Citations

Abstract Background The lack of standardization and harmonization among ferritin assays results in significant variability in clinical values. These assays have different reference ranges and numerous clinical cut-offs for interpreting anemia and iron toxicity. This inconsistency is due to manufacturers using various calibrators. Such variability complicates the interpretation and comparison of results across different clinical settings. Methods Ferritin was ordered for 7815 patient samples in 3 months and assays were performed by DXI. Similarly, 5818 patients’ samples were run by Roche in two months. Both assays are FDA cleared and are commonly used by hundreds of clinical laboratories. Frequency of no of patients flagged low or flagged were calculated with respective reference ranges of Dxi and Cobas. Results 12 percent of the patients were flagged low by the Beckman assay and would have gotten both physician and patients attention. However, by the Roche assay only 4 percent were flagged low. This was alarming to our physicians and lab was told to investigate to find for this shift. Manufacturer/Time Range Total Volume Total High Total Low %High %Low Dxi-May-24 2617 368 326 14.1% 12% Dxi-Jun-24 2391 345 278 14% 12% Dxi-Jul-24 2807 500 308 17.8% 11% Cobas-801 August 2024 - Ferritin Go Live Cobas-801-Sep-24 2545 572 105 22% 4% Cobas-801-Oct-24 2841 695 121 24% 4% Conclusion Lack of Standardization and harmonization has serious consequences for the patients being tested for ferritin to diagnose deficiency of iron or high iron situations. We are planning to do a prospective study to determine clinical cut-offs by correlating Ferritin lab results with other gold standard biomarkers including bone marrow biopsy.

Abstract Background Vitamin D supplementation by human individuals has significantly increased in the world. In US the total stored 25-OH-Vitamin D3 and 25-OH-Vitamin D2 has significantly increased for both in summers and winters. Under sunlight exposure, 7 dehydrocholesterol is converted to Vitamin D3 and is endogenous source in mammals. However, most of the exogenous source for Vitamin D used to be Vitamin D2 which used to be extracted only from mushrooms but is now manufactured by supplement industry as well. In last decade most of the supplementation has been due to chemically synthesized Vitamin D3. Food is now supplemented by both D2 and D3. It is not clear what is the prevalence of D2 supplementation/consumption in American population. Competitive immunoassays do not consistently recover 25-OH-D2 compared to 25-OH-D3 and some antibodies used have variable or no cross reactivity with 25-OH-D2. LC-MS/MS method can easily distinguish the two and can help in providing the precise and accurate results for 25-OH-D2 and 25-OH-D3. Here we present what is the prevalence of Vitamin D2 consumption and toxicity in American population based on our LC-MS/MS methods. Methods The study measured vitamin 25-OH-D levels (total, D2, and D3) in 148,654 patients from Mayo Clinic as well as from other medical centers within the U.S. Patients age ranging from new-born babies to over 100 years, and represents Male, Female and Neutral genders. Samples were analyzed for 25-OH-Vitamin D by LC-MS/MS as published earlier. Unlike immunoassays, LC-MS/MS gave us separate results for 25-OH-D3 and 25-OH-D2 with 100 percent specificity. Results 25-OH-Vitamin D2 levels of greater than 10 was present in at least 10,358 and ranged from 10 to 205 ng/mL. Of 10,358, 51 percent had 20-50 ng/mL, 10 percent had 51-80 ng/mL, and 1.3 percent had >80 ng/mL, ranging from 81-205 ng/mL with a median of 92 ng/mL. Of the patients found at Total Vitamin D >80 ng/mL, toxic levels of both D2 and D3 were found more in females than males. There was no significant gender difference for Vitamin D3 consumption but for D2 consumption, mean and median levels were different in males and females. Conclusion Clinical lab testing should accurately measure both 25-OH-D3 and 25-OH-D2, otherwise the patient total Vitamin D values in circulation will be underestimated.

