Institutional Review Board Research Articles

Role of blood urea nitrogen to creatinine ratio in the assessment of hypovolemia who have undergone major surgeries- a cross-sectional study

BackgroundMajor surgeries are being carried for certain ailments. Surgeries can be major or minor depending on the extent of intervention. Major surgeries are prone to cause lots of complications such as shock, haemorrhage, wound infection, deep vein thrombosis, pulmonary complications, organ rejection, reactions to anaesthetics etc. Early identification of complications could reduce morbidity and mortality. Laboratory variables used in the assessment of hypovolemia include blood urea nitrogen, sodium, osmolality, hematocrit, and arterial blood gas. This study was undertaken to assess the utility of blood urea nitrogen: creatinine ratio (BCR) in the utility of assessment of hypovolemia in the first post-operative day in individuals who had major surgeries.Methods and materialsThe retrospective cross-sectional study included participants from the Departments of Orthopedic Surgery, Obstetrics and Gynecology, General Surgery and Cardiothoracic Surgery. Patients who underwent major surgeries between January 2019 and January 2020 were included. Study participants of 30 to 60 years of both genders were recruited into the study. Data were collected from the Medical Records of a tertiary care hospital in Chennai, India. Ethics approval was obtained, the institutional ethics committee (Ref: CSP/21/SEP/99/479 dated 30–12-2021). Waiver of consent was obtained since the patients were treated and discharged from the hospital. The data were analyzed by SPSS version 16. P value ≤ 0.05 was taken to be significant.ResultsBCR showed statistically significant difference across the groups with P = 0.02. BCR showed statistically significant difference between cardiac patients with total knee replacement and total abdominal hysterectomy surgeries. BCR showed positive correlation with age, fluids intake and negative correlation with pulse rate and respiratory rate.ConclusionBCR is a simple diagnostic tool for identifying hypovolemia in individuals who undergo major surgeries especially in the first postoperative day. It is significantly altered across the groups with highest value in individuals who have undergone knee replacement surgeries. BCR has high specificity and positive predictive value.

Silicone Irregular Hexagon Pessary Versus Polyvinyl Chloride Ring Pessary for Pelvic Organ Prolapse: Randomised Controlled Trial.

Vaginal pessaries are the mainstay of the non-surgical management of pelvic organ prolapse (POP). A flexible silicone irregular hexagonal (SIH) pessary was developed based on the results of a prior vaginal case study. We hypothesised that the SIH pessary would have a higher rate of retention and self-management than the polyvinyl chloride (PVC) pessary. This was a prospective non-blinded, randomised controlled trial with institutional review board approval. Eligible participants were randomised and fitted with the assigned pessary. They were reviewed 1 week, 6 months and 1 year after the initial pessary fitting. Participants who returned for follow-up completed the study questionnaires. The primary outcome was success, defined as continued use of the allocated pessary at 6 months. Secondary outcomes included the ability to perform pessary self-care, treatment satisfaction and pessary-related complications. Statistical tests were performed with alpha or statistical significance defined as a p value of ≤ 0.05, two-tailed. A total of 104 participants were randomised, with 52 subjects in each arm. Primary outcome data were analysed using per protocol analysis. Continuing pessary usage at 6 months was 68.1% for the PVC pessary group and 65.1% for the SIH group, with no statistically significant differences between the two groups (p = 0.765). Subjects with SIH were more likely to perform pessary self-care. There were no significant differences in subjects' satisfaction, quality-of-life scores or treatment complications between groups. The pessary continuation rate between the SIH and the PVC pessary groups was similar at 6 months. Participants with an SIH pessary were more likely to self-manage.

Establishing the Foundations of Emotional Intelligence in Care Companion Robots to Mitigate Agitation Among High-Risk Patients With Dementia: Protocol for an Empathetic Patient-Robot Interaction Study.

An estimated 6.7 million persons are living with dementia in the United States, a number expected to double by 2060. Persons experiencing moderate to severe dementia are 4 to 5 times more likely to fall than those without dementia, due to agitation and unsteady gait. Socially assistive robots fail to address the changing emotional states associated with agitation, and it is unclear how emotional states change, how they impact agitation and gait over time, and how social robots can best respond by showing empathy. This study aims to design and validate a foundational model of emotional intelligence for empathetic patient-robot interaction that mitigates agitation among those at the highest risk: persons experiencing moderate to severe dementia. A design science approach will be adopted to (1) collect and store granular, personal, and chronological data using Personicle (an open-source software platform developed to automatically collect data from phones and other devices), incorporating real-time visual, audio, and physiological sensing technologies in a simulation laboratory and at board and care facilities; (2) develop statistical models to understand and forecast the emotional state, agitation level, and gait pattern of persons experiencing moderate to severe dementia in real time using machine learning and artificial intelligence and Personicle; (3) design and test an empathy-focused conversation model, focused on storytelling; and (4) test and evaluate this model for a care companion robot (CCR) in the community. The study was funded in October 2023. For aim 1, architecture development for Personicle data collection began with a search for existing open-source data in January 2024. A community advisory board was formed and met in December 2023 to provide feedback on the use of CCRs and provide personal stories. Full institutional review board approval was received in March 2024 to place cameras and CCRs at the sites. In March 2024, atomic marker development was begun. For aim 2, after a review of open-source data on patients with dementia, the development of an emotional classifier was begun. Data labeling was started in April 2024 and completed in June 2024 with ongoing validation. Moreover, the team established a baseline multimodal model trained and validated on healthy-person data sets, using transformer architecture in a semisupervised manner, and later retrained on the labeled data set of patients experiencing moderate to severe dementia. In April 2024, empathy alignment of large language models was initiated using prompt engineering and reinforcement learning. This innovative caregiving approach is designed to recognize the signs of agitation and, upon recognition, intervene with empathetic verbal communication. This proposal has the potential to have a significant impact on an emerging field of computational dementia science by reducing unnecessary agitation and falls of persons experiencing moderate to severe dementia, while reducing caregiver burden. PRR1-10.2196/55761.

