Alterations in urinary ceramides, sphingoid bases, and their phosphates among patients with kidney disease.

Background: To avoid an invasive renal biopsy, noninvasive laboratory testing for the differential diagnosis of kidney diseases is a desirable goal. As sphingolipids are demonstrated to be involved in the pathogenesis of various kidney diseases, we investigated the possible usefulness of the simultaneous measurement of urinary sphingolipids for differentiating kidney diseases. Materials and methods: Residual urine specimens were collected from patients who had been clinically diagnosed with chronic glomerulonephritis (CGN), diabetic mellitus (DM), systemic lupus erythematosus (SLE), and arterial hypertension (AH). The urinary sphingolipids-CERs C16:0, C18:0, C18:1, C20:0, C22:0, and C24:0; sphingosine [Sph]; dihydrosphingosine; sphingosine 1-phosphate [S1P]; and dihydroS1P [dhS1P]-were measured by liquid chromatography-tandem mass spectrometry. Based on the results, machine learning models were constructed to differentiate the various kidney diseases. Results: The urinary S1P was higher in patients with DM than in other participants (P < 0.05), whereas dhS1P was lower in the CGN and AH groups compared with control participants (P < 0.05). Sph and dhSph were higher in patients with CGN, AH, and SLE than in those with control participants (P < 0.05). The urinary CERs were significantly higher in patients with CGN, AH, and SLE than in those with control participants (P < 0.05). As a results of constructing a machine learning model discriminating kidney diseases, the resulting diagnostic accuracy and precision were improved from 94.03% and 66.96% to 96.10% and 78.26% respectively, when the urinary CERs, Sph, dhSph, S1P, dhS1P, and their ratios were added to the models. Conclusion: The urinary CERs, sphingoid bases, and their phosphates show alterations among kidney diseases, suggesting their potential involvement in the development of kidney injury.

Long-term outcomes of functional single ventricles associated with heterotaxy syndrome†.

OBJECTIVES: The goal of this study was to determine the long-term surgical outcomes of patients with functional single ventricles associated with heterotaxy syndrome, risk factors for mortality and factors associated with Fontan stage completion. METHODS: Overall, 279 patients with a functional single ventricle associated with heterotaxy syndrome who underwent an initial surgical procedure at our institute between 1978 and 2021 were grouped into 4 "eras" based on the surgical year during which the initial procedure was performed: era 1 (1978-1989, n = 71), era 2 (1990-1999, n = 98), era 3 (2000-2009, n = 64) and era 4 (2010-2021, n = 46). Neonatal surgery was more frequent in eras 3 and 4 than in eras 1 and 2. RESULTS: Overall, 228 patients had right atrial isomerism; 120 patients (43.0%) had a total anomalous pulmonary venous connection; and 58 patients (20.8%) underwent an initial procedure as neonates. Overall survival rates at 10, 20 and 30 years after the initial procedure were 47.1%, 40.6% and 36.1%, respectively. Neonatal surgery (P < 0.001), total anomalous pulmonary venous connection repair at the initial procedure (P < 0.001) and early era (P < 0.001) were identified as risk factors for mortality, with the last 2 variables being negatively associated with Fontan stage completion (P < 0.001 for both). CONCLUSIONS: Although era had a favourable effect on survival, total anomalous pulmonary venous connection with intrinsic pulmonary vein obstruction was associated with both mortality and Fontan stage completion. CLINICAL REGISTRATION NUMBER: R19092.

Comparison of the clinical performance of the Atyp.C parameter of the UF-5000 fully automated urine particle analyzer with that of microscopic urine sediment analysis.

