Krebs von den Lungen-6 levels at admission predicts exercise-induced hypoxemia before and after discharge in patients with COVID-19.

BACKGROUND: There are no reports of exercise-induced hypoxemia in patients with coronavirus disease 2019 (COVID-19). Additionally, the predictive factors and prevalence of exercise-induced hypoxemia are unknown. This study investigated the incidence and predictive factors of exercise-induced hypoxemia before and after discharge in patients with COVID-19. METHODS: We enrolled 77 patients diagnosed with COVID-19 who were hospitalized between November 2020 and October 2021 and who underwent a 6-min walk test before and after discharge. Based on the test results, we classified patients into exercise-induced and non-exercise-induced hypoxemia groups and investigated the predictive factors of exercise-induced hypoxemia using logistic regression analysis. RESULTS: The incidences of exercise-induced hypoxemia in patients with COVID-19 were 37.7% and 19.5% before and after discharge, respectively. At admission, the Krebs von den Lungen-6 levels was the associated factor for exercise-induced hypoxemia in patients with COVID-19 before and after discharge, with cut-off values of 314 U/mL and 367 U/mL, respectively. Age and lactate dehydrogenase levels were the associated factors for exercise-induced hypoxemia in patients with COVID-19 before discharge, with cut-off values of 61 years and 492 U/L, respectively. CONCLUSIONS: Some patients with COVID-19 may continue to experience exercise-induced hypoxemia after discharge. Age, lactate dehydrogenase, and Krebs von den Lungen-6 levels at admission could serve as predictive markers of exercise-induced hypoxemia before and after discharge in these patients.

Circulating TNF receptor levels are associated with estimated glomerular filtration rate even in healthy individuals with normal kidney function.

The association between serum tumor necrosis factor receptor (TNFRs: TNFR1, TNFR2) levels and estimated glomerular filtration rate (eGFR) observed in patients with diabetes has not been comprehensively tested in healthy subjects with normal kidney function. It also remains unclear whether TNFR levels differ by age and sex, and between healthy subjects and diabetics. We measured serum TNFR levels in 413 healthy subjects and 292 patients with type 2 diabetes. In healthy subjects, TNFR levels did not differ between men and women. Additionally, TNFR2, but not TNFR1, levels increased with age. In multivariate analysis, TNFR1 was associated only with cystatin C-based eGFR (eGFR-CysC), whereas TNFR2 was associated with systolic blood pressure in addition to eGFR-CysC. Both TNFRs were associated with lower eGFR (eGFR-Cys < 90 mL/min/1.73 m2) even after adjustment for relevant clinical factors. Upon combining healthy subjects and patients with diabetes, the presence of diabetes and elevated glycated hemoglobin level were significant factors in determining TNFR levels. TNFR levels were associated with eGFR-CysC, but were not affected by age and sex in healthy subjects with normal kidney function. TNFR levels in patients with diabetes appeared to be higher than in healthy subjects.

Evaluation of bone marrow aspirates using the automated hematology analyzer Sysmex XN-3000.

INTRODUCTION: This study evaluated the feasibility of the Sysmex XN-3000 automated hematology analyzer for the assessment of total nucleated cells (TNC) and bone marrow (BM) cell density in routine bone marrow aspiration (BMA) samples. METHODS: A total of 54 BMA samples from 39 hematological patients were evaluated. The number of megakaryocytes was calculated by a specific gating algorithm using the body fluid mode of the WBC differential (WDF) channel. Lipid contents were calculated through a newly developed algorithm utilizing the WDF channel. The ratio of lipid particles over TNCs by the WNR channel was compared with the BM cellularity assessed by the BM biopsy. The myeloid/erythroid (M/E) ratio was calculated by measuring the number of myeloid cells in the WDF channel and the number of nucleated red blood cells (NRBCs) in the WNR channel. RESULTS: XN-3000 counts and microscopic results showed a linear correlation in TNC (R2  = .98, p < .001), megakaryocytes (R2  = .59, p = .002), NRBC (R2  = .84, p < .001), and M/E ratio (R2  = .59, p < .001). There were significant differences in the lipid/TNC ratios of hypercellular, normocellular, and hypocellular BMs measured by XN-3000 (p < .001). Receiver-operating characteristic analysis detected cut-off values of the lipid/TNC ratio of >0.4054 for hypoplasia and <0.157 for hyperplasia. The sensitivity and specificity for hypoplasia were 100% and 88%, and for hyperplasia were 89% and 86%, respectively. CONCLUSION: XN-3000 provides a quantitative assessment of BM cellularity, supporting the qualitative assessment by myelogram and BM biopsy.

