Clinical Efficacy and Safety of Low-Dose Pemafibrate in Patients With Severe Renal Impairment: A Retrospective Study.

BACKGROUND: The management of hypertriglyceridemia in patients with chronic kidney disease (CKD) is important. Pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator with less toxic effects on liver and kidney function than those of other fibrates, has recently been approved for the treatment of patients with an estimated glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m2. However, the efficacy and safety of pemafibrate in patients with severe renal impairment have not yet been established. METHODS: This single-center, retrospective observational study included 12 outpatients with CKD and hypertriglyceridemia, who were newly started on low-dose pemafibrate (0.1 mg/day) treatment between December 2021 and May 2023 and whose eGFRs were less than 30 mL/min/1.73 m2 at baseline. Blood samples were collected before and at 12 weeks after pemafibrate treatment. RESULTS: After 12 weeks of treatment, the serum triglyceride level was significantly decreased, whereas the high-density lipoprotein cholesterol level was significantly increased. The serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and uric acid levels were also significantly decreased, without worsening of the eGFR and serum creatinine levels. In the subgroup analysis, there were no significant differences in the changes in clinical parameters regardless of statin use and CKD stage at baseline. CONCLUSIONS: Low-dose pemafibrate administration in patients with severe renal impairment resulted in significant improvements in triglyceride, high-density lipoprotein cholesterol, and serum uric acid levels, and liver function, without adverse events.

Impact of Albumin Leakage on the Mortality of Patients Receiving Hemodialysis or Online Hemodiafiltration.

Background: Online hemodiafiltration (OHDF) has a lower mortality rate than hemodialysis (HD). We aimed to investigate the impact of the albumin leakage on the mortality of patients receiving HD or OHDF. Methods: In this single-center study, consecutive patients receiving renal replacement therapy between January and April 2018 were retrospectively registered. Using (1:1) propensity score matching, 3-year all-cause mortality was compared between patients receiving HD and OHDF, and the impact of albumin leakage on the mortality rate in both groups was investigated. Results: Of the 460 patients, 137 patients receiving HD were matched with an equal number of patients receiving OHDF. OHDF was associated with higher albumin leakage (p < 0.001) and a lower mortality than HD (log-rank test, p < 0.001). Albumin leakage was associated with mortality in patients receiving HD (per 1 g increase, hazard ratio (HR): 0.495, 95% confidence interval (CI): 0.275-0.888) and patients receiving OHDF (per 1 g increase, HR: 0.734, 95% CI: 0.588-0.915). Patients receiving HD, with the highest albumin leakage tertile (>3 g), had a similar mortality rate to patients receiving OHDF, with similar albumin leakage. Conclusions: The negative relationship between albumin leakage and mortality suggests the benefit of removing middle- to -large-molecular-weight substances to improve survival.

The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Amyloid accumulation in cases of suspected comorbid cerebral amyloid angiopathy and isolated cortical venous thrombosis.

BACKGROUND AND AIM: The differentiation of isolated cortical venous thrombosis (ICVT) from cerebral amyloid angiopathy (CAA) can be difficult because both diseases share similar neurological symptoms and imaging findings. N-methyl-11C-2-(4'-methylaminophenyl)-6-hydroxybenzo-thiazole (11C-PiB) positron emission tomography (PET) functions as a diagnostic modality for CAA by detecting amyloid deposition. The present prospective study evaluated amyloid deposition using 11C-PiB-PET in consecutive patients with suspected ICVT. METHOD: This study was a prospective observational study. Patients who attended or were hospitalized between May 2019 and March 2020 were included in the analysis. Consecutive patients who met the criteria for suspicion of ICVT were enrolled in the study, and the clinical course, symptoms, imaging findings (including magnetic resonance imaging), and the 11C-PiB-PET findings of each case were analyzed. RESULTS: The study cohort included four patients (64-82 years of age, all women). In one younger patient, 11C-PiB-PET afforded no findings suggestive of CAA, whereas the remaining three patients exhibited 11C-PiB-PET findings suggestive of CAA. CONCLUSION: Although 11C-PiB-PET would be a reasonable modality for distinguishing ICVT from CAA, especially in younger patients, it might be difficult to differentiate ICVT from CAA in elderly patients because of the potential deposition of amyloid. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/ Unique identifier: UMIN 000037101.

