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Publication Record


COVID-19 Severity Is Tripled in the Diabetes Community: A Prospective Analysis of the Pandemic's Impact in Type 1 and Type 2 Diabetes.
Gregory JM, Slaughter JC, Duffus SH, Smith TJ, LeStourgeon LM, Jaser SS, McCoy AB, Luther JM, Giovannetti ER, Boeder S, Pettus JH, Moore DJ
(2021) Diabetes Care 44: 526-532
MeSH Terms: COVID-19, Comorbidity, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Electronic Health Records, Female, Hospitalization, Humans, Hypertension, Male, Middle Aged, Odds Ratio, Prospective Studies, Severity of Illness Index
Show Abstract · Added December 7, 2020
OBJECTIVE - To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)-related hospitalization and illness severity in type 1 diabetes.
RESEARCH DESIGN AND METHODS - We conducted a prospective cohort study to identify case subjects with COVID-19 across a regional health care network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity.
RESULTS - We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios of 3.90 (95% CI 1.75-8.69) for hospitalization and 3.35 (95% CI 1.53-7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among patients with type 1 diabetes, glycosylated hemoglobin (HbA), hypertension, race, recent diabetic ketoacidosis, health insurance status, and less diabetes technology use were significantly associated with illness severity.
CONCLUSIONS - Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA) had significant but modest impact compared with comparatively static factors (e.g., race and insurance) in type 1 diabetes, indicating an urgent and continued need to mitigate severe acute respiratory syndrome coronavirus 2 infection risk in this community.
© 2020 by the American Diabetes Association.
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14 MeSH Terms
Timing of Recovery From Moderate to Severe AKI and the Risk for Future Loss of Kidney Function.
Siew ED, Abdel-Kader K, Perkins AM, Greevy RA, Parr SK, Horner J, Vincz AJ, Denton J, Wilson OD, Hung AM, Robinson-Cohen C, Matheny ME
(2020) Am J Kidney Dis 75: 204-213
MeSH Terms: Acute Kidney Injury, Aged, Creatinine, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Male, Prognosis, Recovery of Function, Retrospective Studies, Risk Factors, Severity of Illness Index, Time Factors, United States, Veterans
Show Abstract · Added December 15, 2020
RATIONALE & OBJECTIVE - The extent of recovery of kidney function following acute kidney injury (AKI) is known to be associated with future chronic kidney disease. Less is known about how the timing of recovery affects the rate of future loss of kidney function.
STUDY DESIGN - We performed a retrospective cohort study examining the independent association between the timing of recovery from moderate to severe AKI and future loss of kidney function.
SETTING & PARTICIPANTS - 47,903 adult US veterans with stage 2 or 3 AKI who recovered to within 120% of baseline creatinine level within 90 days of peak injury.
EXPOSURE - The timing of recovery of kidney function from peak inpatient serum creatinine level grouped into 1 to 4, 5 to 10, 11 to 30, and 31 to 90 days.
OUTCOME - A sustained 40% decline in estimated glomerular filtration rate below that calculated from the last serum creatinine level available during the 90-day recovery period or kidney failure (2 outpatient estimated glomerular filtration rates<15mL/min/1.73m, dialysis procedures > 90 days apart, kidney transplantation, or registry within the US Renal Data System).
ANALYTICAL APPROACH - Time to the primary outcome was examined using multivariable Cox proportional hazards regression.
RESULTS - Among 47,903 patients, 29,316 (61%), 10,360 (22%), 4,520 (9%), and 3,707 (8%) recovered within 1 to 4, 5 to 10, 11 to 30, and 31 to 90 days, respectively. With a median follow-up of 42 months, unadjusted incidence rates for the kidney outcome were 2.01, 3.55, 3.86, and 3.68 events/100 person-years, respectively. Compared with 1 to 4 days, recovery within 5 to 10, 11 to 30, and 31 to 90 days was associated with increased rates of the primary outcome: adjusted HRs were 1.33 (95% CI, 1.24-1.43), 1.41 (95% CI, 1.28-1.54), and 1.58 (95% CI, 1.43-1.75), respectively.
LIMITATIONS - Predominately male population, residual confounding, and inability to make causal inferences because of the retrospective observational study design.
CONCLUSIONS - The timing of recovery provides an added dimension to AKI phenotyping and prognostic information regarding the future occurrence of loss of kidney function. Studies to identify effective interventions on the timing of recovery from AKI are warranted.
Published by Elsevier Inc.
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Acute kidney injury risk-based screening in pediatric inpatients: a pragmatic randomized trial.
