The level of discomfort during the use of different circuits of the mechanical ventilator.

Objectives: Endotracheal tube (ETT) intubation is a life-saving procedure in patients with respiratory failure. However, the presence of an ETT can cause significant discomfort. A tracheostomy tube is used to administer a mechanical ventilator, resulting in a more stable airway and fewer serious injuries. Noninvasive ventilators (NIPPVs) administer ventilation through masks and must be tightly fixed to the face. ETT, tracheostomy, and NIPPV are the most common methods of ventilator maintenance. However, these interventions often cause discomfort to patients. This study aimed to compare discomfort associated with ETT, tracheostomy, and NIPPV. Materials and Methods: Forty-nine conscious patients with postextubation NIPPV and eight conscious patients who underwent postextubation tracheotomy were evaluated for discomfort. A questionnaire survey on discomfort was performed before and after NIPPV or tracheostomy. These patients reported their level of discomfort on a visual analog scale. Results: The levels of sore throat, nasal pain, body pain, activity limitation, respiratory discomfort, oral discomfort, difficulty coughing sputum, worry about respiratory tube disconnection, back pain, anxiety, worry about long-term admission, sleep disturbance, and general discomfort during ETT intubation were higher than during tracheostomy or NIPPV (all P < 0.05). The mean level of discomfort was approximately 5-6 points (moderate) in patients with ETT and 2-3 points (mild) in patients with NIPPV or tracheostomy. Conclusion: The level of discomfort was higher in patients who underwent ETT intubation than in those who underwent NIPPV or tracheostomy. However, the level of discomfort was similar between the patients with NIPPV and those who underwent tracheostomy.

Rapid in-situ calibration of computational micro-spectrometer with few-shot meta-learning.

Computational micro-spectrometers comprised of detector arrays and encoding structure arrays, such as on-chip Fabry-Perot (FP) cavity filters, have great potential in many in-situ applications owing to their compact size and snapshot imaging ability. Given manufacturing deviation and environmental influence are inevitable, easy and effective calibration for spectrometer is necessary, especially for in-situ applications. Currently calibration strategies based on iterative algorithms or neural networks require accurate measurements of pixel-level (spectral) encoding functions through monochromator or large amounts of standard samples. These procedures are time-consuming and expensive, thereby impeding in-situ applications. Meta-learning algorithms with few-shot learning ability can address this challenge by incorporating the prior knowledge in the simulated dataset. In this work, we propose a meta-learning algorithm free of measuring encoding function or large amounts of standard samples to calibrate a micro-spectrometer with manufacturing deviation effectively. Our micro-spectrometer comprises 16 types of FP filters covering a wavelength range of 550-720 nm. The center wavelength of each filter type deviates from the design up to 6 nm. After calibration with 15 different color data, the average reconstruction error on the test dataset decreased from 7.2 × 10-3 to 1.2 × 10-3, and further decreased to 9.4 × 10-4 when the calibration data increased to 24. The performance is comparable to algorithms trained with measured encoding function both in reconstruction error and generalization ability. We estimated that the cost of in-situ calibration through reflectance measurements of color chart decreased to one percent of the cost through monochromator measurements. By exploiting prior deviation information in simulation data with meta-learning, the efficiency and cost of calibration are significantly improved, thereby facilitating the large-scale production and in-situ application of micro-spectrometers.

The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

High-intensity aerobic exercise training improves exercise capacity, dyspnea, and fatigue in patients with severe asthma using triple inhaler.