a Objectives: Urinalysis is one of the most common laboratory screening tests to detect problems in the renal and urinary system; however, they cannot detect atypical cells (Atyp.Cs). The Sysmex UF-5000, a fully automated urine particle analyzer, can detect Atyp.Cs via its Atyp.C parameter. This study aimed to compare the clinical value of the Atyp.C parameter with that of urine sediment microscopy. b Method: A total of 471 leftover urine samples were submitted to the Department of Clinical Laboratory at the University of Tokyo Hospital for urinalysis by manual sediment microscopy examination and UF-5000 Atyp.C analysis. c Result: Of 471 submitted samples, 117 were positive for Atyp.Cs by urine sediment and 354 samples were negative. The histological subtypes of the Atyp.Cs included 105 cases of suspected urothelial carcinoma cells, 10 suspected squamous carcinoma cells, and 2 of suspected adenocarcinoma cells. The Atyp.C values for the Atyp.C-positive and -negative groups were 2.64 ± 0.69 and 0.38 ± 0.16, respectively. The optimal Atyp.C cutoff value determined by the receiver operating characteristic curve analysis was 0.4/µL. The area under the curve was 0.856, with a sensitivity of 79.5% and specificity of 85.1%. Atyp.C values of the UF-5000 showed high predictive performance for Atyp.C-positive specimens identified by urine sediment microscopy. d Conclusions: This study shows that a combination of UF-5000 analysis and microscopic examination of urine sediment improves Atyp.C detection in urine sediment analysis. These results suggest that Atyp.C measured by UF-5000 could be a useful screening parameter in routine testing of urine samples.

Death, reoperation, and late cardiopulmonary function after truncus repair.

Objective: To identify the late surgical outcomes of truncus arteriosus. Methods: Fifty consecutive patients with truncus arteriosus who underwent surgery between 1978 and 2020 at our institute were enrolled in this retrospective, single institutional cohort study. The primary outcome was death and reoperation. The secondary outcome was late clinical status, including exercise capacity. The peak oxygen uptake was measured by a ramp-like progressive exercise test on a treadmill. Results: Nine patients underwent palliative surgery, which resulted in 2 deaths. Forty-eight patients went on to truncus arteriosus repair, including 17 neonates (35.4%). The median age and body weight at repair were 92.5 days (interquartile range, 10-272 days) and 3.85 kg (interquartile range, 2.9-6.5 kg), respectively. The survival rate at 30 years was 68.5%. Significant truncal valve regurgitation (P = .030) was a risk factor for survival. Survival rates were similar between in the early 25 and late 25 patients (P = .452). The freedom from death or reoperation rate at 15 years was 35.8%. Significant truncal valve regurgitation was a risk factor (P = .001). The mean follow-up period in hospital survivors was 15.4 ± 12 years (maximum, 43 years). The peak oxygen uptake, which was performed in 12 long-term survivors at a median duration from repair of 19.7 years (interquartile range, 16.8-30.9 years), was 70.2% of predicted normal (interquartile range, 64.5%-80.4%). Conclusions: Truncal valve regurgitation was a risk factor for both survival and reoperation, thus improvement of truncal valve surgery is essential for better life prognosis and quality of life. Slightly reduced exercise tolerance was common in long-term survivors.

Comparison of long-term outcomes of atrial switch with Rastelli and physiological repair using left ventricle-to-pulmonary artery conduit for levo-transposition of the great arteries.

OBJECTIVES: The objectives of this study was to compare the long-term outcomes of anatomic repair using atrial switch with the Rastelli procedure versus physiological repair with left ventricle-to-pulmonary artery conduit for patients with levo-transposition of the great arteries, ventricular septal defect, and left ventricular outflow tract obstruction. METHODS: Of patients with levo-transposition of the great arteries who underwent biventricular repair between 1978 and 2001, 31 hospital survivors after anatomic repair of atrial switch and the Rastelli (anatomic group) and 14 hospital survivors after physiological repair with left ventricle-to-pulmonary artery conduit (physiological group) were enrolled. Survival rates, reoperation rates, and most recent conditions were compared. RESULTS: The overall survival rate at 20 years was 79.7% (95% CI, 66.4%-95.6%) in the anatomic group and 85.1% (95% CI, 68.0%-100%) in the physiological group (P = .87). The reoperation rate at 10 years was 19.8% (95% CI, 5.6%-34.0%) in the anatomic group and 52.0% (95% CI, 25.0%-79.1%) in the physiological group (P = .067). Only patients in the physiological group underwent systemic tricuspid valve replacement. The anatomic group showed a better cardiac index at catheterization (2.79 ± 0.75 L/min/m2 vs 2.30 ± 0.54 L/min/m2; P = .035), lower serum brain natriuretic peptide (73 ± 86 pg/mL vs 163 ± 171 pg/mL; P = .024), and better maximal oxygen uptake in the treadmill test (64.1 ± 16.5% vs 52.7 ± 17.8% of predicted normal; P = .036), although the period until most recent catheterization, blood inspection, and treadmill testing were earlier in the anatomic group. CONCLUSIONS: Preservation of the left ventricle as the systemic ventricle using anatomic repair contributes to better cardiopulmonary condition compared with physiological repair.

