ABSTRACT
Neuromuscular diseases (NMDs) affect â¼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' â¼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a â¼59% 'solved' and â¼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.
Subject(s)
Muscular Dystrophies, Limb-Girdle , Muscular Dystrophies , Neuromuscular Diseases , Peripheral Nervous System Diseases , Humans , Neuromuscular Diseases/genetics , Muscular Dystrophies, Limb-Girdle/diagnosis , DNAABSTRACT
BACKGROUND: Preoperative screening for iron deficiency is a part of patient blood management protocols. This systematic review, meta-analysis, and meta-regression reviews the association between nonanemic iron deficiency and postoperative outcomes in patients undergoing cardiac surgery. We aimed to determine whether preoperative screening for nonanemic iron deficiency should be recommended in patients undergoing cardiac surgery. METHODS: Electronic databases MEDLINE (Ovid), Embase (Ovid), and Scopus were searched from inception until December 9, 2022. Studies were considered for inclusion if they (1) used an observational study design; (2) enrolled adult patients undergoing cardiac surgery; and (3) included an iron-deficient and iron-replete group, defined using serum ferritin and/or transferrin saturation. The primary outcome was the length of acute hospital stay. Secondary outcomes included length of intensive care unit stay, requirement for allogeneic red blood cell transfusion, number of red blood cell units transfused, days alive and at home at postoperative days 30 and 90, all-cause postoperative complications, postoperative infection, mortality, and hospital readmission. Meta-regression was performed to assess the effects of study and patient-level factors on the associations between nonanemic iron deficiency and specific outcomes. Individual study quality was assessed using the Risk of Bias in Non-Randomized Studies of Exposures (ROBINS-E) tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to determine the quality of evidence for each outcome. RESULTS: Eight studies (2683 patients) were included. No significant association was observed between nonanemic iron deficiency and any of the primary or secondary outcomes except for an increased requirement for allogeneic red blood cell transfusion (odds ratio [OR], 1.39 [95% confidence interval, CI, 1.16-1.68; P < .001; I2 2.8%]). Meta-regression did not identify any potential sources of heterogeneity to explain variation in individual study results. The quality of evidence was rated as "low" or "very low" for all outcomes. CONCLUSIONS: Few high-quality studies are available to assess associations between nonanemic iron deficiency and outcomes after cardiac surgery. Acknowledging these limitations, the presence of preoperative nonanemic iron deficiency was not associated with a change in the primary outcome of length of hospital stay, or any patient-centered secondary outcome compared to those without iron deficiency. There was an association with increased requirement for allogeneic red blood cell transfusion, but this did not impact the reported patient-centered outcomes.
Subject(s)
Cardiac Surgical Procedures , Postoperative Complications , Humans , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/mortality , Postoperative Complications/etiology , Postoperative Complications/blood , Postoperative Complications/mortality , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Treatment Outcome , Length of Stay , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/diagnosis , Risk Factors , Iron Deficiencies , Erythrocyte Transfusion/adverse effects , Iron/blood , Female , MaleABSTRACT
BACKGROUND: Platelet transfusion is common in cardiac surgery, but some studies have suggested an association with harm. Accordingly, we investigated the association of perioperative platelet transfusion with morbidity and mortality. METHODS: We conducted a retrospective analysis of prospectively collected data from the Australian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. We included consecutive adults from 2005 to 2018 across 40 centers. We used inverse probability of treatment weighting via entropy balancing to investigate the association of perioperative platelet transfusion with our 2 primary outcomes, operative mortality (composite of both 30-day and in-hospital mortality) and 90-day mortality, as well as multiple other clinically relevant secondary outcomes. RESULTS: Among 119,132 eligible patients, 25,373 received perioperative platelets and 93,759 were considered controls. After entropy balancing, platelet transfusion was associated with reduced operative mortality (odds ratio [OR], 0.63; 99% confidence interval [CI], 0.47-0.84; P < .0001) and 90-day mortality (OR, 0.66; 99% CI, 0.51-0.85; P < .0001). Moreover, it was associated with reduced odds of deep sternal wound infection (OR, 0.57; 99% CI, 0.36-0.89; P = .0012), acute kidney injury (OR, 0.84; 99% CI, 0.71-0.99; P = .0055), and postoperative renal replacement therapy (OR, 0.71; 99% CI, 0.54-0.93; P = .0013). These positive associations were observed despite an association with increased odds of return to theatre for bleeding (OR, 1.55; 99% CI, 1.16-2.09; P < .0001), pneumonia (OR, 1.26; 99% CI, 1.11-1.44; P < .0001), intubation for longer than 24 hours postoperatively (OR, 1.13; 99% CI, 1.03-1.24; P = .0012), inotrope use for >4 hours postoperatively (OR, 1.14; 99% CI, 1.11-1.17; P < .0001), readmission to hospital within 30 days of surgery (OR, 1.22; 99% CI, 1.11-1.34; P < .0001), as well as increased drain tube output (adjusted mean difference, 89.2 mL; 99% CI, 77.0 mL-101.4 mL; P < .0001). CONCLUSIONS: In cardiac surgery patients, perioperative platelet transfusion was associated with reduced operative and 90-day mortality. Until randomized controlled trials either confirm or refute these findings, platelet transfusion should not be deliberately avoided when considering odds of death.
