Comparative effectiveness of neuraminidase inhibitors in patients with influenza: A systematic review and network meta-analysis.

The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the duration of influenza symptoms, and thereby, informing the selection of suitable therapeutic regimens for patients with influenza. We conducted a systematic review of randomized controlled trials comparing the clinical effects of four NAIs administered to patients with influenza and placebo. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry and through hand searching. We carried out NWA to compare the different regimens with each other and across subgroups of age and medical status (high-risk patients). A total of 58 two-arm studies were identified. Five regimens were efficacious in reducing the time to alleviation of influenza symptoms in all populations; this efficacy was comparable. No significant improvements were seen in combination therapy groups. The mean difference in the time to alleviation of symptoms ranged from 12.78 to 19.51 h. According to the summarized mean difference and surface under the cumulative ranking curve (SUCRA), peramivir (SUCRA = 82.6%), zanamivir (SUCRA = 64%), and oseltamivir (SUCRA = 55.1%) were the three top-ranking drugs for treating influenza. Zanamivir and peramivir were the preferred pharmacologic intervention among all investigated interventions based on the calculated "value preference of SUCRA." This study is a network meta-analysis to explore the therapeutic effects of NAIs in patients with influenza. Peramivir might be the best choice for reducing the time to alleviation of symptoms.

Cost-effectiveness evaluation of add-on dapagliflozin for heart failure with reduced ejection fraction from perspective of healthcare systems in Asia-Pacific region.

BACKGROUND: With emerging evidence on the efficacy of adding dapagliflozin to standard care for patients with heart failure with reduced ejection fraction (HFrEF), this study assessed the cost-effectiveness of add-on dapagliflozin to standard care versus standard care alone for HFrEF from the perspective of healthcare systems in the Asia-Pacific region. METHODS: A Markov model was applied to project the outcomes of treatment in terms of lifetime medical cost and quality-adjusted life-years. The transition probabilities between health states in the model were obtained from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. Country-specific costs and utilities were extracted for modeling. The incremental cost-effectiveness ratio against a country-specific willingness-to-pay threshold was applied to determine the cost-effectiveness of treatment. A series of sensitivity analyses were performed to ensure the robustness of the study results. Costs are presented in 2020 United States dollars. RESULTS: The incremental cost-effectiveness ratios for add-on dapagliflozin versus standard care alone were $5277, $9980, $12,305, $16,705, and $23,227 per quality-adjusted life-year gained in Korea, Australia, Taiwan, Japan, and Singapore, respectively. When using add-on dapagliflozin to standard care versus standard care alone, ~ 100% of simulations were cost-effective at a willingness-to-pay threshold of one gross domestic product per capita of the given Asia-Pacific country; however, the probability of being cost-effective for using add-on dapagliflozin decreased when the time horizon for simulation was restricted to 18 months and when the cardiovascular mortality for the two treatments (43.8% and 33.0%, respectively) was assumed to be the same. The cost-effectiveness results were most sensitive to cardiovascular mortality of treatment. CONCLUSIONS: Adding dapagliflozin to standard care is cost-effective for HFrEF in healthcare systems in the Asia-Pacific region, which supports the rational use of dapagliflozin for HFrEF in this region.

Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. RESULTS: We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. CONCLUSIONS: Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Inhaled corticosteroid for patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of inhaled corticosteroid (ICS) in the treatment of patients with COVID-19 has been evaluated in randomized controlled trials (RCTs), however, their findings are not consistent. METHODS: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar were searched to June 10, 2023. Only RCTs that investigated the clinical efficacy and safety of ICS for patients with COVID-19 were included. RESULTS: Eleven RCTs were included. ICS users had significantly higher rate of symptom alleviation at day 14 than the control group (risk ratio [RR], 1.13; 95% CI, 1.04-1.23; I2 = 42%). Additionally, no significant difference between the ICS users and the control group was observed in the composite outcome of urgent care, emergency department (ED) visit or hospitalization (RR, 0.43; 95% CI, 0.08-2.48; I2 = 85%) and hospitalization or death (RR, 0.85; 95% CI, 0.64-1.12; I2 = 0%). Finally, ICS user had a non-significantly lower risk of death at day 28 than the control group (0.63% vs 0.99%; RR, 0.82; 95% CI, 0.43-1.56; I2 = 0%). CONCLUSIONS: Additional ICS use, particularly inhaled budesonide may help symptom relief in patients with COVID-19. However, ICS use did not help reduce the risk of urgent care, ED visit, hospitalization, or death.