Establishment of preanalytical conditions for microRNA profile analysis of clinical plasma samples.

The relationship between the expression of microRNAs (miRNAs) in blood and a variety of diseases has been investigated. MiRNA-based liquid biopsy has attracted much attention, and cancer-specific miRNAs have been reported. However, the results of analyses of the expression of these miRNAs vary among studies. The reproduction of results regarding miRNA expression levels could be difficult if there are differences in the data acquisition process. Previous studies have shown that the anticoagulant type used during plasma preparation and sample storage conditions could contribute to differences in measured miRNA levels. Thus, the impact of these preanalytical conditions on comprehensive miRNA expression profiles was examined. First, the miRNA expression profiles of samples obtained from healthy volunteers were analyzed using next-generation sequencing. Based on an analysis of the library concentration, human genome identification rate, ratio of unique sequences and expression profiles, the optimal preanalytical conditions for obtaining highly reproducible miRNA expression profiles were established. The optimal preanalytical conditions were as follows: ethylenediaminetetraacetic acid (EDTA) as the anticoagulant, whole-blood storage at room temperature within 6 hours, and plasma storage at 4°C or -20°C within 30 days. Next, plasma samples were collected from 60 cancer patients (3 facilities × 20 patients/facility), and miRNA expression profiles were analyzed. There were no significant differences in measurements except in the expression of erythrocyte-derived hsa-miR-451a. However, the variation in hsa-miR-451a levels was smaller among facilities than among individuals. This finding suggests that samples obtained from the same facility could show significantly different degrees of hemolysis across individuals. We found that the standardization of anticoagulant use and storage conditions contributed to reducing the variation in sample quality across facilities. The findings from this study could be useful in developing protocols for collecting samples from multiple facilities for cancer screening tests.

Synthesis of Azacalixarenes and Development of Their Properties.

This review focuses on the synthesis, structure, and interactions of metal ions, the detection of some weak interactions using the structure, and the construction of supramolecules of azacalixarenes that have been reported to date. Azacalixarenes are characterized by the presence of shallow or deep cavities, the simultaneous presence of a basic nitrogen atom and an acidic phenolic hydroxyl group, and the ability to introduce various side chains into the cyclic skeleton. These molecules can be given many functions by substituting groups on the benzene ring, modifying phenolic hydroxyl groups, and converting side chains. The author discusses the evidence of azacalixarene utilizing these characteristics.

Accuracy study of a novel alternate method measuring erythrocyte sedimentation rate for prototype hematology analyzer Celltac α.

INTRODUCTION: The erythrocyte sedimentation rate (ESR) is a nonspecific inflammation indicator. In laboratory testing, automated ESR analyzers may use the reference Westergren method (Reference WG), modified Westergren (Modified WG), or Alternate ESR method (Alternate ESR) based on photometric rheology. A prototype hematology analyzer Celltac α+ (Nihon Kohden Corporation) with built-in Novel ESR analysis technology (Novel ESR) was developed to improve the accuracy of Alternate ESR. Alternate ESR uses only the aggregation phase information of Reference WG. The Novel ESR adds sedimentation and packing phase information obtained by hematology analyzer measurands. High correlation with WG was ensured by predicting the ESR value using Hematocrit (Hct) and MCV values as correcting parameters. METHODS: Novel ESR was compared with Modified WG (MONITOR-40, Joko Corporation) and Reference WG, according to internationally recognized guidelines: Precision, carryover, limit of quantification, comparability, linearity, accuracy, and fibrinogen sensitivity. Samples from healthy volunteers and clinical patients were used. The correction performance of Novel ESR and Modified WG was compared with Reference WG by regression analysis in three range categories for ESR and measurands affecting ESR correction (Hct, MCV, and MCH). RESULTS: Novel ESR showed sufficient basic performance and comparability with Modified WG. In the accuracy study comparing with Reference WG, the regression equation was y = 1.026x + 0.5(r =  .945,P <  .001;n = 271). When evaluating the correction performance, the slopes were within 0.8-1.2, except for the high part of Hct. All intercepts were within 10 mm. CONCLUSION: This study validated the correction performance to the initial estimated ESR value by aggregation phase information using information reflecting sedimentation and packing phase obtained from automated hematology analyzer. The Celltac α+ Novel ESR provided results equivalent to Reference WG.