Clinical Impact of Radiologist’s Alert System on Patient Care for High-risk Incidental CT Findings: A Machine Learning-Based Risk Factor Analysis

Rationale and ObjectivesEfficient communication between radiologists and clinicians ordering computed tomography (CT) examinations is crucial for managing high-risk incidental CT findings (ICTFs). Herein, we introduced a Radiologist’s Alert and Patient Care Follow-up System (APCFS) for high-risk ICTFs. This study aimed to analyze the ICTFs detected by this system and the factors associated with them. Materials and MethodsThis retrospective study was approved by the institutional review board. We analyzed 52,331 CT examinations conducted between 2019 and 2021. In cases where high-risk ICTFs were identified, radiologists utilized APCFS to prompt ordering clinicians for further patient care. We assessed the frequency, affected body organs, presence or absence of therapeutic interventions, and diagnoses of high-risk ICTFs. An automated machine learning platform was employed to analyze the factors associated with high-risk ICTFs. ResultsAmong the 52,331 CT examinations, 507 (0.96%) revealed high-risk ICTFs, primarily affecting the lung (18.0%). Of these 507 high-risk ICTFs, 117 (23.1%) underwent therapeutic interventions, while 362 (71.4%) required only follow-up. Of the 117 cases undergoing interventions, 61 (52.1%) required surgery. Of the 219 high-risk ICTFs leading to a confirmed diagnosis, 146 (66.7%) were neoplastic lesions, including 88 (60.3%) malignancies, and 73 (33.3%) were non-neoplastic lesions. The top three risk factors associated with high-risk ICTFs in the regularized logistic regression model were the imaging protocol (especially aortic valve implantation planning protocol), imaging area (especially whole-body imaging), and clinical department (especially cardiology). ConclusionUtilizing APCFS, high-risk ICTFs were detected in approximately 1% of all CT examinations, likely associated with specific imaging protocols, areas, and clinical departments.

Assessment of Practices on Purchase of Packaged Foods and Utilization Patterns of Food Labels among Adults in Puducherry

Abstract Background: There is an increase in the manufacture and consumption of prepackaged foods as a result of widespread urbanization, long working time, and adaption to a sedentary lifestyle. The majority of these prepackaged foods contain food labels. Food labeling is a community-based strategy that informs customers about a food’s nutritional composition, empowering them to choose healthier foods. To assess the practices on the purchase of packaged foods and utilization patterns of food labels among adults in Puducherry. Material and Methods: A cross-sectional survey in the field practice area of a private medical college at Puducherry was carried out for two months including adults residing for > 6 months in selected villages/wards. A sample size of 460 with a multistage sampling technique was considered. Data collection using a semi-structured questionnaire incorporated into Epi-collect software and was analyzed using SPSS16. Ethical clearance was obtained from Institutional Ethical Committee. Written informed consent was sought from participants. Results: Around 271 (58.91%) and 189 (41.08%) respondents were residing in urban and rural regions, respectively. Purchase of packages was seen in 297 (64.57%) people. Only one-fourth of the subjects had the practice of reading the food labels, with urban residents having a better practice when compared with rural population (P value < 0.05). Conclusion: The study reveals a low level of utilization pattern of food labels among consumers of packaged food products. The findings of this study would be helpful for concerned authorities in creating and improving awareness among consumers and ensuring that their usability is improved.

Differences in Cervical Spine Fractures in Patients Younger or Older Than 65 Years of Age: Implications for the Canadian C-Spine Rule.

