Perioperative Factors Aggravating Pharyngocutaneous Fistula After Total Laryngectomy: A Single-Center Retrospective Analysis Using the Clavien-Dindo Classification.

BACKGROUND: Pharyngocutaneous fistula formation represents a major postoperative complication following total laryngectomy. We aimed to investigate the risk factors for pharyngocutaneous fistula development after total laryngectomy and to identify factors that lead to severe cases of pharyngocutaneous fistula. METHODS: Patients who underwent total laryngectomy between January 2013 and February 2021 were included in the study and were divided into 2 groups: Those with and without pharyngocutaneous fistula. The severity of pharyngocutaneous fistula was graded using the Clavien-Dindo classification. RESULTS: Patients with pharyngocutaneous fistula experienced longer operative time, greater intraoperative blood loss, greater decrease in perioperative hemoglobin level, and longer postoperative hospitalization. Unlike in lower-severity cases, patients with grade IIIb pharyngocutaneous fistula underwent preoperative radiotherapy or chemoradiotherapy; preoperative treatment was thus a risk factor for higher severity of pharyngocutaneous fistula (odds ratio, 35; P = 0.004). CONCLUSION: Salvage laryngectomy was found to be a predictor of severe pharyngocutaneous fistula development. Prolonged operative time, increased intraoperative blood loss, and decreased postoperative hemoglobin level were found to be predictors of postlaryngectomy pharyngocutaneous fistula formation.

Characterization of epitopes of human monoclonal antibodies against cytomegalovirus glycoprotein B for neutralization and antibody-dependent phagocytosis.

As congenital cytomegalovirus (CMV) infections are the leading non-genetic cause of sensorineural hearing loss and significant neurological disabilities in children, the development of CMV vaccines should be given the highest public health priority. Although MF59-adjuvanted glycoprotein B (gB) vaccine (gB/MF59) is safe and immunogenic, its efficacy in terms of protection from natural infection was around 50 % in clinical trials. Although gB/MF59 induced high antibody titers, anti-gB antibodies contributed little to the neutralization of infection. Recent studies have found that non-neutralizing functions, including antibody-dependent phagocytosis of virions and virus-infected cells, are likely to play important roles in pathogenesis and vaccine design. Previously, we isolated human monoclonal antibodies (MAbs) that reacted with the trimeric form of gB ectodomain and found that preferential epitopes for neutralization were present on Domains (Doms) I and II of gB, while there were abundant non-neutralizing antibodies targeting Dom IV. In this study, we analyzed the phagocytosis activities of these MAbs and found the following: 1) MAbs effective for phagocytosis of the virions targeted Doms I and II, 2) the MAbs effective for phagocytosis of the virions and those of virus-infected cells were generally distinct, and 3) the antibody-dependent phagocytosis showed little correlation with neutralizing activities. Taking account of the frequency and levels of neutralization and phagocytosis, incorporation of the epitopes on Doms I and II into developing vaccines is considered desirable for the prevention of viremia.

Gestational exposure to haloperidol changes Cdkn1a and Apaf1 mRNA expressions in mouse hippocampus.

BACKGROUND: The onset of schizophrenia is associated with both genetic and environmental risks during brain development. Environmental factors during pregnancy can represent risk factors for schizophrenia, and we have previously reported that several microRNA and mRNA expression changes in fetal brains exposed to haloperidol during pregnancy may be related to the onset of this disease. This study aimed to replicate that research and focused on apoptotic-related gene expression changes. METHODS: Haloperidol (1 mg/kg) or aripiprazole (1 mg/kg) was injected into pregnant mice. Using RNA sequencing for the hippocampus of each offspring born from pregnant mice exposed to haloperidol, we analyzed genes identified as changed in our previous report and validated two apoptosis-related genes (Cdkn1a and Apaf1) using quantitative polymerase chain reaction (qPCR) methods. Furthermore, we attempted to elucidate the direct effects of haloperidol and aripiprazole on those mRNA expressions in in vitro experiments. RESULTS: RNA sequencing successfully replicated 16 up-regulated and 5 down-regulated genes in this study. Of those, up-regulations of Cdkn1a and Apaf1 mRNA expression were successfully validated by direct quantification. Moreover, haloperidol and aripiprazole dose-dependent upregulation of both mRNA expressions were confirmed in a Neuro2a cell line. CONCLUSIONS: In the hippocampus of offspring, intraperitoneal injection of haloperidol to pregnant mice induced up-regulation of apoptotic genes that representing the phenotypic change without apoptosis. These findings will be useful for understanding the molecular biological mechanisms underlying the effects of antipsychotics on the fetal brain.

