Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

Surgical or percutaneous coronary revascularization for heart failure: an in silico model using routinely collected health data to emulate a clinical trial.

AIMS: The choice of revascularization with coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in people with ischaemic left ventricular dysfunction is not guided by high-quality evidence. METHODS AND RESULTS: A trial of CABG vs. PCI in people with heart failure (HF) was modelled in silico using routinely collected healthcare data. The in silico trial cohort was selected by matching the target trial cohort, identified from Hospital Episode Statistics in England, with individual patient data from the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Allocation to CABG vs. complex PCI demonstrated random variation across administrative regions in England and was a valid statistical instrument. The primary outcome was 5-year all-cause mortality or cardiovascular hospitalization. Instrumental variable analysis (IVA) was used for the primary analysis. Results were expressed as average treatment effects (ATEs) with 95 confidence intervals (CIs). The target population included 13 519 HF patients undergoing CABG or complex PCI between April 2009 and March 2015. After matching, the emulated trial cohort included 2046 patients. The unadjusted primary outcome rate was 51.1 in the CABG group and 70.0 in the PCI group. IVA of the emulated cohort showed that CABG was associated with a lower risk of the primary outcome (ATE 16.2, 95 CI 20.6 to 11.8), with comparable estimates in the unmatched target population (ATE 15.5, 95 CI 17.5 to 13.5). CONCLUSION: In people with HF, in silico modelling suggests that CABG is associated with fewer deaths or cardiovascular hospitalizations at 5 years vs. complex PCI. A pragmatic clinical trial is needed to test this hypothesis and this trial would be feasible.

Adapting prescribing criteria for amyloid-targeted antibodies for adults with Down syndrome.

Prior authorization criteria for Federal Drug Administration (FDA) approved immunotherapeutics, among the class of anti-amyloid monoclonal antibodies (mAbs), established by state drug formulary committees, are tailored for adults with late-onset Alzheimer's disease. This overlooks adults with Down syndrome (DS), who often experience dementia at a younger age and with different diagnostic assessment outcomes. This exclusion may deny DS adults access to potential disease-modifying treatments. To address this issue, an international expert panel convened to establish adaptations of prescribing criteria suitable for DS patients and parameters for access to Centers for Medicare & Medicaid Services (CMS) registries. The panel proposed mitigating disparities by modifying CMS and payer criteria to account for younger onset age, using alternative language and assessment instruments validated for cognitive decline in the DS population. The panel also recommended enhancing prescribing clinicians' diagnostic capabilities for DS and initiated awareness-raising activities within healthcare organizations. These efforts facilitated discussions with federal officials, aimed at achieving equity in access to anti-amyloid immunotherapeutics, with implications for national authorities worldwide evaluating these and other new disease-modifying therapeutics for Alzheimer's disease.

Effects of interventions targeting the systemic inflammatory response to cardiac surgery on clinical outcomes in adults.

BACKGROUND: Organ injury is a common and severe complication of cardiac surgery that contributes to the majority of deaths. There are no effective treatment or prevention strategies. It has been suggested that innate immune system activation may have a causal role in organ injury. A wide range of organ protection interventions targeting the innate immune response have been evaluated in randomised controlled trials (RCTs) in adult cardiac surgery patients, with inconsistent results in terms of effectiveness. OBJECTIVES: The aim of the review was to summarise the results of RCTs of organ protection interventions targeting the innate immune response in adult cardiac surgery. The review considered whether the interventions had a treatment effect on inflammation, important clinical outcomes, or both. SEARCH METHODS: CENTRAL, MEDLINE, Embase, conference proceedings and two trial registers were searched on October 2022 together with reference checking to identify additional studies. SELECTION CRITERIA: RCTs comparing organ protection interventions targeting the innate immune response versus placebo or no treatment in adult patients undergoing cardiac surgery where the treatment effect on innate immune activation and on clinical outcomes of interest were reported. DATA COLLECTION AND ANALYSIS: Searches, study selection, quality assessment, and data extractions were performed independently by pairs of authors. The primary inflammation outcomes were peak IL-6 and IL-8 concentrations in blood post-surgery. The primary clinical outcome was in-hospital or 30-day mortality. Treatment effects were expressed as risk ratios (RR) and standardised mean difference (SMD) with 95% confidence intervals (CI). Meta-analyses were performed using random effects models, and heterogeneity was assessed using I2. MAIN RESULTS: A total of 40,255 participants from 328 RCTs were included in the synthesis. The effects of treatments on IL-6 (SMD -0.77, 95% CI -0.97 to -0.58, I2 = 92%) and IL-8 (SMD -0.92, 95% CI -1.20 to -0.65, I2 = 91%) were unclear due to heterogeneity. Heterogeneity for inflammation outcomes persisted across multiple sensitivity and moderator analyses. The pooled treatment effect for in-hospital or 30-day mortality was RR 0.78, 95% CI 0.68 to 0.91, I2 = 0%, suggesting a significant clinical benefit. There was little or no treatment effect on mortality when analyses were restricted to studies at low risk of bias. Post hoc analyses failed to demonstrate consistent treatment effects on inflammation and clinical outcomes. Levels of certainty for pooled treatment effects on the primary outcomes were very low. AUTHORS' CONCLUSIONS: A systematic review of RCTs of organ protection interventions targeting innate immune system activation did not resolve uncertainty as to the effectiveness of these treatments, or the role of innate immunity in organ injury following cardiac surgery.

