Bronchopulmonary dysplasia with focus on early prediction and treatment: a narrative review

Background and Objective: Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity and mortality in very preterm infants though early non-invasive ventilation and surfactant treatment and other neonatal therapies have improved the outcome. Therefore, it is necessary to find effective supplemental methods for prediction of BPD. Better understanding of the etiology and molecular mechanisms involved in the pathogenesis of BPD is necessary for development of new effective early treatments. It is generally accepted that BPD is a multifactorial disease often associated with intrauterine infections and placental perfusion disorders. Methods: Recently a new method to predict BPD at birth using artificial intelligence (AI) has been developed. This new method improves the likelihood of developing effective early treatments for BPD. The method combines information on early surfactant treatment, birth weight and gestational age (GA) with analysis of the mid-infrared spectrum of the molecules in gastric aspirate which are produced in the newborn’s lungs. The described methods for early treatment of BPD in this review among others covers inositol, retinol, super oxide dismutase, Clara cell 10 protein, corticosteroids, azithromycin, macrolide and stem cell therapy besides general treatments as nasal continuous positive airway pressure (NCPAP), surfactant, caffeine, oxygen saturation targeting and nutrition. The literature search was performed systemically online via the databases PubMed and Medline between January 1, 2011 and December 31, 2022. Key Content and Findings: A method to predict BPD immediately after birth is now available allowing possibility to develop effective early treatments of BPD. Conclusions: The present review focuses on early prediction and the existing pharmacologic interventions highlighting the potential to improve the outcome of infants with BPD

Validação conceitual das características definidoras de diagnósticos de enfermagem respiratórios em neonatos

OBJECTIVE:To develop and validate conceptual and operational definitions for the defining characteristics of the respiratory nursing diagnoses, ineffective breathing pattern, impaired gas exchange and impaired spontaneous ventilation, in newborns.METHODS:This was a methodological study of conceptual validation of the defining characteristics of three respiratory nursing diagnoses, by consensus analysis of a committee of five specialist nurses, and then a group of five non-nursing professionals, using the Delphi technique.RESULTS:After two rounds of evaluation, consensus was obtained that was equal to or greater than 80% on all of the definitions, which were then considered validated.CONCLUSION:The definitions developed for the defining characteristics of three nursing diagnoses were validated with a high level of consensus.OBJETIVO:Elaborar e validar definições conceituais e operacionais para as características definidoras dos diagnósticos de enfermagem respiratórios, Padrão Respiratório Ineficaz, Troca de Gases Prejudicada e Ventilação Espontânea Prejudicada em recém-nascidos.MÉTODOS:Estudo metodológico, de validação conceitual das características definidoras dos três diagnósticos de enfermagem respiratórios por meio da análise de consenso de um comitê de cinco enfermeiras especialistas e de cinco profissionais não enfermeiros, utilizando a técnica Delphi.RESULTADOS:Após duas rodadas de avaliação, obteve-se consenso igual ou superior a 80% na totalidade das definições, sendo consideradas validadas.CONCLUSÃO:As definições elaboradas para as características definidoras dos três diagnósticos de enfermagem foram validadas com elevado grau de consenso.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de EnfermagemUNIFESP, EPESciEL

Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

BACKGROUND: When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. AIM: The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. METHODS: We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. RESULTS: 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. CONCLUSION: 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC

Measurement of the Absolute Magnitude and Time Courses of Mitochondrial Membrane Potential in Primary and Clonal Pancreatic Beta-Cells

The aim of this study was to simplify, improve and validate quantitative measurement of the mitochondrial membrane potential (ΔψM) in pancreatic β-cells. This built on our previously introduced calculation of the absolute magnitude of ΔψM in intact cells, using time-lapse imaging of the non-quench mode fluorescence of tetramethylrhodamine methyl ester and a bis-oxonol plasma membrane potential (ΔψP) indicator. ΔψM is a central mediator of glucose-stimulated insulin secretion in pancreatic β-cells. ΔψM is at the crossroads of cellular energy production and demand, therefore precise assay of its magnitude is a valuable tool to study how these processes interplay in insulin secretion. Dispersed islet cell cultures allowed cell type-specific, single-cell observations of cell-to-cell heterogeneity of ΔψM and ΔψP. Glucose addition caused hyperpolarization of ΔψM and depolarization of ΔψP. The hyperpolarization was a monophasic step increase, even in cells where the ΔψP depolarization was biphasic. The biphasic response of ΔψP was associated with a larger hyperpolarization of ΔψM than the monophasic response. Analysis of the relationships between ΔψP and ΔψM revealed that primary dispersed β-cells responded to glucose heterogeneously, driven by variable activation of energy metabolism. Sensitivity analysis of the calibration was consistent with β-cells having substantial cell-to-cell variations in amounts of mitochondria, and this was predicted not to impair the accuracy of determinations of relative changes in ΔψM and ΔψP. Finally, we demonstrate a significant problem with using an alternative ΔψM probe, rhodamine 123. In glucose-stimulated and oligomycin-inhibited β-cells the principles of the rhodamine 123 assay were breached, resulting in misleading conclusion

Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. The VANISH Randomized Clinical Trial

IMPORTANCE: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. OBJECTIVE: To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. INTERVENTIONS: Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). MAIN OUTCOMES AND MEASURES: The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. RESULTS: A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). CONCLUSIONS AND RELEVANCE: Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN 20769191

Development of Bacterial Biofilms on Artificial Corals in Comparison to Surface-Associated Microbes of Hard Corals

Numerous studies have demonstrated the differences in bacterial communities associated with corals versus those in their surrounding environment. However, these environmental samples often represent vastly different microbial micro-environments with few studies having looked at the settlement and growth of bacteria on surfaces similar to corals. As a result, it is difficult to determine which bacteria are associated specifically with coral tissue surfaces. In this study, early stages of passive settlement from the water column to artificial coral surfaces (formation of a biofilm) were assessed. Changes in bacterial diversity (16S rRNA gene), were studied on artificially created resin nubbins that were modelled from the skeleton of the reef building coral Acropora muricata. These models were dip-coated in sterile agar, mounted in situ on the reef and followed over time to monitor bacterial community succession. The bacterial community forming the biofilms remained significantly different (R = 0.864 p<0.05) from that of the water column and from the surface mucus layer (SML) of the coral at all times from 30 min to 96 h. The water column was dominated by members of the α-proteobacteria, the developed community on the biofilms dominated by γ-proteobacteria, whereas that within the SML was composed of a more diverse array of groups. Bacterial communities present within the SML do not appear to arise from passive settlement from the water column, but instead appear to have become established through a selection process. This selection process was shown to be dependent on some aspects of the physico-chemical structure of the settlement surface, since agar-coated slides showed distinct communities to coral-shaped surfaces. However, no significant differences were found between different surface coatings, including plain agar and agar enhanced with coral mucus exudates. Therefore future work should consider physico-chemical surface properties as factors governing change in microbial diversity

A Mouse Stromal Response to Tumor Invasion Predicts Prostate and Breast Cancer Patient Survival

Primary and metastatic tumor growth induces host tissue responses that are believed to support tumor progression. Understanding the molecular changes within the tumor microenvironment during tumor progression may therefore be relevant not only for discovering potential therapeutic targets, but also for identifying putative molecular signatures that may improve tumor classification and predict clinical outcome. To selectively address stromal gene expression changes during cancer progression, we performed cDNA microarray analysis of laser-microdissected stromal cells derived from prostate intraepithelial neoplasia (PIN) and invasive cancer in a multistage model of prostate carcinogenesis. Human orthologs of genes identified in the stromal reaction to tumor progression in this mouse model were observed to be expressed in several human cancers, and to cluster prostate and breast cancer patients into groups with statistically different clinical outcomes. Univariate Cox analysis showed that overexpression of these genes is associated with shorter survival and recurrence-free periods. Taken together, our observations provide evidence that the expression signature of the stromal response to tumor invasion in a mouse tumor model can be used to probe human cancer, and to provide a powerful prognostic indicator for some of the most frequent human malignancies

Spatial Scales of Bacterial Diversity in Cold-Water Coral Reef Ecosystems

Background: Cold-water coral reef ecosystems are recognized as biodiversity hotspots in the deep sea, but insights into their associated bacterial communities are still limited. Deciphering principle patterns of bacterial community variation over multiple spatial scales may however prove critical for a better understanding of factors contributing to cold-water coral reef stability and functioning. Methodology/Principal Findings: Bacterial community structure, as determined by Automated Ribosomal Intergenic Spacer Analysis (ARISA), was investigated with respect to (i) microbial habitat type and (ii) coral species and color, as well as the three spatial components (iii) geomorphologic reef zoning, (iv) reef boundary, and (v) reef location. Communities revealed fundamental differences between coral-generated (branch surface, mucus) and ambient microbial habitats (seawater, sediments). This habitat specificity appeared pivotal for determining bacterial community shifts over all other study levels investigated. Coral-derived surfaces showed species-specific patterns, differing significantly between Lophelia pertusa and Madrepora oculata, but not between L. pertusa color types. Within the reef center, no community distinction corresponded to geomorphologic reef zoning for both coral-generated and ambient microbial habitats. Beyond the reef center, however, bacterial communities varied considerably from local to regional scales, with marked shifts toward the reef periphery as well as between different in- and offshore reef sites, suggesting significant biogeographic imprinting but wea