Thongprayoon, Charat

Background: Black kidney transplant recipients have worse allograft outcomes compared to White recipients. The feature importance and feature interaction network analysis framework of machine learning random forest (RF) analysis may provide an understanding of RF structures to design strategies to prevent acute rejection among Black recipients. Methods: We conducted tree-based RF feature importance of Black kidney transplant recipients in United States from 2015 to 2019 in the UNOS database using the number of nodes, accuracy decrease, gini decrease, times_a_root, p value, and mean minimal depth. Feature interaction analysis was also performed to evaluate the most frequent occurrences in the RF classification run between correlated and uncorrelated pairs. Results: A total of 22,687 Black kidney transplant recipients were eligible for analysis. Of these, 1330 (6%) had acute rejection within 1 year after kidney transplant. Important variables in the RF models for acute rejection among Black kidney transplant recipients included recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration. The three most frequent interactions consisted of two numerical variables, including recipient age:donor age, recipient age:serum albumin, and recipient age:BMI, respectively. Conclusions: The application of tree-based RF feature importance and feature interaction network analysis framework identified recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration as important variables in the RF models for acute rejection among Black kidney transplant recipients in the United States.

Background: Lactic acidosis is a heterogeneous condition with multiple underlying causes and associated outcomes. The use of multi-dimensional patient data to subtype lactic acidosis can personalize patient care. Machine learning consensus clustering may identify lactic acidosis subgroups with unique clinical profiles and outcomes. Methods: We used the Medical Information Mart for Intensive Care III database to abstract electronic medical record data from patients admitted to intensive care units (ICU) in a tertiary care hospital in the United States. We included patients who developed lactic acidosis (defined as serum lactate ≥ 4 mmol/L) within 48 h of ICU admission. We performed consensus clustering analysis based on patient characteristics, comorbidities, vital signs, organ supports, and laboratory data to identify clinically distinct lactic acidosis subgroups. We calculated standardized mean differences to show key subgroup features. We compared outcomes among subgroups. Results: We identified 1919 patients with lactic acidosis. The algorithm revealed three best unique lactic acidosis subgroups based on patient variables. Cluster 1 (n = 554) was characterized by old age, elective admission to cardiac surgery ICU, vasopressor use, mechanical ventilation use, and higher pH and serum bicarbonate. Cluster 2 (n = 815) was characterized by young age, admission to trauma/surgical ICU with higher blood pressure, lower comorbidity burden, lower severity index, and less vasopressor use. Cluster 3 (n = 550) was characterized by admission to medical ICU, history of liver disease and coagulopathy, acute kidney injury, lower blood pressure, higher comorbidity burden, higher severity index, higher serum lactate, and lower pH and serum bicarbonate. Cluster 3 had the worst outcomes, while cluster 1 had the most favorable outcomes in terms of persistent lactic acidosis and mortality. Conclusions: Consensus clustering analysis synthesized the pattern of clinical and laboratory data to reveal clinically distinct lactic acidosis subgroups with different outcomes.

Background: Lactic acidosis is the most common cause of anion gap metabolic acidosis in the intensive care unit (ICU), associated with poor outcomes including mortality. We sought to compare machine learning (ML) approaches versus logistic regression analysis for prediction of mortality in lactic acidosis patients admitted to the ICU. Methods: We used the Medical Information Mart for Intensive Care (MIMIC-III) database to identify ICU adult patients with lactic acidosis (serum lactate ≥4 mmol/L). The outcome of interest was hospital mortality. We developed prediction models using four ML approaches consisting of random forest (RF), decision tree (DT), extreme gradient boosting (XGBoost), artificial neural network (ANN), and statistical modeling with forward stepwise logistic regression using the testing dataset. We then assessed model performance using area under the receiver operating characteristic curve (AUROC), accuracy, precision, error rate, Matthews correlation coefficient (MCC), F1 score, and assessed model calibration using the Brier score, in the independent testing dataset. Results: Of 1919 lactic acidosis ICU patients, 1535 and 384 were included in the training and testing dataset, respectively. Hospital mortality was 30%. RF had the highest AUROC at 0.83, followed by logistic regression 0.81, XGBoost 0.81, ANN 0.79, and DT 0.71. In addition, RF also had the highest accuracy (0.79), MCC (0.45), F1 score (0.56), and lowest error rate (21.4%). The RF model was the most well-calibrated. The Brier score for RF, DT, XGBoost, ANN, and multivariable logistic regression was 0.15, 0.19, 0.18, 0.19, and 0.16, respectively. The RF model outperformed multivariable logistic regression model, SOFA score (AUROC 0.74), SAP II score (AUROC 0.77), and Charlson score (AUROC 0.69). Conclusion: The ML prediction model using RF algorithm provided the highest predictive performance for hospital mortality among ICU patient with lactic acidosis.

