Differences in coagulation responses to vascular injury between uninterrupted dabigatran and apixaban: A clinical prospective randomized study.

BACKGROUND: The coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants has not been elucidated. OBJECTIVE: Our aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients. METHODS: Patients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected 3 times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10-15 minutes after the start of vascular punctures. RESULTS: Forty-two patients were enrolled. The prothrombin fragment 1+2 level, the primary end point, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median, 83 pmol/L; interquartile range, 56-133 pmol/L) than in the uninterrupted apixaban recipients (median, 1 pmol/L; interquartile range, -3 to 19 pmol/L; P < .001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients. CONCLUSION: Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.

Exploring factors associated with bleeding events after open heart surgery in patients on dialysis - effects of the presence or absence of warfarin therapy.

BACKGROUND: Perioperative management of patients on dialysis is critical for controlling bleeding and thrombotic risk, in addition to infection control. Postoperative anticoagulation is often difficult to control, and different institutions have different policies. Therefore, in this study, we aimed to investigate factors associated with postoperative bleeding events and whether warfarin (WF) therapy affects the incidence of postoperative bleeding events, total mortality, and stroke. METHODS: Patients who were admitted to the cardiovascular surgery department and underwent valve replacement or plasty were included, and those who underwent mechanical valve introduction were excluded. Thirty-nine patients were included in the study. The primary endpoint was to identify factors associated with the composite endpoint of postoperative bleeding events, and the secondary endpoint was to determine the effect size of WF therapy on postoperative bleeding events, all-cause mortality, and stroke and the strength of association between the crossed endpoints. The strength of the association between the crossed items was examined. RESULTS: Low body weight (p = 0.038) was identified as a factor associated with the primary endpoint of postoperative bleeding events. The secondary endpoint of whether or not patients received WF therapy was largely unrelated to bleeding events, all-cause mortality, and postoperative stroke up to 90 days after surgery. CONCLUSIONS: Preliminary studies suggest that low body weight is a risk factor for postoperative bleeding events in patients on dialysis, although further exploration of other factors will be necessary with the accumulation of similar cases.

Streptococcus suis subsp. hashimotonensis subsp. nov.: Lancefield group A antigen-positive organisms isolated from human clinical specimens and wild boar oral cavity samples.

Three Streptococcus suis-like strains positive for Lancefield antigen group A were isolated from human boar bite wounds and the oral cavities of boars in Hashimoto City, Wakayama Prefecture, Japan, and their taxonomic positions were investigated. Application of the VITEK2 system identified all three isolates as S. suis with > 94 % probability. The isolates were assigned to S. suis based on the results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis (Biotyper score of 2.382) but were differentiated according to the characteristic signal peaks (4709 m/z and 9420 m/z) that were not present for S. suis. Sequence analysis of the 16S rRNA and sodA genes determined that the isolates were similar to S. suis; however, these genes appeared on a phylogenetic sub-branch. Phylogenetic analysis of the whole chromosomal DNA showed that the isolate formed a cluster with S. suis but with clear divergence. The average nucleotide index using BLAST between the clinical isolate (PAGU 2482) and a closely related reference strain of S. suis was 94.75 %, which was not clearly conclusive; however, digital DNA-DNA hybridization showed a value of 61.2 %. Biochemical reactions, including those with acid phosphatase, α-chymotrypsin, and tagatose (acidification), distinguished our isolates from S. suis. Thus, based on phylogenetic, genomic, and phenotypic characteristics and MALDI-TOF-MS signal patterns, we propose that the isolate with Lancefield group A positive characteristics be designated as a novel subspecies, Streptococcus suis subsp. hashimotonensis subsp. nov., with the type strain PAGU 2482T (GTC 18290T = CCUG 77434T).

Impact of Age 70 years or Older on Donors for Living-Donor Kidney Transplantation.

Introduction: Kidney transplantation (KT) involving elderly living kidney donors (LKDs) is becoming more frequent because of a profound organ shortage. The efficacy of KT involving grafts obtained from LKDs aged 70 years or older has been reported. However, the safety of donor nephrectomy in LKDs aged 70 years or older, including that associated with changes in the estimated glomerular filtration rate (eGFR), has not been investigated. This study investigated the outcomes of LKDs aged 70 years or older after donor nephrectomy. Methods: This single-center, retrospective cohort study included 1226 LKDs who underwent donor nephrectomy between January 2008 and December 2020. LKDs were stratified into the following age groups: 30 to 49 years (244 LKDs), 50 to 69 years (803 LKDs), and 70 to 89 years (179 LKDs). Surgical outcomes, postoperative eGFR changes, end-stage renal disease (ESRD) rates, and mortality rates were compared among these groups. Results: No significant difference in surgical outcomes was identified among the groups. LKDs aged 70 to 89 years experienced the lowest eGFR changes at all time points and the lowest eGFR improvement; however, ESRD was not identified in any group during the observation period. Mortality was the highest among LKDs aged 70 to 89 years compared to the other age groups. Conclusion: Surgical outcomes, eGFR changes, and ESRD incidences can support the safety of donor nephrectomy in LKDs aged 70 years or older. Considering the advanced age, the high mortality rates in LKDs aged 70 years or older could be considered acceptable.

Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study.

Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [p < 0.001], and 0.09 [p < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.

Asymptomatic 3-methylglutaconic aciduria type 1 detected by high C5-OH on newborn screening.

3-Methylglutaconic aciduria type 1 (MGCA1) is an inborn error of leucine catabolism caused by pathogenic variants of the AUH gene. MGCA1 can be identified by newborn screening (NBS) with elevated C5-OH levels. We herein report a girl with MGCA1 detected by NBS. On day 5 after birth, NBS detected high C5-OH levels of 1.17 µmol/L (1.56 µmol/L [retest]). A urinary organic acid analysis revealed the abnormal excretion of 3-methylglutaconic, 3-methylglutaric, and 3-hydroxyisovaleric acids. Two novel heterozygous loss-of-function variants in the AUH gene were identified by genetic testing. We observed the patient without any treatment, such as a leucine-restricted diet. She had episodes of febrile illness several times in infancy but did not develop febrile convulsions or encephalopathy. She is now two years and six months old, and her physical growth and psychomotor development have progressed normally. In a review of the literature and our case, four children with MGCA1 identified during the neonatal period were asymptomatic or exhibited speech delay, regardless of whether or not they had been managed with specific treatments. Treatments such as dietary leucine restriction and carnitine supplementation may have little effect on MGCA1 in childhood; however, further investigation is warranted to evaluate the benefits of specific treatments to prevent potential long-term neurological complications.