Objectives: Asthma is a chronic respiratory disease that affects millions of people worldwide and causes severe symptoms such as wheezing, coughing, and breathing difficulty. Despite modern treatments, 3%-10% of patients develop severe asthma, which requires high-dose medications, and they may still experience frequent and severe symptoms, exacerbations, and psychological impacts. This study aimed to investigate the effects of high-intensity aerobic exercise training (HIAET) in patients with severe asthma. Materials and Methods: Patients with severe asthma were recruited, and cardiopulmonary exercise tests, dyspnea, and leg fatigue scores were performed before HIAET. Participants underwent a 12-week hospital-based HIAET, which involved exercising twice weekly to reach 80% of their peak oxygen uptake (VO2). Results: Eighteen patients with severe asthma underwent HIAET, which resulted in significant improvement in peak VO2 (1214.0 ± 297.9-1349.4 ± 311.2 mL/min, P = 0.004) and work rate (80.6 ± 21.2-96.2 ± 24.8 watt, P < 0.001) and decrease in dyspnea (5.1 ± 1.8-4.1 ± 1.2, P = 0.017) and fatigue scores (5.2 ± 2.3-4.0 ± 1.2, P = 0.020) at peak exercise. No significant changes were observed in spirometry results, respiratory muscle strength, or circulatory parameters. Conclusion: HIAET can lead to improved exercise capacity and reduced dyspnea and fatigue scores at peak exercise without changes in spirometry, respiratory muscle strength, and circulatory parameters.

Correction: Accelerated weight gain, prematurity, and the risk of childhood obesity: A meta-analysis and systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0232238.].

Pulmonary rehabilitation improves exercise capacity, health-related quality of life, and cardiopulmonary function in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer significantly impairs exercise capacity and health-related quality of life (HRQL). Pulmonary rehabilitation (PR) has demonstrated positive effects on exercise capacity and HRQL in lung cancer patients. However, its impact on cardiopulmonary function needs further exploration. The aim of this study was to explore the effects of PR on cardiopulmonary function, exercise capacity and HRQL in patients with lung cancer. METHODS: Patients with lung cancer were enrolled in a 12-week PR program. Each participant underwent a thorough evaluation, which included spirometry, cardiopulmonary exercise testing, respiratory muscle strength test, and evaluation of HRQL using the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). RESULTS: Fifty-six patients completed the PR program. Following PR, exercise capacity significantly improved, as evidenced by increased peak oxygen uptake and work rate (both p < 0.05). Exertional symptoms were notably reduced, including leg soreness and dyspnea at peak exercise, accompanied by a decrease in the CAT score (all p < 0.05). Furthermore, improvements in cardiopulmonary function were observed, encompassing respiratory muscle strength, ventilatory equivalent, tidal volume, stroke volume index, and cardiac index at peak exercise (all p < 0.05). CONCLUSIONS: PR demonstrated notable enhancements in cardiopulmonary function, exertional symptoms, exercise capacity, and HRQL in patients with lung cancer.

Case Report: Neurally adjusted ventilatory assist as an effective rescue treatment for pulmonary interstitial emphysema in extremely low birth weight infants.

Pulmonary interstitial emphysema (PIE) is a complication observed in extremely low birth weight (ELBW) infants on mechanical ventilation. Despite various proposed therapeutic interventions, the success rates have shown inconsistency. Neurally adjusted ventilatory assist (NAVA) stands out as a novel respiratory support mode, offering lower pressure and tidal volume in comparison to conventional ventilation methods. In this case report, we present five ELBW infants with refractory PIE who were transitioned to NAVA ventilation. Following the switch to NAVA, all cases of PIE gradually resolved. In contrast to traditional modes, NAVA provided respiratory support with significantly lower fraction of inspired oxygen, reduced peak inspiratory pressure, diminished mean airway pressure, and decreased tidal volume within 7 days of NAVA utilization (p = 0.042, 0.043, 0.043, and 0.042, respectively). Consequently, we propose that NAVA could serve as a valuable rescue treatment for ELBW infants with PIE.

Analgesic Effect of Low-Level Laser Therapy before Heel Lance for Pain Management in Healthy Term Neonates: A Randomized Controlled Trial.

