Sarcopenia in chronic kidney disease: from bench to bedside

Sarcopenia is a condition characterized by a loss of muscle mass and function. In chronic kidney disease (CKD), where a chronic catabolic state exists, sarcopenia commonly occurs through various mechanisms, resulting in muscle wasting and decreased muscle endurance. Sarcopenic patients with CKD have high morbidity and mortality rates. Indeed, the prevention and treatment of sarcopenia are mandatory. An imbalance between protein synthesis and degradation in muscle and increased oxidative stress and inflammation persist in CKD and induce muscle wasting. In addition, uremic toxins negatively affect muscle maintenance. A variety of potential therapeutic drugs targeting these muscle-wasting mechanisms in CKD have been investigated, but most of the trials focused on aged patients without CKD, and none of these drugs have been approved for the treatment of sarcopenia so far. Further studies on the molecular mechanisms of sarcopenia in CKD and targets for potential therapeutics are needed to improve the outcomes of sarcopenic patients with CKD.

Serum and urine metabolomic biomarkers for predicting prognosis in patients with immunoglobulin A nephropathy

Immunoglobulin A nephropathy (IgAN) is the most prevalent form of glomerulonephritis worldwide. Prediction of disease progression in IgAN can help to provide individualized treatment based on accurate risk stratification. Methods: We performed proton nuclear magnetic resonance-based metabolomics analyses of serum and urine samples from healthy controls, non-progressor (NP), and progressor (P) groups to identify metabolic profiles of IgAN disease progression. Metabolites that were significantly different between the NP and P groups were selected for pathway analysis. Subsequently, we analyzed multivariate area under the receiver operating characteristic (ROC) curves to evaluate the predictive power of metabolites associated with IgAN progression. Results: We observed several distinct metabolic fingerprints of the P group involving the following metabolic pathways: glycolipid metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-transfer RNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism. In multivariate ROC analyses, the combinations of serum glycerol, threonine, and proteinuria (area under the curve [AUC], 0.923; 95% confidence interval [CI], 0.667–1.000) and of urinary leucine, valine, and proteinuria (AUC, 0.912; 95% CI, 0.667–1.000) showed the highest discriminatory ability to predict IgAN disease progression. Conclusion: This study identified serum and urine metabolites profiles that can aid in the identification of progressive IgAN and proposed perturbed metabolic pathways associated with the identified metabolites.

Hospital mortality and prognostic factors in critically ill patients with acute kidney injury and cancer undergoing continuous renal replacement therapy

Whether continuous renal replacement therapy (CRRT) should be applied to critically ill patients with both acute kidney injury (AKI) and cancer remains controversial because of poor expected outcomes. The present study determined prognostic factors for all-cause in-hospital mortality in patients with AKI and cancer undergoing CRRT. Methods: We included 471 patients with AKI and cancer who underwent CRRT at the intensive care unit of a Korean tertiary hospital from 2013 to 2020, and classified them by malignancy type. The primary outcomes were 28-day all-cause mortality rate and prognostic factors for in-hospital mortality. The secondary outcome was renal replacement therapy (RRT) dependency at hospital discharge. Results: The 28-day mortality rates were 58.8% and 82% in the solid and hematologic malignancy groups, respectively. Body mass index (BMI), presence of oliguria, Sequential Organ Failure Assessment (SOFA) score, and albumin level were common predictors of 28-day mortality in the solid and hematologic malignancy groups. A high heart rate and the presence of severe acidosis were prognostic factors only in the solid malignancy group. Among the survivors, the proportion with RRT dependency was 25.0% and 33.3% in the solid and hematologic malignancy groups, respectively. Conclusion: The 28-day mortality rate of cancer patients with AKI undergoing CRRT was high in both the solid and hematologic malignancy groups. BMI, presence of oliguria, SOFA score, and albumin level were common predictors of 28-day mortality in the solid and hematologic malignancy groups, but a high heart rate and severe acidosis were prognostic factors only in the solid malignancy group.

Effect of Phoxilium on prognostic predictors in patients undergoing continuous venovenous hemodiafiltration

Background@#Phosphorus-containing dialysis solution is used to prevent hypophosphatemia in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). This study evaluated the effect of phosphorus-containing dialysis solution on mortality in patients undergoing CVVHDF based on changes in phosphorus and red cell distribution width-coefficient of variation (RDW-CV) levels. @*Methods@#We included 272 patients with acute kidney injury (AKI) who underwent CVVHDF at the medical intensive care unit from 2017 to 2019 and classified them according to Phoxilium (Baxter Healthcare Ltd.), as a phosphorus-containing dialysis solution, use within 48 hours after CVVHDF initiation. Clinical data were collected at baseline and 48 hours after CVVHDF initiation. The primary outcome was all-cause mortality during the follow-up period. @*Results@#The non-Phoxilium (NP) group had higher phosphorus and lower RDW-CV levels than the Phoxilium (P) group (phosphorus, 7.3 ± 4.3 vs. 5.0 ± 2.8 mg/dL; RDW-CV, 14.6 ± 1.9 vs. 15.7 ± 2.6%; all p 0 mg/dL vs. 0% vs. 0% vs. >–0.2% and <0%; HR, 2.65; 95% CI, 1.12–6.24; p = 0.03), while an increase in delta phosphorus was not. @*Conclusion@#In patients with AKI undergoing CVVHDF, the risk factors for all-cause mortality differed according to the initial phosphorus levels and use of Phoxilium.