Usefulness of duplex ultrasonography to detect collagen sponge misplacement into the arterial lumen during the use of Angio-Seal: A case report.

A 76-year-old man who had undergone percutaneous coronary intervention suffered intermittent claudication. Duplex ultrasonography revealed superficial femoral artery stenosis with an intraluminal heterogeneous echogenic mass. We suspected that stenosis was caused by the puncture procedure of the Angio-Seal. Open surgery revealed that a collagen sponge that should have been outside the arterial wall was misplaced in the wall with massive granulation, and atherectomy with patchplasty was performed. Vessel deterioration was considered due to several factors, including inappropriate access site, arterial wall calcification, and comorbidities like Behçet's disease. Ultrasonography is a convenient and useful method to evaluate arterial lesions.

Prevalence and clinical characteristics of patients with biologically false-positive reactions with serological syphilis testing in contemporary practice: 10-year experience at a tertiary academic hospital.

OBJECTIVES: Biologically false positive (BFP) reactions are well described in early literature. However, only a few recent reports described the incidence and clinical characteristics of patients with BFP reactions. We reviewed the serological test results of patients tested for syphilis in our hospital in the past decade and described the clinical characteristics of patients with BFP reactions. METHODS: This is a retrospective study of patients tested for syphilis in a tertiary academic hospital. All serological results were retrieved from the clinical laboratory database. We calculated the incidence of BFP reactions. Clinical characteristics and laboratory data of patients with BFP reactions were reviewed manually. RESULTS: Among 94 462 subjects, 588 patients had BFP reactions (0.62%). Most BFP reactions were observed in patients aged over 60 years, with a history of malignancy and autoimmune diseases. Eighty-five per cent of patients had low rapid plasma reagin (RPR) titre (≤1:4), but two patients had extremely high RPR titre (≥1:256). BFP reactions were more likely to persist beyond 6 months among patients with RPR titre of ≥1:8. There was no statistically significant correlation between RPR titre and total protein albumin gap, surrogate of immunoglobulin levels among patients with BFP reactions. CONCLUSION: There was a low incidence of BFP reactions in the last decade. A minority of BFP reactions had high non-treponemal antibody titre and persisted longer than 6 months. In the era of re-emergence of syphilis, this information could help clinicians interpret the results of well-established diagnostic tests for syphilis.

Analysis of vasovagal syncope in the blood collection room in patients undergoing phlebotomy.

Vasovagal syncope (VVS) is well-known to occur in patients undergoing phlebotomy, however, there have been no large-scale studies of the incidence of VVS in the blood collection room. The aim of our present retrospective study was to investigate the conditions of phlebotomy and determine the incidence/factors predisposing to the development of VVS. We investigated 677,956 phlebotomies performed in outpatients in the blood collection room, to explore factors predisposing to the development of VVS. Our analysis revealed an overall incidence of VVS of 0.004% and suggested that use of more than 5 blood collection tubes and a waiting time of more than 15 min were associated with a higher risk of VVS. The odds ratios of these factors were 8.10 (95% CI 3.76-17.50) and 3.69 (95% CI 0.87-15.60), respectively. This is the large-scale study to analyze factors of the development of VVS in the blood collection room, and according to our results, use of a large number of blood collection tubes and a prolonged waiting time for phlebotomy may be risk factors for the development of VVS.