Subject(s)
Cardiac Surgical Procedures , Platelet Transfusion , Adult , Humans , Platelet Transfusion/adverse effects , Retrospective Studies , Entropy , Australia , Cardiac Surgical Procedures/adverse effectsABSTRACT
BACKGROUND: Fresh frozen plasma (FFP) transfusion is used to manage coagulopathy and bleeding in cardiac surgery patients despite uncertainty about its safety and effectiveness. METHODS: We performed a propensity score matched analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database including patients from 39 centres from 2005 to 2018. We investigated the association of perioperative FFP transfusion with mortality and other clinical outcomes. RESULTS: Of 119,138 eligible patients, we successfully matched 13,131 FFP recipients with 13,131 controls. FFP transfusion was associated with 30-day mortality (odds ratio (OR), 1.41; 99% CI, 1.17-1.71; p < .0001), but not with long-term mortality (hazard ratio (HR), 0.92; 99% CI, 0.85-1.00; p = .007, Holm-Bonferroni α = 0.0004). FFP was also associated with return to theatre for bleeding (OR, 1.97; 99% CI, 1.66-2.34; p < .0001), prolonged intubation (OR, 1.15; 99% CI, 1.05-1.26; p < .0001) and increased chest tube drainage (Mean difference (MD) in mL, 131; 99% CI, 120-141; p < .0001). It was also associated with reduced postoperative creatinine levels (MD in g/L, -6.33; 99% CI, -10.28 to -2.38; p < .0001). CONCLUSION: In a multicentre, propensity score matched analysis, perioperative FFP transfusion was associated with increased 30-day mortality and had variable associations with secondary clinical outcomes.
Subject(s)
Cardiac Surgical Procedures , Plasma , Humans , Female , Male , Aged , Middle Aged , Perioperative Care/methods , Propensity Score , Blood Transfusion/statistics & numerical data , Blood Transfusion/methods , Treatment Outcome , Australia , Blood Component Transfusion/statistics & numerical data , New Zealand , Postoperative Complications/epidemiologyABSTRACT
OBJECTIVES: To assess whether there are sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: At a tertiary academic referral center. PARTICIPANTS: Adult patients who underwent cardiac surgery from 2014 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the cumulative oral morphine equivalent dose (OMED) for the postoperative admission. Secondary outcomes were the daily difference in OMED and the administration of nonopioid analgesics. The authors developed multivariate regression models controlling for known confounders, including weight and length of stay. A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% CI, -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (odds ratio, 1.91; 95% CI, 1.42-2.58; p < 0.001). The authors found no association between patient sex and the administration of other nonopioid analgesics or specific types of opioid analgesics. The authors found no association between patient sex and pain scores recorded within the first 48 hours after extubation, or the number of opioids administered in close proximity to pain assessments. CONCLUSIONS: Female sex was associated with significantly lower amounts of opioids administered after cardiac surgery.