There has been a distinction made in the 2001 Canadian C-Spine Rule regarding patients 65 and older and younger than 65 years of age as far as indications for cervical spine CT scanning. We sought to determine if there are differences in the symptoms, mechanisms of injury, fracture locations, and types that are still relevant in 2024. The institutional review board approved this retrospective study of cervical spine CT emergency department results from 2 hospitals in our health system after reviewing 5 years of data in patients experiencing trauma. In addition to the primary variable of age (younger than 65 years and 65 years and older), we looked at injury mechanism, fracture types, sites, symptoms, and operative or medical treatments. Because the demographics of our home site is different from most towns in the United States, we provide race/ethnicity data. Of 21,986 cervical spine CTs, 190/9455 (2.0%) participants 65 years of age and older and 199/12,531 (1.6%) participants younger than 65 years of age had fractures (total, 389/21,986, 1.8%). There were more cases of falls from standing (106, 55.8%) and falls from a height (46, 4.2%) in those 65 years and older and this mechanism was associated with a higher risk of C1 and C2 fractures (52, 27.4%; and 78, 41.1%, respectively). Among the C1 fractures, anterior and posterior arch fractures predominated (37, 19.5%). For C2 fractures, types 2 and 3 odontoid fractures (39, 20.5%; and 12, 6.3%) were more common in the older cohort. Motor vehicle collisions were more common in the younger cohort (89, 44.7%), and they were associated with more C5-C7 fractures (47, 23.6%; 60, 30.2%; and 66, 33.2%, respectively) including the facets (49, 24.6%), spinous processes (31, 15.6%), and transverse processes (52, 26.1%). Overall, the rates of instability, surgical intervention, and asymptomatic fractures were similar in the 2 age groups. Cervical spine fractures appear in about 1.8% of the CT scans performed in a busy emergency department environment. Fractures in the elderly occur more commonly due to falls, are located at C1 and C2, and may involve ligamentous injuries. Younger patients incur trauma more commonly due to motor vehicle collisions, and they are more likely to affect the posterior elements, especially C5-C7. The differences in trends for fractures in the 65 years of age and older and younger than 65 years of age groups have persisted since the Canadian C-Spine Rule 1996-1998 data were collected.

A-159 Re-evaluating Ferritin Cutoffs for the Diagnosis of Iron Deficiency and Iron Deficiency Anemia

Abstract Background Iron deficiency (ID) is the most common nutrient deficiency in the world and iron deficiency anemia (IDA) is estimated to affect 1.24 billion people. Serum ferritin is an iron storage protein commonly used as a biomarker for ID and IDA. The ferritin lower limit of normal (LLN) defined in many clinical laboratories is lower than evidence-based cutoffs and may not detect ID and IDA with adequate sensitivity, particularly when sex-based reference intervals (RIs) are used. This may be due in part to the use of asymptomatic, iron-depleted individuals for RI studies. Recent efforts have been made to increase the LLN for ferritin to at least 30 ng/mL and re-evaluate sex based RIs to improve diagnosis of ID and IDA. In this study, we aimed to investigate LLN ferritin cutoffs for ID and IDA in our patient population. Methods Patient data from June 2022-May 2023 were collected with approval from the Institutional Review Board (IRB), including age, sex, and values for ferritin, iron, transferrin saturation, and hemoglobin. Patients were classified as iron replete (IR), ID, or IDA based on measurements for iron, transferrin saturation, and hemoglobin. IR patients were defined as having iron and transferrin saturation values within current RIs, while those below the cutoff were grouped as ID. ID and IDA were further classified based on hemoglobin values. A range of ferritin concentrations between 1 and 100 ng/mL were used to calculate true and false positive rates (TPR and FPR) and diagnostic accuracy (DA). Receiver operator characteristic (ROC) curve and J index analysis were used to define optimal ferritin cutoffs for ID and IDA. Results Data from 26,455 patients (65% female) were used in this study. Conclusions These findings highlight the need to re-examine ferritin RIs in the context of ID/IDA, especially for those patients assigned female at birth.

B-311 Relation of Free Immunoglobulin Ligh Chain Concentration to Overflow Proteinuria

Abstract Background Free immunoglobulin light chains are small proteins that undergo substantial glomerular filtration. When high serum concentrations of free light chains occur in multiple myeloma, the high filtered load of light chains exceeds the uptake capacity of proximal tubules, and overflow proteinuria ensues. Massive excretion of light chains can lead to cast formation and renal injury. The present study sought to determine the relation of serum light chain concentration to overflow proteinuria. Methods Results for patients with plasma cell disorders were reviewed as approved by an institutional review board. A Binding Site Optilite analyzer measured serum free light chain concentrations. Urine and serum protein electrophoresis were performed on Helena agarose gels. A total of 170 paired serum and 24-hour urine specimens were evaluated for 36 patients with increased kappa light chains and 26 patients with increased lambda light chains. Results Overflow proteinuria with either immunoglobulin light chain presented with light chain as the major urinary protein and limited increases of urinary albumin. Light chain excretion exceeded albumin excretion when light chain excretion surpassed 100 mg/d. Similar results were obtained for cases with increased kappa and lambda free light chains. There was a general relation of increased serum kappa and lambda light chains and urinary excretion of the corresponding light chain. Limited urinary excretion of light chains (<120 mg/d) was seen when the serum light chain concentration was < 250 mg/L, representing an approximate threshold for substantial overflow proteinuria. Overflow proteinuria exceeding 2,000 g/d was seen only when serum free light chain concentrations exceeded 800 mg/L. However, a few patients with high serum light chain values (>1,000/L) had low urinary light chain excretion that was discordant from the relation of serum light chain concentration to light chain excretion. Serum light chain values >4,000 mg/L (N = 10) were all associated with overflow proteinuria of > 1,500 mg/d and, in 7 cases, >10,000 mg/d. In a few cases, there was evidence that serum light chain assays overestimated light chain concentrations. In one case, the serum free light chain value was twice the total protein and about 12-fold higher than the serum M-spike, suggestive of substantial overestimation. Conclusions Defining the relation between serum free light chain concentrations and the magnitude of overflow proteinuria helps identify patients at low and high risk of massive overflow proteinuria that can cause renal injury. Limited overflow proteinuria (<120 mg/d) occurred when serum light chain concentration was < 250 mg/L, and substantial overflow proteinuria occurred when serum light chains exceeded 4,000 mg/L Serum free light chain concentrations above 250 mg/L were incompletely predictive of urinary free light chain excretion; a few discordant cases with high measured serum light chain concentrations (>1,000 mg/L) and low excretion of light chains were observed. Further investigation is indicated for cases with possible overestimation of free light chains or discordance between serum light chain values and urinary light chain excretion. Unexpected results in some cases could relate to polymerization of free light chains as previously reported.