Currently, the prevention, assessment, and management of procedural pain in neonates continues to challenge clinicians and researchers. Objective. To investigate the analgesic effect of low-level laser therapy (LLLT) during heel lance compared to breast milk (BM) feeding in healthy term neonates. In this randomized controlled trial, healthy term neonates who underwent heel lance were randomly assigned to an LLLT or a BM group. The LLLT group received laser therapy to the heel lance site for 20 s before heel lance. The BM group received 5 mL expressed BM via a syringe before heel lance. The primary outcomes were behavioral responses. The secondary outcomes were physiological responses and levels of salivary cortisol and α-amylase. A total of 125 neonates were included, of whom 55 in the LLLT group and 59 in the BM group completed the study. There were no significant differences in latency to first cry and cry duration between the two groups. The squeeze time was significantly shorter in the LLLT group than in the BM group (p = 0.047). There were no significant differences in pain scores, heart rate, respiratory rate, oxygen saturation, and blood pressure before and after heel lance between the two groups. There were no significant differences in salivary cortisol and α-amylase levels in the LLLT group before and after heel lance; however, the differences were significant in the BM group. These findings suggest that the analgesic effect of LLLT is similar to that of BM during heel lance in healthy term neonates. LLLT has potential as an analgesic treatment.

Predictive role of neutrophil-percentage-to-albumin, neutrophil-to-lymphocyte and eosinophil-to-lymphocyte ratios for mortality in patients with COPD: Evidence from NHANES 2011-2018.

BACKGROUND AND OBJECTIVE: This study evaluated the predictive roles of hematologic inflammatory biomarkers including neutrophil-percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR) for mortality in community-dwelling individuals with chronic obstructive pulmonary disease (COPD). METHODS: This longitudinal study extracted data of adults 40-79 years who had physician-diagnosed COPD from the United States (US) National Health and Nutrition Examination Survey (NHANES) 1999-2018. Cox regressions determined the associations between NPAR, NLR, ELR and their components, with all-cause mortality, cardiovascular disease (CVD) mortality and mortality from chronic lower respiratory disease (CLRD). Receiver operating characteristic (ROC) curve analysis estimated the predictive performances of these biomarkers for 5-year all-cause mortality. RESULTS: Data of 1158 subjects were analysed. After adjustment, higher NPAR was significantly associated with increased all-cause and CVD mortality, and mortality from CLRD (adjusted hazard ratio [aHR] = 1.14, 1.15 and 1.16). Higher NLR was associated with an increased all-cause and CVD mortality (aHR = 1.16 and 1.29). Higher neutrophil was associated with increased all-cause mortality and mortality from CLRD (aHR = 1.13 and 1.34). Albumin was associated with decreased all-cause and CVD mortality (aHR = 0.91 and 0.86). ELR, eosinophil or lymphocyte was not significantly associated with either mortality outcomes. Adjusted AUC of NPAR and NLR in predicting 5-year all-cause mortality were 0.808 (95% CI: 0.722-0.845) and 0.799 (95% CI: 0.763-0.835), respectively. CONCLUSION: In community-dwelling US adults with COPD, increased NPAR and NLR are associated with mortality risks. NPAR outperforms the other hematologic inflammatory biomarkers in predicting 5-year all-cause mortality.

A Three-Arm, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Lactobacillus salivarius AP-32 and Bifidobacterium animalis CP-9 Used Individually in Healthy Infants.

Probiotics are considered safe and beneficial to human health. However, the safety of Lactobacillus salivarius AP-32 and Bifidobacterium animalis CP-9 in infants has not been confirmed. This study was to assess the safety of long-term oral administration of L. salivarius AP-32 and B. animalis CP-9 in healthy infants compared with placebo. A three-arm, randomized, double-blind, placebo-controlled trial was conducted in healthy, full-term infants. Eighty-eight infants between 7 days and 2 months (60 ± 7 days) of age were selected and randomized to treatment with L. salivarius AP-32, B. animalis CP-9 or placebo for 4 months. The unblinding indicated subjects were randomized to receive B. animalis CP-9 (N = 28), L. salivarius AP-32 (N = 29), or placebo (N = 31). A total of 76 infants completed the 4-month treatment with fully compliance. The primary outcome was weight gain, with no significant difference in infant weight at 4 months when comparing AP-32 or CP-9 group with the placebo group, either. The head circumference and recumbent length of the CP-9 group were not significantly different from those of the placebo group. The recumbent length of the AP-32 group was slightly lower than that in the placebo group at month 4, but there was no difference between the two groups in head circumference. Overall, the growth trend of all treatments was similar without significant difference. Furthermore, there were no apparent differences between each group in digestive tolerance, the occurrence of adverse events, crying/fussing time and episodes, alpha diversity, and beta diversity. The CP-9 group showed a significant increase in the abundance of the Bacteroides genus, while the AP-32 group demonstrated a significant increase in the abundance of the Lactobacillus genus when comparing the two probiotic groups. Our study findings indicate that the oral administration of both AP-32 and CP-9 strains has a positive impact on the maintenance of a healthy gut flora in infants. Long-term use of L. salivarius AP-32 or B. animalis CP-9 is safe for infants from 7 days to 6 months of age.