Draft Genome Sequence of the White-Rot Fungus Schizophyllum commune IUM1114-SS01

The monokaryotic strain, Schizophyllum commune strain IUM1114-SS01, was generated from a basidiospore of dikaryotic parental strain IUM1114. It even showed the decolorizing activities for several textile dyes much better than its parental strain. Based on the results of a single-molecule real-time sequencing technology, we present the draft genome of S. commune IUM1114-SS01, comprising 41.1 Mb with GC contents of the genome were 57.44%.Among 13,380 protein-coding genes, 534 genes are carbon hydrate-active enzyme coding genes.

Fitz-Hugh–Curtis syndrome occurring after removal of a peritoneal catheter

No abstract available.

Diagnostic value of peripheral blood immune profiling in colorectal cancer

PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b−CD314+CD3−CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.

Comparison of FcRgamma-Deficient and CD57+ Natural Killer Cells Between Cord Blood and Adult Blood in the Cytomegalovirus-Endemic Korean Population

BACKGROUND: FcRgamma-deficient natural killer (NK) cells (g-NK cells) have been associated with cytomegalovirus (CMV) infection. However, the frequency of g-NK cells in a CMV-endemic area (i.e., Korea) has not yet been studied. We examined the frequency of g-NK cells and expression of CD57 on NK cells in cord blood (CB) and adult blood (AB). METHODS: Of the 24 AB samples collected, 95.8% (23/24) were CMV IgG+/IgM-, while 100% of the 13 healthy CB samples were CMV IgG+/IgM-. We performed whole-blood flow cytometry assays to analyze intracellular FcRgamma and CD3zeta expression of CD3-/CD56dim NK cells from 13 CB and 24 AB samples, and surface CD57 expression on CD3-/CD56dim/CD16+ NK cells from 13 CB and 19 AB samples. RESULTS: All CMV seropositive AB samples contained g-NK cells (23/23), and the median proportion of g-NK cells in the CD3-/CD56dim NK cell pool was 35.0% (range: 11-77%). CD57+ NK cells in the CD3-/CD56dim/CD16+ NK cell population were detected in all 19 AB samples tested, but not in any CB samples. CONCLUSIONS: Our data suggest that g-NK cells and CD57+ NK cells are present at a very high frequency in CMV-seropositive AB, but rare in CMV-naive CB.

ERRATUM / 대한진단검사의학회지

No abstract available.

Incidence and Causes of Hypereosinophilia in the Patients of a University Hospital / 대한진단검사의학회지

BACKGROUND: Eosinophilia may be associated with various primary and reactive conditions. The incidence and the causes of eosinophilia might have been changed according to the changes in the incidence of diseases such as cancer, chronic degenerative diseases, etc. We have conducted a retrospective study to investigate the incidence and causes of eosinophilia. METHODS: Eosinophilia and hypereosinophilia were defined when absolute eosinophil count was greater than 500/microL and 1,500/microL, respectively. Patient's clinical records were reviewed to find out the underlying clinical conditions responsible for causes of hypereosinophilia. Conventional chromosomal analysis, reverse transcriptase PCR and FISH for gene rearrangement were performed to check the presence of clonal eosinophilia. RESULTS: Out of 41,137 patients who had a hematology profile performed, 5,019 (12.2%) and 373 patients (0.9%) were found to have eosinophilia and hypereosinophilia, respectively. Among patients with hypereosinophilia, 227 patients (60.9%) had identifiable and/or possible causes. The major causes of hypereosinophilia were malignancy (35.2%), allergy and skin diseases (18.1%), infectious diseases (15.4%), hepatobiliary diseases (7.5%), bone marrow clonal diseases (6.6%) and parasite infections (6.6%). We also found a rare case of FIP1L1-PDGFRalpha positive chronic eosinophilic leukemia combined with light chain multiple myeloma. CONCLUSIONS: We found a difference in the distribution of causes of hypereosinophilia in comparison with previous Korean studies, and the most common cause of hypereosinophilia in the current study was malignancy. A rare case of clonal eosinophilia (chronic eosinophilic leukemia) associated with multiple myeloma was confirmed using molecular studies.