Low-density Lipoprotein Receptor Activities, Lipids, Apolipoprotein, and Clinical Course of Patients with Steroid-resistant Nephrotic Syndrome Treated with Low-density Lipoprotein Apheresis: A Case Series.

We herein report three cases of steroid-resistant nephrotic syndrome successfully treated with low-density lipoprotein apheresis (LDL-A). All patients were treated with a combination of steroids, cyclosporine, and LDL-A. In all cases, the serum concentrations of LDL, total and high-density lipoprotein cholesterol, and triglycerides were significantly lowered following LDL-A administration. Furthermore, the estimated LDL receptor activity increased, while both serum LDL and total cholesterol levels decreased, suggesting that LDL-A increases LDL receptor activity by driving changes in serum cholesterol concentration. This case series suggests that LDL-A increases LDL receptor activity, which may improve the intracellular uptake of cyclosporine.

Effects of switching from agalsidase-α to agalsidase-ß on biomarkers, renal and cardiac parameters, and disease severity in fabry disease forming neutralizing antidrug antibodies: a case report.

Fabry disease is an X-linked hereditary disorder caused by deficient α-galactosidase A (GLA) activity. Patients with Fabry disease are often treated with enzyme replacement therapy (ERT). However, ERT often induces the formation of neutralizing antidrug antibodies (ADAs), which may impair the therapeutic efficacy. Here, we report the case of a 32-year-old man with Fabry disease and resultant neutralizing ADAs who was treated by switching from agalsidase-α to agalsidase-ß. We monitored biomarkers, such as plasma globotriaosylsphingosine (lyso-Gb3), urinary globotriaosylceramide (Gb3), urinary mulberry bodies, renal and cardiac parameters, and disease severity during the treatment period. Although plasma lyso-Gb3 and urinary Gb3 levels quickly decreased within two months after the initiation of ERT with agalsidase-α, they gradually increased thereafter. The urinary mulberry bodies continued to appear. Both the ADA titer and serum mediated GLA inhibition rates started to increase after two months. Moreover, 3.5 years after ERT, the vacuolated podocyte area in the renal biopsy decreased slightly from 23.1 to 18.9%. However, plasma lyso-Gb3 levels increased, and urinary Gb3, mulberry body levels, and ADA titers remained high. Therefore, we switched to agalsidase-ß which reduced, but did not normalize, plasma lyso-Gb3 levels and stabilized renal and cardiac parameters. Disease severity was attenuated. However, urinary Gb3 and mulberry body levels did not decrease noticeably in the presence of high ADA titers. The kidneys take up a small amount of the administered recombinant enzyme, and the clearance of Gb3 that has accumulated in the kidney may be limited despite the switching from agalsidase-α to agalsidase-ß.

Reducing the Sodium Intake of Patients With Chronic Kidney Disease Through Education and Estimating Salt Excretion: A Propensity Score Matching Analysis.

BACKGROUND: Japanese people traditionally consume high quantities of salt. This study aimed to investigate the effects of educating patients with chronic kidney disease (CKD) on simple methods for reducing their daily dietary salt intake. METHODS: This single-center, retrospective observational study included 115 outpatients with CKD at Kawashima Hospital (Tokushima, Japan). One physician routinely recommended that patients should reduce their salt intake and provided tips for salt restriction. The physician estimated the patients' daily salt intake using spot urine samples at each medical examination (education group; n = 61). The other physicians' outpatients only received dietary guidance on recommended salt intake (control group; n = 54). The estimated 24-hour urinary sodium excretion (24hUNaV) and 24-hour potassium excretion (24hUKV) were calculated using Tanaka's equation. RESULTS: Estimated 24hUNaV was positively correlated with body mass index (BMI), estimated 24hUKV, and urinary Na/K ratio. The patients in the education group were younger and had a lower BMI, higher estimated glomerular filtration rate, and lower systolic blood pressure (SBP). Using 38 pairs of patients obtained by propensity score matching with these variables, estimated 24hUNaV, estimated 24hUKV, and diastolic blood pressure (DBP) after one year were significantly reduced in the education group. CONCLUSION: A simple salt reduction education may reduce salt intake in outpatients with CKD.