Subject(s)
Analgesics, Non-Narcotic , Cardiac Surgical Procedures , Adult , Humans , Female , Male , Analgesics, Opioid , Retrospective Studies , Sex Characteristics , Pain, Postoperative/diagnosis , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Morphine , Cardiac Surgical Procedures/adverse effectsABSTRACT
BACKGROUND: Pediatric heart failure is associated with high mortality rates and is a current clinical burden. There is only one FDA approved pediatric VAD, Berlin Heart EXCOR, for treatment. Thrombo-embolic complications are a significant clinical challenge, which can lead to devastating complications such as stroke and impair efficient EXCOR function. Currently, clinicians perform largely qualitative periodic assessment of EXCOR operation by observing the motion of a rapidly moving membrane, which can be prone to human error and can lead to missing out on crucial information. METHODS: In this study, we design and implement a quantitative early warning system for accurate and quantitative assessment of the EXCOR membrane, named EXCOR Membrane Motion Analyzer (EMMA). Using a combination of image analysis, computer vision and custom designed algorithm, we perform rigorous frame by frame analysis of EXCOR membrane video data. We developed specialized metrics to identify relative smoothness between successive peaks, time between peaks and overall smoothness indicators to quantify and compare between multiple cases. RESULTS: Our results demonstrate that EMMA can successfully identify the motion and wrinkles on each video frame and quantify the smoothness and identify the phases of each cardiac cycle. Moreover, EMMA can obtain the smoothness of each frame and the temporal evolution of membrane smoothness across all image frames for the video sequence. CONCLUSIONS: EMMA allows for a fast, accurate, quantitative assessment to be completed and reduces user error. This enables EMMA to be used effectively as an early warning system to rapidly identify device abnormalities.
ABSTRACT
BACKGROUND: Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting. METHODS: We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity. RESULTS: Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18-1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50-3.72). Postoperative NLR measurements were not of prognostic significance. CONCLUSIONS: Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.
Subject(s)
Acute Kidney Injury , Cardiac Surgical Procedures , Humans , Prognosis , Neutrophils , Lymphocytes , Cardiac Surgical Procedures/adverse effects , Biomarkers , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiologyABSTRACT
RED CELL DISTRIBUTION WIDTH (RDW) is a routinely available biomarker of likely erythropoietic dysfunction, which may be associated with adverse outcomes after cardiac surgery. This systematic review and meta-analysis aimed to clarify the prognostic value of RDW in patients undergoing cardiac surgery. The authors searched MEDLINE, Embase, and the Cochrane Library from inception to May 10, 2022 for studies investigating the association between elevated RDW (as defined by the authors of included studies) and adverse outcomes after cardiac surgery. Herein, the authors extracted maximally adjusted hazard ratios (HRs) and odds ratios (ORs) with associated CIs, and pooled them using random-effects inverse- variance modeling. The authors explored interstudy heterogeneity using metaregression. The authors included 26 studies involving 48,092 patients who had undergone cardiac surgery. Elevated preoperative RDW was associated with long-term mortality (pooled HR 1.63, 95% CI 1.05-2.52), short-term mortality (pooled OR 2.16, 95% CI 1.21-3.87), acute kidney injury (AKI; pooled OR 1.30, 95% CI 1.19-1.41) and postoperative atrial fibrillation (POAF; pooled OR 1.44, 95% CI 1.05-1.96). Some studies suggested a significant association between preoperative RDW elevation and neurologic complications; however, their number was insufficient for meta-analysis. The postoperative RDW levels were less consistently reported and could not be meta-analyzed. In conclusion, the authors found that elevated preoperative RDW was associated with increased short- and long-term mortality, POAF, and AKI after cardiac surgery. Further research is needed to investigate its role in the risk stratification of patients undergoing cardiac surgery.