Preterm infants' biobehavioral responses to caregiving and positioning over 24 hours in a neonatal unit in Taiwan.

This prospective, descriptive study used a repeated-measures design to explore preterm infants' biobehavioral responses to 24-hour neonatal caregiving and positioning, and the factors associated with changes in their biobehavioral responses. Thirty preterm infants (gestational age 27.6-36.1 weeks) were observed for 3 days to record biobehavioral responses. Infants' disorganized behaviors increased as caregiving intrusiveness and supine positioning increased. Social interactions did not lead to increases in infants' disorganized behaviors, but to increased regulatory behaviors. Non-nutritive sucking (NNS), and prone positioning reduced occurrences of infant disorganized behaviors. Routine caregiving increased instability of oxygen saturation, but lateral and prone positioning improved physiological stability. Clinicians can appropriately provide NNS, positioning, and social interactions to promote biobehavioral stability.

Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis.

BACKGROUND: The implication of sepsis-induced cardiomyopathy (SIC) to prognosis is controversial, and its association with mortality at different stages remains unclear. We conducted a systematic review and meta-analysis to understand the association between SIC and mortality in septic patients. METHODS: We searched and appraised observational studies regarding the mortality related to SIC among septic patients in PubMed and Embase from inception until 8 July 2021. Outcomes comprised in-hospital and 1-month mortality. We adopted the random-effects model to examine the mortality risk ratio in patients with and without SIC. Meta-regression, subgroup, and sensitivity analyses were applied to examine the outcome's heterogeneity. RESULTS: Our results, including 20 studies and 4,410 septic patients, demonstrated that SIC was non-statistically associated with increased in-hospital mortality, compared to non-SIC (RR 1.28, [0.96-1.71]; p = 0.09), but the association was statistically significant in patients with the hospital stay lengths longer than 10 days (RR 1.40, [1.02-1.93]; p = 0.04). Besides, SIC was significantly associated with a higher risk of 1-month mortality (RR 1.47, [1.17-1.86]; p < 0.01). Among SIC patients, right ventricular dysfunction was significantly associated with increased 1-month mortality (RR 1.72, [1.27-2.34]; p < 0.01), while left ventricular dysfunction was not (RR 1.33, [0.87-2.02]; p = 0.18). CONCLUSIONS: With higher in-hospital mortality in those hospitalized longer than 10 days and 1-month mortality, our findings imply that SIC might continue influencing the host's system even after recovery from cardiomyopathy. Besides, right ventricular dysfunction might play a crucial role in SIC-related mortality, and timely biventricular assessment is vital in managing septic patients.

Clinical efficacy of SGLT2 inhibitors with different SGLT1/SGLT2 selectivity in cardiovascular outcomes among patients with and without heart failure: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Some sodium-glucose co-transporter-2 (SGLT2) inhibitors showed benefits on heart failure (HF), but different SGLT2/SGLT1 selectivity might influence the treatment effect. This study aimed to meta-analyze the treatment effects of SGLT2 inhibitors and the diversity of receptor selectivity for patients with and without HF. METHODS: Randomized controlled trials were searched in PubMed, Embase, Cochrane databases and ClinicalTrials.gov registry from inception to October 2020. The interest outcomes were analyzed with random-effects models and presented with a risk ratio (RR) and 95% confidence interval (CI). Subgroup analyses examined the treatment effects among SGLT2 inhibitors with different SGLT2/SGLT1 selectivity. RESULTS: The final analyses included 10 trials and 52,607 patients. The RR of total cardiovascular (CV) death or hospitalization for HF (HHF) between SGLT2 inhibitors and placebo was 0.79 (95% CI 0.74-0.84, I2 = 31%). With SGLT2 inhibitors, HF patients had reduced mortality risks (RR 0.89, 95% CI 0.80-0.99, I2 = 0), and non-HF patients had lower risks of major adverse CV events (RR 0.92, 95% CI 0.85-0.99, I2 = 0). The risk reduction of HHF was consistent in groups of HF (RR 0.72, 95% CI 0.64-0.80, I2 = 8%) and non-HF (RR 0.74, 95% CI 0.61-0.89, I2 = 0), but the effect of the low SGLT2/SGLT1 selectivity inhibitor was insignificant in non-HF patients. CONCLUSION: The efficacy of SGLT2 inhibitors on risk reduction of total CV death or HHF is consistent with the previous studies. The regimen is beneficial for reducing mortality in patients with HF and major adverse CV events in those without HF. Different SGLT2/SGLT1 selectivity may differ in the treatment effects in patients with and without HF.