X-linked Alport Syndrome with Type IV Collagen α5 Chain Staining Revealing Normal Expression in the Glomerular Basement Membrane and Negative on Bowman's Capsule and Distal Tubular Basement Membrane: A Case Report.

X-linked Alport syndrome is a hereditary progressive renal disease resulting from the disruption of collagen α3α4α5 (IV) heterotrimerization caused by pathogenic variants in the COL4A5 gene. This study aimed to report a male case of X-linked Alport syndrome with a mild phenotype accompanied by an atypical expression pattern of type IV collagen α5 [α5 (IV)] chain in glomerulus. A 38-year-old male presented with proteinuria (2.3 g/day) and hematuria. He has been detected urinary protein and occult blood since childhood. A renal biopsy was performed at the age of 29 years; however, a diagnosis of Alport syndrome was not considered. A renal biopsy 9 years later revealed diffuse thinning and lamellation of the glomerular basement membrane. Α staining for α5 (IV) revealed a normal expression pattern in the glomerular basement membrane and a complete negative expression in Bowman's capsule and distal tubular basement membrane. Using next-generation sequencing, we detected a COL4A5 missense variant within exon 35 (NM_000495.5: c.3088G>A, p. G1030S). The possibility of X-linked Alport syndrome should be considered when negative expression of α5 (IV) staining on Bowman's capsule was observed.

Evaluation of 18F labeled glial fibrillary acidic protein binding nanobody and its brain shuttle peptide fusion proteins using a neuroinflammation rat model.

Astrogliosis is a crucial feature of neuroinflammation and is characterized by the significant upregulation of glial fibrillary acidic protein (GFAP) expression. Hence, visualizing GFAP in the living brain of patients with damaged central nervous system using positron emission tomography (PET) is of great importance, and it is expected to depict neuroinflammation more directly than existing neuroinflammation imaging markers. However, no PET radiotracers for GFAP are currently available. Therefore, neuroimaging with antibody-like affinity proteins could be a viable strategy for visualizing imaging targets that small molecules rarely recognize, such as GFAP, while we need to overcome the challenges of slow clearance and low brain permeability. The E9 nanobody, a small-affinity protein with high affinity and selectivity for GFAP, was utilized in this study. E9 was engineered by fusing a brain shuttle peptide that facilitates blood-brain barrier permeation via two different types of linker domains: E9-GS-ApoE (EGA) and E9-EAK-ApoE (EEA). E9, EGA and EEA were radiolabeled with fluorine-18 using cell-free protein radiosynthesis. In vitro autoradiography showed that all radiolabeled proteins exhibited a significant difference in neuroinflammation in the brain sections created from a rat model constructed by injecting lipopolysaccharide (LPS) into the unilateral striatum of wildtype rats, and an excess competitor displaced their binding. However, exploratory in vivo PET imaging and ex vivo biodistribution studies in the rat model failed to distinguish neuroinflammatory lesions within 3 h of 18F-EEA intravenous injection. This study contributes to a better understanding of the characteristics of small-affinity proteins fused with a brain shuttle peptide for further research into the use of protein molecules as PET tracers for imaging neuropathology.

Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report.

BACKGROUND: Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy. CASE PRESENTATION: A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia. CONCLUSION: Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.

Removal performance of pre- and post-dilution online hemodiafiltration using identical hemodiafilters in the same patients.