Subject(s)
Acute Kidney Injury , Cardiac Surgical Procedures , Humans , Erythrocyte Indices , Prognosis , Cardiac Surgical Procedures/adverse effects , Biomarkers , Acute Kidney Injury/etiologyABSTRACT
OBJECTIVES: To investigate the independent association of platelet transfusion with hospital mortality and key relevant clinical outcomes in cardiac surgery. DESIGN: A single-center, propensity score-matched, retrospective, cohort study. SETTING: At an American tertiary teaching hospital data from the Medical Information Mart for Intensive Care III and IV databases from 2001 to 2019. PARTICIPANTS: Consecutive adults undergoing coronary artery bypass graft and/or cardiac valvular surgery. INTERVENTIONS: Platelet transfusion during perioperative intensive care unit (ICU) admission. MEASUREMENTS AND MAIN RESULTS: Overall, 12,043 adults met the study inclusion criteria. Of these, 1,621 (13.5%) received apheresis-leukoreduced platelets, with a median of 1.19 units per recipient (IQR: 0.93-1.19) at a median of 1.78 hours (IQR: 0.75-4.25) after ICU admission. The platelet count was measured in 1,176 patients (72.5%) before transfusion, with a median count of 120 × 109/L (IQR: 89.0-157.0), and only 53 (3.3%) had platelet counts below 50 × 109/L. After propensity matching of 1,046 platelet recipients with 1,046 controls, perioperative platelet transfusion carried no association with in-hospital mortality (odds ratio [OR]: 1.28; 99% CI: 0.49-3.35; p = 0.4980). However, it was associated with a pattern of decreased odds of suspected infection (eg, respiratory infection, urinary tract infection, septicaemia, or other; OR: 0.70; 99% CI: 0.50-0.97; p = 0.0050), days in the hospital (adjusted mean difference [AMD]: 0.86; 99% CI: -0.27 to 1.98; p = 0.048), or days in intensive care (AMD 0.83; 99% CI: -0.15 to 1.82; p = 0.0290). CONCLUSIONS: Platelet transfusion was not associated with hospital mortality, but it was associated with decreased odds of suspected infection and with shorter ICU and hospital stays.
Subject(s)
Cardiac Surgical Procedures , Platelet Transfusion , Adult , Humans , Cohort Studies , Retrospective Studies , Blood TransfusionABSTRACT
INTRODUCTION: Fresh frozen plasma (FFP) transfusion in the intensive care unit (ICU) is commonly used to treat coagulopathy and bleeding in cardiac surgery, despite suggestion that it may increase the risk of morbidity and mortality through mechanisms such as fluid overload and infection. METHODS: We retrospectively studied consecutive adults undergoing cardiac surgery from the Medical Information Mart for Intensive Care III and IV databases. We applied propensity score matching to investigate the independent association of within-ICU FFP transfusion with mortality and other key clinical outcomes. RESULTS: Of our 12,043 adults who met inclusion criteria, 1585 (13.2%) received perioperative FFP with a median of 2.48 units per recipient (interquartile range [IQR]: 2.04, 4.33) at a median time of 1.83 h (IQR: 0.75, 3.75) after ICU admission. After propensity matching of 952 FFP recipients to 952 controls, we found no significant association between FFP use and hospital mortality (odds ratio (OR): 1.58; 99% confidence interval (CI): 0.57, 3.71), suspected infection (OR: 0.72; 99% CI: 0.49, 1.08), or acute kidney injury (OR: 1.23; 99% CI: 0.91, 1.67). However, FFP was associated with increased days in hospital (adjusted mean difference (AMD): 1.28; 99% CI: 0.27, 2.41; p = .0050), days in intensive care (AMD: 1.28; 99% CI: 0.27, 2.28; p = .0011), and chest tube output in millilitres up to 8 h after transfusion (AMD: 92.98; 99% CI: 52.22, 133.74; p < .0001). CONCLUSIONS: After propensity matching, FFP transfusion was not associated with increased hospital mortality, but was associated with increased length of stay and no decrease in bleeding in the early post-transfusion period.
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OBJECTIVES: The association of cryoprecipitate transfusion with patient outcomes after cardiac surgery is unclear. We aimed to investigate the predictors of, and outcomes associated with, postoperative cryoprecipitate transfusion in cardiac surgery patients. METHODS: We used the Medical Information Mart for Intensive Care III and IV databases. We included adults undergoing cardiac surgery, and propensity score matched cryoprecipitate-treated patients to controls. Using the matched cohort, we investigated the association of cryoprecipitate use with clinical outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were infection, acute kidney injury, intensive care unit length of stay, hospital length of stay, and chest tube output at 2-hour intervals. RESULTS: Of 12,043 eligible patients, 283 (2.35%) patients received cryoprecipitate. The median dose was 5.83 units (IQR 4.17-7.24) given at a median first transfusion time of 1.75 hours (IQR 0.73-4.46) after intensive care unit admission. After propensity scoring, we matched 195 cryoprecipitate recipients to 743 controls. Postoperative cryoprecipitate transfusion was not significantly associated with in-hospital mortality (odds ratio [OR] 1.10; 99% confidence interval [CI] 0.43-2.84; p=0.791), infection (OR 0.77; 99% CI 0.45-1.34; p=0.220), acute kidney injury (OR 1.03; 99% CI 0.65-1.62; p=0.876) or cumulative chest tube output (adjusted mean difference 8 hrs post transfusion, 11 mL; 99% CI -104 to 125; p=0.804). CONCLUSIONS: Although cryoprecipitate was typically given to sicker patients with more bleeding, its administration was not associated with worse outcomes. Large, multicentred studies are warranted to further elucidate cryoprecipitate's safety profile and patterns of use in cardiac surgery.
