Yuya Ishihara

BACKGROUND AND OBJECTIVES: Reports on the changes in plasma fibrinogen levels in patients receiving cryoprecipitates synthesized using different methods are lacking. Therefore, we investigated these changes in patients who underwent cardiovascular surgery. MATERIALS AND METHODS: We included 309 patients who underwent cardiovascular surgery and received 12 cryoprecipitate units between February 2020 and March 2024 and 204 patients were selected by propensity score matching. The cryoprecipitates were prepared using two methods. Fresh frozen plasma (FFP) was thawed at 2 to 6°C for 24 h and centrifuged to remove the supernatant in the one-step method, whereas FFP was thawed, refrozen at -20°C, and subsequently rethawed in the two-step method. We investigated the association between different cryoprecipitate preparation methods and ICU admission for ≥ 1 week, with in-hospital mortality considered as a competing risk in the analysis. In addition, we evaluated the changes in plasma fibrinogen levels before and after cryoprecipitate administration. RESULTS: Baseline plasma fibrinogen levels were significantly higher in the two-step method group than in the one-step method group. Differences in cryoprecipitate preparation methods were not significantly associated with ICU admission for ≥ 1 week, in the analysis that considered in-hospital mortality as a competing risk (P = 0.93). The increase in plasma fibrinogen levels after cryoprecipitate administration was significantly higher with the two-step method than with the one-step method (36 mg/dL vs. 51 mg/dL, P = 0.020). CONCLUSION: The cryoprecipitates synthesized using the two-step method showed a higher increase in plasma fibrinogen levels than those prepared using the one-step method. These findings may help guide appropriate transfusion protocols by confirming intraoperative plasma fibrinogen levels.

We investigated the prognostic value of cardiac myosin-binding protein C (cMyC), a novel cardiospecific marker, both independently and in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP), for predicting 6-month all-cause mortality in patients without acute coronary syndrome (ACS) treated at medical (nonsurgical) cardiac intensive care units (CICUs). Admission levels of cMyC, high-sensitivity cardiac troponin T (hs-cTnT), and NT-proBNP were measured in 1032 consecutive patients (mean age; 70 years) without ACS hospitalized acutely in medical CICUs for the treatment of cardiovascular disease. Serum cMyC was closely correlated with hs-cTnT and moderately with NT-proBNP (r = 0.92 and r = 0.49, respectively, p < 0.0001). During the 6-month follow-up period after admission, there were 109 (10.6%) all-cause deaths, including 72 cardiovascular deaths. Both cMyC and NT-proBNP were independent predictors of 6-month all-cause mortality (all p < 0.05). Combining cMyC and NT-proBNP with a baseline model of established risk factors improved patient classification and discrimination beyond any single biomarker (all p < 0.05) or the baseline model alone (both p < 0.0001). Moreover, patients were divided into nine groups using cMyC and NT-proBNP tertiles, and the adjusted hazard ratio (95% confidence interval) for 6-month all-cause mortality in patients with both biomarkers in the highest vs. lowest tertile was 9.67 (2.65-35.2). When cMyC was replaced with hs-cTnT, similar results were observed for hs-cTnT. In addition, the C-indices for addition of cMyC or hs-cTnT to the baseline model were similar (0.798 vs. 0.800, p = 0.94). In conclusion, similar to hs-cTnT, cMyC at admission may be a potent, independent predictor of 6-month all-cause mortality in patients without ACS treated at medical CICUs, and their prognostic abilities may be comparable. Combining cMyC or hs-cTnT with NT-proBNP may substantially improve early risk stratification of this population.