Aberrant Expression of GABA-Related Genes in the Hippocampus of 3xTg-AD Model Mice from the Early to End Stages of Alzheimer's Disease.

BACKGROUND: We explored the gene expression levels in the brain of 3xTg-AD model mice to elucidate the molecular pathological changes from the early to end stages of Alzheimer's disease (AD). OBJECTIVE: We re-analyzed our previously published microarray data obtained from the hippocampus of 3xTg-AD model mice at 12 and 52 weeks of age. METHODS: Functional annotation and network analyses of the up- and downregulated differentially expressed genes (DEGs) in mice aged 12 to 52 weeks were performed. Validation tests for gamma-aminobutyric acid (GABA)-related genes were also performed by quantitative polymerase chain reaction (qPCR). RESULTS: In total, 644 DEGs were upregulated and 624 DEGs were downregulated in the hippocampus of both the 12- and 52-week-old 3xTg-AD mice. In the functional analysis of the upregulated DEGs, 330 gene ontology biological process terms, including immune response, were found, and they interacted with each other in the network analysis. In the functional analysis of the downregulated DEGs, 90 biological process terms, including several terms related to membrane potential and synapse function, were found, and they also interacted with each other in the network analysis. In the qPCR validation test, significant downregulation was seen for Gabrg3 at the ages of 12 (p = 0.02) and 36 (p = 0.005) weeks, Gabbr1 at the age of 52 weeks (p = 0.001), and Gabrr2 at the age of 36 weeks (p = 0.02). CONCLUSION: Changes in immune response and GABAergic neurotransmission may occur in the brain of 3xTg mice from the early to end stages of AD.

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.

Groin and anterolateral thigh flaps for hemiglossectomy reconstruction: A comparison based on Japanese speech intelligibility.

OBJECTIVE: The differences in speech function between groin flap reconstruction and anterolateral thigh (ALT) flap reconstruction after hemiglossectomy have not been clarified to date. This study aimed to compare Japanese speech intelligibility after hemiglossectomy reconstruction using groin and ALT flaps of similar thickness. METHODS: Data of patients who underwent hemiglossectomy reconstruction with groin or ALT flaps between April 2010 and March 2020 were collected from the medical chart database. The ALT flap was the first choice for hemiglossectomy reconstruction, and a groin flap was used when the ALT flap was >10 mm. Cases in which speech intelligibility assessments based on Hirose's 10-point scoring system, the TKR speech test, and the Japanese speech intelligibility test for 100 monosyllables were performed after 6 months postoperatively were extracted. The per-patient scores for each assessment were initially compared between the two flap groups. Then, the results of the Japanese speech intelligibility test for 100 monosyllables were reanalyzed on a syllable-by-syllable basis. RESULTS: Among the 44 hemiglossectomy patients who underwent free-flap reconstruction during the study period, 14 (seven each in the groin flap and ALT flap groups) underwent all three conventional speech intelligibility assessments after 6 months postoperatively. The two groups showed no significant difference in postoperative speech intelligibility in any of the three patient assessment methods. However, in intergroup comparisons based on per-syllable accuracy for each of the 100 monosyllables, the groin flap group showed 19 syllables with a significantly higher accuracy, whereas the ALT flap group showed one such syllable. In particular, five out of the six alveolar consonants (/t/ and /d/) were more accurately articulated in the groin flap group. Per-syllable accuracy was significantly higher in the groin flap group (74.6% vs. 66.7%; 95% confidence interval: 4.6-11.1, p < 0.001). CONCLUSION: In patients undergoing hemiglossectomy reconstruction, our new analysis method, which compared intelligibility by syllables, showed that the groin flap yielded higher speech intelligibility than the ALT flap. This difference was evident at all four articulation points involving the tongue, whereas there was no significant difference at the two articulation points without tongue involvement.

Nephrotic Syndrome as an Extramuscular Manifestation of Anti-EJ Antibody-Positive Dermatomyositis: A Case Report and Review of the Literature.

