iron acquisition system to the virulence of APEC and UPEC, isogenic mutants affecting iron uptake in APEC E058 and UPEC U17 were constructed and compared in a chicken challenge model. RESULTS: Salmochelin-defective mutants E058ΔiroD and U17ΔiroD showed significantly decreased pathogenicity compared to the wild-type strains. Aerobactin defective mutants E058ΔiucD and U17ΔiucD demonstrated reduced colonization in several internal organs, whereas the heme defective mutants E058ΔchuT and U17ΔchuT colonized internal organs to the same extent as their wild-type strains. The triple mutant ΔchuTΔiroDΔiucD in both E058 and U17 showed decreased pathogenicity compared to each of the single mutants. The histopathological lesions in visceral organs of birds challenged with the wild-type strains were more severe than those from birds challenged with ΔiroD, ΔiucD or the triple mutants. Conversely, chickens inoculated with the ΔchuT mutants had lesions comparable to those in chickens inoculated with the wild-type strains. However, no significant differences were observed between the mutants and the wild-type strains in resistance to serum, cellular invasion and intracellular survival in HD-11, and growth in iron-rich or iron-restricted medium. CONCLUSIONS: Results indicated that APEC and UPEC utilize similar iron acquisition mechanisms in chickens. Both salmochelin and aerobactin systems appeared to be important in APEC and UPEC virulence, while salmochelin contributed more to the virulence. Heme bounded by ChuT in the periplasm appeared to be redundant in this model, indicating that other periplasmic binding proteins likely contributed to the observed no phenotype for the heme uptake mutant. No differences were observed between the mutants and their wild-type parents in other phenotypic traits, suggesting that other virulence mechanisms compensate for the effect of the mutations.