B-170 Age-Specific reference intervals for ethanolamine plasmalogen species in red blood cells using liquid chromatography tandem mass spectrometry

Abstract Background Plasmalogens are critical membrane structural components that are mainly generated by de novo synthesis starting in peroxisomes. Hence, patients with defects in peroxisome biogenesis (PBD) exhibit markedly reduced plasmalogen levels. Plasmalogen ratios are traditionally measured by gas chromatography-mass spectrometry (GC-MS); however, this method entails a lengthy sample extraction and derivatization and does not report concentrations of individual plasmalogen species. We have developed a robust and easy-to-implement liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify the 18 most abundant ethanolamine plasmalogen (PlsEtn) species in packed red blood cells (RBCs). However, no reference intervals have been published for individual PlsEtn. Here, we describe the establishment of age-specific reference intervals for individual PlsEtn species and their total values (16:0, 18:0, 18:1 species, and total plasmalogens). Methods Plasmalogens were extracted using methanol containing two labeled internal standards, shaking for one hour at room temperature. Chromatographic separation was performed using an Acquity Premier BEH C18 UPLC column with a binary gradient of 5 mM ammonium acetate in water:methanol (15:85) and 5 mM ammonium acetate in methanol. Analysis was performed using a XEVO TQ-XS Mass Spectrometer with Ultra-High Performance Liquid Chromatography (Waters) in multiple reaction monitoring mode. Eighteen PlsEtn species were quantified using four commercially available standards; additionally, totals were calculated for 16:0, 18:0 or 18:1 species, and for total plasmalogens. Reference intervals were established using 376 RBCs from self-reported healthy volunteers and de-identified clinical samples referred for unrelated testing (182 females and 194 males; range 0 to 88 years). Data was analyzed using the R programming language. The study was approved by the Institutional Review Board of the University of Utah. Results Initial age groups were identified using a model-based clustering algorithm followed by iterative Harris-Boyd analysis. Finally, the adjacent groups were merged if their means differed by less than 10%. Once the final age groups were partitioned, data in each individual age group were analyzed using parametric or non-parametric statistics to determine reference intervals (95%, with 90%confidence intervals). PlsEtn species displayed the lowest concentration in the first few months of life, which increased in childhood until adolescence or adulthood (depending on PlsEtn). For most species, the concentrations increased over time reaching a plateau between 18 and 48 years of age, and then starting to decrease. The total values followed the same trend, with neonates showing significantly lower values compared to other age groups. Conclusions We applied a novel statistical approach to identify age groups and determine age-specific reference intervals for 18 individual PlsEtn in RBC and their totals. Lacking previously published data, this study is critical for supporting test implementation in clinical laboratories.

A-342 Precision Evaluation of the pH, PO2 and PCO2 tests in the i-STAT® G3+ Cartridge using the i-STAT 1 System for Venous, Arterial and Capillary Whole Blood Specimens in Clinical Settings

Abstract Background Precise and accurate measurements of blood gases are important for the diagnosis, monitoring and treatment of respiratory, metabolic, and acid-base disturbances. This study demonstrates the precision of the pH, partial pressure of oxygen (PO2), and partial pressure of carbon dioxide (PCO2) tests in the i-STAT G3+ cartridge with the i-STAT 1 System in arterial, venous, and capillary whole blood specimens in point-of-care or clinical laboratory settings. Methods The precision of the i-STAT pH, PO2, and PCO2 tests in the i-STAT G3+ cartridge was assessed at external clinical sites by end-users using whole blood specimens across the measurement range for each test: pH (6.500 - 7.800 pH units), PO2 (5 - 700 mmHg), PCO2 (5.0 - 130.0 mmHg). The study included venous whole blood samples from ∼140 adult subjects (≥ 18 years) and arterial whole blood samples from ∼140 adult subjects at 3 clinical sites. Each whole blood sample was run in duplicate on the i-STAT G3+ cartridge. In addition, ∼140 specimens were collected in capillary tubes using two fingerstick draws from adult subjects and ∼20 capillary heel-stick specimens were collected into two capillary tubes from neonate subjects (birth - 28 days) at two clinical sites. Specimens used in this study were prospectively collected venous, arterial, or capillary specimens under an Institutional Review Board approved informed consent or were de-identified leftover venous or arterial specimens. For each specimen type, duplicates from each subject were grouped into subintervals based on their mean values. The subintervals included the medical decision levels of 7.300, 7.350 and 7.450 pH units for pH, 30, 45 and 60 mmHg for PO2 and 35, 45, 50 and 70 mmHg for PCO2. The estimates of the pooled standard deviation (SD) and pooled coefficient of variation (%CV), as well as their respective 95% confidence intervals were calculated for each subinterval. Results Across all specimen types (excluding outliers), the pooled SD for pH ranged from 0.00591 - 0.01747 pH units for subintervals 6.500 - 7.300, >7.300 - 7.450, >7.450 - 7.800 pH units. For PO2, the pooled SD ranged from 0.71 - 3.76 mmHg for subintervals 10 - 40 mmHg and >40 - 50 mmHg and the pooled %CV ranged from 1.63 - 8.76 %CV for subintervals >50 - 100 mmHg, >100 - 250 mmHg and >250 - 700 mmHg. For PCO2, the pooled SD ranged from 0.000 - 1.709 mmHg for subintervals 5.0 - 35.0 mmHg, >35.0 - 50.0 mmHg and >50.0 - 62.5 mmHg and the pooled %CV ranged from 1.10 - 3.62 %CV for subinterval >62.5 - 130.0 mmHg. Conclusions The precision study demonstrated that the pH, PO2 and PCO2 tests in the i-STAT G3+ cartridge when tested using the i-STAT 1 System deliver precise results within ∼2 minutes for venous, arterial, and capillary whole blood patient specimens when tested by end users in a point-of-care or clinical laboratory setting. These studies were funded by Abbott Laboratories.