Topical antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: a systematic review and meta-analysis.

BACKGROUND: Topical antibiotics are widely prescribed as prophylaxis for surgical site infection (SSI). Despite giving high drug concentrations at local wound sites, their efficacy remains controversial. This study is a systematic review and meta-analysis designed to compare the efficacy and safety of topical antibiotics with non-antibiotic agents in preventing SSI. METHODS: Randomized controlled trials (RCTs) comparing topical antibiotics in patients with clean and clean-contaminated postsurgical wounds were included. Relevant trials published before 30 September 2020, were searched in the PubMed, Embase, and Cochrane databases, without language restrictions. The primary outcome was the incidence of SSIs, presented as the event rate. The secondary outcome was the incidence of contact dermatitis (safety outcome). Data were synthesized using the random-effects model, with the results expressed as risk ratio (RR) with 95 per cent confidence intervals (c.i.). RESULTS: Thirteen RCTs were included. The incidence of SSIs and contact dermatitis showed no significant difference between topical antibiotics and non-antibiotic agents (RR 0.89, 95 per cent c.i. 0.59 to 1.32 (P = 0.56, I2 = 48 per cent); and RR 2.79, 95 per cent c.i. 0.51 to 15.19 (P = 0.24, I2 = 0 per cent), respectively). In the subgroup analyses, a reduction in SSIs was also not observed in dermatological (RR 0.77, 95 per cent c.i. 0.39 to 1.55; P = 0.46, I2 = 65 per cent), ocular (RR 0.08, 95 per cent c.i. 0.00 to 1.52; P = 0.09), spinal (RR 1.34, 95 per cent c.i. 0.65 to 2.77; P = 0.43, I2 = 0 per cent), orthopaedic (RR 0.69, 95 per cent c.i. 0.37 to 1.29; P = 0.25, I2 = 0 per cent), or cardiothoracic surgeries (RR 1.60, 95 per cent c.i. 0.79 to 3.25; P = 0.19). CONCLUSION: Given the current evidence, the routine application of topical antibiotics to surgical wounds did not reduce the incidence of SSI. Further trials are needed to assess their effectiveness in high-risk surgeries or in selected patient groups.

Cost-Effectiveness Evaluation of Add-on Empagliflozin in Patients With Heart Failure and a Reduced Ejection Fraction From the Healthcare System's Perspective in the Asia-Pacific Region.

Background: EMPEROR-Reduced trial provides promising evidence on the efficacy of empagliflozin adding to the standard treatment in patients with heart failure and reduced ejection fraction (HFrEF). This study aimed to investigate the cost-effectiveness of add-on empagliflozin vs. standard therapy alone in HFrEF from the perspective of the Asia-Pacific healthcare systems. Methods: A Markov model was constructed to simulate HFrEF patients and to project the lifetime direct medical costs and quality-adjusted life years (QALY) of both therapies. Transitional probabilities were derived from the EMPEROR-Reduced trial. Country-specific costs and utilities were extracted from published resources. Incremental cost-effectiveness ratio (ICER) against willingness to pay (WTP) threshold was used to examine the cost-effectiveness. A series of sensitivity analyses was performed to ensure the robustness of the results. Results: The ICERs of add-on empagliflozin vs. standard therapy alone in HFrEF were US$20,508, US$24,046, US$8,846, US$53,791, US$21,543, and US$20,982 per QALY gained in Taiwan, Japan, South Korea, Singapore, Thailand, and Australia, respectively. Across these countries, the probabilities of being cost-effective for using add-on empagliflozin under the WTP threshold of 3-times country-specific gross domestic product per capita were 93.7% in Taiwan, 95.6% in Japan, 96.3% in South Korea, 94.2% Singapore, 51.9% in Thailand, and 95.9% in Australia. The probabilities were reduced when shortening the time horizon, assuming the same cardiovascular mortality for both treatments, and setting lower WTP thresholds. Conclusion: Adding empagliflozin to HFrEF treatment is expected to be a cost-effective option among the Asia-Pacific countries. The cost-effectiveness is influenced by the WTP thresholds of different countries.