The Clinical Characteristics, Microbiology and Risk Factors for Adverse Outcomes in Neonates with Gram-Negative Bacillary Meningitis.

Background: We aimed to describe the clinical features of Gram-negative bacillary (GNB) meningitis in neonates and investigate the risk factors associated with final adverse outcomes of neonatal GNB meningitis. Methods: From 2003 to 2020, all neonates (aged ≤ 90 days old) with bacterial meningitis who were hospitalized in four tertiary-level neonatal intensive care units (NICUs) of two medical centers in Taiwan were enrolled. Neonates with GNB meningitis were compared with those with Streptococcus agalactiae (group B streptococcus, GBS) meningitis. Results: During the study period, a total of 153 neonates with bacterial meningitis were identified and enrolled. GNB and GBS accounted for 40.5% (n = 62) and 35.3% (n = 54) of all neonatal bacterial meningitis, respectively. In neonates with GNB meningitis, the final mortality rate was 6.5% (4 neonates died); 48 (77.4%) had neurological complications, and 26 (44.8%) of 58 survivors had neurological sequelae at discharge. Although the final outcomes were comparable between neonates with GNB meningitis and those with GBS meningitis, neonates with GNB meningitis were more likely to have more severe clinical manifestations initially and have ventriculomegaly at follow-up. After multivariate logistic regression analysis, neonates with seizure at onset, early onset sepsis, and requirement of surgical intervention for neurological complications were independently associated with final adverse outcomes. Conclusions: GNB meningitis was associated with a high risk of neurological complications and sequelae, although it did not significantly increase the final mortality rate. Close monitoring of the occurrence of neurological complications and advanced therapeutic strategies to optimize the outcomes are urgently needed in the future.

Evaluation of the relationship of tricuspid regurgitation peak gradient/tricuspid annulus plane systolic excursion to exercise capacity, cardiac index, and ventilatory function during exercise in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) often causes cardiopulmonary dysfunction, which deteriorates exercise capacity. Cardiopulmonary exercise testing (CPET) and echocardiography are common tools for evaluating cardiovascular function. No studies have analyzed the correlation between echocardiography-derived parameters and cardiopulmonary response during exercise. OBJECTIVES: We analyzed the correlation between echocardiographic parameters such as tricuspid regurgitation peak gradient (TRPG), tricuspid annular plane systolic excursion (TAPSE), TRPG/TAPSE and CPET-derived parameters. METHODS: Seventy-seven patients with COPD were evaluated. We analyzed the correlation between parameters derived from echocardiography, exercise capacity, cardiovascular and ventilatory parameters derived from CPET. RESULTS: The correlation between TRPG/TAPSE and work rate (WR) was moderate and negative (-0.4423, p = 0.0003), while TRPG had a weak negative correlation with WR (r= -0.3099, p = 0.0127). Oxygen uptake at peak exercise was weakly negatively correlated with TRPG/TAPSE (-0.3404, p = 0.0059), TRPG (r= -0.3123, p = 0.0120), and the ratio of early mitral inflow velocity to early mitral annular diastolic velocity (E/E'). The correlation between TRPG/TAPSE and exercise capacity was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE exhibited a moderate negative correlation with cardiac index, whereas TRPG and TAPSE showed a weak correlation. The correlation between TRPG/TAPSE and cardiac function during exercise was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE, TRPG, TAPSE, and E/E' were weakly negatively correlated with lung function. CONCLUSIONS: In assessing exercise capacity, cardiac function, and gas exchange, TRPG/TAPSE proves to be superior to other cardiac parameters. Higher TRPG/TAPSE levels corresponded to lower exercise capacity, cardiovascular and ventilatory function.