Effects of late, repetitive remote ischaemic conditioning on myocardial strain in patients with acute myocardial infarction.

Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks' daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5-7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from - 16.2 ± 5.2 at baseline to - 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from - 15.5 ± 4.0 to - 15.2 ± 4.7, p = 0.81; for change: - 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (- 1.2 ± 4.4 versus - 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611 .

Probing the proteome to explore potential correlates of increased Alzheimer's-related cerebrovascular disease in adults with Down syndrome.

Cerebrovascular disease is associated with symptoms and pathogenesis of Alzheimer's disease (AD) among adults with Down syndrome (DS). The cause of increased dementia-related cerebrovascular disease in DS is unknown. We explored whether protein markers of neuroinflammation are associated with markers of cerebrovascular disease among adults with DS. Participants from the Alzheimer's disease in Down syndrome (ADDS) study with magnetic resonance imaging (MRI) scans and blood biomarker data were included. Support vector machine (SVM) analyses examined the relationship of blood-based proteomic biomarkers with MRI-defined cerebrovascular disease among participants characterized as having cognitive decline (n = 36, mean age ± SD = 53 ± 6.2) and as being cognitively stable (n = 78, mean age = 49 ± 6.4). Inflammatory and AD markers were associated with cerebrovascular disease, particularly among symptomatic individuals. The pattern suggested relatively greater inflammatory involvement among cognitively stable individuals and greater AD involvement among those with cognitively decline. The findings help to generate hypotheses that both inflammatory and AD markers are implicated in cerebrovascular disease among those with DS and point to potential mechanistic pathways for further examination.

An outbreak of adenovirus D8 keratoconjunctivitis in Leicester, United Kingdom, from March to August 2019.

We report a large epidemic (n = 126) of keratoconjunctivitis predominantly with two lineages of adenovirus (AdV) type D8 in patients seen in eye casualty between march and August 2019. Other AdV species identified by viral sequencing included B, C, and E. Despite various features of more severe eye disease being present, these were not significantly different between the different AdV species, with similar rates of pseudomembrane formation and keratitis observed in patients with AdV species B as for those with AdV species D.

Alzheimer-Related Cerebrovascular Disease in Down Syndrome.

OBJECTIVE: Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology by their 5th decade. Compared with the general population, traditional vascular risks in adults with DS are rare, allowing examination of cerebrovascular disease in this population and insight into its role in AD without the confound of vascular risk factors. We examined in vivo magnetic resonance imaging (MRI)-based biomarkers of cerebrovascular pathology in adults with DS, and determined their cross-sectional relationship with age, beta-amyloid pathology, and mild cognitive impairment or clinical AD diagnostic status. METHODS: Participants from the Biomarkers of Alzheimer's Disease in Down Syndrome study (n = 138, 50 ± 7 years, 39% women) with MRI data and a subset (n = 90) with amyloid positron emission tomography (PET) were included. We derived MRI-based biomarkers of cerebrovascular pathology, including white matter hyperintensities (WMH), infarcts, cerebral microbleeds, and enlarged perivascular spaces (PVS), as well as PET-based biomarkers of amyloid burden. Participants were characterized as cognitively stable (CS), mild cognitive impairment-DS (MCI-DS), possible AD dementia, or definite AD dementia based on in-depth assessments of cognition, function, and health status. RESULTS: There were detectable WMH, enlarged PVS, infarcts, and microbleeds as early as the 5th decade of life. There was a monotonic increase in WMH volume, enlarged PVS, and presence of infarcts across diagnostic groups (CS < MCI-DS < possible AD dementia < definite AD dementia). Higher amyloid burden was associated with a higher likelihood of an infarct. INTERPRETATION: The findings highlight the prevalence of cerebrovascular disease in adults with DS and add to a growing body of evidence that implicates cerebrovascular disease as a core feature of AD and not simply a comorbidity. ANN NEUROL 2020;88:1165-1177.

