Daily Ards Research Analysis

We explored pharmacotherapeutic response patterns of lipopolysaccharides (LPS)-induced pneumonia and sepsis as direct and indirect acute lung injury (ALI), and efficacy of a combined surfactant (S) and inhaled nitric oxide (iNO), simulating critical care, in rabbits of post-neonatal infancy. Anaesthetized 7-day-old healthy rabbits were injected intratracheally (IT) or intravenously (IV) with LPS (15-20-25 mg/kg, L) or saline as a control (C), and subjected to initial 2-hour mechanical ventilation (MV) with standardized tidal volume to induce ALI. They were then treated with S (200 mg/kg) and iNO (10 ppm, N), or not, thereby allocating to 6 groups (ITC, ITL, ITLSN, IVC, IVL, IVLSN) for another 8 h. Survival time/rate (ST), and variables as biomarkers in lung physiology, histopathology, biochemistry, and pathophysiology were measured. The survival was LPS-route, but not dosing, dependent. Compared to the IVL, ITL had relatively higher ST, lung injury score (LIS), lower intrapulmonary phospholipid pools, mRNA expressions in surfactant proteins (SPs) and pulmonary vascular endothelial cell injury (VEI)-related variables. ITLSN had higher phospholipid pools but no improvement in ST, lung mechanics, LIS or mRNA expression of SPs, proinflammatory mediators and VEI-related variables. IVLSN had improved lung mechanics, LIS, phospholipid pools, and SP-A mRNA expression, but worse ST, metabolic acidosis, higher interleukin mRNA expression in the lungs, liver and kidney, suspected as sepsis-associated multiorgan involvement. Using the infant rabbit LPS-ALI model, we characterized the survival as LPS-route dependent, the lung impairment and response pattern in surfactant and iNO treatment ineffectiveness/failure, as pharmacotherapeutic response patterns, with causal implication pertinent to the underlying pathophysiology of experimental pediatric ARDS.

BACKGROUND: Tropical coinfections (CI) are the simultaneous occurrence of two or more vector-borne diseases in a single host. The prevalence of such illnesses is not uncommon among tropical and subtropical regions such as India; however, these CIs have not been systematically studied prospectively. Mixed infections can prove potentially detrimental if underdiagnosed or undertreated. We undertook this study to estimate the prevalence and compare the clinical profile, laboratory characteristics, and various outcomes among the patients with tropical CI who presented with acute undifferentiated febrile illness (AUFI). MATERIALS AND METHODS: A prospective, observational study was conducted on adult patients hospitalized with tropical CIs. As per the clinical suspicion, a panel of tests for dengue fever (D), malaria (M), scrub typhus (S), leptospirosis (L), chikungunya (C), and brucella (B) was carried out. Statistical analysis was done using standard methods. RESULTS: The mean age of the population was 39.4 ± 17.3 years. Among 986 patients presenting with AUFI, 8.1% of the patients had CIs. Of these CIs, 95% had dual infections, and 5% had CIs with three tropical pathogens. We observed 17 diverse tropical CI combinations; four predominant being D + L, D + S, D + C, and S + L with a prevalence of 26.2, 25, 15, and 13.8%, respectively. 16.25% of the patients with tropical CIs died, mostly those suffering from D + S and D + L. Coinfection with D + S had predominant acute kidney injury (AKI), whereas acute transaminitis was highest in the D + L category. Acute respiratory distress syndrome (ARDS) was clinically significant in S + L, and multiorgan dysfunction was highest in the D + S combination. Using logistic regression, AKI, hepatitis, ARDS, shock, gastrointestinal bleeding, and myocarditis were independent risk factors for mortality. CONCLUSION: Our study identified 17 different combinations of CIs. Four groups, i.e., D + L, D + S, D + C, and S + L-accounted for 80% of CIs. Despite significant organ involvement in certain CI combinations, we conclude that a clinical bedside differentiation of tropical CIs from monomicrobial infections is often difficult. Hence, optimal treatment for a possible CI may well be commenced empirically and early, bearing in mind an 8% probability of a concurrent tropical coinfection.

High-dose intravenous vitamin C (IVC) achieves plasma concentrations that are not attainable by oral administration and has been investigated as an adjunct in sepsis, oncology, and symptom management. To synthesize the evidence regarding the clinical benefits and risks of high-dose IVC, as well as the potential advantages of on-site infusion, a PRISMA-informed search of PubMed/PMC, Scopus, and Web of Science (2010-2025) was conducted, prioritizing randomized controlled trials, systematic reviews, and high-quality observational studies. Pharmacokinetic and mechanistic studies of IVC support plausible physiologic benefits through antioxidant effects, catecholamine biosynthesis, and immune modulation, with recent evidence showing down regulation of pro-inflammatory STAT1/PD-L1 pathways in experimental sepsis. Oncology phase I and II studies demonstrate safety and quality-of-life improvements; a randomized phase II pancreatic trial reported a promising survival benefit when combined with chemotherapy. Some of the major risks include oxalate nephropathy and hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, especially with very large or repeated doses, suggesting pre-screening to avoid these risks. Furthermore, the literature on home infusion and IV therapies is limited; however, the expanding home infusion infrastructure offers an avenue for monitored IVC delivery. In conclusion, evidence does not support routine use of high-dose IVC in sepsis, and its role in oncology remains supportive and exploratory, with potential risks requiring caution. Furthermore, interest in home-based infusion services is increasing in several healthcare systems, although clinical outcome data specific to high-dose IVC in these settings remain limited.