A-120 Analytical and Clinical Verification of the Elecsys® Alzheimer’s Disease Cerebrospinal Fluid Biomarkers pTau/Abeta42 and Total-Tau/Abeta42

Abstract Background Alzheimer’s disease (AD) is the most common form of dementia characterized by amyloid beta (Abeta) plaques and neurofibrillary tau tangles in the brain. Cerebrospinal fluid (CSF) biomarkers Abeta42, total tau (tTau), and phosphorylated tau (pTau181) offer a high degree of sensitivity and specificity in the diagnosis of AD and have utility in monitoring disease progression. AD biomarker ratios, pTau181/Abeta42 and tTau/Abeta42, correlate with amyloid positron emission tomography (PET) imaging, and several assays have received FDA clearance. This study was designed to evaluate the analytical performance and clinical utility of AD-related Abeta and tau biomarkers on the Roche cobas e601. Methods Precision studies were performed using Roche PreciControl kits. Intra- and inter-precision samples were tested ten times in a single day or twice a day for ten days, respectively. Five levels of Roche Calcheck material were measured in triplicate for linearity. Method comparison was carried out using 39 samples from the Elecsys CSF Correlation Sample Panel from Roche. Qualitative comparisons to amyloid PET Centiloid scores were performed using 35 CSF samples (n=11 PET negative, n=24 PET positive). CSF samples and PET interpretation were obtained from the Cleveland Clinic Institutional Review Board approved Cleveland Alzheimer's Disease Research Center (CADRC) and Cleveland Clinic Lou Ruvo Center for Brain Health Aging and Neurodegenerative Disease Biobank (LRCBH-Biobank). Results Conclusions Evaluation of AD biomarkers on the Roche cobas e601 revealed reliable precision and analytical accuracy. The pTau181/Abeta42 and tTau/Abeta42 ratios demonstrated excellent positive agreement when compared to amyloid PET, but poor negative agreement. This may be due to the small sample size of PET-negative patients. Alternatively, as amyloid PET detects neuritic plaque accumulation, the CSF biomarker-positive/PET-negative patients may have early non-neuritic amyloid plaque pathology not detectable by imaging. Overall, this assay is suitable for use and may serve as a valuable tool in AD diagnosis.

A-309 Multicenter Performance Evaluation of the ProNephro AKITM Assay and Sample Stability in Pediatric Patients