Online hemodiafiltration (OHDF) for renal replacement therapy has two modes: pre- (pre-OHDF) and post-dilution OHDF (post-OHDF). To elucidate the precise differences between the two modes, a clinical study was performed using the same polysulfone hemodiafilters in the same patients. Eight patients were treated with ABH™-22PA for 6 weeks: 3 weeks of pre-OHDF (with substitution volumes of 24, 36, and 48 L) and 3 weeks of post-OHDF (6, 8, and 10 L). The reduction ratios of urea, uric acid (UA), creatinine (CRE), inorganic phosphorus (iP), beta-2-microglobulin (ß2-MG), and alpha-1-microglobulin (α1-MG) were evaluated. The removal amounts of ß2-MG, α1-MG, and albumin were also evaluated by analyzing the spent dialysis fluids. The types and numbers of adverse events (AEs) and device malfunctions were recorded. The reduction ratios of urea, UA, CRE, iP, and ß2-MG were comparable among all conditions, while that of α1-MG tended to be slightly higher in post-OHDF than in pre-OHDF. The removal amounts of α1-MG and albumin in pre-OHDF and post-OHDF were significantly greater with the maximum substitution volume than with the minimum volume. However, the selective removal indices, which were obtained by dividing the amount of α1-MG removed by the albumin level, tended to be slightly higher in pre- than in post-OHDF. No device-related AEs or device malfunctions occurred in either mode. No significant differences in inflammatory responses, evaluated by high-sensitivity C-reactive protein and interleukin-6, were observed. This study provides removal performance and safety data regarding the application of ABH-22PA for pre- and post-OHDF.

The quantification of muscle activities during arm elevation following reverse shoulder arthroplasty or superior capsular reconstruction for irreparable rotator cuff tears using positron emission tomography.

BACKGROUND: Reverse shoulder arthroplasty (RSA) and superior capsular reconstruction (SCR) are recognized as surgical options for an irreparable rotator cuff tear. However, the postoperative changes of the muscle activity patterns remain unclear. The purpose of this study was to investigate the quantified muscle activities on shoulder elevation in patients treated with RSA or SCR using fluorine-18-labelled fluorodeoxyglucose-positron emission tomography. METHODS: Asymptomatic shoulders that underwent RSA or SCR and those without a rotator cuff tear were analyzed as the RSA, SCR, and control groups. All subjects underwent shoulder elevation exercise, followed by a fluorine-18-labelled fluorodeoxyglucose-positron emission tomography examination. Using previously established methods to quantify the uptake of each muscle on positron emission tomography images, the standard uptake values (SUVs) for 16 portions of the deltoid, rotator cuff, and periscapular muscles were obtained to compare the muscle activity patterns among 3 groups. RESULTS: The deltoid muscle showed the most characteristic differences according to the surgeries. The mean SUVs of the anterior, middle, and posterior deltoid were 3.3, 3.7, and 1.5 for the RSA group; 2.7, 4.2, and 1.5 for the SCR group; and 1.3, 2.0, and 0.9 for the control group, respectively. In comparison to the control group, both the RSA and SCR groups showed significantly increased SUVs at all portions of the deltoid muscle. The RSA group showed similar SUVs for the anterior and middle deltoid, whereas the SCR and control groups showed greatest SUVs at the middle deltoid. In addition, the serratus anterior, levator scapulae, and upper portion of the trapezius in the RSA group showed greater SUVs than in the control group. CONCLUSION: The deltoid muscle showed increased activity in the RSA and SCR groups. The middle deltoid was mainly used in the SCR group, whereas the anterior and middle deltoid, as well as the upward rotator muscles of the scapula, were mainly used in the RSA group.

Change in the graphics of journal articles in the life sciences field: analysis of figures and tables in the journal "Cell".

The purpose of this study is to examine how trends in the use of images in modern life science journals have changed since the spread of computer-based visual and imaging technology. To this end, a new classification system was constructed to analyze how the graphics of a scientific journal have changed over the years. The focus was on one international peer-reviewed journal in life sciences, Cell, which was founded in 1974, whereby 1725 figures and 160 tables from the research articles in Cell were sampled. The unit of classification was defined as a graphic and the figures and tables were divided into 5952 graphics. These graphics were further classified into hierarchical categories, and the data in each category were aggregated every five years. The following categories were observed: (1) data graphics, (2) explanation graphics, and (3) hybrid graphics. Data graphics increased by more than sixfold between 1974 and 2014, and some types of data graphics including mechanical reproduction images and bar charts displayed notable changes. The representation of explanatory graphics changed from hand-painted illustrations to diagrams of Bezier-curves. It is suggested that in addition to the development of experimental technologies such as fluorescent microscopy and big data analysis, continuously evolving application software for image creation and researchers' motivation to convince reviewers and editors have influenced these changes.

