High-Flow Nasal Cannula Compared With Conventional Oxygen Therapy or Noninvasive Ventilation Immediately Postextubation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Reintubation after failed extubation is associated with increased mortality and longer hospital length of stay. Noninvasive oxygenation modalities may prevent reintubation. We conducted a systematic review and meta-analysis to determine the safety and efficacy of high-flow nasal cannula after extubation in critically ill adults. DATA SOURCES: We searched MEDLINE, EMBASE, and Web of Science. STUDY SELECTION: We included randomized controlled trials comparing high-flow nasal cannula to other noninvasive methods of oxygen delivery after extubation in critically ill adults. DATA EXTRACTION: We included the following outcomes: reintubation, postextubation respiratory failure, mortality, use of noninvasive ventilation, ICU and hospital length of stay, complications, and comfort. DATA SYNTHESIS: We included eight randomized controlled trials (n = 1,594 patients). Compared with conventional oxygen therapy, high-flow nasal cannula decreased reintubation (relative risk, 0.46; 95% CI, 0.30-0.70; moderate certainty) and postextubation respiratory failure (relative risk, 0.52; 95% CI, 0.30-0.91; very low certainty), but had no effect on mortality (relative risk, 0.93; 95% CI, 0.57-1.52; moderate certainty), or ICU length of stay (mean difference, 0.05 d fewer; 95% CI, 0.83 d fewer to 0.73 d more; high certainty). High-flow nasal cannula may decrease use of noninvasive ventilation (relative risk, 0.64; 95% CI, 0.34-1.22; moderate certainty) and hospital length of stay (mean difference, 0.98 d fewer; 95% CI, 2.16 d fewer to 0.21 d more; moderate certainty) compared with conventional oxygen therapy, however, certainty was limited by imprecision. Compared with noninvasive ventilation, high-flow nasal cannula had no effect on reintubation (relative risk, 1.16; 95% CI, 0.86-1.57; low certainty), mortality (relative risk, 1.12; 95% CI, 0.82-1.53; moderate certainty), or postextubation respiratory failure (relative risk, 0.82; 95% CI, 0.48-1.41; very low certainty). High-flow nasal cannula may reduce ICU length of stay (moderate certainty) and hospital length of stay (moderate certainty) compared with noninvasive ventilation. CONCLUSIONS: High-flow nasal cannula reduces reintubation compared with conventional oxygen therapy, but not compared with noninvasive ventilation after extubation.

Moderate Certainty Evidence Suggests the Use of High-Flow Nasal Cannula Does Not Decrease Hypoxia When Compared With Conventional Oxygen Therapy in the Peri-Intubation Period: Results of a Systematic Review and Meta-Analysis.

OBJECTIVE: The role of high-flow nasal cannula during and before intubation is unclear despite a number of randomized clinical trials. Our objective was to conduct a systematic review and meta-analysis examining the benefits of high-flow nasal cannula in the peri-intubation period. DATA SOURCES: We performed a comprehensive search of relevant databases (MEDLINE, EMBASE, and Web of Science). STUDY SELECTION: We included randomized clinical trials that compared high-flow nasal cannula to other noninvasive oxygen delivery systems in the peri-intubation period. DATA EXTRACTION: Our primary outcome was severe desaturation (defined as peripheral oxygen saturation reading < 80% during intubation). Secondary outcomes included peri-intubation complications, apneic time, PaO2 before and after intubation, PaCO2 after intubation, ICU length of stay, and short-term mortality. DATA SYNTHESIS: We included 10 randomized clinical trials (n = 1,017 patients). High-flow nasal cannula had no effect on the occurrence rate of peri-intubation hypoxemia (relative risk, 0.98; 95% CI, 0.68-1.42; 0.3% absolute risk reduction, moderate certainty), serious complications (relative risk, 0.87; 95% CI, 0.71-1.06), apneic time (mean difference, 10.3 s higher with high-flow nasal cannula; 95% CI, 11.0 s lower to 31.7 s higher), PaO2 measured after preoxygenation (mean difference, 3.6 mm Hg higher; 95% CI, 3.5 mm Hg lower to 10.7 mm Hg higher), or PaO2 measured after intubation (mean difference, 27.0 mm Hg higher; 95% CI, 13.2 mm Hg lower to 67.2 mm Hg higher), when compared with conventional oxygen therapy. There was also no effect on postintubation PaCO2, ICU length of stay, or 28-day mortality. CONCLUSIONS: We found moderate-to-low certainty evidence that the use of high-flow nasal cannula likely has no effect on severe desaturation, serious complications, apneic time, oxygenation, ICU length of stay, or overall survival when used in the peri-intubation period when compared with conventional oxygen therapy.