Abstract Background Acute Kidney Injury (AKI), defined by increased serum creatinine or decreased urine volume, is highly prevalent in critically ill pediatric patients. Those who develop AKI experience worsened outcomes, raising the need for accurate and early biomarkers for AKI. Relying in serum creatinine for AKI diagnosis is unreliable due to its diagnostic inaccuracy and delayed rise in the AKI pathophysiology. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a novel and widely studied biomarker for early identification of AKI. During pathological progression, NGAL is elevated in blood and urine within two hours of the insult, making it useful for early diagnosis and management of kidney injury in critically ill children. This study aims at evaluating the performance characteristics of a quantitative test for NGAL in urine intended for use in critically ill pediatric patients, and investigating the stability of NGAL in pediatric urine. Methods The ProNephroAKITM is a particle-enhanced turbidimetric immunoassay on the Roche cobas® c501 analyzer to measure NGAL quantitatively in urine in pediatric patients 3 months to 21 years of age. These studies were approved by the respective institutional review boards. The limits of blank (LOB), detection (LOQ) and quantitation (LOQ) were determined following CLSI EP17A2. Linearity was assessed across the measurement range (MR) of 50-3000 ng/mL. The assay repeatability, between-run, between-day and total imprecision were determined in pediatric urine samples (n=9, covering the MR) and controls (n=2) following CLSI EP5-03 guidelines. Likewise, multisite reproducibility was evaluated in pediatric urine (n=7, covering the MR) and controls (n=2) in 3 laboratories and alternating operators. The assay specificity was assessed in the presence of several endogenous and exogeneous substances (e.g. drugs, contrast agents), potential related cross-reactant molecules, and several pH-values. The stability of NGAL in urine was evaluated using freshly collected pediatric urine samples covering the MR from 16 consented patients after storage at ambient (15-30°C), refrigerated (2-8°C), and frozen temperatures (≤-70°C), and following 3 freeze/thaw cycles. Results The ProNephroAKITM is linear across the MR of 50-3000 ng/mL. The LOB, LOD and LOQ were 9, 14 and 18 ng/mL, respectively. The coefficients of variation (CVs) for repeatability, between-run, between-day and total precision were ≤5.0%, ≤3.1%, ≤1.7% and ≤4.9%, respectively in urine and control samples. The reproducibility across 3 independent laboratories was ≤6.6%. The recovery of NGAL was not significantly affected by endogenous substances, contrast agents, pH (3.3-10.3), and common and special pharmaceutical compounds (exception: very high Cefepime concentrations may decrease NGAL), and potential cross-reactants. Freshly collected urine samples spanning concentrations from 71-2,373 ng/mL were stable (±10% recovery) for 2 days at ambient, 4 days refrigerated and 13 months frozen, and after 3 freeze/thaw cycles. Conclusions We report the performance characteristics of the ProNephroAKITM assay, including excellent precision and adequate reproducibility across 3 laboratories, sensitivity, specificity, and urine sample stability. The test was determined to meet the analytical performance required for clinical use in critically ill pediatric patients at risk of developing or having persistent AKI.

A-341 Precision Evaluation of the i-STAT® Glucose Test in the i-STAT G Cartridge using thei-STAT 1 System for Venous, Arterial and Capillary Whole Blood Specimens in Clinical Settings

Abstract Background Precise and accurate measurements of whole blood glucose levels are important for the diagnosis and treatment of patients suffering from diabetes and hypoglycemia. This study demonstrates the precision of the i-STAT G cartridge with the i-STAT 1 System in arterial, venous, or capillary whole blood in point of care or clinical laboratory settings. Methods The precision of the i-STAT G cartridge was assessed at external clinical sites by intended end users with whole blood specimens across the measurement range of 20 - 700 mg/dL. The study included testing venous whole blood samples from 154 adult (≥ 18 years) patients and arterial whole blood samples from 173 adult patients at three clinical sites. Each whole blood sample was run in duplicate on the i-STAT G cartridge. In addition, 139 capillary whole blood specimens from both adult subjects and neonate subjects (birth - 28 days) were collected and tested for capillary whole blood precision. Duplicate fingerstick draws were collected in capillary tubes from 119 adult subjects at two clinical sites and duplicate heel-stick specimens were collected in capillary tubes from 20 neonate subjects at two clinical sites. Specimens used in this study were prospectively collected venous, arterial, or capillary specimens under an Institutional Review Board approved informed consent or were de-identified leftover venous or arterial specimens. For each specimen type, duplicates from each subject were grouped into subintervals based on their mean values. The subintervals included the glucose medical decision levels of 45 mg/dL, 120 mg/dL and 180 mg/dL. The estimates of the pooled standard deviation (SD) and pooled coefficient of variation (%CV), as well as their respective 95% confidence intervals (CI) were calculated for each subinterval (20-90 mg/dL, >90-150 mg/dL, >150-250 mg/dL, >250-700 mg/dL or >250-400 mg/dL and >400-700 mg/dL, as applicable). The precision estimates for each subinterval were compared against an acceptance criteria of the greater of 3 mg/dL or 5% of the mean (mg/dL) of the subinterval. Results The whole blood precision was found to be less than or equal to 5.00 %CV for all subintervals for each specimen type. For venous specimens, the %CV ranged from 0.35% to 0.43%; for arterial specimens the %CV ranged from 0.26% to 0.46% and for capillary specimens (adult and neonate combined), the %CV ranged from 1.38% to 2.71%. Conclusions The study demonstrated that the i-STAT Glucose test in the i-STAT G cartridge when tested using the i-STAT 1 System delivers precise results within ∼2 minutes for venous, arterial, and capillary whole blood patient specimens across a glucose range of 20 - 700 mg/dL when tested by end users in a point of care or clinical laboratory setting. The studies were funded by Abbott Laboratories.

A-066 Does essential fatty acid deficiency alter ethanolamine plasmalogen concentrations in red blood cells? Implications for clinical testing