Histamine Neuroimaging in Stress-Related Disorders.

Although histamine plays a major role in animal models of stress-related disorders, human neuroimaging data are sparse. Histamine H1 receptors in the human brain were first imaged by Professor Kazuhiko Yanai in 1992 by using 11C-doxepin, a potent ligand of H1 receptors, and positron emission tomography (PET). Subsequent work revealed that H1 receptors are reduced in the prefrontal and anterior cingulate cortices in patients with major depressive disorders. A sex difference in H1 receptor binding in the brain has also been found, with women exhibiting more abundant H1 receptor binding than men. Moreover, female patients with anorexia nervosa show higher H1 receptor binding in the amygdala and lentiform nucleus. These studies also found an inverse correlation of depression scores with H1 receptor binding. Histamine is considered to play a major role in the pathophysiology of irritable bowel syndrome (IBS), a representative disorder of brain-gut interactions. Along these lines, hypnotic suggestion dramatically changes the waveforms of viscerosensory cerebral evoked potentials in response to electrical rectal stimulation and these changes are modified by the administration of H1 antagonist. The direction of the H1 antagonist-induced changes in the viscerosensory cerebral evoked potentials differs between IBS patients and healthy controls. Thus, histamine likely plays an important role in stress-related disorders. Further histamine brain imaging studies of humans are warranted.

A complicated case of Serratia marcescens catheter-related bloodstream infection misdiagnosed as hypersensitivity reactions to bicarbonate dialysate containing acetate.

Recurrent fever during/post-dialysis can occur due to infectious or non-infectious causes. We present the case of a 79-year-old patient who had persistent post-dialysis fever after long-term tunneled central venous catheterization with acetate-containing bicarbonate dialysate. Drug-induced lymphocyte stimulation test (DLST) was positive for acetate dialysate, and he was suspected of having acetate dialysate-induced hypersensitivity reaction. However, switching to acetate-free dialysate did not attenuate the fever. Since Serratia marcescens had been isolated twice from the blood, catheter-related bloodstream infection (CRBSI) was suspected. The culture of the catheter tip confirmed CRBSI caused by S. marcescens. Elevation of ß-d-glucan levels and appearance of pulmonary nodular shadow on chest computed tomography images indicated complicated fungal infections. Administration of antibiotics and antifungals led to resolution of the pulmonary nodular shadow with attenuation of fever and C-reactive protein levels. DLST for acetate dialysate was negative, and its reuse did not aggravate the symptoms; hence, the first result was considered false-positive. An indwelling catheter is a risk factor for S. marcescens-related CRBSI, which leads to post-dialysis fever. Hypersensitivity reactions to dialysates must be diagnosed considering the clinical course and DLST results.

Successful Treatment of Nephrotic Syndrome Due to Collapsing Focal Segmental Glomerulosclerosis Accompanied by Acute Interstitial Nephritis.

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.

18F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies.

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters. Methods: 18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination-Revised, and Frontal Assessment Battery, Unified Parkinson's Disease Rating Scale Motor Score, and PSP Rating Scale. Results: 18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP. Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.

Hereditary spherocytosis diagnosed with extremely low glycated hemoglobin compared to plasma glucose levels.

