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Fostering pulmonary research for managing pulmonary threat requires a potential alternative approach mimicking the in vivo complexities. This review expounds on lung-on-chip microfluidic simulator devices to foster pulmonary drug discovery and personalized medicine.

Cardiovascular disease (CVD), a broad-spectrum term comprising coronary artery disease, stroke, hypertension, and heart failure, presents as one of the most significant strains on global healthcare systems. Coronary artery disease, caused by atherosclerosis, has various modifiable risk factors such as dietary changes and exercise. Since these risk factors are found to be linked to oxidative stress and inflammations, the dietary supplementation with vitamins’ role in treating and preventing the diseases has been of much debate. With various vitamins having anti-inflammatory and antioxidative properties, studies have explored their correlation with cardiovascular health. Therefore, this narrative review explores and evaluates the benefits and risks of all vitamin supplementations in patients with CVD and provides future recommendations.

ImportanceThere is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).ObjectiveTo determine whether the use of steroids within 2 days of admission for non–MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.Design, Setting, and ParticipantsThis cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non–MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.ExposureAdministration of steroids within 2 days of admission.Main Outcomes and MeasuresLength of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.ResultsA total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score–matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.Conclusions and RelevanceSteroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Abstract Introduction Late‐onset Alzheimer's disease (LOAD) is a complex neurodegenerative disease characterized by multiple progressive stages, glucose metabolic dysregulation, Alzheimer's disease (AD) pathology, and inexorable cognitive decline. Discovery of metabolic profiles unique to sex, apolipoprotein E ( APOE ) genotype, and stage of disease progression could provide critical insights for personalized LOAD medicine. Methods Sex‐ and APOE ‐specific metabolic networks were constructed based on changes in 127 metabolites of 656 serum samples from the Alzheimer's Disease Neuroimaging Initiative cohort. Results Application of an advanced analytical platform identified metabolic drivers and signatures clustered with sex and/or APOE ɛ4, establishing patient‐specific biomarkers predictive of disease state that significantly associated with cognitive function. Presence of the APOE ɛ4 shifts metabolic signatures to a phosphatidylcholine‐focused profile overriding sex‐specific differences in serum metabolites of AD patients. Discussion These findings provide an initial but critical step in developing a diagnostic platform for personalized medicine by integrating metabolomic profiling and cognitive assessments to identify targeted precision therapeutics for AD patient subgroups through computational network modeling.

Objective: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model. Summary of Background Data: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation. Methods: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), regulated hepatic reperfusion (RHR)-N, and RHR-S (n = 5 each). The biochemical, metabolic, and transcriptomic profiles, as well as mitochondrial function were analyzed. Results: Compared to the other groups, RHR-S treated group showed significantly lower post-reperfusion aspartate aminotransferase levels in the reperfusion effluent and histologic findings of hepatocyte viability and lesser degree of congestion and necrosis. RHR-S resulted in a significantly higher mitochondrial respiratory control index and calcium retention capacity. Transcriptomic profile analysis showed that treatment with RHR-S activated cell survival and viability, cellular homeostasis as well as other biological functions involved in tissue repair such as cytoskeleton or cytoplasm organization, cell migration, transcription, and microtubule dynamics. Furthermore, RHR-S inhibited organismal death, morbidity and mortality, necrosis, and apoptosis. Conclusion: Subnormothermic RHR mitigates IRI and preserves hepatic mitochondrial function after warm and cold hepatic ischemia. This organ resuscitative therapy may also trigger the activation of protective genes against IRI. Sub- normothermic RHR has potential applicability to clinical liver transplantation.

INTRODUCTION: Functional Dyspepsia (FD) is a common functional GI disorder in the upper abdomen (above the navel). The estimated prevalence is 15-30% worldwide. There are currently no FDA-approved medications for the treatment of FD. Proton pump inhibitors (PPIs) are commonly prescribed off-label. However, long-term use of these drugs has been associated with serious health concerns. Prokinetic agents are also often used off-label. However, many are associated with significant side effects (e.g. metoclopramide). A safe, effective, and readily available treatment option for FD is greatly needed. This study describes an important 24-month post-marketing point on an option for FD that has already demonstrated good efficacy and low side effects in RCTs. These RCTs have demonstrated that the combination of caraway oil and peppermint oil improves FD symptoms. Caraway oil plus L-menthol (the major component of peppermint oil) with site-specific targeting (COLM-SST) is a novel delivery system of triple-coated, solid-state microspheres designed to target the duodenum, the main center of disturbance in FD. This study was conducted to report on the overall safety profile of COLM-SST and to determine if any unexpected pattern of side effects emerged. METHODS: A call-in number for reporting adverse events (AEs) was provided on all boxes containing COLM-SST. An independent call center with pharmacovigilance-trained health care personnel, in accordance with the FDA and global regulatory guidelines on properly reporting AEs, was retained to receive and record customer AEs. The AEs for this study were collected and processed from July 8, 2016 to July 8, 2018. RESULTS: An estimated 558,345 individual patients used COLM-SST during the surveillance. An analysis of the data showed that there were no serious AEs reported. Additionally, the self-reporting rate of non-serious AEs was low, with only 148 events received (from 127 patients), a 0.023% event rate for COLM-SST. The top reported, non-serious AEs were abdominal pain/discomfort/distension (18; 0.0032%), which were consistent with the pattern of commonly reported symptoms of FD, and headache (7; 0.0013%). CONCLUSION: 24 months of monitoring in-market, real-world use of caraway oil and L-menthol with site-specific targeting, for the treatment of FD demonstrates an extremely low rate of self-reported AEs. These data, combined with earlier RCT data, indicates that COLM-SST is a safe and effective therapy for FD, and is a viable alternative to PPIs and prokinetics.