Subject(s)
Blood Transfusion , Cardiac Surgical Procedures , Adult , Humans , Cardiac Surgical Procedures/adverse effects , Hemorrhage/etiology , Retrospective StudiesABSTRACT
OBJECTIVE: A study was undertaken to assess whether cerebral small vessel disease (SVD) computed tomographic (CT) biomarkers are associated with long-term outcome after intracerebral hemorrhage. METHODS: We performed a prospective, community-based cohort study of adults diagnosed with spontaneous intracerebral hemorrhage between June 1, 2010 and May 31, 2013. A neuroradiologist rated the diagnostic brain CT for acute intracerebral hemorrhage features and SVD biomarkers. We used severity of white matter lucencies and cerebral atrophy, and the number of lacunes to calculate the CT SVD score. We assessed the association between CT SVD biomarkers and either death, or death or dependence (modified Rankin Scale scores = 4-6) 1 year after first-ever intracerebral hemorrhage using logistic regression, adjusting for known predictors of outcome. RESULTS: Within 1 year of intracerebral hemorrhage, 224 (56%) of 402 patients died. In separate models, 1-year death was associated with severe atrophy (adjusted odds ratio [aOR] = 2.54, 95% confidence interval [CI] = 1.44-4.49, p = 0.001) but not lacunes or severe white matter lucencies, and CT SVD sum score ≥ 1 (aOR = 2.50, 95% CI = 1.40-4.45, p = 0.002). Two hundred seventy-seven (73%) of 378 patients with modified Rankin Scale data were dead or dependent at 1 year. In separate models, 1-year death or dependence was associated with severe atrophy (aOR = 3.67, 95% CI = 1.71-7.89, p = 0.001) and severe white matter lucencies (aOR = 2.18, 95% CI = 1.06-4.51, p = 0.035) but not lacunes, and CT SVD sum score ≥ 1 (aOR = 2.81, 95% CI = 1.45-5.46, p = 0.002). INTERPRETATION: SVD biomarkers on the diagnostic brain CT are associated with 1-year death and dependence after intracerebral hemorrhage, independent of known predictors of outcome. ANN NEUROL 2021;89:266-279.
Subject(s)
Brain/diagnostic imaging , Cerebral Small Vessel Diseases/diagnostic imaging , Hemorrhagic Stroke/diagnostic imaging , Stroke, Lacunar/diagnostic imaging , White Matter/diagnostic imaging , Aged , Aged, 80 and over , Atrophy , Brain/pathology , Cohort Studies , Female , Hemorrhagic Stroke/physiopathology , Humans , Logistic Models , Male , Middle Aged , Mortality , Multivariate Analysis , Odds Ratio , Prognosis , Prospective Studies , Severity of Illness Index , Tomography, X-Ray ComputedABSTRACT
Cardiac troponin is well known as a highly specific marker of cardiomyocyte damage, and has significant diagnostic accuracy in many cardiac conditions. However, the value of elevated recipient troponin in diagnosing adverse outcomes in heart transplant recipients is uncertain. We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020. We generated summary sensitivity, specificity, and Bayesian areas under the curve (BAUC) using bivariate Bayesian modelling, and standardised mean differences (SMDs) to quantify the diagnostic relationship of recipient troponin and adverse outcomes following cardiac transplant. We included 27 studies with 1,684 cardiac transplant recipients. Patients with acute rejection had a statistically significant late elevation in standardised troponin measurements taken at least 1 month postoperatively (SMD 0.98, 95% CI 0.33-1.64). However, pooled diagnostic accuracy was poor (sensitivity 0.414, 95% CrI 0.174-0.696; specificity 0.785, 95% CrI 0.567-0.912; BAUC 0.607, 95% CrI 0.469-0.723). In summary, late troponin elevation in heart transplant recipients is associated with acute cellular rejection in adults, but its stand-alone diagnostic accuracy is poor. Further research is needed to assess its performance in predictive modelling of adverse outcomes following cardiac transplant. Systematic Review Registration: identifier CRD42021227861.