Small-molecule arone protects from neuroinflammation in LPS-activated microglia BV-2 cells by targeting histone-remodeling chaperone ASF1a.

Histone post-translational modifications (PTMs) have been shown to be highly associated with inflammation response, suggesting a therapeutic significance of pharmacologically editing histone PTMs. Currently reported anti-inflammation small-molecules mainly target histone PTMs writers or erasers for methylation, phosphorylation, and acetylation. Although histone chaperones also appear to be involved in inflammation signaling cascades, whether small-molecules could target histone chaperones to show anti-inflammation effects has still been rarely discovered. In this study, natural product artone was found to show obvious inhibitory effects on microglia-mediated neuroinflammation by directly targeting ASF1a, which is a histone-remodeling chaperone. Mechanism study revealed that artone modulated histone H3 PTMs profile by down-regulating acetylation and trimethylation modification levels at sites K4, K9, K18 and K27. Artone-dependent regulations on PTMs further caused an effective inhibition on transcription factor NF-κB assembling to promoters of pro-inflammatory cytokine genes including Tnf-α, Il-6 and Rgs3, indicating a distinctive anti-neuroinflammation mechanism. Collectively, we reported artone as the first small-molecule targeting histone-remodeling chaperone ASF1a for anti-neuroinflammation. Moreover, these findings broaden our knowledge of histone chaperone as a druggable target protein for neuroinflammation inhibition, and open a new avenue to novel therapy strategy for inflammation-associated neurological disorders.

Cystatin C-Based Renal Function in Predicting the Long-Term Outcomes of Chronic Total Occlusion After Percutaneous Coronary Intervention.

Renal function estimated by various biomarkers predicting for adverse cardiovascular events has not been well-identified in received percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), the advanced stages of atherosclerosis. We aim to determine whether the serum cystatin C-based-estimated glomerular filtration rate (eGFR) can have an improved predictive value in patients with CTO lesions undergoing PCI as compared with multiple creatinine-based estimates of kidney function. Six hundred and seventy-one patients received CTO PCI were retrospectively included in the study. The eGFR was calculated by modification of diet in renal disease equation for Chinese (cMDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations at baseline, respectively. Then, the cohort was categorized into three groups according to standard KDIGO kidney stages based on eGFR. The primary endpoint was all-cause mortality, and the secondary endpoint was cardiac death. Strikingly, cystatin C-based eGFR showed a better performance with the greater area being under the receiver operating characteristic (ROC) curve (0.73 for all-cause mortality and 0.73 for cardiac death, separately) and a better assessment for survival free from adverse event across renal levels among four eGFR equations. Compared with eGFR calculated by other formulas, serum cystatin C-based eGFR showed the highest prognostic value for both all-cause mortality (adjusted HR 3.6, 95% CI 1.6-8.1, P = 0.002) and cardiac death (adjusted HR 2.9, 95% CI 1.0-8.1, P = 0.028). Moreover, cystatin C-based eGFR significantly improved the risk reclassification of event with a high value of net reclassification improvement and integrated discrimination improvement. This study may prove that cystatin C-based eGFR is a better predictor of both all-cause mortality and cardiac death than other equations in populations with CTO undergoing PCI.

[Rethinking oxygen therapy for premature infants in terms of oxidative stress].

Oxygen therapy is one of the most common interventions in the care of premature infants in the neonatal intensive care unit (NICU). Premature infants are at risk of oxidant injury due to inadequate anti-oxidant defenses. Common complications of premature infants such as retinopathy, chronic lung disease, intraventricular hemorrhaging, and periventricular leukomalacia may also be associated with secondary oxidant injuries. This article explores relationships between oxygen and complications linked to premature delivery. It also outlines correct concepts and practices of oxygen therapy for NICU nurses to reduce the oxygen-related complications associated with premature births and promote the health and life quality of premature infants.

Comparative effectiveness of antifungal agents in patients with hematopoietic stem cell transplantation: a systematic review and network meta-analysis.

