Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2)

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Reactivity to sodium tetrachloropalladate (Na-2[PdCl4]) compared to PdCl2 and NiCl2 in lymphocyte proliferation tests

Background:  For patch testing, replacement of the commonly used palladium dichloride (PdCl2) by sodium tetrachloropalladate (Na2[PdCl4]) was recently demonstrated to improve test accuracy and show a significant correlation with nickel (Ni), supporting the concept of cross-reactivity between Pd and Ni. A promising alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LTT). Objectives:  The aim of this study was to test whether Na2[PdCl4] is also more sensitive for diagnosing Pd allergy with a standardized LTT. Patients/methods:  After determining optimal nontoxic and nonmitogenic concentrations for Na2[PdCl4], blood samples from 105 patients with clinical suspicion of metal allergy were tested with an LTT called memory lymphocyte immuno stimulation assay for Na2[PdCl4], PdCl2 and NiCl2. Reaction profiles were analysed for concordant positive reactions. Results:  Using the conventional cut-off of stimulation index ≥ 3, 74.3% showed a positive reaction to NiCl2, 15.2% to PdCl2 and 28.6% to Na2[PdCl4]. All positive results to PdCl2 were covered by Na2[PdCl4]. From the 30 positive reactions to Na2[PdCl4], 26 (87%) were concordant for NiCl2 reactivity. Conclusion:  In LTT, the use of Na2[PdCl4] results in more positive reactions in Pd allergy testing which are in concordance with positive reactions to PdCl2 and NiCl2

Travelling theory: Western knowledge and its Indian object

From the1830s the colonial government in India became the agency for the promotion of ‘Western education’, that is, education that sought to disseminate modern, Western, rational knowledge through modern institutions and pedagogic processes. This paper examines a historical episode in which certain key categories of modern Western thought were pressed into service to explain a consequence of the dissemination of Western knowledge in colonial India. The episode in question was that of the alleged ‘moral crisis’ of the educated Indian, who, many argued, had been plunged into confusion and moral disarray following his exposure to Western knowledge in the schools and universities established by his British ruler. In the discourse of moral crisis, the knowledge being disseminated through Western education was simultaneously put to use in explaining an unanticipated effect of this education. How adequate was Western knowledge to explaining its own effects? More generally –for this paper is drawn from a larger study of how modern Western knowledge ‘travelled’ when transplanted to colonial India – what is the status of the knowledge we produce when we ‘apply’ the categories of modern Western thought in order to understand or explain India

Risks posed by intercrops and weeds as alternative hosts to xanthomonas campestris pv. Musacearum in Banana Fields

Alternative host plants are important in the survival and perpetuation of several crop pathogens and have been suspected to play a role in the survival of Xanthomonas campestris pv. musacearum (Xcm) and perpetuation of Xanthomonas wilt (XW) disease of banana and enset. This study determined the potential risk posed by two weeds (Canna spp. and wild sorghum) and common banana intercrops (maize, millet, sorghum, taro, and sugarcane) as alternative hosts to Xcm. The study employed screenhouse experiments, laboratory procedures and diagnosis of banana fields in XW-affected landscapes. Typical XW symptoms were only observed in artificially inoculated Canna sp., with an incidence of 96%. Leaf lesions characteristic of xanthomonads occurred on millet (50%) and sorghum (35%), though the plants recovered. No symptoms occurred in maize, sugarcane, taro or wild sorghum. However, Xcm was recovered from all these plant species, with higher recoveries in Canna sp. (47%), millet (27%), sugarcane (27%), and wild sorghum (25%). Only isolates recovered from Canna sp., millet, sorghum and wild sorghum caused disease in banana plantlets. The presence and incidence of XW on-farm was positively associated with the presence of susceptible ABB Musa genotypes and negatively with number of banana cultivars on farm and household access to training on XW management. Only 0.02% of field sampled Canna spp. plants had Xcm. Risk posed by Canna spp. on-farm could be limited to tool transmission as it has persistent floral bracts that prevent insect-mediated infections. Given the high susceptibility, perennial nature and propagation through rhizomes of Canna sp., it could pose a moderate-high risk, thus warranting some attention in the management of XW disease. Sugarcane could offer a low-moderate risk due to its perennial nature and propagation through rhizomes while risk from maize, millet, and sorghum was deemed zero-low due to their annual nature, wind-mediated mode of pollination and propagation through seed. Understanding the interactions of a crop pathogen with other plants is thus important when diversifying agroecosystems. The study findings also suggest other factors such as cultivar composition and management of the disease at farm and landscape level to be important in the perpetuation of XW disease.</p

Micronutrient Gaps and Supplement Use in a Diverse Cohort of Pregnant Women

Background: Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes. Objective: Estimate micronutrient intake from food and dietary supplements in a diverse cohort of pregnant women and compare intake to the Dietary Reference Intakes (DRIs). Design: Secondary analysis of women enrolled in a multi-site clinical trial of docosahexaenoic acid (DHA) supplementation who provided their dietary intake using the diet history questionnaire-II (n = 843) or multiple 24 h recalls (n = 178) at baseline and their intake of nutritional supplements at baseline through 30 days postpartum. Participants/Setting: 1021 participants from the parent trial who had reliable data for dietary intake, supplement intake, or both. Main outcome measures: Micronutrient intake from dietary and supplement sources and percentage of intakes meeting the DRIs for pregnancy. Statistical analyses performed: Percent of participants whose intake was below the estimated average requirement (EAR) or adequate intake (AI) and above the tolerable upper limit (UL). Results: Dietary intakes of choline, folate, iron, vitamin D, zinc, vitamin E, magnesium, and potassium, were below the AI or EAR for 30–91% of the participants; thiamin and vitamin B6 were also below the AI or EAR for non-Hispanic/Latina women. Supplement intake improved the intake for most; however, 80% of the group remained below the AI for choline and 52.5% for potassium while 30% remained below the EAR for magnesium. Folate and iron intakes were above the UL for 80% and 19%, respectively. Conclusions: Dietary supplements, despite their variability, allowed the majority of this cohort of pregnant women to achieve adequate intakes for most micronutrients. Choline, magnesium, and potassium were exceptions. Of interest, folate intake was above the tolerable UL for the majority and iron for 16.8% of the participants. Clinicians have the opportunity to address the most common nutrient deficits and limits with advice on food sources that provide choline, magnesium, and potassium and to ensure folate is not overabundant. More research is needed to determine if these findings are similar in a cross-sectional population. © 2023 by the authors.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]