Glycated hemoglobin (HbA1c) is an important indicator of glycemic control in patients with diabetes. High-performance liquid chromatography (HPLC) is the most commonly used method for measuring HbA1c levels; as HPLC measures all hemoglobin types, the values can be influenced by hemoglobin variants. Moreover, as HPLC-HbA1c levels are low in some diseases, including hemolytic anemia, it may be difficult to differentiate hemoglobin variants from these diseases based on HPLC-HbA1c levels alone. Similar HbA1c values using both HPLC and immunoassays (IAs) are noted for these diseases, while discrepancies are noted in the case of hemoglobin variants. Herein, we describe our process of differential diagnosis for hereditary spherocytosis, the most common inherited hemolytic anemia, in a 56-year-old man presenting with a low HPLC-HbA1c level compared to the glucose concentration, concomitant with anemia, jaundice, hyperbilirubinemia, cholelithiasis, and splenomegaly. There was a discrepancy between HbA1c levels measured with HPLC and IAs and glycated albumin levels. The possibility of hemoglobin variants was unlikely, based on the chromatography and isoelectric focusing results. The haptoglobin levels and reticulocyte counts were low and high, respectively. The direct and indirect Coomb's tests were negative. The presence of spherocytes on blood smears and flow cytometric analysis of the eosin-5-maleimide binding test supported a diagnosis of hereditary spherocytosis. We recommend that when a discrepancy between HPLC-HbA1c levels and glucose concentrations is noted, clinicians should consider hemolysis or hemoglobin variants as the diagnosis. It should be considered that a discrepancy between HbA1c levels measured with HPLC and IAs does not specifically exclude hemolysis.

Splenic abscess diagnosed following relapsing sterile peritonitis in a peritoneal dialysis patient: A case report with literature review.

Peritoneal dialysis (PD)-related peritonitis is sometimes complicated with other infections; however, few cases of splenic abscess have been reported. We present the case of a 64-year-old PD patient with complicated splenic abscesses diagnosed following relapsing sterile peritonitis. After PD induction, he presented with turbid peritoneal fluid and was diagnosed with PD-related peritonitis. A plain abdominal computed tomography (CT) did not reveal any intra-abdominal focus of infection. After empiric intravenous antibiotics, the peritoneal dialysate was initially cleared, with a decrease in dialysate white blood cells (WBC) to 20/µL. However, WBC and C-reactive protein (CRP) levels remained elevated. A contrast-enhanced abdominal CT showed two areas of low-density fluid with no enhancement in a mildly enlarged spleen, making it difficult to distinguish abscesses from cysts. Due to relapsing sterile peritonitis, we performed an abdominal ultrasonography, and suspected splenic abscesses due to rapid increase in size. Repeated imaging tests were useful in establishing a diagnosis of splenic abscesses. Considering the persistent elevation of WBC and CRP levels, imaging findings, and episodes of relapsing peritonitis, we comprehensively formed the diagnosis, and performed a splenectomy as a rescue therapy. We should consider the possibility of other infectious foci with persistent inflammation after resolving PD-related peritonitis.

Clinical Characteristics and Risk Factors for Mortality due to Bloodstream Infection of Unknown Origin in Hemodialysis Patients: A Single-Center, Retrospective Study.

INTRODUCTION: Hemodialysis patients are at a high risk of bloodstream infection (BSI). The risk factors for BSI-associated mortality, especially of unknown origin, remain uncertain. BSI of unknown origin is highly prevalent and related to high mortality. The present study aimed to investigate the clinical and microbiological characteristics of BSI and risk factors for BSI-associated mortality, including BSI of unknown origin, in hemodialysis patients. METHODS: This study was a single-center, retrospective study conducted from August 2012 to July 2019 in hemodialysis patients with BSI at Kawashima Hospital. Data related to demographics, clinical parameters, BSI sources, causative microorganisms, and initial treatments were collected from the medical records. The predictors for mortality associated with BSI were evaluated by logistic regression. RESULTS: Among 174 patients, 55 (30.9%) had the infection from unknown origin. The most frequent bacterium was Staphylococcus aureus. Low serum albumin level was an independent predictor of mortality due to BSI (odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.13-0.59). A lower serum albumin level (≤2.5 g/dL) was associated with poorer mortality. Methicillin-resistant Staphylococcus aureus (MRSA) was independently associated with mortality due to BSI of unknown origin (OR: 6.20, 95% CI: 1.04-37.1); 87.5% cases with BSI of unknown origin due to MRSA were not initially administrated anti-MRSA antibiotics, and in such patients, the mortality rate was 85.7%. CONCLUSIONS: Serum albumin level of 2.5 g/dL is a cutoff value, which could predict the mortality due to BSI in hemodialysis patients. Considering the high mortality rate of MRSA-associated BSI of unknown origin, wherein no focus of infection was identified in the present study, initial empiric treatment should be considered for MRSA-associated BSI of unknown origin.