Renal involvement is underestimated as an extramuscular manifestation of dermatomyositis (DM). Here, we describe a 67-year-old woman with anti-glycyl-transfer ribonucleic acid synthetase (anti-EJ) antibody and anti-ribonucleoprotein antibody-positive DM complicated by systemic sclerosis, who developed nephrotic syndrome concurrently with the exacerbation of DM, as indicated by incremental serum creatine kinase levels, high-intensity lesions on muscle magnetic resonance imaging, and active interstitial pneumonitis on chest computed tomography. Renal biopsy revealed the presence of immune-deposition in the glomerulus by immunofluorescence. To our knowledge, this is the first report describing the coexistence of anti-EJ antibody-positive DM and nephrotic syndrome. More reports of similar cases are warranted to substantiate the association.

Clinical variables, including novel joint index, associated with future patient-physician discordance in global assessment of rheumatoid arthritis (RA) disease activity based on a large RA database in Japan.

BACKGROUND: Discordance between patient global assessment (PGA) and physician global assessment (PhGA) of rheumatoid arthritis (RA) disease activity is mainly determined by pain and functional disabilities. This study aimed to investigate the shift in PGA-PhGA discordance and the variables associated with future positive discordance (PGA > PhGA) based on the NinJa database in Japan. METHODS: We examined 7557 adults with RA registered in both NinJa 2014 and 2018, with a discordance cutoff of 3 on a 10-cm scale. The affected joint distribution was investigated using the joint indices x, y, and z, which were calculated as indices for the upper joint, lower joint, and large joint involvement, respectively. The variables in NinJa 2014 that were associated with positive discordance in NinJa 2018 were examined using binary stepwise logistic regression analysis. RESULTS: Due to the small number of patients with RA categorized as having negative discordance (PGA < PhGA), we focused on patients with RA categorized as having either concordance or positive discordance. Logistic regression analysis revealed that positive discordance in NinJa 2018 was associated with age, pain, modified Health Assessment Questionnaire (mHAQ) score, corticosteroid use, and existent positive discordance and was inversely associated with C-reactive protein (CRP) and x at baseline (NinJa 2014). The same findings were observed when patients with RA were divided based on the discordance status at baseline. Persistence (positive discordance to positive discordance) was associated with pain and mHAQ scores but inversely associated with CRP. CONCLUSIONS: Positive discordance may persist. Circumventing this requires adequate management of pain and functional impairment.

Association Study and Meta-Analysis of Polymorphisms and Blood mRNA Expression of the ALDH2 Gene in Patients with Alzheimer's Disease.

BACKGROUND: Late-onset Alzheimer's disease (LOAD) is a complex disease in which neuroinflammation plays an important pathophysiological role, and exposure to neurotoxic substrates such as aldehydes may contribute. Blood mRNA expression levels of neuroinflammation-related genes appear to be potential biological markers of LOAD. A relationship between ALDH2 and LOAD has been suggested. OBJECTIVE: Our objective was to examine blood ALDH2 expression in Japanese LOAD patients, conduct a genetic association study, and add new studies to an extended meta-analysis of the Asian population. METHODS: A blood expression study (45 AD subjects, 54 controls) in which total RNA was isolated from whole peripheral blood samples and ALDH2 expression measured was conducted. In addition, a genetic association study (271 AD subjects, 492 controls) using genomic DNA from whole peripheral blood samples was conducted. Finally, a meta-analysis examined the relationship between ALDH2*2 frequency and the risk of LOAD. RESULTS: ALDH2 mRNA expression was significantly higher in LOAD than in controls, and also higher in men with LOAD than in women with LOAD (p = 0.043). The genotypes in the two classified groups and the allele frequency were significantly different between AD and control subjects. The meta-analysis showed a significant difference in the ALDH2*2 allele, with an increased AD risk (OR = 1.38; 95% CI = 1.02-1.85; p = 0.0348, I2 = 81.1%). CONCLUSION: There was a significant increase in blood ALDH2 expression, and a genetic association with ALDH2*2 in LOAD. ALDH2 may have significant roles in the pathogenesis of LOAD in the Asian population.

Distal Interphalangeal Joint Involvement May Be Associated with Disease Activity and Affected Joint Distribution in Rheumatoid Arthritis.

