The Impact of Fluid Balance on Acute Kidney Injury in Nontraumatic Subarachnoid Hemorrhage.

Background: Nontraumatic subarachnoid hemorrhage (SAH) can lead to poor neurologic outcomes, particularly when delayed cerebral ischemia (DCI) occurs. Maintenance of euvolemia following SAH is thought to reduce the risk of DCI. However, attempts at maintaining euvolemia often err on the side of hypervolemia. In this study, we assessed the relationship between fluid balance and acute kidney injury (AKI) in SAH patients, assessing hypervolemia versus euvolemia and their impact on AKI. Methods: In a quaternary care center, neuroscience intensive care unit we conducted a retrospective longitudinal analysis in adult patients who suffered a nontraumatic SAH. Results: Out of 139 patients, 15 (10.8%) patients developed an AKI while hospitalized, with 7 stage I, 3 stage II, and 5 stage III injuries. Acute kidney injury patients had higher peak sodium (150.1 mEq/L vs 142.7 mEq/L, 95% confidence interval [CI]: [2.7-12.1 mEq/L]), higher discharge chloride (109.1 mEq/L vs 104.9 mEq/L, 95% CI: [0.7-7.6 mEq/L]), and lower hemoglobin at discharge (9.3 g/dL vs 11.3 g/dL, 95% CI: [1.0-2.9 g/dL]). At 7 days, AKI patients had a fluid balance that was 1.82 L higher (P = .04), and 3.38 L higher at 14 days (P = .02), in comparison to day 3. Acute kidney injury was associated with significant mortality increases. This increase in mortality was found at 30 days from admission with a 9.52-fold increase, and at 60 days with a 6.25-fold increase. As a secondary outcome, vasospasm (19 patients, 13.7%) showed no association with AKI. Conclusions: Acute kidney injury following SAH is correlated with clinically significant hypervolemia, elevated sodium, elevated chloride, decreased urine output, and decreased hemoglobin at discharge-risk factors for all SAH patients. This study further elucidates the harm of hypervolemia and gives greater practical evidence to physicians attempting to balance the dangers of vasospasm and AKI.

Undiagnosed Cirrhosis and Hepatic Encephalopathy in a National Cohort of Veterans With Dementia.

Importance: Dementia and hepatic encephalopathy (HE) are challenging to distinguish clinically. Undiagnosed cirrhosis in a patient with dementia can lead to missed opportunities to treat HE. Objective: To examine the prevalence and risk factors of undiagnosed cirrhosis and therefore possible HE in veterans with dementia. Design, Setting, and Participants: A retrospective cohort study was conducted between 2009 and 2019 using data from the Veterans Health Administration (VHA) and 2 separate validation cohorts from the Richmond Veterans Affairs Medical Center. Data analysis was conducted from May 20 to October 15, 2023. Participants included 177 422 US veterans with a diagnosis of dementia at 2 or more clinic visits, no prior diagnosis of cirrhosis, and with sufficient laboratory test results to calculate the Fibrosis-4 (FIB-4) score. Exposures: Demographic and clinical characteristics. Main Outcomes and Measures: An FIB-4 score (>2.67 suggestive of advanced fibrosis and >3.25 suggestive of cirrhosis), capped at age 65 years even for those above this cutoff who were included in the analysis. Results: Among 177 422 veterans (97.1% men; 80.7% White; mean (SD) age, 78.35 [10.97] years) 5.3% (n = 9373) had an FIB-4 score greater than 3.25 and 10.3% (n = 18 390) had an FIB-4 score greater than 2.67. In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with older age (odds ratio [OR], 1.07; 95% CI, 1.06-1.09), male gender (OR, 1.43; 95% CI, 1.26-1.61), congestive heart failure (OR, 1.48; 95% CI, 1.43-1.54), viral hepatitis (OR, 1.79; 95% CI, 1.66-1.91), Alcohol Use Disorders Identification Test score (OR, 1.56; 95% CI, 1.44-1.68), and chronic kidney disease (OR, 1.11; 95% CI, 1.04-1.17), and inversely associated with White race (OR, 0.79; 95% CI, 0.73-0.85), diabetes (OR, 0.78; 95% CI, 0.73-0.84), hyperlipidemia (OR, 0.84; 95% CI, 0.79-0.89), stroke (OR, 0.85; 95% CI, 0.79-0.91), tobacco use disorder (OR, 0.78; 95% CI, 0.70-0.87), and rural residence (OR, 0.92; 95% CI, 0.87-0.97). Similar findings were associated with the FIB-4 greater than 2.67 threshold. These codes were associated with cirrhosis on local validation. A local validation cohort of patients with dementia showed a similar percentage of high FIB-4 scores (4.4%-11.2%). Conclusions and Relevance: The findings of this cohort study suggest that clinicians encountering patients with dementia should be encouraged to screen for cirrhosis using the FIB-4 score to uncover reversible factors associated with cognitive impairment, such as HE, to enhance outcomes.