Abstract Background Hemoglobin A1c is used to assess glycemic control to both diagnose and monitor diabetes mellitus. Several different methodologies are available including high performance liquid chromatography (HPLC), capillary electrophoresis (CE), and immunoassay (IA). These methods are standardized and traceable to the Diabetes Control and Complications Trial (DCCT). The aim of this study was to evaluate the difference in HbA1c results between methods and percent of reportable results in variant samples. Methods The HPLC (Bio-Rad Laboratories, Inc; D-100), the CE(Sebia Inc; Capillarys 3), and IA(Roche Diagnostics Inc; Tina-quant Generation 3) were compared using two sets of residual patient samples left after physician ordered testing was complete: 1) samples with an absence of abnormal hemoglobin peaks (i.e. non-variant) detected by HPLC; 2) samples with abnormal hemoglobin peaks (i.e. variant) characterized by hemoglobin electrophoresis performed clinically or lacking an A1c peak by HPLC/CE. The samples were tested within manufacturers stability claims. 317 non-variant samples were compared between the HPLC and CE methods. The absolute difference was calculated for each method using this equation (HbA1c%avg – HbA1c%X) where HbA1c%avg is the average of the methods that produced reportable results and X is the result from each method evaluated. Differences less than or equal to +/-0.3% were considered acceptable. 28 of the 317 non-variant and 47 variant samples were tested by all 3 methodologies. The 47 variant samples grouped into 3 cohorts: common heterozygous variants (HbC, HbD, HbE, HbS and HbF, n=10), uncommon heterozygous variants (n=29) and homozygous variants lacking HbA (n=8). The absolute differences in variant sample results were calculated for samples that did not surpass manufacturer’s claims for producing an accurate result. The frequency of producing a numeric result in variant samples was calculated for each method. Results The HPLC/CE non-variant sample comparison (N=317) had results spanning the measuring range (3.8% - 14.0%) with average(range) of absolute difference=0.1(-0.4to0.6%) with 293/317(92.4%) samples within +/-0.3%. The HPLC/CE/IA non-variant sample comparison (N=28) had a result range=4.0%-9.4%, the average(range) of difference=0.1(-0.2to0.5%) with 25/28 (89.2%) of samples within +/-0.3%. Common heterozygous variant samples gave numeric results with no disqualifying flags in 9 of 10(HPLC), 8 of 10(CE), and 9 of 10(IA) samples tested. The average(range) difference from average=0.0(-0.3,0.5%) for HPLC, 0.0(-0.2,0.3%) for CE, and -0.1(-0.6,0.2%) for IA. Uncommon variant samples gave results in 4 of 29 (HPLC), 20 of 29 (CE), and 26 of 29 (IA) of samples tested. The average(range) difference from average=-0.1(-0.3,0.1%) for HPLC, 0.0(-1.0,1.1%) for CE, and 0.0(-1.1,1.0%) for IA. The homozygous variant (no HbA) samples gave results in 0 of 8 (HPLC), 0 of 8 (CE), and 4 of 8 (IA) of those tested. Conclusion All three methods meet their claims for accurately measuring hemoglobin A1c from non-variant and common hemoglobin variants. The advantage of HPLC and CE is the ability to identify hemoglobin variants that may impact HbA1c quantitation. The IA method provides the most numeric results. IA gave results even when HbA was absent. The lab should understand the capabilities and limitations of their HbA1c method on the population served.

Abstract Objective To share findings of a quality improvement initiative to capture employment status in the electronic medical record (EMR) to mitigate the potential impact of work loss on the health of patients by utilizing the results to identify eligible individuals for resources to assist return-to-work efforts. Materials and Methods Patients self-identified employment status through a structured new social determinants of health (SDOH) question within the EMR. An electronic outreach campaign was developed to provide information via the patient portal detailing services within healthcare and the community that could benefit the patients. Results Over the course of 12 months, 2059 patients were identified from the employment SDOH question. Resources to support stay at work and return to work efforts were provided to patients through an automated electronic portal campaign with 87% of patients reading the message and 7% engaging with a healthcare return to work case manager. Discussion Loss of employment has detrimental impacts on individual and population health. Most EMRs do not capture information on employment status. Adding this simple question identified individuals with potential gaps in SDOH, and in this case allowed specific resources to be shared with patients with an illness or injury that was acutely impacting work. Conclusion Medical center decision makers and EMR programmers should consider adding employment status as a social determinant of health.

Background. The spirometric response to standard-of-care (SOC) immunosuppressive therapy for the management of bronchiolitis obliterans syndrome (BOS) has been sparsely reported in the literature. Data from a Medicare-approved Registry were analyzed to characterize the effectiveness/durability of a wide range of SOC interventions to manage the decline of lung function and to validate the study spirometric criteria for initiation of rescue therapy. Methods. Lung transplant recipients with refractory BOS at 21 US collaborating centers were enrolled in the Registry. Data included both nonspirometric (eg, demographic, Immunosuppressive Regimens for management of BOS) and spirometric parameters (ie, forced expiratory volume in 1 s [FEV 1 ] measurements and derived indices). The utility of study FEV 1 criteria for treatment (ie, statistically significant rate of FEV 1 decline >30 mL/mo) was evaluated by comparing the spirometric course between participants who met or did not meet this criterion. Results. Only 21% of participants treated with SOC therapy had >50% decrease (76 ± 25% decrease) in the rate of FEV 1 decline. Although 51% of participants had a partial response (rate of FEV 1 decline decreased on average 71%), 49% of participants had a substantial increase (mean increase 224%). The FEV 1 criterion for treatment was able to identify 19% of participants (48/258) who achieved durable stabilization (ie, nonsignificant rate of FEV 1 <30 mL/mo) with SOC therapy. Conclusions. Patients with BOS have a widely variable response to SOC therapy. Our findings support the use of FEV 1 rate of decline to assess response to SOC therapy and to ensure appropriate assignment of participants with refractory BOS to rescue therapy treatment cohorts.