We investigated the relationship between distal interphalangeal (DIP) joint involvement and disease activity in 10,038 patients with adult-onset rheumatoid arthritis (RA). The affected joint distribution was investigated using the joint indices (JI) x, y, and z, corresponding to the upper and lower joints, and the predominance of large-joint involvement, respectively. DIP joint involvement (defined by the presence of tenderness and/or swelling in DIP joints) was present in 206 (2.1%) of 10,038 patients with RA. Patients with RA exhibiting DIP joint involvement were significantly younger, and more frequently women. DIP joint involvement was positively associated with Disease Activity Score-28 using C-reactive protein, and clinical variables related to high RA disease activity, including JIs x and y, and was negatively associated with JI z. JI x was significantly higher than JI y in RA patients with DIP joint involvement. An odds ratio analysis revealed that small-to-medium sized and upper-extremity joints ranked first, second, and fourth among the eight variables significantly associated with DIP joint involvement. The correlation coefficients revealed that small-sized and upper-extremity joints ranked first and second among the five significant variables. DIP joint involvement, albeit rare, is significantly associated with high RA disease activity with predominance of small-sized and upper-extremity joints.

Blood CDKN2A Gene Expression in Aging and Neurodegenerative Diseases.

BACKGROUND: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging. OBJECTIVE: This study assessed the utility of blood CDKN2A mRNA expression levels and methylation status as a potential biomarker for aging and the pathogenesis of Alzheimer's disease (AD). METHODS: The correlation between CDKN2A mRNA expression levels and age was examined in 45 healthy subjects, after which mRNA expression levels were compared among 46 AD patients, 20 mild cognitive impairment due to AD patients, 21 Parkinson's disease patients, 21 dementia with Lewy bodies patients, and 55 older healthy controls. The methylation rates of the second exon of the CDKN2A gene, known to influence its expression levels, was also examined. RESULTS: A significant correlation between CDKN2A mRNA expression levels and age was found (Spearman's rank correlation coefficient: r = 0.407, p = 0.005). CDKN2A mRNA expression levels in blood were significantly decreased in AD patients, although those of healthy controls were significantly increased with age. Further, only in AD patients were CDKN2A mRNA expression levels significantly and positively correlated with methylation rates. CONCLUSION: Although further research with a larger sample size is needed to elucidate the relationships between CDKN2A gene expression in blood and the development of other neurodegenerative diseases, CDKN2A mRNA expression in blood may be a biomarker for differentiating AD from normal aging and other neurodegenerative diseases.

PICALM mRNA Expression in the Blood of Patients with Neurodegenerative Diseases and Geriatric Depression.

BACKGROUND: Phosphatidylinositol-binding clathrin assembly protein (PICALM) is a validated genetic risk factor for late-onset Alzheimer's disease (AD) and is associated with other neurodegenerative diseases. However, PICALM expression in the blood of neurodegenerative diseases remains elusive. OBJECTIVE: This study aimed to assess the usefulness of PICALM expression levels in the blood of patients with AD, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and geriatric major depressive disorder (MDD) as a diagnostic biomarker. METHODS: In total, 45, 20, 21, and 19 patients with AD, PD, DLB, and geriatric MDD, respectively, and 54 healthy controls (HCs) were enrolled in the study. Expression data from Gene Expression Omnibus database (GSE97760), (GSE133347) and (GSE98793), (GSE48350), and (GSE144459) were used to validate the ability of biomarkers in the blood of patients with AD, PD, geriatric MDD, and a postmortem human AD brain and animal model of AD (3xTg-AD mouse), respectively. RESULTS: PICALM mRNA expression in human blood was significantly increased in patients with AD compared with that in HCs. PICALM mRNA expression and age were negatively correlated only in patients with AD. PICALM mRNA expression in human blood was significantly lower in patients with PD than in HCs. No changes in PICALM mRNA expression were found in patients with DLB and geriatric MDD. CONCLUSION: PICALM mRNA expression in blood was higher in patients with AD, but lower in patients with PD, which suggests that PICALM mRNA expression in human blood may be a useful biomarker for differentiating neurodegenerative diseases and geriatric MDD.

Clinical presentation of a neuropsychiatric lupus patient with symmetrical basal ganglia lesions containing cytotoxic oedema cores surrounded by vasogenic oedema.