Van Driest SL, Wang L, McLemore MF, Bridges BC, Fleming GM, McGregor TL, Jones DP, Shirey-Rice J, Gatto CL, Gay JC, Byrne DW, Weitkamp A, Roden DM, Bernard G
(2020) Pediatr Res 87: 118-124
MeSH Terms: Acute Kidney Injury, Adolescent, Age Factors, Biomarkers, Child, Creatinine, Decision Support Systems, Clinical, Female, Hospital Information Systems, Humans, Infant, Inpatients, Intensive Care Units, Pediatric, Length of Stay, Male, Predictive Value of Tests, Reminder Systems, Risk Assessment, Risk Factors, Severity of Illness Index, Tennessee, Time Factors
Show Abstract · Added March 24, 2020
BACKGROUND - Pediatric acute kidney injury (AKI) is common and associated with increased morbidity, mortality, and length of stay. We performed a pragmatic randomized trial testing the hypothesis that AKI risk alerts increase AKI screening.
METHODS - All intensive care and ward admissions of children aged 28 days through 21 years without chronic kidney disease from 12/6/2016 to 11/1/2017 were included. The intervention alert displayed if calculated AKI risk was > 50% and no serum creatinine (SCr) was ordered within 24 h. The primary outcome was SCr testing within 48 h of AKI risk > 50%.
RESULTS - Among intensive care admissions, 973/1909 (51%) were randomized to the intervention. Among those at risk, more SCr tests were ordered for the intervention group than for controls (418/606, 69% vs. 361/597, 60%, p = 0.002). AKI incidence and severity were the same in intervention and control groups. Among ward admissions, 5492/10997 (50%) were randomized to the intervention, and there were no differences between groups in SCr testing, AKI incidence, or severity of AKI.
CONCLUSIONS - Alerts based on real-time prediction of AKI risk increased screening rates in intensive care but not pediatric ward settings. Pragmatic clinical trials provide the opportunity to assess clinical decision support and potentially eliminate ineffective alerts.
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22 MeSH Terms
Identification of drug-specific public TCR driving severe cutaneous adverse reactions.
Pan RY, Chu MT, Wang CW, Lee YS, Lemonnier F, Michels AW, Schutte R, Ostrov DA, Chen CB, Phillips EJ, Mallal SA, Mockenhaupt M, Bellón T, Tassaneeyakul W, White KD, Roujeau JC, Chung WH, Hung SI
(2019) Nat Commun 10: 3569
MeSH Terms: Adoptive Transfer, Adult, Aged, Animals, Carbamazepine, Disease Models, Animal, Female, HLA-B15 Antigen, Humans, Male, Mice, Transgenic, Middle Aged, Receptor-CD3 Complex, Antigen, T-Cell, Receptors, Antigen, T-Cell, alpha-beta, Severity of Illness Index, Skin, Stevens-Johnson Syndrome, T-Lymphocytes, Cytotoxic
Show Abstract · Added March 30, 2020
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αβTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
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Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass.
Krispinsky LT, Stark RJ, Parra DA, Luan L, Bichell DP, Pietsch JB, Lamb FS
(2020) Pediatr Crit Care Med 21: 42-49
MeSH Terms: Acetylcholine, Biomarkers, Cardiac Surgical Procedures, Cardiopulmonary Bypass, Cardiovascular Diseases, Child, Child, Preschool, Cytokines, Endothelium, Vascular, Heart Defects, Congenital, Humans, Infant, Microcirculation, Nitric Oxide, Pilot Projects, Postoperative Complications, Prospective Studies, Severity of Illness Index, Vascular Resistance, Vasodilator Agents, Vasomotor System
Show Abstract · Added July 2, 2019
OBJECTIVES - Cardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants.
DESIGN - Single-center prospective observational cohort pilot study.
SETTING - Pediatric cardiac ICU at a tertiary children's hospital.
PATIENTS - Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion.
MEASUREMENTS AND MAIN RESULTS - Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008).
CONCLUSIONS - Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.
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21 MeSH Terms
Real-world electronic health record identifies antimalarial underprescribing in patients with lupus nephritis.
