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Serum and Urine Metabolites and Kidney Function

Yeo, Wan-Jin; Surapaneni, Aditya L; Hasson, Denise; Schmidt, Insa M; Sekula, Peggy; Köttgen, Anna; Eckardt, Kai-Uwe; Rebholz, Casey M; Yu, Bing; Waikar, Sushrut S; Rhee, Eugene P; Schrauben, Sarah J; Feldman, Harold I; Vasan, Ramachandran S; Kimmel, Paul L; Coresh, Josef; Grams, Morgan E; Schlosser, Pascal
BACKGROUND:Metabolites represent a read-out of cellular processes underlying states of health and disease. METHODS:We evaluated cross-sectional and longitudinal associations between 1255 serum and 1398 urine known and unknown (denoted with "X" in name) metabolites (Metabolon HD4, 721 detected in both biofluids) and kidney function in 1612 participants of the Atherosclerosis Risk in Communities (ARIC) Study. All analyses were adjusted for clinical and demographic covariates, including for baseline eGFR and UACR in longitudinal analyses. RESULTS:At visit 5 of the ARIC study, the mean age of participants was 76 years (SD 6), 56% were women, mean eGFR was 62 ml/min/1.73m2 (SD 20), and median urine albumin-to-creatinine level (UACR) was 13 mg/g (IQR 25). In cross-sectional analysis, 675 serum and 542 urine metabolites were associated with eGFR (Bonferroni-corrected p < 4.0E-5 for serum analyses and p < 3.6E-5 for urine analyses), including 248 metabolites shared across biofluids. Fewer metabolites (75 serum and 91 urine metabolites, including 7 shared across biofluids) were cross-sectionally associated with albuminuria. Guanidinosuccinate, N2,N2-dimethylguanosine, hydroxy-N6,N6,N6-trimethyllysine, X-13844, and X-25422 were significantly associated with both eGFR and albuminuria. Over a mean follow-up of 6.6 years, serum mannose (HR 2.3 [1.6,3.2], p = 2.7E-5) and urine X-12117 (HR 1.7 [1.3,2.2], p = 1.9E-5) were risk factors for UACR doubling, whereas urine sebacate (HR 0.86 [0.80,0.92], p = 1.9E-5) was inversely associated. Compared to clinical characteristics alone, including the top 5 endogenous metabolites in serum and urine associated with longitudinal outcomes improved the outcome prediction (AUCs for eGFR decline: clinical model = 0.79, clinical + metabolites model = 0.87, p = 8.1E-6; for UACR doubling: clinical model = 0.66, clinical + metabolites model = 0.73, p = 2.9E-5). CONCLUSIONS:Metabolomic profiling in different biofluids provided distinct and potentially complementary insights into the biology and prognosis of kidney diseases.
PMID: 38844075
ISSN: 1533-3450
CID: 5665692

Cardiac Surgery-Associated Acute Kidney Injury in Neonates Undergoing the Norwood Operation: Retrospective Analysis of the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network Dataset, 2015-2018

Bertrandt, Rebecca A; Gist, Katja; Hasson, Denise; Zang, Huaiyu; Reichle, Garrett; Krawczeski, Catherine; Winlaw, David; Bailly, David; Goldstein, Stuart; Selewski, David; Alten, Jeffrey; ,
OBJECTIVES/OBJECTIVE:Cardiac surgery-associated acute kidney injury (CS-AKI) is associated with adverse outcomes. Single-center studies suggest that the prevalence of CS-AKI is high after the Norwood procedure, or stage 1 palliation (S1P), but multicenter data are lacking. DESIGN/METHODS:A secondary analysis of the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) multicenter cohort who underwent S1P. Using neonatal modification of Kidney Disease Improving Global Outcomes (KDIGO) criteria, perioperative associations between CS-AKI with morbidity and mortality were examined. Sensitivity analysis, with the exclusion of prophylactic peritoneal dialysis (PD) patients, was performed. SETTING/METHODS:Twenty-two hospitals participating in the Pediatric Cardiac Critical Care Consortium (PC 4 ) and contributing to NEPHRON. PATIENTS/METHODS:Three hundred forty-seven neonates (< 30 d old) with S1P managed between September 2015 and January 2018. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Of 347 patients, CS-AKI occurred in 231 (67%). The maximum stages were as follows: stage 1, in 141 of 347 (41%); stage 2, in 51 of 347 (15%); and stage 3, in 39 of 347 (11%). Severe CS-AKI (stages 2 and 3) peaked on the first postoperative day. In multivariable analysis, preoperative feeding was associated with lower odds of CS-AKI (odds ratio [OR] 0.48; 95% CI, 0.27-0.86), whereas prophylactic PD was associated with greater odds of severe CS-AKI (OR 3.67 [95% CI, 1.88-7.19]). We failed to identify an association between prophylactic PD and increased creatinine (OR 1.85 [95% CI, 0.82-4.14]) but cannot exclude the possibility of a four-fold increase in odds. Hospital mortality was 5.5% ( n = 19). After adjusting for risk covariates and center effect, severe CS-AKI was associated with greater odds of hospital mortality (OR 3.67 [95% CI, 1.11-12.16]). We failed to find associations between severe CS-AKI and respiratory support or length of stay. The sensitivity analysis using PD failed to show associations between severe CS-AKI and outcome. CONCLUSIONS:KDIGO-defined CS-AKI occurred frequently and early postoperatively in this 2015-2018 multicenter PC 4 /NEPHRON cohort of neonates after S1P. We failed to identify associations between resource utilization and CS-AKI, but there was an association between severe CS-AKI and greater odds of mortality in this high-risk cohort. Improving the precision for defining clinically relevant neonatal CS-AKI remains a priority.
PMID: 38483198
ISSN: 1529-7535
CID: 5657152