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

BACKGROUND: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. OBJECTIVES: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. METHODS: We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. RESULTS: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. CONCLUSIONS: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.

High-Flow Nasal Cannula in the Immediate Postoperative Period: A Systematic Review and Meta-analysis.

BACKGROUND: Studies have demonstrated that high-flow nasal cannula (HFNC) prevents intubation in acute hypoxic respiratory failure when compared with conventional oxygen therapy (COT). However, the data examining routine HFNC use in the immediate postoperative period are less clear. RESEARCH QUESTION: Is routine HFNC use superior to COT or noninvasive ventilation (NIV) use in preventing intubation in patients postoperatively? STUDY DESIGN AND METHODS: We comprehensively searched databases (PubMed, Embase, Web of Science) to identify randomized controlled trials (RCTs) that compared the effect of HFNC use with that of COT or NIV in the immediate postoperative period on reintubation, escalation of respiratory support, hospital mortality, ICU and hospital length of stay (LOS), postoperative hypoxemia, and treatment complications. We assessed individual study risk of bias (RoB) by using the revised Cochrane RoB 2 tool and rated certainty in outcomes by using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS: We included 11 RCTs enrolling 2,201 patients. Ten compared HFNC with COT and one with NIV. Compared with COT use, HFNC use in the postoperative period was associated with a lower reintubation rate (relative risk [RR], 0.32; 95% CI, 0.12-0.88; absolute risk reduction [ARR], 2.9%; moderate certainty) and decreased escalation of respiratory support (RR, 0.54; 95% CI, 0.31-0.94; ARR, 5.8%; very low certainty). Post hoc subgroup analysis suggested that this effect was driven by patients who were obese and/or at high risk (subgroup differences, P = .06). We did not find differences in any of the other stated outcomes between HFNC and COT. HFNC was also no different from NIV in reintubation rate, respiratory therapy failure, or ICU LOS. INTERPRETATION: With evidence of moderate certainty, prophylactic HFNC reduces reintubation and escalation of respiratory support compared with COT in the immediate postoperative period after cardiothoracic surgery. This effect is likely driven by patients who are at high risk and/or obese. These findings support postoperative prophylactic HFNC use in the patients who are at high risk and/or obese undergoing cardiothoracic surgery.

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.

PURPOSE: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. METHODS: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. RESULTS: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). CONCLUSIONS: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians.

A Candidate-Gene Approach Identifies Novel Associations Between Common Variants in/Near Syndromic Obesity Genes and BMI in Pediatric and Adult European Populations.