Xiong WW, Boone JB, Wheless L, Chung CP, Crofford LJ, Barnado A
(2019) Lupus 28: 977-985
MeSH Terms: Adult, Aged, Antimalarials, Cohort Studies, Creatinine, Cross-Sectional Studies, Electronic Health Records, Female, Humans, Logistic Models, Lupus Erythematosus, Systemic, Lupus Nephritis, Male, Middle Aged, Severity of Illness Index, United States
Show Abstract · Added March 25, 2020
Antimalarials (AMs) reduce disease activity and improve survival in patients with systemic lupus erythematosus (SLE), but studies have reported low AM prescribing frequencies. Using a real-world electronic health record cohort, we examined if patient or provider characteristics impacted AM prescribing. We identified 977 SLE cases, 94% of whom were ever prescribed an AM. Older patients and patients with SLE nephritis were less likely to be on AMs. Current age (odds ratio = 0.97,  < 0.01) and nephritis (odds ratio = 0.16,  < 0.01) were both significantly associated with ever AM use after adjustment for sex and race. Of the 244 SLE nephritis cases, only 63% were currently on AMs. SLE nephritis subjects who were currently prescribed AMs were more likely to be followed by a rheumatologist than a nephrologist and less likely to have undergone dialysis or renal transplant (both  < 0.001). Non-current versus current SLE nephritis AM users had higher serum creatinine ( < 0.001), higher urine protein ( = 0.05), and lower hemoglobin levels ( < 0.01). As AMs reduce disease damage and improve survival in patients with SLE, our results demonstrate an opportunity to target future efforts to improve prescribing rates among multi-specialty providers.
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Classifying intracranial stenosis disease severity from functional MRI data using machine learning.
Waddle SL, Juttukonda MR, Lants SK, Davis LT, Chitale R, Fusco MR, Jordan LC, Donahue MJ
(2020) J Cereb Blood Flow Metab 40: 705-719
MeSH Terms: Brain, Case-Control Studies, Cerebral Angiography, Cerebrovascular Circulation, Female, Humans, Image Processing, Computer-Assisted, Machine Learning, Magnetic Resonance Angiography, Middle Aged, Moyamoya Disease, Sensitivity and Specificity, Severity of Illness Index, Young Adult
Show Abstract · Added March 24, 2020
Translation of many non-invasive hemodynamic MRI methods to cerebrovascular disease patients has been hampered by well-known artifacts associated with delayed blood arrival times and reduced microvascular compliance. Using machine learning and support vector machine (SVM) algorithms, we investigated whether arrival time-related artifacts in these methods could be exploited as novel contrast sources to discriminate angiographically confirmed stenotic flow territories. Intracranial steno-occlusive moyamoya patients ( = 53; age = 45 ± 14.2 years; sex = 43 F) underwent (i) catheter angiography, (ii) anatomical MRI, (iii) cerebral blood flow (CBF)-weighted arterial spin labeling, and (iv) cerebrovascular reactivity (CVR)-weighted hypercapnic blood-oxygenation-level-dependent MRI. Mean, standard deviation (std), and 99th percentile of CBF, CVR, CVR, and CVR were calculated in major anterior and posterior flow territories perfused by vessels with vs. without stenosis (≥70%) confirmed by catheter angiography. These and demographic variables were input into SVMs to evaluate discriminatory capacity for stenotic flow territories using k-fold cross-validation and receiver-operating-characteristic-area-under-the-curve to quantify variable combination relevance. Anterior circulation CBF-std, attributable to heterogeneous endovascular signal and prolonged arterial transit times, was the best performing single variable and CVR-mean and CBF-std, both reflective of delayed vascular compliance, were a high-performing two-variable combination (specificity = 0.67; sensitivity = 0.75). Findings highlight the relevance of hemodynamic imaging and machine learning for identifying cerebrovascular impairment.
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14 MeSH Terms
Procalcitonin versus C-reactive protein: review of kinetics and performance for diagnosis of neonatal sepsis.
Eschborn S, Weitkamp JH
(2019) J Perinatol 39: 893-903
MeSH Terms: Bacteria, Biomarkers, C-Reactive Protein, Humans, Infant, Low Birth Weight, Infant, Newborn, Neonatal Sepsis, Procalcitonin, Severity of Illness Index, Virulence
Show Abstract · Added April 16, 2021
Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers, but their diagnostic advantage for neonatal early-onset (EOS) or late-onset (LOS) sepsis is controversial. In a comprehensive literature review we found significant heterogeneity between studies in sample timing, cut-off values, consideration of blood culture results for sepsis classification, and definition of EOS versus LOS. We identified 39 studies directly comparing PCT with CRP, but only four in very low birth weight (VLBW) neonates. The mean sensitivity for EOS, LOS, and EOS + LOS was 73.6%, 88.9%, and 76.5% for PCT, compared to 65.6%, 77.4%, and 66.4% for CRP, respectively. Mean specificity of PCT and CRP was 82.8% versus 82.7% for EOS, 75.6% versus 81.7% for LOS, and 80.4% versus 91.3% for EOS + LOS. More studies directly comparing both biomarkers for EOS and LOS, especially in extremely and very-low-birth-weight infants, are needed to determine their clinical value for guidance of antibiotic therapy in neonatal sepsis.