Species-Specific Differences in Rhodamine 6G Accumulation of Candida Isolates Detected by Flow Cytometric Analysis / 대한진단검사의학회지

BACKGROUND: Fluorescent dye Rhodamine 6G (R6G) is a substrate of multidrug resistance pumps and its accumulation is reduced in some azole-resistant Candida isolates with the upregulation of multidrug efflux transporter genes. Despite reports on species-specific differences in azole susceptibility in various Candida species, only a few studies have been reported on the R6G accumulation among clinical isolates of Candida species. In this study, we compared R6G accumulation between six different Candida species. METHODS: The intracellular accumulation of R6G and minimal inhibitory concentrations (MICs) of three triazole agents were investigated in 48 strains of six Candida species (14 C. albicans, 9 C. tropicalis, 8 C. glabrata, 8 C. krusei, 7 C. parapsilosis, and 2 C. haemulonii). R6G accumulation was measured by using flow cytometry and the geometric mean of the fluorescence intensity (GMF) was used to compare the accumulation between the Candida isolates. RESULTS: The GMF values for the C. tropicalis, C. albicans, C. krusei, C. parapsilosis, and C. glabrata isolates were 167.3+/-18.5, 126.9+/-6.6, 88.5+/-18.5, 50.8+/-7.0, and 38.1+/-3.9, respectively. C. glabrata had a significantly lower mean GMF than all the other Candida species (P<0.05). While some Candida strains with trailing growth phenomenon and increased fluconazole MIC did not have a reduced GMF, three Candida strains with increased MICs to all three triazole agents had a reduced GMF. CONCLUSIONS: This study found species-specific differences in R6G accumulation in Candida. In addition, the intracellular R6G accumulation can be used to investigate the drug efflux mechanism in azole-resistant Candida strains.

Evaluation of VITEK-2 Antifungal Susceptibility Test (AST-YS01) for Candida Species Isolates in Korea / 대한임상미생물학회지

BACKGROUND: VITEK-2 yeast susceptibility test (AST- YS01; bioMerieux, Hazelwood, MO, USA) has recently been introduced as a fully automated commercial antifungal susceptibility test system that determines MIC (minimum inhibitory concentrations) endpoints spectrophotometrically, thereby eliminating subjective errors. We compared the VITEK-2 system with the CLSI (the Clinical and Laboratory Standards Institute) M27 method for susceptibility testing of Candida isolates from Korea. METHODS: A total of 175 Candida bloodstream isolates were collected from two hospitals during a 18-month period. We compared the MIC results for amphotericin B, fluconazole and voriconazole obtained with the VITEK-2 system to those obtained by the CLSI M27 broth microdilution method after 24-hr and 48-hr incubation. RESULTS: VITEK-2 system MIC endpoints for 175 isolates were determined after 11.75 to 35.50 hr of incubation (mean, 16.3+/-4.8 hr). The essential agreement (within 2 dilutions) between amphotericin B, fluconazole and voriconazole MICs obtained by the VITEK-2 system and CLSI method was 98.3%, 90.9% and 96.0%, respectively, at 24-hr incubation and 100%, 92.6% and 94.9%, at 48-hr incubation. The categorical discrepancy for fluconazole was 6.3% (major error, 2.9% and minor error, 3.4%) at 24-hr and 6.3% (major error, 2.3% and minor error, 4.0%) at 48-hr. The categorical discrepancy for voriconazole was 1.7% (major error, 1.1% and minor error, 0.6%) at both 24-hr and 48-hr. There were no very major errors for fluconazole and voriconazole. CONCLUSION: The VITEK-2 antifungal susceptibility test system appears to be rapid and highly correlative with the CLSI method, sugesting that this system can be effective for antifungal susceptibility testing for Candida species in the clinical laboratory.

Laboratory Evaluation of Bone Marrow Metastasis: Single Institute Study / 대한진단검사의학회지

BACKGROUND: The incidence of bone marrow (BM) metastasis might be related with the occurrence of malignant tumors in ethnic groups. So, we investigated the type and the frequency of metastatic tumors of BM and analyzed the clinicopathologic variables of BM metastasis. METHODS: This study included 932 cases of primary malignant tumor which were requested for BM study from January 1995 to June 2006 in Chonnam National University Hospital and Chonnam National University Hwasun Hospital. Peripheral blood smears (PBS); aspirates, touch prints, and trephine biopsies of BM; and medical records including other laboratory test results were reviewed. RESULTS: Overall frequency of BM metastasis was 11.9% (111/932). Primary tumors with BM involvement in children comprised neuroblastoma (74.1%), rhabdomyosarcoma (7.4%), and malignant lymphoma (7.4%). For adult patients, they consisted of malignant lymphoma (56.0%), gastrointestinal cancer (20.2%), and lung cancer (6.0%). In the case of malignant lymphoma, diffuse large cell lymphoma was the most frequent one. Laboratory findings of patients with BM metastasis commonly showed anemia and thrombocytopenia; in addition, serum LD, ALP, AST and ALT were elevated in 81.5% (75/92), 63.4% (59/93), 63.5% (61/96) and 33.3% (32/96), respectively. Leukoerythroblastosis was observed only in 19.8% (22/111) on PBS examination. CONCLUSIONS: The most common non-hematopoietic metastatic tumor was neuroblastoma in children and gastrointestinal tumors in adults. Leukoerythroblastosis, anemia, and the elevation of serum LD, ALP, and AST were useful markers for the prediction of BM metastasis.