Key Points Increased protein expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase was observed in old adults compared with young adults. In old adults, overexpressed proteins were enriched in mitochondrial processes while under expressed proteins enriched in RNA metabolism. Validated differentially expressed proteins were not significantly correlated with kidney pathology after adjusting for age. Background Kidney aging is characterized by a loss of glomeruli, predominantly in the superficial cortex, with a resultant decline in GFR and an increased risk of various kidney-related diseases. The early molecular alterations in glomeruli associated with the aging process are not well studied. Methods We combined laser capture microdissection and mass spectrometry–based unbiased proteomic analysis of nonsclerosed, nonischemic glomeruli in the superficial cortex from young and old adults who underwent a radical nephrectomy for a tumor to understand the age-related molecular changes in glomeruli. Twenty-four young and 30 old adults were used for the discovery dataset, and the significant differentially expressed proteins were further validated using an independent set comprising six young and eight old adults. Results Kidneys from old adults had lower eGFR, less kidney parenchyma on computed tomography imaging, and more glomerulosclerosis and arteriosclerosis on histology. Quantitative proteomic analysis of nonsclerosed, nonischemic glomeruli identified increased expression of tissue inhibitor of metalloproteinase-3, glypican 6, synuclein γ , apolipoprotein A-4, and Ecto-5′-nucleotidase in old adults that were further validated in an independent set. Pathway analysis indicated that proteins with increased expression in old adults were enriched in mitochondrial translational processes, aerobic respiration, and TCA cycle, whereas proteins with decreased expression in old adults were enriched in mRNA splicing, mRNA processing, and nonsense mediated decay. Furthermore, validated differentially expressed proteins did not show any significant correlation with the kidney pathology independent of age group. Conclusions Overall, this study identified proteins that are specifically associated with the aging process in otherwise normal-appearing glomeruli.

BACKGROUND: The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has significantly increased in recent years. GLP-1 RAs delay gastric emptying, resulting in early satiety and weight loss. This may increase the risk of pulmonary aspiration of residual gastric contents (RGC) during anesthesia delivery. Evidence is urgently needed to guide perioperative anesthesia management for patients taking GLP-1 RAs. This study evaluated preoperative factors that may be associated with high RGC. METHODS: Adult patients who were taking GLP-1 RAs and scheduled to receive anesthesia at 3 hospitals between June 30, 2023, and August 15, 2024, were evaluated via preoperative point-of-care gastric ultrasonography (GUS). The primary outcome was high RGC, defined by the presence of solids food or >1.5 mL/kg of clear liquids on GUS, and its association with preoperative factors (eg, existing medical conditions, indication and route of taking GLP-1 RAs, length of taking GLP-1 RAs, days of withholding GLP-1 RAs before surgery, and preoperative fasting periods). Data are presented as median (interquartile range [IQR]). RESULTS: Among the 316 patients (60.9 years [52.1–68.9] of age; 167 [52.8%] females) included in the study, 113 (35.8%) had high RGC. A higher percentage (5.3%; 6/113) of patients in the high RGC group had an opioid prescription for pain management within 3 months of the GUS assessment compared to the low RGC group (1.0%; 2/203; P = .027). No statistical difference was found between the groups in other existing medical conditions, indication and route of taking GLP-1 RAs, and length of taking GLP-1 RAs. Of the 294 patients taking weekly injections, there were 187 (63.6%) with low RGC and 107 (36.4%) with high RGC. Patients with low RGC withheld their GLP-1 RAs for 8 days [5–10], while patients with high RGC withheld for 6 days [3–9] ( P = .003). Receiver operating characteristic (ROC) analysis found ≤7.5 days of withholding the medication as cutoff for increased prevalence of high RGC in patients taking GLP-1 RA injections. Patients with low RGC fasted from solid food for 20.0 hours [14.8–40.8], and patients with high RGC fasted from solid food for 15.0 hours [12.8–19.0] ( P < .001). ROC found ≤21.3 hours of fasting from solid food as the cutoff for increased prevalence of high RGC. CONCLUSIONS: GLP-1 RA usage may delay gastric emptying. In preoperatively fasting adults, ≤7.5 days of withholding injections and ≤21.3 hours of fasting from solid food are associated with high RGC.