ABSTRACT Background Hospitalized patients with hypokalemia are heterogeneous and cluster analysis, an unsupervised machine learning methodology, may discover more precise and specific homogeneous groups within this population of interest. Our study aimed to cluster patients with hypokalemia at hospital admission using an unsupervised machine learning approach and assess the mortality risk among these distinct clusters. Methods We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities and laboratory data among 4763 hospitalized adult patients with admission serum potassium ≤3.5 mEq/L. We calculated the standardized mean difference of each variable and used the cutoff of ±0.3 to identify each cluster's key features. We assessed the association of the hypokalemia cluster with hospital and 1-year mortality. Results Consensus cluster analysis identified three distinct clusters that best represented patients’ baseline characteristics. Cluster 1 had 1150 (32%) patients, cluster 2 had 1344 (28%) patients and cluster 3 had 1909 (40%) patients. Based on the standardized difference, patients in cluster 1 were younger, had less comorbidity burden but higher estimated glomerular filtration rate (eGFR) and higher hemoglobin; patients in cluster 2 were older, more likely to be admitted for cardiovascular disease and had higher serum sodium and chloride levels but lower eGFR, serum bicarbonate, strong ion difference (SID) and hemoglobin, while patients in cluster 3 were older, had a greater comorbidity burden, higher serum bicarbonate and SID but lower serum sodium, chloride and eGFR. Compared with cluster 1, cluster 2 had both higher hospital and 1-year mortality, whereas cluster 3 had higher 1-year mortality but comparable hospital mortality. Conclusion Our study demonstrated the use of consensus clustering analysis in the heterogeneous cohort of hospitalized hypokalemic patients to characterize their patterns of baseline clinical and laboratory data into three clinically distinct clusters with different mortality risks.

Background: We aimed to cluster patients with acute kidney injury at hospital admission into clinically distinct subtypes using an unsupervised machine learning approach and assess the mortality risk among the distinct clusters. Methods: We performed consensus clustering analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 4289 hospitalized adult patients with acute kidney injury at admission. The standardized difference of each variable was calculated to identify each cluster’s key features. We assessed the association of each acute kidney injury cluster with hospital and one-year mortality. Results: Consensus clustering analysis identified four distinct clusters. There were 1201 (28%) patients in cluster 1, 1396 (33%) patients in cluster 2, 1191 (28%) patients in cluster 3, and 501 (12%) patients in cluster 4. Cluster 1 patients were the youngest and had the least comorbidities. Cluster 2 and cluster 3 patients were older and had lower baseline kidney function. Cluster 2 patients had lower serum bicarbonate, strong ion difference, and hemoglobin, but higher serum chloride, whereas cluster 3 patients had lower serum chloride but higher serum bicarbonate and strong ion difference. Cluster 4 patients were younger and more likely to be admitted for genitourinary disease and infectious disease but less likely to be admitted for cardiovascular disease. Cluster 4 patients also had more severe acute kidney injury, lower serum sodium, serum chloride, and serum bicarbonate, but higher serum potassium and anion gap. Cluster 2, 3, and 4 patients had significantly higher hospital and one-year mortality than cluster 1 patients (p < 0.001). Conclusion: Our study demonstrated using machine learning consensus clustering analysis to characterize a heterogeneous cohort of patients with acute kidney injury on hospital admission into four clinically distinct clusters with different associated mortality risks.