Abstract Background Plasmalogens are glycerophospholipids characterized by a fatty alcohol at the sn-1 position, a polyunsaturated fatty acid at the sn-2 position, most commonly docosahexaenoic acid (DHA) or arachidonic acid, and a polar head group at the sn-3 position, mainly phosphoethanolamine. Markedly reduced plasmalogens are seen in peroxisome biogenesis defects, including Zellweger spectrum disorders (ZSD), since the first two steps of plasmalogen synthesis occur in peroxisomes. Disruption of the peroxisomal β-oxidation pathway also causes DHA deficiency in ZSD patients. Since plasmalogens are composed of fatty acids, the deficiency of DHA or other essential fatty acids could further decrease the plasmalogen level in ZSD patients and lower the results of plasmalogen testing in patients without ZSD. To test this hypothesis, we evaluated the impact of essential fatty acid (EFA) deficiency on plasmalogens in patients with ZSD and individuals with EFA deficiency due to unrelated causes. Methods Red blood cell (RBC) samples were obtained from individuals without ZSD referred to ARUP laboratories for clinical EFA testing (n = 80; age range: birth - 89 years), and from patients with ZSD (n = 7; age range birth - 9 years). Three ZSD patients were older and with a less severe phenotype. A total of 18 intact ethanolamine plasmalogen species were extracted from packed RBCs and quantified using a XEVO TQ-XS Mass Spectrometer in conjunction with Ultra-High Performance Liquid Chromatography (Waters). Total plasmalogen values were also calculated; plasmalogen deficiency was defined as ≤60% of age-matched control median. Fatty acids (FAs) were quantified by gas chromatography negative chemical ionization-mass spectrometry (GC-NCI-MS). EFA deficiency was diagnosed by increased Triene/Tetraene ratio (Mead acid/Arachidonic acid). Data was analyzed using Prism v.8.3.0 software (La Jolla, CA). The study was approved by the Institutional Review Board of the University of Utah. Results Out of the 80 samples from individuals without ZSD referred for EFA testing, 18% had normal fatty acid profile, 57% were receiving dietary supplements and 25% had elevated Triene/Tetraene ratio suggesting EFA deficiency. EFA deficiency was accompanied by low DHA only in two individuals without ZSD, whereas it was present in most of the samples from ZSD patients evaluated (5/7). None of the individuals without ZSD were deficient in plasmalogens. Moreover, when compared to individuals without ZSD with a normal FA profile, there was no significant difference observed with EFA deficiency or FA supplementation. Although our ZSD cohort is small, no correlation between EFA deficiency and plasmalogen levels was also seen in ZSD: 2 patients with milder phenotype had EFA deficiency but normal plasmalogens, 2 patients had EFA deficiency and low plasmalogens, 2 patients with low plasmalogens had low DHA without EFA deficiency, and 1 patient had low plasmalogens but normal EFA. Conclusions Plasmalogen quantitation in RBCs by LC-MS/MS is not significantly affected by EFA deficiency. Although more data is warranted to elucidate the correlation between plasmalogen levels and ZSD phenotype, plasmalogens can be within normal reference intervals in ZSD regardless of EFA status.

Effect of teleneurology on door-to-needle times for tenecteplase in acute ischemic stroke

IntroductionIntravenous thrombolysis remains the primary treatment for acute ischemic stroke (AIS); however, administration is time sensitive. Teleneurology services have increased in popularity in recent years due to their ability to aid in triaging patients with neurological conditions. Teleneurology services were implemented at this comprehensive stroke center, in August 2023 to aid in streamlining the administration of tenecteplase in AIS patients. Currently, there are no studies assessing whether the implementation of teleneurology services at a comprehensive stroke center influences tenecteplase door-to-needle time. The purpose of this study is to evaluate the difference in door-to-needle times when tenecteplase is administered with versus without a teleneurology consult. MethodsThis was an institutional review board approved, retrospective cohort study conducted at a single comprehensive stroke center. Adult patients who presented to the emergency department between January 1st, 2022 and April 1st, 2023 were included if they received tenecteplase for the treatment of AIS. The primary outcome was door-to-needle time, defined as the moment the patient first enters the door of the emergency department to the moment the IV bolus of fibrinolytic is administered. Secondary outcomes included the proportion of patients with door-to-needle time within 45 min, neurological improvement at 24 h and discharge, and rate of hemorrhagic conversion. ResultsA total of 93 patients were included with 43 patients in the pre-teleneurology group and 50 patients in the post-teleneurology group. Baseline characteristics were comparable between both treatment groups. The median door-to-needle time was significantly reduced in the post-teleneurology group (49 minutes [IQR, 40.0–70.0] preintervention vs. 34.5 minutes [IQR, 23.8–43.0] postintervention, p < 0.01). For secondary outcomes, the post-teleneurology group had more patients with a door-to-needle time within 45 minutes (44.2% vs. 80.0%, p < 0.01). There was no significant difference in early neurological improvement (58.1% vs. 54.0%), neurological improvement at discharge (60.5% vs. 62.0%), or hemorrhagic conversion (7.0% vs. 12.0%). ConclusionAmong patients who received tenecteplase for the treatment of AIS, there was a significant reduction in door-to-needle time with the use of teleneurology services. There was no difference in neurological improvement or rate of hemorrhagic conversion.