Pharmacological interventions for the prevention of renal injury in surgical patients: a systematic literature review and meta-analysis.

BACKGROUND: The aim of this systematic review was to summarise the results of randomised controlled trials (RCTs) that have evaluated pharmacological interventions for renoprotection in people undergoing surgery. METHODS: Searches were conducted to update a previous review using the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to August 23, 2019. RCTs evaluating the use of pharmacological interventions for renal protection in the perioperative period were included. The co-primary outcome measures were 30-day mortality and acute kidney injury (AKI). Pooled effect estimates were expressed as risk ratios (RRs) (95% confidence intervals). RESULTS: We included 228 trials enrolling 56 047 patients. Twenty-three trials were considered to be at low risk of bias across all domains. Atrial natriuretic peptides (14 trials; n=2207) reduced 30-day mortality (RR: 0.63 [0.41, 0.97]) and AKI events (RR: 0.43 [0.33, 0.56]) without heterogeneity. These effects were consistent across cardiac surgery and vascular surgery subgroups, and in sensitivity analyses restricted to studies at low risk of bias. Inodilators (13 trials; n=2941) reduced mortality (RR: 0.71 [0.53, 0.94]) and AKI events (RR: 0.65 [0.50, 0.85]) in the primary analysis and in cardiac surgery cohorts. Vasopressors (4 trials; n=1047) reduced AKI (RR: 0.56 [0.36, 0.86]). Nitric oxide donors, alpha-2-agonists, and calcium channel blockers reduced AKI in primary analyses, but not after exclusion of studies at risk of bias. Overall, assessment of the certainty of the effect estimates was low. CONCLUSIONS: There are multiple effective pharmacological renoprotective interventions for people undergoing surgery.

Patient blood management interventions do not lead to important clinical benefits or cost-effectiveness for major surgery: a network meta-analysis.

BACKGROUND: Patient blood management (PBM) interventions aim to improve clinical outcomes by reducing bleeding and transfusion. We assessed whether existing evidence supports the routine use of combinations of these interventions during and after major surgery. METHODS: Five systematic reviews and a National Institute of Health and Care Excellence health economic review of trials of common PBM interventions enrolling participants of any age undergoing surgery were updated. The last search was on June 1, 2019. Studies in trauma, burns, gastrointestinal haemorrhage, gynaecology, dentistry, or critical care were excluded. The co-primary outcomes were: risk of receiving red cell transfusion and 30-day or hospital all-cause mortality. Treatment effects were estimated using random-effects models and risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity assessments used I2. Network meta-analyses used a frequentist approach. The protocol was registered prospectively (PROSPERO CRD42018085730). RESULTS: Searches identified 393 eligible randomised controlled trials enrolling 54 917 participants. PBM interventions resulted in a reduction in exposure to red cell transfusion (RR=0.60; 95% CI 0.57, 0.63; I2=77%), but had no statistically significant treatment effect on 30-day or hospital mortality (RR=0.93; 95% CI 0.81, 1.07; I2=0%). Treatment effects were consistent across multiple secondary outcomes, sub-groups and sensitivity analyses that considered clinical setting, type of intervention, and trial quality. Network meta-analysis did not demonstrate additive benefits from the use of multiple interventions. No trial demonstrated that PBM was cost-effective. CONCLUSIONS: In randomised trials, PBM interventions do not have important clinical benefits beyond reducing bleeding and transfusion in people undergoing major surgery.

Activation of the innate immune response and organ injury after cardiac surgery: a systematic review and meta-analysis of randomised trials and analysis of individual patient data from randomised and non-randomised studies.