Early pulmonary rehabilitation of COVID-19 patients in an isolation ward and intensive care unit.

When patient with coronavirus disease 2019 (COVID-19) are hospitalized, the limited space for activity, disease itself causes fever, muscle aches, fatigue, respiratory failure with mechanical ventilation, or medications such as steroids or neuromuscular blocking can cause muscle dysfunction. Pulmonary rehabilitation (PR) should be arranged for these patients with COVID-19. However, the literature on early PR within 1 week of admission on patients with COVID-19 are limited. This review focuses on early PR in COVID-19 patients admitted to isolation wards or intensive care units. The essential components of early PR programs include education, breathing exercise, airway clearance, and physical activity training. Breathing exercises, including diaphragmatic and pursed-lip breathing, are known to improve lung function in chronic obstructive pulmonary disease and are also recommended for COVID-19 patients. Poor airway clearance can further aggravate pneumonia. Airway clearance techniques help patients to clear sputum and prevent the aggravation of pneumonia. Early physical activity training allows patients to maintain limb muscle function during hospitalization. It is recommended to design appropriate indoor exercise training for patients with frequency 1-2 times a day, and intensity should not be too high (dyspnea Borg Scale ≤3) in the acute stage. In order to achieve safe training, criteria for selecting stable patients and training termination are important. Early PR may help reduce the length of hospital stay, maintain functional status, improve symptoms of dyspnea, relieve anxiety, and maintain health-related quality of life in these patients after discharge.

Impact of bisoprolol and amlodipine on cardiopulmonary responses and symptoms during exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have exercise intolerance. The prevalence of hypertension in COPD patients ranges from 39-51%, and ß-blockers and amlodipine are commonly used drugs for these patients. OBJECTIVES: We aimed to study the impact of ß-blockers and amlodipine on cardiopulmonary responses during exercise. METHODS: A total 81 patients with COPD were included and the patients underwent spirometry, cardiopulmonary exercise tests, and symptoms questionnaires. RESULTS: There were 14 patients who took bisoprolol and 67 patients who did not. Patients with COPD taking ß-blockers had lower blood oxygen concentration (SpO2) and more leg fatigue at peak exercise but similar exercise capacity as compared with patients not taking bisoprolol. There were 18 patients treated with amlodipine and 63 patients without amlodipine. Patients taking amlodipine had higher body weight, lower blood pressure at rest, and lower respiratory rates during peak exercise than those not taking amlodipine. Other cardiopulmonary parameters, such as workload, oxygen consumption at peak exercise, tidal volume at rest or exercise, cardiac index at rest or exercise were not significantly different between patients with or without bisoprolol or amlodipine. Smoking status did not differ between patients with or without bisoprolol or amlodipine. CONCLUSIONS: COPD is often accompanied by hypertension, and ß-blockers and amlodipine are commonly used antihypertensive drugs for these patients. Patients with COPD taking bisoprolol had lower SpO2 and more leg fatigue during peak exercise. Patients taking amlodipine had lower respiratory rates during exercise than those not taking amlodipine. Exercise capacity, tidal volume, and cardiac index during exercise were similar between patients with and without bisoprolol or amlodipine.

General-purpose mid-infrared micro-spectrometer based on hierarchical residual CNN and data augmentation.

Taking advantage of broad response range and snap-shot operation mode, reconstructive spectrometers based on integrated frequency-modulation microstructure and computational techniques attract lots of attention. The key problems in reconstruction are sparse samplings related with the limited detectors and generalization ability due to data-driving principle. Here, we demonstrate abstractly a mid-infrared micro-spectrometer covering 2.5-5 µm, which utilizes a grating-integrated lead selenide detector array for sampling and a hierarchal residual convolutional neural network (HRCNN) for reconstructions. Leveraging data augmentation and the powerful feature extraction ability of HRCNN, a spectral resolution of 15 nm is realized. Over one hundred chemicals, including untrained chemicals species tested with an average reconstruction error of ∼1E-4, exhibit the excellent reliability of the micro-spectrometer. The demonstration of the micro-spectrometer promotes the development of the reconstructed strategy.