We hypothesized that monogenic syndromic obesity genes are also involved in the polygenic variation of BMI. Single-marker, tag single nucleotide polymorphism (tagSNP) and gene-based analysis were performed on common variants near 54 syndromic obesity genes. We used publicly available data from meta-analyses of European BMI genome-wide association studies conducted by the Genetic Investigation of ANthropometric Traits (GIANT) Consortium and the UK Biobank (UKB) (N = 681,275 adults). A total of 33 loci were identified, of which 19 of 33 (57.6%) were located at SNPs previously identified by the GIANT Consortium and UKB meta-analysis, 11 of 33 (33.3%) were located at novel SNPs, and 3 of 33 (9.1%) were novel genes identified with gene-based analysis. Both single-marker and tagSNP analyses mapped the previously identified 19 SNPs by the GIANT Consortium and UKB meta-analysis. Gene-based analysis confirmed 15 of 19 (78.9%) of the novel SNPs' associated genes. Of the 11 novel loci, 8 were identified with single-marker analysis and the remaining 3 were identified with tagSNP analysis. Gene-based analysis confirmed 4 of 11 (36.3%) of these loci. Meta-analysis with the Early Growth Genetics (EGG) Consortium (N = 35,668 children) was conducted post hoc for top SNPs, confirming 17 of 33 (51.5%) loci, of which 5 were novel. This study supports evidence for a continuum between rare monogenic syndromic and common polygenic forms of obesity.

Comprehensive identification of pleiotropic loci for body fat distribution using the NHGRI-EBI Catalog of published genome-wide association studies.

We conducted a hypothesis-free cross-trait analysis for waist-to-hip ratio adjusted for body mass index (WHRadjBMI ) loci derived through genome-wide association studies (GWAS). Summary statistics from published GWAS were used to capture all WHRadjBMI single-nucleotide polymorphisms (SNPs), and their proxy SNPs were identified. These SNPs were used to extract cross-trait associations between WHRadjBMI SNPs and other traits through the NHGRI-EBI GWAS Catalog. Pathway analysis was conducted for pleiotropic WHRadjBMI SNPs. We found 160 WHRadjBMI SNPs and 3675 proxy SNPs. Cross-trait analysis identified 239 associations, of which 100 were for obesity traits. The remaining 139 associations were filtered down to 101 unique linkage disequilibrium block associations, which were grouped into 13 categories: lipids, red blood cell traits, white blood cell counts, inflammatory markers and autoimmune diseases, type 2 diabetes-related traits, adiponectin, cancers, blood pressure, height, neuropsychiatric disorders, electrocardiography changes, urea measurement, and others. The highest number of cross-trait associations were found for triglycerides (n = 10), high-density lipoprotein cholesterol (n = 9), and reticulocyte counts (n = 8). Pathway analysis for WHRadjBMI pleiotropic SNPs found immune function pathways as the top canonical pathways. Results from our original methodology indicate a novel genetic association between WHRadjBMI and reticulocyte counts and highlight the pleiotropy between abdominal obesity, immune pathways, and other traits.

Novel Genetic Locus of Visceral Fat and Systemic Inflammation.

CONTEXT: Visceral fat (VF), more than fat elsewhere in the body [mostly subcutaneous fat (SF)], promotes systemic inflammation and related disease. The mechanisms of preferentially visceral accumulation of body fat are largely unknown. OBJECTIVE: To identify genetic loci and mechanistic pathways of preferential accumulation of VF and associated low-grade systemic inflammation. DESIGN: Genome-wide association study (GWAS). SETTING AND PARTICIPANTS: Population-based cohort of 1586 adolescents (aged 12 to 19 years) and adults (aged 36 to 65 years). MAIN OUTCOME MEASURES: Abdominal VF and SF were measured with MRI, total body fat (TBF) was assessed with bioimpedance, and low-grade systemic inflammation was examined by serum C-reactive protein (CRP) measurement. RESULTS: This GWAS of preferential accumulation of VF identified a significant locus on chromosome 6 at rs803522 (P = 1.1 × 10-9 or 4.3 × 10-10 for VF adjusted for SF or TBF, respectively). The major allele was associated with more VF; the association was similar in adolescents and adults. The allele was also associated with higher CRP level, but this association was stronger in adults than adolescents (P for interaction = 4.5 × 10-3). In adults, VF was a significant mediator (P = 1.9× 10-4) in the association between the locus and CRP, explaining 30% of the mediation. The locus was near ATG5, encoding an autophagy molecule reported to modulate adipocyte size and macrophage polarization. CONCLUSION: A genetic locus near ATG5 regulates preferential accumulation of VF (vs SF) in youth and adulthood and contributes to the development of systemic inflammation in adulthood.