Purpose: The aim of this study was to use a network meta-analysis to evaluate the relative efficacy of various agents at preventing invasive fungal infections (IFIs). In this way, suitable prophylactic regimens may be selected for patients with hematopoietic stem cell transplantation (HSCT). Methods: We conducted a systematic review of randomized controlled trials comparing the prophylactic effects of two antifungal agents or an antifungal agent and a placebo administered to patients with HSCT. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry. Results: Sixteen two-arm studies were identified. Compared with placebo, all six antifungal agents (amphotericin B, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole) presented with greater efficacy at controlling proven IFIs. OR ranged from 0.08 to 0.29. Voriconazole (surface under the cumulative ranking curve [SUCRA]=71.6%), posaconazole (SUCRA=68.9%), and itraconazole (SUCRA=64.7%) were the three top-ranking drugs for preventing proven IFIs. Itraconazole ranked highest (SUCRA=83.1%) and had the greatest efficacy at preventing invasive candidiasis. Posaconazole and micafungin were the two top-ranking drugs (SUCRA=81.3% and 78.4%, respectively) at preventing invasive aspergillosis. Micafungin and voriconazole were the drugs of choice because they lowered mortality more than the other agents (SUCRA=74.6% and 61.1%, respectively). Conclusion: This study is the first network meta-analysis to explore the prophylactic effects of antifungal agents in patients with HSCT. Voriconazole was the best choice for the prevention of proven IFIs in HSCT patients.

Tumor-like cerebral perivasculitis in a pediatric patient with systemic lupus erythematosus.

Nervous system manifestations are present in up to 70% of patients with systemic lupus erythematosus (SLE). The spectrum of clinical symptoms varies widely, from severe, life-threatening symptoms at presentation, such as transverse myelitis, to symptoms of more subtle and subclinical abnormalities of neurocognitive function. We report the case of a 14-year-old patient with SLE and lupus nephritis under regular steroid therapy, who had a sudden onset of consciousness change. Brain magnetic resonance imaging showed a huge mass lesion. After surgical decompression and corticosteroid pulse therapy, the patient's neurologic symptoms improved dramatically. Brain biopsy revealed perivasculitis of the brain with marked perivascular infiltration of eosinophils, macrophages, and neutrophils. Microhemorrhage was also evident. The patient recovered without obvious neurologic sequelae.

Determinants of airleak flow during humming V high-frequency oscillatory ventilation in an open-compartment ex-vivo model of airleak.

High-frequency oscillatory ventilation (HFOV) using small tidal volumes and maintaining sufficient end-expiratory lung volume may be beneficial in the treatment of airleak. However, few published guidelines exist to advise clinicians on appropriate ventilator settings in this clinical scenario. The present experiment aimed to determine the effect of frequency, stroke volume (SV) and mean airway pressure (MAP) on airleak from an isolated lung model ventilated with a Humming V HFOV. We performed a crossover non-randomized experiment using the repeated measurement method to test the hypothesis that MAP is the major determinate for airleak. The lungs of 13 healthy juvenile New Zealand white rabbits were isolated and ventilated with high peak pressure to create airleak. The dataset obtained was analyzed using the generalized estimating equation method. We found that airleak flow did not change as frequency was raised from 13 to 17 Hz (P = 0.463) with MAP and SV kept constant. SV was positively correlated to the amount of change in airleak (P < 0.01, coefficients +/- SEM = 1.2 +/- 0.1 ml/min/ml). Leakage flow increased significantly from 275 +/- 168 ml/min to 1,721 +/- 552 ml/min as MAP was increased from 5 cm H(2)O to 30 cm H(2)O (P < 0.001, coefficients +/- SEM = 56.1 +/- 3.0 ml/min/cm H(2)O) while inspiratory flow increased less and amplitude pressure remained about the same. We concluded that MAP (lung volume) was the main independent factor for airleak, whilst SV (tidal volume) exerted a lesser effect. Within the operational range of the Humming V, frequency did not affect airleak.

Breastfeeding-associated neonatal hypernatremic dehydration in a medical center: a clinical investigation.