Perinatal Characteristics and the Sensitization to Cow Milk, Egg Whites and Wheat in Children up to 3 Years of Age.

Food sensitization in early life identifies children at risk of developing allergic diseases. We investigated the sensitization to cow milk (CM), egg whites, and wheat. Newborns and infants under 3 years of age with available specific immunoglobulin E (sIgE) data were identified. A retrospective survey was conducted using data from the Chang Gung Research Database. Perinatal characteristics, such as singleton or multiples in a single pregnancy, parity, meconium staining, maternal age, spontaneous delivery or cesarean section, meconium passage, weeks of gestation, birth length, body weight, head and chest circumferences, and season, were obtained. The data on sIgE were collected, and a logistic regression model was used to determine the odds of sensitization. Positive sIgE for CM and egg whites was more likely to occur in boys than in girls. Early-life egg white and wheat sensitization was associated with increased birth body length and weight. A multivariate analysis indicated an association between egg white sIgE positivity and logarithmic total IgE. Higher total IgE levels and younger age were associated with egg white sensitization, and elevated weight and length at birth were linked to food sensitization, particularly to egg whites and wheat.

Neurally adjusted ventilatory assist for rapid weaning in preterm infants.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a new mode of subject-triggered ventilation. Experience with the use of NAVA in preterm infants is limited. This study compared the effects of invasive mechanical ventilation with NAVA to conventional intermittent mandatory ventilation (CIMV) in terms of reducing the duration of oxygen requirement and invasive ventilator support in preterm infants. METHODS: This was a prospective study. We enrolled infants of less than 32 weeks' gestation who were then randomized to receive either NAVA or CIMV support during hospitalization. We recorded and analyzed data on the maternal history during pregnancy, use of medications, neonatal data at admission, neonatal diseases, and respiratory support in the neonatal intensive care unit. RESULTS: There were 26 preterm infants in the NAVA group and 27 preterm infants in the CIMV group. Significantly fewer infants in the NAVA group received supplemental oxygen at 28 days of age (12 [46%] vs. 21 [78%], p = 0.0365), and they required significantly fewer days of invasive ventilator support: 7.73 (± 2.39) vs. 17.26 (± 3.65), p = 0.0343. CONCLUSIONS: Compared with CIMV, NAVA appears to allow for more rapid weaning from invasive ventilation and decreases the incidence of bronchopulmonary dysplasia, especially in preterm infants with severe respiratory distress syndrome treated with surfactants.

Influences of Initial Empiric Antibiotics with Ampicillin plus Cefotaxime on the Outcomes of Neonates with Respiratory Failure: A Propensity Score Matched Analysis.

Background: Empiric antibiotics are often prescribed in critically ill and preterm neonates at birth until sepsis can be ruled out. Although the current guideline suggests narrow-spectrum antibiotics, an upgrade in antibiotics is common in the neonatal intensive care unit. The impacts of initial broad-spectrum antibiotics on the outcomes of critically ill neonates with respiratory failure requiring mechanical intubation have not been well studied. Methods: A total of 1162 neonates from a tertiary level neonatal intensive care unit (NICU) in Taiwan who were on mechanical ventilation for respiratory distress/failure at birth were enrolled, and neonates receiving ampicillin plus cefotaxime were compared with those receiving ampicillin plus gentamicin. Propensity score-matched analysis was used to investigate the effects of ampicillin plus cefotaxime on the outcomes of critically ill neonates. Results: Ampicillin plus cefotaxime was more frequently prescribed for intubated neonates with lower birth weight, higher severity of illness, and those with a high risk of early-onset sepsis. Only 11.1% of these neonates had blood culture-confirmed early-onset sepsis and/or congenital pneumonia. The use of ampicillin plus cefotaxime did not significantly contribute to improved outcomes among neonates with early-onset sepsis. After propensity score-matched analyses, the critically ill neonates receiving ampicillin plus cefotaxime had significantly worse outcomes than those receiving ampicillin plus gentamicin, including a higher risk of late-onset sepsis caused by multidrug-resistant pathogens (11.2% versus 7.1%, p = 0.027), longer duration of hospitalization (median [IQR], 86.5 [47-118.8] days versus 78 [45.0-106.0] days, p = 0.002), and a significantly higher risk of in-hospital mortality (14.2% versus 9.6%, p = 0.023). Conclusions: Ampicillin plus cefotaxime should not be routinely prescribed as the empiric antibiotics for critically ill neonates at birth because they were associated with a higher risk of infections caused by multidrug-resistant pathogens and final worse outcomes.