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Serum Polyunsaturated Fatty Acids Correlate with Serum Cytokines and Clinical Disease Activity in Crohn's Disease.
Scoville EA, Allaman MM, Adams DW, Motley AK, Peyton SC, Ferguson SL, Horst SN, Williams CS, Beaulieu DB, Schwartz DA, Wilson KT, Coburn LA
(2019) Sci Rep 9: 2882
MeSH Terms: Adipokines, Adult, Biomarkers, Case-Control Studies, Crohn Disease, Cytokines, Fatty Acids, Unsaturated, Female, Follow-Up Studies, Humans, Inflammation Mediators, Male, Middle Aged, Prognosis, Prospective Studies, Severity of Illness Index
Show Abstract · Added March 16, 2019
Crohn's disease (CD) has been associated with an increased consumption of n-6 polyunsaturated fatty acid (PUFA), while greater intake of n-3 PUFA has been associated with a reduced risk. We sought to investigate serum fatty acid composition in CD, and associations of fatty acids with disease activity, cytokines, and adipokines. Serum was prospectively collected from 116 CD subjects and 27 non-IBD controls. Clinical disease activity was assessed by the Harvey Bradshaw Index (HBI). Serum fatty acids were measured by gas chromatography. Serum cytokines and adipokines were measured by Luminex assay. Dietary histories were obtained from a subset of patients. Nine serum cytokines and adipokines were increased in CD versus controls. CD subjects had increased percentage serum monounsaturated fatty acids (MUFA), dihomo-gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and oleic acid, but decreased arachidonic acid (AA) versus controls. The % total n-3 fatty acids and % EPA directly correlated with pro-inflammatory cytokine levels and HBI, whereas the % total n-6 fatty acids were inversely correlated with pro-inflammatory cytokine levels and HBI. CD subjects had increased caloric intake versus controls, but no alterations in total fat or PUFA intake. We found differences in serum fatty acids, most notably PUFA, in CD that correlated both with clinical disease activity and inflammatory cytokines. Our findings indicate that altered fatty acid metabolism or utilization is present in CD and is related to disease activity.
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16 MeSH Terms
Preoperative quality-of-life measures predict acute postoperative pain in endoscopic sinus surgery.
Chowdhury NI, Turner JH, Dorminy C, Wu J, Chandra RK
(2019) Laryngoscope 129: 1274-1279
MeSH Terms: Adolescent, Adult, Aged, Chronic Disease, Endoscopy, Female, Humans, Male, Middle Aged, Otorhinolaryngologic Surgical Procedures, Pain, Postoperative, Paranasal Sinuses, Preoperative Period, Prognosis, Quality of Life, Rhinitis, Severity of Illness Index, Sinusitis, Young Adult
Show Abstract · Added July 23, 2020
OBJECTIVES - Recent increases in opioid-related mortality have prompted a critical evaluation of postoperative pain management across all specialties. However, successfully limiting narcotic overprescription requires perioperative identification of patients who are at risk for high postoperative pain. Unfortunately, quality data to guide practice patterns are lacking. We therefore prospectively investigated several possible predictive factors of postoperative pain after endoscopic sinus surgery (ESS).
METHODS - Sixty-four consecutive patients undergoing ESS were enrolled. Baseline 22-item SinoNasal Outcomes Test (SNOT-22) and Short-Form 8 (SF-8) scores were obtained. Pain scores were collected postoperatively using a numeric rating scale. Spearman correlations and univariate linear regression models were used to investigate relationships between postoperative pain, patient factors, and SNOT-22/SF-8 domain scores. Multivariate linear regression was then performed to control for potential confounding variables.
RESULTS - Day-of-surgery pain scores were significantly correlated with the SF-8 role-physical domain (Rs = 0.32, P = 0.04). Whereas SF-8 pain scores were initially nonsignificant, at postoperative day 3 (POD3) the preoperative SF-8 pain score became correlated with self-reported pain (Rs = 0.39, P = 0.02). SNOT-22 total and subdomain scores were not associated with pain scores at any time point. Multivariate linear regression modelling identified baseline SF-8 role-physical and pain scores, smoking status, and undergoing a modified Lothrop procedure as significant independent predictors of POD3 pain (adjusted R = 0.359, P < 0.0001).
CONCLUSION - Baseline patient-reported global quality-of-life measures are associated with postoperative pain after ESS. Large multicenter studies are necessary to validate these findings and investigate additional factors associated with postoperative pain following ESS.
LEVEL OF EVIDENCE - 2c Laryngoscope, 129:1274-1279, 2019.
© 2019 The American Laryngological, Rhinological and Otological Society, Inc.
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