Prediction of Postoperative Delirium after Gastrointestinal Surgery Using the Mie Constructional Apraxia Scale.

BACKGROUND: Postoperative delirium (POD) is a transient postoperative complication that occurs after surgical procedures. Risk factors reported for POD include dementia and cognitive decline. The purpose of this study was to identify predictors of POD by examining the use of preoperative neuropsychological tests, including the Mie Constructional Apraxia Scale (MCAS), and patient background factors. METHOD: The study was performed as a retrospective cohort study. The subjects were 33 patients (mean age, 75.8 ± 10.9 years; male:female ratio, 26:7) who underwent gastrointestinal surgery at Matsusaka City Hospital between December 2019 and April 2021. Data were collected retrospectively from medical records. The study was started after receiving approval from the institution's ethics committee. The survey items included general patient information, nutritional assessment, surgical information, and neuropsychological tests. Subjects were classified into 2 groups according to the presence or absence of POD. If a significant difference was observed between the 2 groups, the sensitivity, specificity, and area under the curve were calculated using a receiver operating characteristic (ROC) curve. RESULT: There were 10 patients in the POD group (male:female ratio, 6:4) and 23 patients in the non-POD group (20:3). The POD group had a shorter education history (p = 0.047) and significantly higher MCAS scores (p = 0.007) than the non-POD group. The ROC curve showed a sensitivity of 90%, a specificity of 69%, and an area under the curve of 0.798 when the MCAS cutoff value was set at 3 points. CONCLUSION: Preoperative MCAS results were capable of predicting the occurrence of POD after gastrointestinal surgery. In addition, a relatively short education background was also considered a risk factor for POD.

A Prediction Equation to Assess Resting Energy Expenditure in Japanese Patients with COPD.

BACKGROUND: Medical nutrition therapy is important in the management of chronic obstructive pulmonary disease (COPD) patients. Determination of resting energy expenditure is essential to define therapeutic goals for medical nutrition. Previous studies proposed the use of equations to predict resting energy expenditure. No prediction equation is currently available for the Japanese population. The objective of this study was to develop an equation to predict resting energy expenditure in Japanese chronic obstructive pulmonary disease patients. To this end, we investigated clinical variables that correlate with the resting energy expenditure. METHODS: This study included 102 COPD patients admitted at the Matsusaka Municipal Hospital Respiratory Center. We measured resting energy expenditure by indirect calorimetry and explored the relationship of resting energy expenditure with clinical variables by univariate and stepwise linear regression analysis. RESULTS: The resting energy expenditure by indirect calorimetry was significantly correlated with fat-free mass, body weight, body mass index, height, gender, and pulmonary function test by univariate analysis. In the stepwise linear regression analysis, the fat-free mass, body weight, and age remained significantly correlated with indirect calorimetry's resting energy expenditure. The fat-free mass, body weight, and age explained 50.5% of the resting energy expenditure variation. CONCLUSION: Fat-free mass, body weight, and age were significantly correlated with resting energy expenditure by stepwise linear regression analysis, and they were used to define a predictive equation for Japanese COPD patients.

Donor-Donor'-Acceptor Triads Based on [3.3]Paracyclophane with a 1,4-Dithiafulvene Donor and a Cyanomethylene Acceptor: Synthesis, Structure, and Electrochemical and Photophysical Properties.

Donor-donor'-acceptor triads (1, 2), based on [3.3]paracyclophane ([3.3]PCP) as a bridge, with electron-donating properties (D') using 1,4-dithiafulvene (DTF; TTF half unit) as a donor and dicyanomethylene (DCM; TCNE half unit) or an ethoxycarbonyl-cyanomethylene (ECM) as an acceptor were designed and synthesized. The pulse radiolysis study of 1 a in 1,2-dichloroethane allowed the clear assignment of the absorption bands of the DTF radical cation (1 a.+ ), whereas the absorption bands due to the DCM radical anion could not be observed by γ-ray radiolysis in 2-methyltetrahydrofuran rigid glass at 77 K. Electrochemical oxidation of 1 a first generates the DTF radical cation (1 a.+ ), the absorption bands of which are in agreement with those observed by a pulse radiolysis study, followed by dication (1 a2+ ). The ESR spectrum of 1 a.+ showed a symmetrical signal with fine structure and an ESR simulation predicted that the spin of 1 a.+ is delocalized over S and C atoms of the DTF moiety and the central C atom of the trimethylene bridge bearing the DTF moiety. Pulse radiolysis, ESR, and electrochemical studies indicate that the DTF radical cation of 1 a.+ is more stable than that of 6.+ , and the latter shows a strong tendency to dimerize. This result indicates that the [3.3]PCP moiety as a bridge can stabilize the DTF radical cation more than the 1,3-diphenylpropane moiety because of kinetic stability due to its rigid structure and the weak electronic interaction of DTF and DCM moieties through [3.3]PCP.