Exhaled breath condensate identifies metabolic dysregulation in patients with radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a consequence of therapeutic thoracic irradiation (TR) for many cancers, and there are no FDA-approved curative strategies. Studies report that 80% of patients who undergo TR will have CT-detectable interstitial lung abnormalities, and strategies to limit the risk of RILI may make radiotherapy less effective at treating cancer. Our lab and others have reported that lung tissue from patients with idiopathic pulmonary fibrosis (IPF) exhibits metabolic defects including increased glycolysis and lactate production. In this pilot study, we hypothesized that patients with radiation-induced lung damage will exhibit distinct changes in lung metabolism that may be associated with the incidence of fibrosis. Using liquid chromatography/tandem mass spectrometry to identify metabolic compounds, we analyzed exhaled breath condensate (EBC) in subjects with CT-confirmed lung lesions after TR for lung cancer, compared with healthy subjects, smokers, and cancer patients who had not yet received TR. The lung metabolomic profile of the irradiated group was significantly different from the three nonirradiated control groups, highlighted by increased levels of lactate. Pathway enrichment analysis revealed that EBC from the case patients exhibited concurrent alterations in lipid, amino acid, and carbohydrate energy metabolism associated with the energy-producing tricarboxylic acid (TCA) cycle. Radiation-induced glycolysis and diversion of lactate to the extracellular space suggests that pyruvate, a precursor metabolite, converts to lactate rather than acetyl-CoA, which contributes to the TCA cycle. This TCA cycle deficiency may be compensated by these alternate energy sources to meet the metabolic demands of chronic wound repair. Using an "omics" approach to probe lung disease in a noninvasive manner could inform future mechanistic investigations and the development of novel therapeutic targets.NEW & NOTEWORTHY We report that exhaled breath condensate (EBC) identifies cellular metabolic dysregulation in patients with radiation-induced lung injury. In this pilot study, untargeted metabolomics revealed a striking metabolic signature in EBC from patients with radiation-induced lung fibrosis compared to patients with lung cancer, at-risk smokers, and healthy volunteers. Patients with radiation-induced fibrosis exhibit specific changes in tricarboxylic acid (TCA) cycle energy metabolism that may be required to support the increased energy demands of fibroproliferation.

Early paracentesis is associated with better prognosis compared with late or no-paracentesis in hospitalized veterans with cirrhosis and ascites.

Guidelines recommend that all hospitalized patients with cirrhosis and ascites receive an early (<24 h from admission) paracentesis. However, national data are not available regarding compliance with and the consequences of this quality metric. We used the national Veterans Administration Corporate Data Warehouse and validated International Classification of Disease codes to evaluate the rate and subsequent outcomes of early, late, and no paracentesis for patients with cirrhosis and ascites during their first inpatient admission between 2016 and 2019. Of 10,237 patients admitted with a diagnosis of cirrhosis with ascites, 14.3% received an early paracentesis, 7.3% received a late paracentesis, and 78.4% never received a paracentesis. In multivariable modeling, compared with an early paracentesis: both late paracentesis and no-paracentesis were significantly associated with increased odds of acute kidney injury (AKI) development [OR: 2.16 (95% CI, 1.59-2.94) and 1.34 (1.09-1.66), respectively]; intensive care unit (ICU) transfer [OR: 2.43 (1.71-3.47) and 2.01 (1.53-2.69), respectively] and inpatient death [OR: 1.54 (1.03-2.29) and 1.42 (1.05-1.93), respectively]. Nationally, only 14.3% of admitted veterans with cirrhosis and ascites received the American Association for the Study of Liver Diseases (AASLD) guideline-recommended diagnostic paracentesis within 24 hours of admission. Failure to complete early paracentesis was associated with higher odds of AKI, ICU transfer, and inpatient mortality. Universal and site-specific barriers to this quality metric should be evaluated and addressed to improve patient outcomes.

Primary prophylaxis for spontaneous bacterial peritonitis is linked to antibiotic resistance in the Veterans Health Administration.