Subject(s)
Graft Rejection , Heart Transplantation , Adult , Bayes Theorem , Biomarkers , Graft Rejection/diagnosis , Heart Transplantation/adverse effects , Humans , TroponinABSTRACT
BACKGROUND: The epidemiology of persistent postoperative opioid use at least 3 months after cardiac surgery is poorly characterised despite its potential public health importance. METHODS: We searched MEDLINE, Embase, and Google Scholar from inception to December 2021 and included studies reporting the rate and risk factors of persistent postoperative opioid use after cardiac surgery in opioid-naive and opioid-exposed patients. We recorded incidence rates and odds ratios (ORs) with 95% confidence intervals (CIs) for risk factors from individual studies and used random-effects inverse variance modelling to generate pooled estimates. RESULTS: From 10 studies involving 112 298 patients, the pooled rate of persistent postoperative opioid use in opioid-naive patients was 5.7% (95% CI: 4.2-7.2%). Risk factors included female sex (OR 1.18; 95% CI: 1.09-1.29), smoking (OR 1.34; 95% CI: 1.06-1.69), alcohol use (OR 1.43; 95% CI: 1.17-1.76), congestive cardiac failure (OR 1.17; 95% CI: 1.08-1.27), diabetes mellitus (OR 1.21; 95% CI: 1.07-1.37), chronic lung disease (OR 1.42; 95% CI: 1.16-1.75), chronic kidney disease (OR 1.35; 95% CI: 1.08-1.68), and length of hospital stay (per day) (OR 1.03; 95% CI: 1.02-1.04). CONCLUSIONS: Persistent postoperative opioid use after cardiac surgery affects at least one in 20 patients. The identification of risk factors, such as female sex, smoking, alcohol use, congestive cardiac failure, diabetes mellitus, chronic lung disease, chronic kidney disease, and length of hospital stay, should help target interventions aimed at decreasing its prevalence.
Subject(s)
Cardiac Surgical Procedures , Heart Failure , Opioid-Related Disorders , Analgesics, Opioid/adverse effects , Cardiac Surgical Procedures/adverse effects , Female , Heart Failure/chemically induced , Humans , Opioid-Related Disorders/etiology , Pain, Postoperative/drug therapy , Pain, Postoperative/epidemiologyABSTRACT
OBJECTIVES: Neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker that has been evaluated across a variety of surgical disciplines and is widely predictive of poor postoperative outcome, but its value in cardiac surgery is unclear. The authors did this systematic review and meta-analysis to determine the impact of elevated perioperative NLR on survival after cardiac surgery. DESIGN: Systematic review and meta-analysis of study-level data. SETTING: Multiple hospitals involved in an international pool of studies. PARTICIPANTS: Adults undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors searched multiple databases from inception until November 2020. They generated summary hazard ratios (HR) and odds ratios (OR) for the association of elevated preoperative NLR with long-term and short-term mortality following cardiac surgery. They separately reported on elevated postoperative NLR. Between-study heterogeneity was explored using metaregression. The authors included 12 studies involving 13,262 patients undergoing cardiac surgery. Elevated preoperative NLR was associated with worse long-term (>30 days) (hazard ratio [HR] 1.56; 95% CI [confidence interval], 1.18-2.06; 8 studies) and short-term (<30 days) mortality (OR 3.18; 95% CI, 1.90-5.30; 7 studies). One study reported the association of elevated postoperative NLR with long-term mortality (HR 8.58; 95% CI, 2.55-28.85). There was considerable between-study heterogeneity for the analysis of long-term mortality (I2 statistic 94.39%), which mostly was explained by study-level variables, such as the number of variables adjusted for by included studies and how many of these significantly increased the risk of long-term mortality, high risk of bias, and number of study centers, as well as participant level factors, such as average participant age and hypertension prevalence. CONCLUSIONS: Perioperative NLR is an independent predictor of short-term and long-term postoperative mortality following cardiac surgery. Further research is required to determine which patient-level factors modify the prognostic value of NLR and to evaluate its role in routine clinical practice.