Evaluation of cell count and classification capabilities in body fluids using a fully automated Sysmex XN equipped with high-sensitive Analysis (hsA) mode and DI-60 hematology analyzer system.

The XN series automated hematology analyzer has been equipped with a body fluid (BF) mode to count and differentiate leukocytes in BF samples including cerebrospinal fluid (CSF). However, its diagnostic accuracy is not reliable for CSF samples with low cell concentration at the border between normal and pathologic level. To overcome this limitation, a new flow cytometry-based technology, termed "high sensitive analysis (hsA) mode," has been developed. In addition, the XN series analyzer has been equipped with the automated digital cell imaging analyzer DI-60 to classify cell morphology including normal leukocytes differential and abnormal malignant cells detection. Using various BF samples, we evaluated the performance of the XN-hsA mode and DI-60 compared to manual microscopic examination. The reproducibility of the XN-hsA mode showed good results in samples with low cell densities (coefficient of variation; % CV: 7.8% for 6 cells/µL). The linearity of the XN-hsA mode was established up to 938 cells/µL. The cell number obtained using the XN-hsA mode correlated highly with the corresponding microscopic examination. Good correlation was also observed between the DI-60 analyses and manual microscopic classification for all leukocyte types, except monocytes. In conclusion, the combined use of cell counting with the XN-hsA mode and automated morphological analyses using the DI-60 mode is potentially useful for the automated analysis of BF cells.

Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer.

Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode "XN-BF gating algorithm" to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples.

Electrochemical Control of Bioluminescence by Blocking the Adsorption of the Bacterial Luciferase Using a Mercaptobipyridine Self-assembled Monolayer.

An N-butyl-N'-(4-mercaptobutyl)-4,4'-bipyridinium (4BMBP) was modified on a gold electrode to improve the electrochemical control of the bacterial luciferase (BL) luminescence system. The 4BMBP-modified gold electrode (4BMBP/Au) was able to prevent the adsorption of BL on the electrode surface, and enhanced the electrochemical regeneration rate of the reduced flavin mononucleotide (FMNH2), which is one of the substrates of the BL luminescence reaction. By using the 4BMBP/Au, the luminescence intensity increased by about 27% compared to that of a bare gold electrode (bare Au). Moreover, the modified electrode improved the time required for analysis because the modified layer prevented BL adsorption. Even without a refreshing procedure for each measurement, a constant luminescence intensity could be observed, and the analysis time was reduced to half (about 10 min) for one sample. The 4BMBP/Au is not only useful to control of the BL luminescence system, but also for electrochemical measurements in the presence of proteins.

Pancreatic lipase activity in overnight effluent predicts high transport status in peritoneal dialysis patients.

BACKGROUND: Long-term peritoneal dialysis (PD) causes peritoneal morphological and functional changes, resulting in high transport status featuring increased peritoneal permeability. High transport status is diagnosed by peritoneal equilibration test (PET), a reliable but time-consuming method. We identifed a reliable biomarker in peritoneal effluent to predict high transport status in PD patients. METHODS: We collected peritoneal effluent and serum from 33 PD patients and measured common laboratory test parameters. High transport status was determined by PET if the dialysate/plasma ratio of creatinine at 4h dwell (D/P Cr 4h) was ≥0.81. RESULTS: There were significant correlations between D/P Cr 4h and some laboratory parameters in overnight effluent (pancreatic lipase activity, r=0.65, p<0.001; ß2-microglobulin concentration, r=0.59, p<0.001; IL-6 concentration, r=0.53, p<0.001; and CA125 concentration, r=0.29, p=0.027). In a multivariate logistic regression analysis, the pancreatic lipase activity in overnight effluent was identified as an independent predictor of high transport status even after adjusting for age, PD duration, and glomerular filtration rate [OR=1.43 (95% CI: 1.11-1.83), p=0.005]. CONCLUSIONS: The pancreatic lipase activity in overnight effluent is an independent predictor of high transport status in PD patients.