Tranexamic acid in cardiac surgery: a systematic review and meta-analysis (protocol).

INTRODUCTION: Bleeding during cardiac surgery is associated with increased morbidity and mortality. Tranexamic acid is an antifibrinolytic with proven efficacy in major surgeries. Current clinical practice guidelines recommend intraoperative use in cardiac procedures. However, several complications have been reported with tranexamic acid including seizures. This review intends to summarise the evidence examining the efficacy and safety of tranexamic acid in patients undergoing cardiac surgery. METHODS/DESIGN: We will search MEDLINE, Embase, PubMED, ACPJC, CINAHL and the Cochrane trial registry for eligible randomised controlled trials, the search dates for all databases will be from inception until 1 January 2019, investigating the perioperative use of topical and/or intravenous tranexamic acid as a stand-alone antifibrinolytic agent compared with placebo in patients undergoing open cardiac surgery. We categorised outcomes as patient critical or patient important. Selected patient-critical outcomes are: mortality (intensive care unit, hospital and 30-day endpoints), reoperation within 24 hours, postoperative bleeding requiring transfusion of packed red blood cells, myocardial infarction, stroke, pulmonary embolism, bowel infarction, upper or lower limb deep vein thrombosis and seizures. Those outcomes, we perceived as clinical experts to be most patient valued and patients were not involved in outcomes selection process. We will not apply publication date, language, journal or methodological quality restrictions. Two reviewers will independently screen and identify eligible studies using predefined eligibility criteria and then review full reports of all potentially relevant citations. A third reviewer will resolve disagreements if consensus cannot be achieved. We will present the results as relative risk with 95% CIs for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95% CIs. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication TRIAL REGISTRATION NUMBER: CRD42018105904.

Metabolomics in plasma of Malawian children 7 years after surviving severe acute malnutrition: "ChroSAM" a cohort study.

BACKGROUND: More children are now surviving severe acute malnutrition (SAM), but evidence suggests that early-life malnutrition is associated with increased risk of long-term cardio-metabolic disorders. To better understand potential mechanisms, we studied the metabolite profiles of children seven years after treatment for SAM. METHODS: We followed-up children (n = 352) treated for SAM in 2006-2007, at Queen Elizabeth Central Hospital, in Malawi. Using nuclear magnetic resonance spectroscopy, tandem mass spectrometry and enzyme-linked immunosorbent assay, we measured circulating metabolites in fasting blood in a subset of SAM survivors (n = 69, 9·6 ±â€¯1·6 years), siblings (n = 44, 10·5 ±â€¯2·7 years), and age and sex-matched community controls (n = 37, 9·4 ±â€¯1·8 years). Data were analysed using univariate and sparse partial least square (sPLS) methods. Differences associated with SAM survival, oedema status, and anthropometry were tested, adjusting for age, sex, HIV, and wealth index. FINDINGS: Based on 194 measured metabolites, the profiles of SAM survivors were similar to those of siblings and community controls. IGF1, creatinine, and FGF21, had loading values >0·3 and ranked stably in the top 10 distinguishing metabolites, but did not differ between SAM survivors and controls with univariate analysis. Current stunting was associated with IGF1 (ß = 15·2, SE = 3·5, partial R2 = 12%, p < 0·0001) and this relationship could be influenced by early childhood SAM (ß = 17·4, SE = 7·7, partial R2 = 2·8%, p = 0·025). No metabolites were associated with oedema status, duration of hospital stay, anthropometry measured during hospitalization, nor with changes in anthropometry since hospitalization. INTERPRETATION: In this group of survivors, SAM was not associated with longer-term global metabolic changes 7 years after treatment. However, SAM may influence the relationship between current stunting and IGF1. Further risk markers for NCDs in SAM survivors may only be revealed by direct metabolic challenge or later in life.