Subject(s)
Cardiac Surgical Procedures , Neutrophils , Adult , Biomarkers , Cardiac Surgical Procedures/adverse effects , Humans , Lymphocytes , PrognosisABSTRACT
BACKGROUND: Machine learning (ML) models are promising tools for predicting adverse postoperative outcomes in cardiac surgery, yet have not translated to routine clinical use. We conducted a systematic review and meta-analysis to assess the predictive performance of ML approaches. METHODS: We conducted an electronic search to find studies assessing ML and traditional statistical models to predict postoperative outcomes. Our primary outcome was the concordance (C-) index of discriminative performance. Using a Bayesian meta-analytic approach we pooled the C-indices with the 95% credible interval (CrI) across multiple outcomes comparing ML methods to logistic regression (LR) and clinical scoring tools. Additionally, we performed critical difference and sensitivity analysis. RESULTS: We identified 2792 references from the search of which 51 met inclusion criteria. Two postoperative outcomes were amenable for meta-analysis: 30-day mortality and in-hospital mortality. For 30-day mortality, the pooled C-index and 95% CrI were 0.82 (0.79-0.85), 0.80 (0.77-0.84), 0.78 (0.74-0.82) for ML models, LR, and scoring tools respectively. For in-hospital mortality, the pooled C-index was 0.81 (0.78-0.84) and 0.79 (0.73-0.84) for ML models and LR, respectively. There were no statistically significant results indicating ML superiority over LR. CONCLUSION: In cardiac surgery patients, for the prediction of mortality, current ML methods do not have greater discriminative power over LR as measured by the C-index.
Subject(s)
Cardiac Surgical Procedures , Machine Learning , Bayes Theorem , Cardiac Surgical Procedures/adverse effects , Hospital Mortality , Humans , Logistic ModelsABSTRACT
The investigation of children presenting with infantile and childhood epileptic encephalopathies (ICEE) is challenging due to diverse aetiologies, overlapping phenotypes and the relatively low diagnostic yield of MRI, electroencephalography (EEG) and biochemical investigations. Careful history and thorough examination remain essential as these may identify an acquired cause or indicate more targeted investigation for a genetic disorder. Whole exome sequencing (WES) with analysis of a panel of candidate epilepsy genes has increased the diagnostic yield. Whole genome sequencing (WGS), particularly as a trio with both parents' DNA, is likely to supersede WES. Modern genomic investigation impacts on the timing and necessity of other testing. We propose a structured approach for children presenting with ICEE where there is diagnostic uncertainty, emphasising the importance of WGS or, if unavailable, WES early in the investigative process. We note the importance of expert review of all investigations, including radiology, neurophysiology and biochemistry, to confirm the technique used was appropriate as well as the results. It is essential to counsel families on the risks associated with the procedures, the yield of the procedures, findings that are difficult to interpret and implication of 'negative' results. Where children remain without a diagnosis despite comprehensive investigation, we note the importance of ongoing multidisciplinary care.
Subject(s)
Brain Diseases , Epilepsy , Child , Epilepsy/diagnosis , Epilepsy/genetics , Genomics , Humans , Referral and Consultation , Exome SequencingABSTRACT
PURPOSE: Platelet count, mean platelet volume, platelet distribution width, and plateletcrit are standard indices of platelet activation that have been studied in retinal vein occlusion (RVO) and its subtypes: branch retinal vein occlusion and central retinal vein occlusion. This systematic review and meta-analysis aimed to assess the association between these platelet parameters and RVO. METHODS: We searched for studies investigating the association between these platelet indices and RVO in multiple online databases from inception to August 2020. Mean differences and the associated confidence intervals were obtained and calculated for each included study and pooled using random-effects inverse variance modeling. Meta-regression was used to explore interstudy and intrastudy heterogeneity. RESULTS: Thousand three hundred and twenty-five unique studies were screened, from which 24 studies encompassing 2,718 patients were included. Mean platelet volume and platelet distribution width were significantly elevated in RVO, with pooled mean differences of 0.45 fL (95% CI 0.24-0.66, P < 0.0001) and 1.43% (95% CI 0.57-2.29, P = 0.0011), respectively. Platelet count and plateletcrit were not significantly associated with RVO. Mean platelet volume was also independently elevated in branch retinal vein occlusion and central retinal vein occlusion. CONCLUSION: Mean platelet volume and platelet distribution width are significantly elevated in RVO. Further research is required to explore the independence and potential prognostic significance of these associations.