Background: The goal of this study was to categorize patients with abnormal serum phosphate upon hospital admission into distinct clusters utilizing an unsupervised machine learning approach, and to assess the mortality risk associated with these clusters. Methods: We utilized the consensus clustering approach on demographic information, comorbidities, principal diagnoses, and laboratory data of hypophosphatemia (serum phosphate ≤ 2.4 mg/dL) and hyperphosphatemia cohorts (serum phosphate ≥ 4.6 mg/dL). The standardized mean difference was applied to determine each cluster’s key features. We assessed the association of the clusters with mortality. Results: In the hypophosphatemia cohort (n = 3113), the consensus cluster analysis identified two clusters. The key features of patients in Cluster 2, compared with Cluster 1, included: older age; a higher comorbidity burden, particularly hypertension; diabetes mellitus; coronary artery disease; lower eGFR; and more acute kidney injury (AKI) at admission. Cluster 2 had a comparable hospital mortality (3.7% vs. 2.9%; p = 0.17), but a higher one-year mortality (26.8% vs. 14.0%; p < 0.001), and five-year mortality (20.2% vs. 44.3%; p < 0.001), compared to Cluster 1. In the hyperphosphatemia cohort (n = 7252), the analysis identified two clusters. The key features of patients in Cluster 2, compared with Cluster 1, included: older age; more primary admission for kidney disease; more history of hypertension; more end-stage kidney disease; more AKI at admission; and higher admission potassium, magnesium, and phosphate. Cluster 2 had a higher hospital (8.9% vs. 2.4%; p < 0.001) one-year mortality (32.9% vs. 14.8%; p < 0.001), and five-year mortality (24.5% vs. 51.1%; p < 0.001), compared with Cluster 1. Conclusion: Our cluster analysis classified clinically distinct phenotypes with different mortality risks among hospitalized patients with serum phosphate derangements. Age, comorbidities, and kidney function were the key features that differentiated the phenotypes.

Background: Sleep apnea is one of the most common conditions around the world. This disorder can significantly impact cardiovascular morbidity and mortality. Atrial overdrive pacing (AOP) is a treatment modality that can potentially decrease respiratory events. There is currently a lack of evidence to confirm the benefits of AOP. We aimed to assess the impact of AOP in patients with obstructive sleep apnea (OSA), central sleep apnea (CSA), and mixed type. Methods: A literature search for studies that reported the impact on apnea–hypopnea index (AHI) by cardiac implantable electronic devices with different pacing modes was conducted using MEDLINE, Embase, and Cochrane Database from inception through July 2020. Pooled standard mean difference with 95%CI was calculated using a random-effects model. Results: Fifteen studies, including thirteen randomized studies and two observational studies containing 440 patients, were identified. The standard mean difference in apnea–hypopnea index of atrial overdrive pacing demonstrated less duration of apnea/hypopnea in patients with atrial overdrive pacing (AOP) (SMD −0.29, 95%CI: −0.48, −0.10, I2 = 57%). Additional analysis was performed to assess the effect of atrial overdrive pacing in patients with or without severe sleep apnea syndrome (mean AHI < 30 defined as non-severe). There was no statistically significant difference in standardized mean in AHI in both subgroups between AOP and control groups (SMD −0.25, severe sleep apnea syndrome SMD −0.03, I2 = 0.00%). Conclusions: AOP was associated with a statistically significant reduction in AHI, but the magnitude of reduction was small. AOP may potentially be used as an adjunctive treatment with other modalities in treating patients with sleep apnea.