Improving acute kidney injury diagnostic precision using biomarkers

Hasson, Denise; Menon, Shina; Gist, Katja M
Acute kidney injury (AKI) is common in hospitalized patients of all ages and is associated with significant morbidity and mortality. Accurate prediction and early identification of AKI is of utmost importance because no therapy exists to mitigate AKI once it has occurred. Yet, serum creatinine lacks adequate sensitivity and specificity, and quantification of urine output is challenging in incontinent children without indwelling bladder catheters. Integration of clinically available biomarkers have the potential to delineate unique AKI phenotypes that could have important prognostic and therapeutic implications. Plasma Cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL) and the urinary product of tissue inhibitor metalloproteinase (TIMP-2) and insulin growth factor binding protein-7 (IGFBP7) are clinically available. These biomarkers have been studied in heterogenous populations across the age spectrum and in a variety of clinical settings for prediction of AKI. The purpose of this review is to describe and discuss the clinically available AKI biomarkers including how they have been used to delineate AKI phenotypes.
PMCID:9046880
PMID: 35494424
ISSN: 2352-5517
CID: 5228452

The application of omic technologies to research in sepsis-associated acute kidney injury

Hasson, Denise; Goldstein, Stuart L; Standage, Stephen W
Acute kidney injury (AKI) is common in critically ill children and adults, and sepsis-associated AKI (SA-AKI) is the most frequent cause of AKI in the ICU. To date, no mechanistically targeted therapeutic interventions have been identified. High-throughput "omic" technologies (e.g., genomics, proteomics, metabolomics, etc.) offer a new angle of approach to achieve this end. In this review, we provide an update on the current understanding of SA-AKI pathophysiology. Omic technologies themselves are briefly discussed to facilitate interpretation of studies using them. We next summarize the body of SA-AKI research to date that has employed omic technologies. Importantly, omic studies are helping to elucidate a pathophysiology of SA-AKI centered around cellular stress responses, metabolic changes, and dysregulation of energy production that underlie its clinical features. Finally, we propose opportunities for future research using clinically relevant animal models, integrating multiple omic technologies and ultimately progressing to translational human studies focusing therapeutic strategies on targeted disease mechanisms.
PMCID:7606209
PMID: 32356189
ISSN: 1432-198x
CID: 5228432

Do I Need Proof of the Culprit? Decreasing Respiratory Viral Testing in Critically Ill Patients

Innis, Katherine; Hasson, Denise; Bodilly, Lauren; Sveen, William; Stalets, Erika L; Dewan, Maya
PMCID:7769206
PMID: 33323392
ISSN: 2154-1671
CID: 5228442

Prospects of Photo- and Thermoacoustic Imaging in Neurosurgery

Ravina, Kristine; Lin, Li; Liu, Charles Y; Thomas, Debi; Hasson, Denise; Wang, Lihong V; Russin, Jonathan J
The evolution of neurosurgery has been, and continues to be, closely associated with innovations in technology. Modern neurosurgery is wed to imaging technology and the future promises even more dependence on anatomic and, perhaps more importantly, functional imaging. The photoacoustic phenomenon was described nearly 140 yr ago; however, biomedical applications for this technology have only recently received significant attention. Light-based photoacoustic and microwave-based thermoacoustic technologies represent novel biomedical imaging modalities with broad application potential within and beyond neurosurgery. These technologies offer excellent imaging resolution while generally considered safer, more portable, versatile, and convenient than current imaging technologies. In this review, we summarize the current state of knowledge regarding photoacoustic and thermoacoustic imaging and their potential impact on the field of neurosurgery.
PMID: 31620798
ISSN: 1524-4040
CID: 5228422

The importance of preoperative diagnosis of blister aneurysms

Russin, Jonathan J; Kramer, Daniel R; Thomas, Debi; Hasson, Denise; Liu, Charles Y; Amar, Arun P; Mack, William J; Giannotta, Steven L
We describe a series of 14 surgical blister aneurysm (BA) patients and compare outcomes in those with known cerebral BA to those lacking preoperative BA diagnosis/recognition. BA are broad, fragile, pathologic dilatations of the intracranial arteries. They have a low prevalence but are associated with substantially higher surgical morbidity and mortality rates than saccular aneurysms. A confirmed, preoperative BA diagnosis can alter operative management and technique. We performed a retrospective review of prospectively collected data on aneurysm patients undergoing surgery at a major academic institution. All patients from 1990 to 2011 with a postoperative BA diagnosis were included. Chart reviews were performed to identify patients with preoperative BA diagnoses and collect descriptive data. We identified 14 patients, 12 of whom presented with subarachnoid hemorrhage. The age of the cohort (mean ± standard deviation: 41.8 ± 13.9 years) was lower than that generally reported for saccular aneurysm populations. Preoperatively diagnosed BA had an intraoperative rupture (IOR) rate of 28.6% (2/7) compared to a 57.1% (4/7) rate in the undiagnosed patients. The mortality rate in the preoperatively diagnosed cohort was 14.3% (1/7) while that of the undiagnosed group was 42.8% (3/7). BA remain a diagnostic and treatment challenge with morbidity and mortality rates exceeding those of saccular aneurysms. Preoperative BA diagnosis may decrease IOR and mortality rates and improve patient outcomes.
PMID: 25960141
ISSN: 1532-2653
CID: 5228402