BACKGROUND: It is unclear whether the innate immune response represents a therapeutic target for organ protection strategies in cardiac surgery. METHODS: A systematic review of trials of interventions targeting the inflammatory response to cardiac surgery reporting treatment effects on both innate immune system cytokines and organ injury was performed. The protocol was registered at the International Prospective Register of Systematic Reviews: CRD42020187239. Searches of the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase were performed. Random-effects meta-analyses were used for the primary analysis. A separate analysis of individual patient data from six studies (n=785) explored sources of heterogeneity for treatment effects on cytokine levels. RESULTS: Searches to May 2020 identified 251 trials evaluating 24 interventions with 20 582 participants for inclusion. Most trials had important limitations. Methodological limitations of the included trials and heterogeneity of the treatment effects on cytokine levels between trials limited interpretation. The primary analysis demonstrated inconsistency in the direction of the treatment effects on innate immunity and organ failure or death between interventions. Analyses restricted to important subgroups or trials with fewer limitations showed similar results. Meta-regression, pooling available data from all trials, demonstrated no association between the direction of the treatment effects on inflammatory cytokines and organ injury or death. The analysis of individual patient data demonstrated heterogeneity in the association between the cytokine response and organ injury after cardiac surgery for people >75 yr old and those with some chronic diseases. CONCLUSIONS: The certainty of the evidence for a causal relationship between innate immune system activation and organ injury after cardiac surgery is low.

Blood Transfusion Threshold in Patients Receiving Extracorporeal Membrane Oxygenation Support for Cardiac and Respiratory Failure-A Systematic Review and Meta-Analysis.

OBJECTIVE: To review studies that have evaluated the effects of liberal or restrictive red cell transfusion thresholds on clinical outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) support for cardiac or respiratory failure. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: The study comprised 1,070 patients from observational studies and randomized controlled trials analyzing transfusion policies in venoarterial (VA) and venovenous (VV) ECMO adult populations. MEASUREMENTS AND MAIN RESULTS: Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials, Medline, and EMBASE until March 4, 2020, using a combination of subject headings and text words. Risk of bias assessment was performed to assess study quality according to the ROBINS-I tool and the case series studies appraisal checklist. There was high risk of bias in the studies analyzed, and none had methodologic adequacy. Three studies analyzed VA ECMO and VV ECMO patients separately. Five datasets were related exclusively or mostly to VA ECMO. Four were retrospective analyses, and one was conducted as a prospective observational study; the median transfusion threshold reported was 8 g/dL, with a mean mortality of 52%. Eight datasets were related either exclusively or mostly to VV ECMO. Six were retrospective and two were prospective observational studies; the median transfusion threshold was 8 g/dL, and the mean mortality rate was 33%. CONCLUSIONS: The present study did not resolve uncertainty as to transfusion management in ECMO, although several studies (most of them in VV ECMO) demonstrated that a restrictive threshold has acceptable outcomes in single-center cohorts.

Evaluation of the National Task Group-Early Detection Screen for Dementia: Sensitivity to 'mild cognitive impairment' in adults with Down syndrome.

BACKGROUND: The accuracy of the National Task Group-Early Detection Screen for Dementia (NTG-EDSD) was evaluated in a sample of 185 adults with Down syndrome (DS), emphasizing 'mild cognitive impairment (MCI-DS)'. METHOD: Knowledgeable informants were interviewed with the NTG-EDSD, and findings were compared to an independent dementia status rating based on consensus review of detailed assessments of cognition, functional abilities and health status (including physician examination). RESULTS: Results indicated that sections of the NTG-EDSD were sensitive to MCI-DS, with one or more concerns within the 'Memory' or 'Language and Communication' domains being most informative. CONCLUSIONS: The NTG-EDSD is a useful tool for evaluating dementia status, including MCI-DS. However, estimates of sensitivity and specificity, even for detecting frank dementia, indicated that NTG-EDSD findings need to be supplemented by additional sources of relevant information to achieve an acceptable level of diagnostic/screening accuracy.

Biomarkers of Inflammation and Lung Recovery in Extracorporeal Membrane Oxygenation Patients With Persistent Pulmonary Hypertension of the Newborn: A Feasibility Study.