[Evaluation of capability of cell count and detection of tumor cells in cerebrospinal and body fluids by automated hematology analyzer].

Sysmex XE-5000 offers the body fluid modus which provides the opportunity to count and differentiate leukocytes in body fluids and cerebrospinal fluid (CFS). In this study, we evaluated the basic performance of this application using routinely obtained samples in comparison with manual counting. Reproducibility study yielded good results in samples with a high white blood cell (WBC) count, whereas relatively high imprecision was observed at low WBC counts. Linearity was established up to 1,500 cells/microL in CFS and 5,600 cells/microL in body fluid. The cell count by XE-5000 was highly correlated with that of the microscopic reference method. Highly fluorescent body fluid cells percent (HF-BF%) was observed in samples with tumor cells or activated macrophages, which provides information about the possible presence of tumor cells. In conclusion, total and differential WBC counts in body fluid and CFS can be reliably determined by XE-5000 in samples with increased cell counts. XE-5000 also provides screening information about the presence of tumor cells for further manual examination.

Cytologic, immunocytochemical and ultrastructural characterization of lymphangioleiomyomatosis cell clusters in chylous effusions of patients with lymphangioleiomyomatosis.

OBJECTIVE: To establish the cytologic and immunocytochemical features of lymphangioleiomyomatosis (LAM) cell clusters (LCCs) and to clarify its diagnostic significance for LAM. STUDY DESIGN: We evaluated 17 samples of LAM-associated chylous effisions from 13 patients with LAM. We performed Papanicolaou staining and immunocytochemistry for muscular antigens, melanoma-related antigens, female 'hormone receptors and markers for lymphatic endothelial cells (LECs). RESULTS: The cytologic features of LCCs were a well-organized, globular cluster consisting of LAM cells enveloped by LECs. The LAM cells were observed to form a tightly cohesive core and had a moderate nuclear/cytoplasmic ratio. These are distinct characteristics from cancer cell clusters. Immunocytochemical examinations revealed the LAM cells to be positive for muscular antigens, melanoma-related antigens and progesterone receptor, but only 2 of 7 specimens were positive for estrogen receptor. The surface monolayer cells were confirmed to be immunopositive for various LEC markers. Ultrastructural study confirmed that LCCs were covered by LECs. CONCLUSION: LCCs were detected in all LAM-associated chylous effusion samples. The cytologic and immunocytochemical examinations of chylous effusions are thus considered to have diagnostic significance for LAM that may therefore enable patients to avoid undergoing such invasive tests as lung biopsies.

A uranyl ion complex of N-methyl-p-tert-butyldihomoammoniocalix[4]arene with diaquadipyridinelithium as counter-ion.

The title complex, diaquadipyridinelithium (N-methyl-p-tert-butyldihomoammoniocalix[4]arene-kappa(4)O)dioxouranium(VI) tripyridine solvate monohydrate, [Li(C(5)H(5)N)(2)(H(2)O)(2)][UO(2)(C(46)H(58)NO(4))].3C(5)H(5)N.H(2)O, contains an 'internal' tetraphenoxide-coordinated uranyl complex of the macrocycle, in which the protonated N atom is involved in an intramolecular hydrogen bond with the uranyl oxo group located in the cavity. The Li(+) ion is in a tetrahedral environment and its two water ligands are involved in hydrogen bonds with two phenoxide O atoms, two pyridine molecules and one water molecule. This arrangement is compared with those obtained previously for other homoazacalixarenes and also for homooxacalixarenes in the presence of alkali metal hydroxides.

A Potassium Complex of a Fluorine-Containing Macrocyclic Cage Compound: Interactions between Fluorine Atoms and Metal Ions.

A new donor, the C-F unit, can be added to the field of host-guest chemistry. The interaction between fluorine atoms and a potassium ion was proven with the fluorine-containing cage compound 1 as a host. The six fluorine atoms of K+ ⊂1 are coordinated to K+ in a distorted octahedral fashion.