Midstream urine sampling is necessary for accurate measurement of the urinary level of neutrophil gelatinase-associated lipocalin in healthy female subjects.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin is an established biomarker of acute kidney injury, however, the levels are affected by the number of white blood cells in the urine. As we suspected the portion of the urinary stream sampled could also have a significant influence on the urinary NGAL levels in female subjects, we investigated the influence of the urine sampling procedure on the urinary NGAL levels. METHODS: We collected 25-mL urinary specimens from each of initial-stream and midstream urinary specimens, including 28 healthy adult female volunteers without kidney diseases or UTI. Then we compared the WBC count, NGAL level, and creatinine level between these specimens. RESULTS: We observed that the urinary NGAL levels were significantly higher in the specimens obtained from initial-stream urinary samples than in midstream specimens, and that they were strongly correlated with the leukocyte esterase activity and WBC count. Moreover, the differences in the urinary NGAL levels between the initial- and midstream urine samples were greater for initial-stream samples with higher leukocyte esterase activities, with a significant difference even for the initial-stream samples with no detectable leukocyte esterase activity. CONCLUSION: Therefore, midstream urine sampling is strongly recommended for accurate measurement of the urinary NGAL levels.

Successful Staged Repair for Truncus Arteriosus With Anomalous Arch Vessels and Left Coronary Artery.

A patient was born with truncus arteriosus type 2, left aortic arch, anomalous origin of arch vessels, left coronary artery from the right common carotid artery, and multiple extracardiac anomalies. Surgery involving translocation of the left coronary artery to the truncal root, division of branch pulmonary arteries from the truncal artery, and right ventricle-to-branch pulmonary arteries conduit placement was performed at the age of four months. Closure of the ventricular septal defect using a one-way fenestrated patch and conduit upsizing was performed successfully when the patient reached four years of age.

Sphingosine 1-phosphate release from platelets during clot formation: close correlation between platelet count and serum sphingosine 1-phosphate concentration.

BACKGROUND: Sphingosine 1-phosphate (Sph-1-P), abundantly stored in platelets and released extracellularly upon activation, plays important roles as an extracellular mediator by interacting with specific cell surface receptors, especially in the area of vascular biology and immunology/hematology. Although the plasma Sph-1-P level is reportedly determined by red blood cells (RBCs), but not platelets, this may not be true in cases where the platelets have been substantially activated. METHODS AND RESULTS: We measured the Sph-1-P and dihydrosphingosine 1-phosphate (DHSph-1-P) levels in serum samples (in which the platelets had been fully activated) from subjects with (n = 21) and without (n = 33) hematological disorders. We found that patients with essential thrombocythemia exhibited higher serum Sph-1-P and DHSph-1-P concentrations. The serum Sph-1-P concentration was closely correlated with the platelet count but was very weakly correlated with the RBC count. Similar results were obtained for DHSph-1-P. The serum Sph-1-P and DHSph-1-P levels were inversely correlated with the level of autotaxin (ATX), a lysophosphatidic acid-producing enzyme. A multiple regression analysis also revealed that the platelet count had the greatest explanatory impact on the serum Sph-1-P level. CONCLUSIONS: Our present results showed close correlations between both the serum Sph-1-P and DHSph-1-P levels and the platelet count (but not the RBC count); these results suggest that high concentrations of these sphingoid base phosphates may be released from platelets and may mediate cross talk between platelet activation and the formation of atherosclerotic lesions.

[The current status of leukemia genetic testing and the trial of its standardization].

The pathogenic chromosome translocations present in various hematological malignancies result in the formation of fusion genes, which are detected by a reverse transcription-polymerase chain reaction (RT PCR) method. Furthermore, with this method, it is possible to detect minimal residual disease (MRD) sensitively, which is difficult with morphological testing. It has been established that the detection of MRD is important for diagnosis, evaluation of prognosis, and monitoring of leukemia. In particular, quantitative analysis of MRD load transition during the initial phase of treatment is of high prognostic value. At present, however, there is no standard laboratory procedure for leukemia genetic testing. Here, the problems related to external precision management are discussed.