BACKGROUND: Hypernatremic dehydration amongst exclusively breastfed neonates due to inadequate breastfeeding or underfeeding is a potentially devastating condition. We investigated the epidemiological and clinic features of hypernatremic dehydration. METHODS: We retrospectively reviewed the medical records of neonates that were less than 28 days of age, weighing > or =2000 g with gestational age of 36 weeks born between January 2002 and December 2005, who had meet the criteria of hypernatremic dehydration, including (1) exclusively breastfed; (2) loss of weight 12% or more from birth weight; and (3) serum sodium concentration of at least 150 mmol/L at presentation, that had been subsequently admitted to our institution. RESULTS: Totally nine cases were found during this four-year period, an incidence of 2.3 per 1000 live births. Involved infants' age at presentation ranged from 3 days to 14 days (mean t Standard Deviation = 7 +/- [3.8]); five presented symptoms or signs within the first week of life. Study-involved infants featured a birth-weight loss ranging from 12% to 29% (mean +/- [SD] = 17.0 +/- [5.9]), and also hypernatremia (mean +/- [SD] = 153.5 +/- [3.2] mEq/L ). Sodium concentration of breast milk ranged from 15 mEq/L to 54 mEq/L (mean +/- [SD]= 36.0 +/- [14.32]). Subsequently, all were supplemented with breast milk or, alternatively, formula. None of the study-involved neonates suffered subsequent complications or a relapse of their condition. CONCLUSIONS: Neonatal hypernatremic dehydration due to inadequate breastfeeding or underfeeding would appear to be a rather common problem. In order to avoid serious morbidity and mortality, all breastfed infants should receive regular follow-up by health-care worker. Furthermore, we advocate that all mothers should be taught the skills of breastfeeding, and warning signs of breastfeeding failure and hypernatremia, accompanied with the monitoring of the weight of infants until growth commences, in order to reduce the likelihood of this condition arising, especially for first-time mothers.

Bubble CPAP elicits decreases in exhaled nitric oxide in rabbits.

Endogenous nitric oxide (NO) has a key role in pulmonary function, and the application of positive end-expiratory pressure (PEEP) can increase exhaled NO (FE(NO)) in anesthetized animals and isolated lungs. The influence of continuous positive airway pressure (CPAP), which is similar to PEEP, on the FE(NO) level has not been investigated in humans or in animals. The present study was undertaken to determine whether and how the application of CPAP in spontaneously breathing rabbits influences levels of FE(NO). We performed a randomized crossover study to measure FE(NO) levels in 12 ketamine-anesthetized rabbits that were intubated via tracheostomy for bubble CPAP (B-CPAP) or ventilator-derived CPAP (V-CPAP), which are two of the most popular CPAP modes and which have different pressure sources. The baseline FE(NO) level was 23.8 +/- 2.6 ppb, which increased to 27.1 +/- 2.9 ppb (P < 0.001) during V-CPAP and decreased to 18.6 +/- 2.2 ppb (P < 0.001) during B-CPAP. We used one high-frequency oscillatory ventilator to repeat the experiment, in which the conventional ventilation function of the ventilator was used in the baseline and V-CPAP periods, and the high-frequency function was used to replace B-CPAP. Changes in FE(NO) were similar to our previous findings. This study demonstrated that the application of CPAP did influence levels of FE(NO). We speculate that the decrease in FE(NO) during B-CPAP may have been related to the bubble-associated high-frequency oscillation.

[Effect of captopril on pulmonary vascular remodeling induced by left-to-right shunt in rats].

OBJECTIVE: To investigate the therapeutic effect of angiotensin converting enzyme inhibitor on pulmonary vascular remodeling of pulmonary hypertension induced by high pulmonary blood flow. METHODS: An arterial-venous shunt was surgically created between abdominal aorta and inferior vena cava in the rat of all groups except the control group. Captopril was given to all of the rats. Six weeks after the operation,pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP) and right ventricular systolic pressure (RVSP) were measured. The rats' hearts were weighted to calculate the ratio of right ventricle mass to left ventricle plus septum mass. Immunohistochemical stains were used to identify alpha-actin and PCNA distribution in pulmonary arteries. Morphometric parameters (vascular wall thickness and muscularization) were used to assess the remodeling of small pulmonary arteries. RESULTS: The PASP, PADP, RVSP, RV/(LV+S), RV/BW, and (LV + S)/BW of the rats in the shunt group were significantly greater than those of the control group. Muscularization of small pulmonary arteries and pulmonary artery medial hypertrophy (wall thickness) were evident in the shunt group. The proliferation index of the smooth muscle cells of the small and medium-sized pulmonary arteries was significantly higher and the alpha-actin IOD was significantly lower in the rats of the shunt group than those of the control. By contrast, the levels of PASP, PADP, RVSP, RV/(LV+S), RV/BW, (LV+ S)/BW, and muscularization were lower in the rats of captopril group than those of the control. CONCLUSIONS: Captopril slows down pulmonary hypertension and remodeling development. Captopril and losartan may have preventive and therapeutic effects on pulmonary hypertension induced by congenital left-to-right shunts.