Subject(s)
Retinal Vein Occlusion/blood , Retinal Vein/pathology , Humans , Mean Platelet Volume , Retinal Vein Occlusion/diagnosis , Risk FactorsABSTRACT
OBJECTIVE(S): Using the Medical Information Mart for Intensive Care III (MIMIC-III) database, we compared the performance of machine learning (ML) to the to the established gold standard scoring tool (POAF Score) in predicting postoperative atrial fibrillation (POAF) during intensive care unit (ICU) admission after cardiac surgery. METHODS: Random forest classifier (RF), decision tree classifier (DT), logistic regression (LR), K neighbours classifier (KNN), support vector machine (SVM), and gradient boosted machine (GBM) were compared to the POAF Score. Cross-validation was used to assess the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of ML models. POAF Score performance confidence intervals were generated using 1,000 bootstraps. Risk profiles for GBM were generated using Shapley additive values. RESULTS: A total of 6,349 ICU admissions encompassing 6,040 patients were included. POAF occurred in 1,364 of the 6,349 admissions (21.5%). For predicting POAF during ICU admission after cardiac surgery, GBM, LR, RF, KNN, SVM and DT achieved an AUC of 0.74 (0.71-0.77), 0.73 (0.71-0.75), 0.72 (0.69-0.75), 0.68 (0.67-0.69), 0.67 (0.66-0.68) and 0.59 (0.55-0.63) respectively. The POAF Score AUC was 0.63 (0.62-0.64). Shapley additive values analysis of GBM generated patient level explanations for each prediction. CONCLUSION: Machine learning models based on readily available preoperative data can outperform clinical scoring tools for predicting POAF during ICU admission after cardiac surgery. Explanatory models are shown to have potential in personalising POAF risk profiles for patients by illustrating probabilistic input variable contributions. Future research is required to evaluate the clinical utility and safety of implementing ML-driven tools for POAF prediction.
Subject(s)
Atrial Fibrillation , Cardiac Surgical Procedures , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Cardiac Surgical Procedures/adverse effects , Humans , Intensive Care Units , Machine Learning , ROC CurveABSTRACT
BACKGROUND: The prognostic value of asymptomatic perioperative troponin rise in vascular surgery is unclear. We conducted this systematic review and meta-analysis to determine the significance of clinical and subclinical troponin elevation after vascular surgery. METHODS: We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library, without language restriction, from inception to May 2019 and included studies that reported associations between elevated postoperative troponin and short-term mortality, major adverse cardiac events (MACEs), or long-term mortality in a vascular surgery cohort. We synthesized study-level data on the maximally adjusted estimates using mixed effects modeling to generate summary odds ratios (ORs) for fixed-interval outcomes and summary hazard ratios for long-term mortality. Between-study heterogeneity was assessed with meta-regression. Methodologic quality and publication bias were formally assessed. RESULTS: We included 24 studies involving 11,657 participants. Postoperative troponin was found to have a strong, positive association with short-term mortality (OR, 4.95; 95% confidence interval [CI], 2.87-8.52; 7 studies; 2661 people) and MACEs (OR, 5.33; 95% CI, 1.59-17.82; 12 studies; 5047 people) independent of meeting the criteria for myocardial infarction. Subclinical postoperative troponin elevation was further demonstrated to be associated with greater long-term mortality (hazard ratio, 1.94; 95% CI, 1.56-2.42; 13 studies; 7630 people; median follow-up, 24 months). Time to troponin sampling, hypertension, and type of surgery partially accounted for between-study heterogeneity. The methodologic quality of included studies was variable, and publication bias was not detected. CONCLUSIONS: Elevated postoperative troponin is strongly prognostic of worse survival and greater likelihood of MACEs after vascular surgery, regardless of whether symptoms of myocardial ischemia are present. These data support the benefit of postoperative troponin monitoring in identifying patients at increased risk of worse outcomes and who may be candidates for personalized preventive interventions.