A-040 Association of GATA-4 and Platelet Derived Growth Factor-B in Metabolic (Dysfunction) Associated Fatty Liver Disease

Abstract Background Metabolic (dysfunction) associated fatty liver disease is a global concern as its prevalence is rising steeply ranging from 38.7% to 50.7%. MAFLD is a multifaceted burden of diseases such as diabetes, obesity, and cardio-metabolic diseases. It is the leading cause of hepatocellular carcinoma. GATA-4 is a zinc finger transcription factor located in liver sinusoidal endothelial cells and plays a critical role in liver regeneration. Platelet-derived growth factor-B (PDGF-B) plays a role in the profibrogenic trans-differentiation of Hepatic stellate cells and is actively involved in the development of hepatic fibrosis. Therefore, the study hypothesized that GATA-4 and PDGF-B are dysregulated and involved in the progression of MAFLD. Thus, the study aimed to assess the association of GATA 4 and PDGF-B in MAFLD, disease control, and healthy control. Methods 80 subjects were recruited after exclusion criteria from Gastroenterology and Medicine OPD at AIIMS, New Delhi, and divided into 3 groups: Group 1 (healthy control)-20, Group 2 (disease control)-20, and Group 3 (MAFLD)-40. Institutional ethical committee approval was obtained. The demographic and anthropometric details, blood investigations, Non-invasive scores (AST/ALT ratio, APRI &amp; FIB-4), and Transient elastography findings were illustrated in all the groups. The correlation between the GATA-4, PDGF-B, and platelet indices (MPV, P-LCR, PDW, and PCT) was done. STATA version 15 software was used for statistical analysis. Results GATA 4 was significantly decreased (p&amp;lt;0.001) and PDGF-B (p&amp;lt;0.001) was significantly increased in MAFLD subjects compared to healthy controls. However, no significant correlation was observed between GATA-4 and PDGF-B with platelet indices (P-LCR, PCT, and PDW). In contrast, mean platelet volume (MPV) was statistically significant (p&amp;lt;0.001) but it was clinically insignificant between the study groups. Similarly, HOMA-IR and GATA-4 did not show any significant correlation among MAFLD. However, CAP, LSM parameters of Transient elastography, APRI, and FIB-4 scores were statistically significant (p&amp;lt;0.001) in MAFLD when compared to healthy control. AUROC of non-invasive scores were found with weak discrimination and clinically not robust to distinguish the fibrosis grading. Conclusions GATA-4 and PDGF-B could be potential biomarkers, as no drugs are available so far to fill the global gap. However, pharmacological aspects need to be formulated for the treatment of MAFLD.

Implementation of a Multidisciplinary Enhanced Recovery After Surgery (ERAS) Program for Cytoreductive Surgery (CRS) With Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can be associated with prolonged hospital stays. A novel Enhanced Recovery After Surgery (ERAS) based on ERAS Society guidelines was designed and implemented. The primary outcome was ERAS compliance. Secondary outcomes included length of stay (LOS) and postoperative complications. A retrospective study on patients who underwent CRS/HIPEC between 2018 and 2022, with ERAS implementation in 2022. Health records were reviewed. Statistical analysis included descriptive statistics, Wilcoxon tests, Student t-test, and χ2 and binomial negative regression. Health Ethics Research Board approval was obtained. Eighty patients underwent CRS/HIPEC: 59 in the pre-ERAS group and 21 in the post-ERAS group. Groups were similar in age, comorbidities, and Peritoneal Carcinomatosis Index. ERAS compliance increased from 32.8% to 70.8% (p < 0.001). Median LOS decreased from 14 to 9 days (p < 0.001). Comparing pre-ERAS to post-ERAS showed no significant difference in the major morbidity rate (13.6% vs. 9.5%) or 30-day readmission (9.4% vs. 4.8%) and no mortalities. Controlling for patient characteristics, the mean LOS decreased by 6.94 days (p < 0.001). Implementation of an ERAS CRS/HIPEC program is safe and allows for improved compliance to ERAS protocols and a significant reduction in LOS.

INhaled Sedation versus Propofol in REspiratory failure in the Intensive Care Unit (INSPiRE-ICU1): protocol for a randomised, controlled trial

IntroductionSedation in mechanically ventilated adults in the intensive care unit (ICU) is commonly achieved with intravenous infusions of propofol, dexmedetomidine or benzodiazepines. Significant limitations associated with each can impact their...

Infection control nursing competency model for nurses in intensive care units: A Delphi study

Intensive care unit (ICU) nurses require advanced expertise and skills in critical care and need infection control nursing competency (ICNC). Given the lack of research on it, this study aimed to develop a model of ICU nurses' ICNC. A Delphi panel consisting of experts in intensive care nursing and infection control was organized to provide discerning and professional perspective on ICNC. Approved by the Institutional Review Board, a 3-round Delphi survey was conducted via email from July to December 2023. The content validity ratio and the coefficient of variation were calculated for panel responses. Among 17, 15 nurses (88.2%) participated and completed the surveys. About80% were female, and the panel had an average working experience of 14.2years specifically in theICUs or infection control departments at hospitals. After the initial round, a preliminary model was developed, consisting of 10 main components and 59 subelements. After eliminating 5 elements with content validity ratio values below 0.49 in the second survey, the final model, consisting of 10 main components and 54 subelements, was confirmed in the third survey. ICU nurses' ICNC can be understood based on this study's results, and further research can be designed to improve this competency.

Cryptosporidiosis in individuals with inflammatory bowel disease: a scoping review protocol

IntroductionCryptosporidiosis is a leading cause of moderate-to-severe diarrhoea globally, and, while it is often self-limited, in immunocompromised individuals, the infection can be associated with significant morbidity and mortality. Diagnosis might...