OBJECTIVES: Extracorporeal membrane oxygenation is a treatment for Persistent Pulmonary Hypertension of the Newborn with high mortality. HYPOTHESIS: the extracorporeal membrane oxygenation circuit results in inflammatory responses that mitigate against successful weaning. DESIGN: Single-center prospective observational feasibility study. SETTING: PICU. PATIENTS: Twenty-four neonates requiring extracorporeal membrane oxygenation support for Persistent Pulmonary Hypertension of the Newborn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The reference outcome was death or more than 7 days of extracorporeal membrane oxygenation support. Other outcomes included serial measures of plasma-free hemoglobin and markers of its metabolism, leucocyte, platelet and endothelial activation, and biomarkers of inflammation. Of 24 participants recruited between February 2016 and June 2017, 10 died or required prolonged extracorporeal membrane oxygenation support. These patients were sicker at baseline with higher levels of plasma-free hemoglobin within 12 hours of cannulation (geometric mean ratio, 1.92; 95% CIs, 1.00-3.67; p = 0.050) but not thereafter, versus those requiring less than 7 days extracorporeal membrane oxygenation. Serum haptoglobin concentrations were significantly elevated in both groups. Patients who died or required prolonged extracorporeal membrane oxygenation support demonstrated elevated levels of platelet-leucocyte aggregation, but decreased concentrations of mediators of the inflammatory response: interleukin-8, C-reactive protein, and tumor necrosis factor α. CONCLUSIONS: Clinical status at baseline and not levels of plasma-free hemoglobin or the systemic inflammatory response may determine the requirement for prolonged extracorporeal membrane oxygenation support in neonates.

Further understanding the connection between Alzheimer's disease and Down syndrome.

Improved medical care of individuals with Down syndrome (DS) has led to an increase in life expectancy to over the age of 60 years. In conjunction, there has been an increase in age-related co-occurring conditions including Alzheimer's disease (AD). Understanding the factors that underlie symptom and age of clinical presentation of dementia in people with DS may provide insights into the mechanisms of sporadic and DS-associated AD (DS-AD). In March 2019, the Alzheimer's Association, Global Down Syndrome Foundation and the LuMind IDSC Foundation partnered to convene a workshop to explore the state of the research on the intersection of AD and DS research; to identify research gaps and unmet needs; and to consider how best to advance the field. This article provides a summary of discussions, including noting areas of emerging science and discovery, considerations for future studies, and identifying open gaps in our understanding for future focus.

Correction to: does stress perfusion imaging improve the diagnostic accuracy of late gadolinium enhanced cardiac magnetic resonance for establishing the etiology of heart failure?

Following publication of the original article [1], the author reported his name has erroneously spelled as Abishek Shetye. The correct name is Abhishek Shetye.

Adult height and risk of 50 diseases: a combined epidemiological and genetic analysis.

BACKGROUND: Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear. We examined the association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms. METHODS: We examined the associations for adult height (using logistic regression adjusted for potential confounders) and genetically determined height (using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables) in 417,434 individuals of white ethnic background participating in the UK Biobank. We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases. RESULTS: Height was associated with 32 diseases and genetically determined height associated with 12 diseases. Of these, 11 diseases showed a concordant association in both analyses, with taller height associated with reduced risks of coronary artery disease (odds ratio per standard deviation (SD) increase in height ORepi = 0.80, 95% CI 0.78-0.81; OR per SD increase in genetically determined height ORgen = 0.86, 95% CI 0.82-0.90), hypertension (ORepi = 0.83, 95% CI 0.82-0.84; ORgen = 0.88, 95% CI 0.85-0.91), gastro-oesophageal reflux disease (ORepi = 0.85, 95% CI 0.84-0.86; ORgen = 0.94, 95% CI 0.92-0.97), diaphragmatic hernia (ORepi = 0.81, 95% CI 0.79-0.82; ORgen = 0.91, 95% CI 0.88-0.94), but increased risks of atrial fibrillation (ORepi = 1.42, 95% CI 1.38-1.45; ORgen = 1.33, 95% CI 1.26-1.40), venous thromboembolism (ORepi = 1.18, 95% CI 1.16-1.21; ORgen = 1.15, 95% CI 1.11-1.19), intervertebral disc disorder (ORepi = 1.15, 95% CI 1.13-1.18; ORgen = 1.14, 95% CI 1.09-1.20), hip fracture (ORepi = 1.19, 95% CI 1.12-1.26; ORgen = 1.27, 95% CI 1.17-1.39), vasculitis (ORepi = 1.15, 95% CI 1.11-1.19; ORgen = 1.20, 95% CI 1.14-1.28), cancer overall (ORepi = 1.09, 95% CI 1.08-1.11; ORgen = 1.06, 95% CI 1.04-1.08) and breast cancer (ORepi = 1.08, 95% CI 1.06-1.10; ORgen = 1.07, 95% CI 1.03-1.11). Pathway analysis showed multiple height-associated pathways associating with individual diseases. CONCLUSIONS: Adult height is associated with risk of a range of diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis. Multiple biological mechanisms affecting height may affect the risks of these diseases.