Abstract BACKGROUND: Rituximab (RTX) has been previously reported as directed treatment in patients with connective-tissue disease-related interstitial lung diseases (CTD-ILD). A systematic assessment of treatment effect size on pulmonary function outcomes and related adverse effects in patients with CTD-ILD has not been previously reported.METHODS: We performed a systematic review and meta-analysis of published reports from PubMed, Embase, and Cochrane Libraries. Randomized and non-randomized controlled trials, case-control, cohort, and case series (with five or more cases) containing individual pulmonary function data and adverse effects were included. Study endpoints were pre and post treatment change in percent predicted forced vital capacity (FVC %) and diffusion capacity for carbon monoxide (DLCO%), along with reported drug-related adverse events. RESULTS: Twenty studies totaling 411 patients were identified with 14 included in the meta-analysis of pulmonary function and six in the descriptive review. Random effects meta-analysis of pre and post-treatment pulmonary function findings demonstrated increases in FVC% (n =296) (mean difference (MD) 4.57%, [95% CI 2.63-6.51]) and DLCO% (n = 246) (MD 5.0% [95% CI 2.71-7.29]) after RTX treatment. RTX treatment-related adverse effects were reported in 13.6% of the pooled cohort. CONCLUSIONS: A systematic assessment of post-treatment effect size suggests a potential role for RTX in stabilizing or improving lung function in patients with CTD-ILD, with a modest but not insignificant adverse effect profile.

Background The presence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) dramatically increases higher morbidity and mortality. Recent studies have suggested that early rhythm control may alleviate the burden of poor outcomes. Currently, there remain limited data on whether rhythm or rate control has better efficacy. This study sought to compare both strategies in HFpEF patients with AF. Methods Databases were searched throughout 2020. Studies that reported cardiovascular outcomes amongst HFpEF patients with AF who received either rhythm or rate control were included. Estimates of the effects from the individual studies were extracted and combined using random-effects, a generic inverse variance method of DerSimonian and Laird. Results Five observational studies were included in the analysis, consisting of 16,953 patients, 13.8% of whom were receiving rhythm control. In comparison with rate control, rhythm control was associated with decreased overall mortality rates (pooled RR 0.85, 95% CI 0.75–0.95, with I2 = 0%, p value = 0.009). Conclusions In HFpEF patients with AF, rhythm control was associated with lower mortality, compared to rate control. Further studies are warranted to validate our observation.

Background and Objectives: Despite the association between hyperchloremia and adverse outcomes, mortality risks among patients with hyperchloremia have not consistently been observed among all studies with different patient populations with hyperchloremia. The objective of this study was to characterize hyperchloremic patients at hospital admission into clusters using an unsupervised machine learning approach and to evaluate the mortality risk among these distinct clusters. Materials and Methods: We performed consensus cluster analysis based on demographic information, principal diagnoses, comorbidities, and laboratory data among 11,394 hospitalized adult patients with admission serum chloride of >108 mEq/L. We calculated the standardized mean difference of each variable to identify each cluster’s key features. We assessed the association of each hyperchloremia cluster with hospital and one-year mortality. Results: There were three distinct clusters of patients with admission hyperchloremia: 3237 (28%), 4059 (36%), and 4098 (36%) patients in clusters 1 through 3, respectively. Cluster 1 was characterized by higher serum chloride but lower serum sodium, bicarbonate, hemoglobin, and albumin. Cluster 2 was characterized by younger age, lower comorbidity score, lower serum chloride, and higher estimated glomerular filtration (eGFR), hemoglobin, and albumin. Cluster 3 was characterized by older age, higher comorbidity score, higher serum sodium, potassium, and lower eGFR. Compared with cluster 2, odds ratios for hospital mortality were 3.60 (95% CI 2.33–5.56) for cluster 1, and 4.83 (95% CI 3.21–7.28) for cluster 3, whereas hazard ratios for one-year mortality were 4.49 (95% CI 3.53–5.70) for cluster 1 and 6.96 (95% CI 5.56–8.72) for cluster 3. Conclusions: Our cluster analysis identified three clinically distinct phenotypes with differing mortality risks in hospitalized patients with admission hyperchloremia.