Spontaneous bacterial peritonitis (SBP) is a major cause of mortality. Although SBP primary prophylaxis (SBPPr) with fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) is often used, resistance could reduce its benefit. AIM: Analyze peritoneal fluid resistance patterns in patients with a first SBP episode with/without SBPPr using the Veterans Health Administration corporate data warehouse and to evaluate national antibiograms. Corporate data warehouse data were extracted using validated International Classification of Disease-9/10 codes, culture, resistance data, and outcomes of 7553 patients who developed their first inpatient SBP between 2009 and 2019 and compared between those with/without SBPPr. Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) sensitivity to ciprofloxacin and TMP-SMX was calculated using 2021 Veterans Health Administration antibiogram data from all states. The most common isolates were E. coli , K. pneumoniae , and Staphylococcus species. Veterans taking ciprofloxacin SBBPr had higher fluoroquinolone resistance (34% vs 14% no SBPPr, p <0.0001); those taking TMP-SMX had higher TMP-SMX resistance (40% vs 14%, p <0.0001). SBPPr patients showed higher culture positivity, greater length of stay, higher second SBP, and higher probability of liver transplant rates versus no SBPPr. Multivariable models showed SBBPr to be the only variable associated with gram-negative resistance, and SBPPr was associated with a trend toward longer length of stay. E. coli ciprofloxacin sensitivity rates were 50%-87% and 43%-92% for TMP-SMX. K. pneumoniae ciprofloxacin sensitivity was 76%-100% and 72%-100% for TMP-SMX. CONCLUSION: Among patients who developed their first SBP episode, there was a higher prevalence of antibiotic resistance in those on SBPPr, with a high rate of fluoroquinolone resistance across the Veterans Health Administration sites.

DNA Methylation Changes in Autologous Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: Blood cancers may be potentially cured with hematopoietic stem cell transplantation (HCT); however, standard pre-assessments for transplant eligibility do not capture all contributing factors for transplant outcomes. Epigenetic biomarkers predict outcomes in various diseases. This pilot study aims to explore epigenetic changes (epigenetic age and differentially methylated genes) in patients before and after autologous HCT, that can serve as potential biomarkers to better predict HCT outcomes. METHODS: This study used a prospective longitudinal study design to compare genome wide DNA methylation changes in 36 autologous HCT eligible patients recruited from the Cellular Immunotherapies and Transplant clinic at a designated National Cancer Center. RESULTS: Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 850K BeadChip, showed a significant difference in DNA methylation patterns post-HCT compared to pre-HCT. Compared to baseline levels of DNA methylation pre-HCT, 3358 CpG sites were hypo-methylated and 3687 were hyper-methylated. Identified differentially methylated positions overlapped with genes involved in hematopoiesis, blood cancers, inflammation and immune responses. Enrichment analyses showed significant alterations in biological processes such as immune response and cell structure organization, however no significant pathways were noted. Though participants had an advanced epigenetic age compared to chronologic age before and after HCT, both epigenetic age and accelerated age decreased post-HCT. CONCLUSION: Epigenetic changes, both in epigenetic age and differentially methylated genes were observed in autologous HCT recipients, and should be explored as biomarkers to predict transplant outcomes after autologous HCT in larger, longitudinal studies.

Toward a fully de-identified biomedical information warehouse.

The Information Warehouse at the Ohio State University Medical Center is a comprehensive repository of business, clinical, and research data from various source systems. Data collected here is a valuable resource that facilitates both translational research and personalized healthcare. The use of such data in research is governed by federal privacy regulations with oversight by the Institutional Review Board. In 2006, the Information Warehouse was recognized by the OSU IRB as an "Honest Broker" of clinical data, providing investigators with de-identified or limited datasets under stipulations contained in a signed data use agreement. In order to streamline this process even further, the Information Warehouse is developing a de-identified data warehouse that is suitable for direct user access through a controlled query tool that is aimed to support both research and education activities. In this paper we report our findings on performance evaluation of different de-identification schemes that may be used to ensure regulatory compliance while also facilitating practical database updating and querying. We also discuss how date-shifting in the de-identification process can impact other data elements such as diagnosis and procedure codes and consider a possible solution to those problems.

Honest broker protocol streamlines research access to data while safeguarding patient privacy.

At Ohio State University Medical Center, The Honest Broker Protocol provides a streamlined mechanism whereby investigators can obtain de-identified clinical data for non-FDA research without having to invest the significant time and effort necessary to craft a formalized protocol for IRB approval.

Innovative applications of an enterprise-wide information warehouse.

The Information Warehouse at The Ohio State University Medical Center is a comprehensive effort integrating data from over 70 sources throughout the enterprise. The IW serves a broad diversity of customers in all mission areas of the medical center, from clinical operations and administration to education, to research. This comprehensiveness has facilitated an innovative application of cross-disciplinary technologies and methodologies to problem domains beyond the roles traditionally envisioned for data warehousing.

Prototype integration of protein electrophoresis laboratory results in an information warehouse to improve workflow and data analysis.

This poster demonstrates our efforts to enhance workflow and clinical analysis of protein electrophoresis (PEP) data through integration with the Information Warehouse (IW) at The Ohio State University Medical Center (OSUMC). A new desktop application has been developed with the aim of enabling more efficient and accurate gel analysis by clinical pathologists. This tool gives the pathologists the ability to perform their analysis conveniently from anywhere on the OSUMC network along with the aid of numerical analysis algorithms, image enhancement techniques, and access to historical PEP results for the given patient.