Puzzling undetectable haptoglobin in a transfused pregnant patient.

BACKGROUND-AIM: Pregnancy induces physiological changes that can affect serologic and immunologic markers, potentially resulting in lower or undetectable haptoglobin values compared to non-pregnant counterparts. Such variations may lead to inaccurate diagnosis of hemolysis. METHODS: We report a case of a patient in second trimester of pregnancy receiving induction chemotherapy due to B-cell acute lymphocytic leukemia with undetectable haptoglobin levels in a routine laboratory sample collected less than 12 h posttransfusion of red cell unit. Despite undetectable haptoglobin, lactate dehydrogenase (LD) was within reference intervals (RI). The patient was evaluated for acute hemolytic transfusion reaction (AHTR) and followed up. Haptoglobin levels showed an upward trend during follow-up visits, reaching 15 mg/dL, and within RI in the third trimester. RESULTS: The patient did not meet the Center for Disease Control (CDC) criteria for AHTR. Alternative explanations for the observed laboratory findings were explored. Undetectable haptoglobin levels were attributed to various factors, including recent RBC transfusion, pregnancy-related physiological changes, and potential hyperhydration treatment plan due to chemotherapy. CONCLUSION: This case underscores the importance of cautious interpretation of laboratory results in pregnant patients, necessitating trimester-specific reference intervals for haptoglobin. A multidisciplinary approach to patient care is crucial for accurate diagnosis and management.

Comprehensive Clinical and Genetic Analyses of Circulating Bile Acids and Their Associations With Diabetes and Its Indices.

Bile acids (BAs) are cholesterol-derived compounds that regulate glucose, lipid, and energy metabolism. Despite their significance in glucose homeostasis, the association between specific BA molecular species and their synthetic pathways with diabetes is unclear. Here, we used a recently validated, stable-isotope dilution, high-performance liquid chromatography with tandem mass spectrometry method to quantify a panel of BAs in fasting plasma from 2,145 study participants and explored structural and genetic determinants of BAs linked to diabetes, insulin resistance, and obesity. Multiple 12α-hydroxylated BAs were associated with diabetes (adjusted odds ratio [aOR] range, 1.3-1.9; P < 0.05 for all) and insulin resistance (aOR range, 1.3-2.2; P < 0.05 for all). Conversely, multiple 6α-hydroxylated BAs and isolithocholic acid (iso-LCA) were inversely associated with diabetes and obesity (aOR range, 0.3-0.9; P < 0.05 for all). Genome-wide association studies revealed multiple genome-wide significant loci linked with 9 of the 14 diabetes-associated BAs, including a locus for iso-LCA (rs11866815). Mendelian randomization analyses showed genetically elevated deoxycholic acid levels were causally associated with higher BMI, and iso-LCA levels were causally associated with reduced BMI and diabetes risk. In conclusion, comprehensive, large-scale, quantitative mass spectrometry and genetics analyses show circulating levels of multiple structurally specific BAs, especially DCA and iso-LCA, are clinically associated with and genetically linked to obesity and diabetes.

Exploratory Mass Spectrometry of Cerebrospinal Fluid from Persons with Autopsy-Confirmed LATE-NC.

Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management. Participants (n = 29) had been autopsied and had antemortem CSF draws in a longitudinal cohort of older adults at the University of Kentucky AD Research Center. Cases were designated as LATE-NC + if they had LATE-NC stage > 1 (n = 9); the remaining 20 cases were designated LATE-NC-. This convenience sample of CSF specimens was analyzed in two separate processes: From one group, aliquots were depleted of highly abundant proteins using affinity spin columns. Tryptic digests of sample proteins were subjected to liquid chromatographic separation and mass spectrometry. Relative quantification was performed using Sciex software. Peptides referent to a total of 949 proteins were identified in the samples depleted of abundant proteins, and 820 different proteins were identified in the non-depleted samples. When the Bonferroni/false-discovery statistical correction was applied to account for having made multiple comparison tests, only 4 proteins showed differential expression (LATE-NC + vs LATE-NC-) in the non-depleted samples (RBP4, MIF, IGHG3, and ITM2B). Post hoc western blots confirmed that RBP4 expression was higher in the LATE-NC + cases at the group level. In summary, an exploratory assessment of proteomes of autopsy-confirmed LATE-NC and non-LATE-NC CSF did not demonstrate a clear-cut proteomic fingerprint that distinguished the two groups. There was, however, an increase in RBP4 protein levels in CSF from LATE-NC cases.