Comparison of global myocardial strain assessed by cardiovascular magnetic resonance tagging and feature tracking to infarct size at predicting remodelling following STEMI.

BACKGROUND: To determine if global strain parameters measured by cardiovascular magnetic resonance (CMR) acutely following ST-segment Elevation Myocardial Infarction (STEMI) predict adverse left ventricular (LV) remodelling independent of infarct size (IS). METHODS: Sixty-five patients with acute STEMI (mean age 60 ± 11 years) underwent CMR at 1-3 days post-reperfusion (baseline) and at 4 months. Global peak systolic circumferential strain (GCS), measured by tagging and Feature Tracking (FT), and global peak systolic longitudinal strain (GLS), measured by FT, were calculated at baseline, along with IS. On follow up scans, volumetric analysis was performed to determine the development of adverse remodelling - a composite score based on development of either end-diastolic volume index [EDVI] ≥20% or end-systolic volume index [ESVI] ≥15% at follow-up compared to baseline. RESULTS: The magnitude of GCS was higher when measured using FT (-21.1 ± 6.3%) than with tagging (-12.1 ± 4.3; p < 0.001 for difference). There was good correlation of strain with baseline LVEF (r 0.64-to 0.71) and IS (ρ -0.62 to-0.72). Baseline strain parameters were unable to predict development of adverse LV remodelling. Only baseline IS predicted adverse remodelling - Odds Ratio 1.05 (95% CI 1.01-1.10, p = 0.03), area under the ROC curve 0.70 (95% CI 0.52-0.87, p = 0.04). CONCLUSION: Baseline global strain by CMR does not predict the development of adverse LV remodelling following STEMI.

Does stress perfusion imaging improve the diagnostic accuracy of late gadolinium enhanced cardiac magnetic resonance for establishing the etiology of heart failure?

BACKGROUND: Late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) has excellent specificity, sensitivity and diagnostic accuracy for differentiating between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NICM). CMR first-pass myocardial perfusion imaging (perfusion-CMR) may also play role in distinguishing heart failure of ischemic and non-ischemic origins, although the utility of additional of stress perfusion imaging in such patients is unclear. The aim of this retrospective study was to assess whether the addition of adenosine stress perfusion imaging to LGE-CMR is of incremental value for differentiating ICM and NICM in patients with severe left ventricular systolic dysfunction (LVSD) of uncertain etiology. METHODS: We retrospectively identified 100 consecutive adult patients (median age 69 years (IQR 59-73)) with severe LVSD (mean LV EF 26.6 ± 7.0%) referred for perfusion-CMR to establish the underlying etiology of heart failure. The cause of heart failure was first determined on examination of CMR cine and LGE images in isolation. Subsequent examination of complete adenosine stress perfusion-CMR studies (cine, LGE and perfusion images) was performed to identify whether this altered the initial diagnosis. RESULTS: On LGE-CMR, 38 patients were diagnosed with ICM, 46 with NICM and 16 with dual pathology. With perfusion-CMR, there were 39 ICM, 44 NICM and 17 dual pathology diagnoses. There was excellent agreement in diagnoses between LGE-CMR and perfusion-CMR (κ 0.968, p<0.001). The addition of adenosine stress perfusion images to LGE-CMR altered the diagnosis in only two of the 100 patients. CONCLUSION: The addition of adenosine stress perfusion-CMR to cine and LGE-CMR provides minimal incremental diagnostic yield for determining the etiology of heart failure in patients with severe LVSD.