BACKGROUND: Ethylenediamine tetraacetate/glycine acid (EGA) and chloroquine diphosphate (CDP) are used in transfusion testing to dissociate IgG antibodies from red blood cells (RBCs). However, the ability of these reagents to dissociate IgM antibodies sensitized to RBCs has not been comprehensively elucidated. We investigated whether EGA and CDP could dissociate cold-reactive antibodies from RBCs and their effect on RBCs after dissociation treatment. STUDY DESIGN AND METHODS: Cold-reactive antibody-sensitized RBC samples were prepared by mixing group A RBCs and group B plasma and treated with EGA, CDP, and dithiothreitol (DTT). Before and after the dissociation treatment, changes in the agglutination of these RBCs were assessed using the test tube method. Flow cytometric analysis was used to confirm the nature of antibodies bound to RBCs. Additionally, RBC morphology was evaluated using scanning electron microscopy. This study utilized off-label use of EGA and CDP. RESULTS: Flow cytometric analysis showed that antibodies sensitized to RBCs were mainly IgM antibodies. After antibody dissociation, agglutination disappeared in the EGA-treated samples to the same degree as in the DTT-treated samples. However, IgM antibodies remained in the CDP-treated samples. Regarding RBC morphology, RBC surface appeared coarser in both EGA- and CDP-treated samples, and RBC area was significantly smaller in the CDP-treated samples than in the EGA-treated samples. DISCUSSION: EGA could dissociate cold-reactive antibodies, whereas CDP had a higher residual antibody content. This difference in dissociation ability appears to correlate with the antibody pH of the dissociation reagent. EGA treatment may be useful in cases of sensitization by high-titer cold-reactive antibodies.

Acute heart failure is an important cause of unplanned hospitalizations and poses a significant burden through increased mortality and frequent hospitalizations. Heart failure with preserved ejection fraction (HFpEF) presents as a diverse condition characterized by complex cardiovascular and non-cardiovascular pathology. This study aimed to identify distinct clinical phenotypes in acute decompensated HFpEF (ADHF) using cluster analysis and assess their prognostic significance. We applied a latent class analysis to 1,281 ADHF patients admitted to a single cardiac intensive care unit between 2008 and 2022 with a left ventricular ejection fraction ≥ 50%. We used 83 factors obtained at hospitalization. We evaluated the association between phenogroups and clinical outcomes using either Cox regression model or Fine-Gray competing risk model. We identified 4 phenogroups: Phenogroup 1 (n = 133, 10%) included younger patients with metabolic disorders and a low level of B-type natriuretic peptide (BNP); Phenogroup 2 (n = 346, 27%) had systemic congestion and high BNP levels; Phenogroup 3 (n = 514, 40%) had multiple comorbidities and vascular disorders; Phenogroup 4 (n = 288, 22%) included older patients with bradyarrhythmia and atrial fibrillation. After adjusting for age, sex, and Get with the Guidelines-Heart Failure risk score, Phenogroup 2 had the highest risk of all-cause death and cardiac death. In conclusion, we identified 4 clinically relevant phenogroups of ADHF patients, each associated with different adverse outcomes. Phenotyping may provide a better understanding of the underlying mechanisms involved in the heterogeneity of ADHF and decompensation. Furthermore, it may facilitate the search for phenotype-specific therapeutic strategies.

BACKGROUND: Activated partial thromboplastin time (APTT) is susceptible to reagent composition. This study aimed to investigate a large number of specimens and determine the cause of discrepancies. METHOD: This study included 18,994 subjects who underwent coagulation tests at our hospital from May 2020 to December 2020. Measuring reagents included HemosIL SynthASil APTT (APTT-SS, Instrumentation Laboratory) and Coagpia APTT-N (APTT-N, Sekisui Medical). RESULTS: A total of 451 patients demonstrated APTT-N of >39 seconds and an APTT-N/SS ratio of >1.3. A C-reactive protein (CRP) level of ≥1.4 mg/L demonstrated a significant positive correlation, with a higher APTT-N/SS indicating higher CRP levels. All 28 subjects receiving no anticoagulants and who had remaining specimens underwent a cross-mixing test (CMT). Of them, 17 were suspected for lupus anticoagulant (LA) by both the waveform shape and the index of circulating anticoagulant (ICA) value, 6 by the ICA value, and 5 were difficult to determine. CONCLUSION: This study revealed that the APTT-N prolongation correlated with CRP degree and the transient involvement of LA in CMT results due to CRP. This study indicated various reactivities depending on the assay reagents used. Further testing is warranted if LA is suspected, considering the patient's background.