Bile Duct Stone Size May Influence the Efficacy of Endoscopic Sphincterotomy With or Without Large-Balloon Dilation: A Meta-Analysis.

Purpose: Endoscopic sphincterotomy (EPT) combined with endoscopic papillary large balloon dilatation (EPBD) are used to remove large common bile duct (CBD) stones. This meta-analysis compared the efficacy and safety of EPT+EPBD versus EPT alone in the removal of stones based on stone size. Materials and Methods: Twenty-two studies (11 randomized control trials [RCTs] and 11 non-RCTs) were identified and reviewed based on searches of Embase, PubMed, and Web of Science. CBD stone's size was measured with reference to diameter of the duodenoscope (13 mm) and size of the large dilatation balloon (17 mm) seen on cholangiogram. The stone clearance rate, required mechanical lithotripsy (ML), procedure time, and pancreatitis were compared according to the mean stone size, and further divided into Groups A (small) 10-13 mm, B (medium) 13-17 mm, and C (large) >17 mm. Results: Subgroup analysis according to CBD stone size showed EPT + EPBD had a significantly better initial stone clearance rate than EPT in Groups B (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.20-4.77) and C (OR = 3.05, 95% CI: 1.86-5.03), but not for Group A (OR = 1.41, 95% CI: 0.90-2.21). EPT+EPBD also required significantly less ML than EPT in Groups B (OR = 0.34, 95% CI: 0.15-0.77) and C (OR = 0.31, 95% CI: 0.13-0.73). EPT+EPBD had significantly shorter procedure time than EPT in Group B (standardized mean difference = -1.20, 95% CI: -2.08 to 0.32). In meta-regression analysis, Group B had a better OR in initial stone clearance rate and less ML usage rate correlation with the size of CBD stone, but not for Group C with larger stones. Conclusions: EPT+EPBD had a significantly better initial stone clearance rate, and required less ML with shorter procedure time than EPT for removing medium-sized CBD stones, but the efficacy was limited to large CBD stones. The study protocol and trial registration had been registered in PROSPERO (Registration No. CRD42020171689).

Coculture engineering for efficient production of vanillyl alcohol in Escherichia coli.

Vanillyl alcohol is a precursor of vanillin, which is one of the most widely used flavor compounds. Currently, vanillyl alcohol biosynthesis still encounters the problem of low efficiency. In this study, coculture engineering was adopted to improve production efficiency of vanillyl alcohol in E. coli. First, two pathways were compared for biosynthesis of the immediate precursor 3, 4-dihydroxybenzyl alcohol in monocultures, and the 3-dehydroshikimate-derived pathway showed higher efficiency than the 4-hydroxybenzoate-derived pathway. To enhance the efficiency of the last methylation step, two strategies were used, and strengthening S-adenosylmethionine (SAM) regeneration showed positive effect while strengthening SAM biosynthesis showed negative effect. Then, the optimized pathway was assembled in a single cell. However, the biosynthetic efficiency was still low, and was not significantly improved by modular optimization of pathway genes. Thus, coculturing engineering strategy was adopted. At the optimal inoculation ratio, the titer reached 328.9 mg/L. Further, gene aroE was knocked out to reduce cell growth and improve 3,4-DHBA biosynthesis of the upstream strain. As a result, the titer was improved to 559.4 mg/L in shake flasks and to 3.89 g/L in fed-batch fermentation. These are the highest reported titers of vanillyl alcohol so far. This work provides an effective strategy for sustainable production of vanillyl alcohol.