Neuropsychiatric (NP) manifestations of systemic lupus erythematosus (SLE) are diverse, but involvement of basal ganglia is rare. We describe here a 28-year-old woman with NPSLE presenting aseptic meningitis accompanied by elevated interleukin-6 levels in the cerebrospinal fluid, who developed symmetrical basal ganglia lesions, containing a cytotoxic oedematous core, surrounded by vasogenic oedema upon magnetic resonance imaging. We were able to observe these lesions from a de novo appearance during the disease onset to its disappearance during immunosuppressive treatment. Reversibility upon immunosuppressive treatment indicated that autoimmune mediated mechanisms could contribute to the basal ganglia lesions in NPSLE.

Identifying Blood Transcriptome Biomarkers of Alzheimer's Disease Using Transgenic Mice.

The testing of pathological biomarkers of Alzheimer's disease (AD), such as amyloid beta and tau, is time-consuming, expensive, and invasive. Here, we used 3xTg-AD mice to identify and validate putative novel blood transcriptome biomarkers of AD that can potentially be identified in the blood of patients. mRNA was extracted from the blood and hippocampus of 3xTg-AD and control mice at different ages and used for microarray analysis. Network and functional analyses revealed that the differentially expressed genes between AD and control mice modulated the immune and neuroinflammation systems. Five novel gene transcripts (Cdkn2a, Apobec3, Magi2, Parp3, and Cass4) showed significant increases with age, and their expression in the blood was collated with that in the hippocampus only in AD mice. We further assessed previously identified candidate biomarker genes. The expression of Trem1 and Trem2 in both the blood and brain was significantly increased with age. Decreased Tomm40 and increased Pink1 mRNA levels were observed in the mouse blood. The changes in the expression of Snca and Apoe mRNA in the mouse blood and brain were similar to those found in human AD blood. Our results demonstrated that the immune and neuroinflammatory system is involved in the pathophysiologies of aging and AD and that the blood transcriptome might be useful as a biomarker of AD.

Development of Eosinophilic Temporal Arteritis and Digital Ischemia in a Patient with Hypereosinophilic Syndrome.

We describe a case of eosinophilic temporal arteritis in a 61-year-old woman with hypereosinophilic syndrome, who developed subcutaneous nodules in the temporal areas and digital cyanosis with small nodules on the sides of her fingers. Ultrasound revealed occlusion and corkscrew-like changes of the temporal and digital arteries, respectively. Temporal artery biopsy revealed eosinophilic vasculitis without giant cell formation. Angiography showed occlusion of the ulnar and digital arteries. Administration of low-dose corticosteroid improved the temporal artery swelling and digital cyanosis. More reports of similar cases are required to characterize this type of non-giant cell eosinophilic vasculitis that affects the peripheral arteries.

Influence of albumin leakage on glycated albumin in patients with type 2 diabetes undergoing hemodialysis.

Glycated albumin (GA) is recommended as a better glycemic indicator than HbA1c in patients undergoing hemodialysis, because the red blood cell lifespan is generally faster than that in normal subjects. However, GA can be also affected by protein loss in urine and hemodialysis fluid. Therefore, in this study, we investigated the effect of albumin leakage induced by hemodialysis on GA. Nine patients undergoing hemodialysis with a large or small amount of albumin leakage were observed for 9 months in a crossover manner. As a result, it was shown that albumin leakage could affect GA, but the effect was practically small considering the prescription of diabetic drugs. The correlations between HbA1c and blood glucose levels and between GA and blood glucose levels were similar in our study. In conclusion, GA was a reliable indicator, even with the change of hemodialysis modality. The influence of albumin leakage induced by hemodialysis on GA was negligible practically. We should recognize that the preferable glycemic indicator in patients undergoing hemodialysis depends on the hemoglobin and albumin metabolism of each patient.

Influence of seasonal changes on disease activity and distribution of affected joints in rheumatoid arthritis.

BACKGROUND: Previous studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan. METHODS: We investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance. RESULTS: Mean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index. CONCLUSIONS: RA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.

Intravenous Cyclophosphamide for Gastric Antral Vascular Ectasia Associated with Systemic Sclerosis Refractory to Endoscopic Treatment: A Case Report and Review of the Pertinent Literature.

Gastric antral vascular ectasia (GAVE) is a rare cause of chronic gastric hemorrhaging and iron deficiency anemia and is characterized by a distinctive endoscopic appearance. The main treatment of GAVE is endoscopic; however, medication is necessary in refractory cases. We herein report a 69-year-old woman with systemic sclerosis (SSc) who developed recurrent severe anemia after endoscopic treatment of GAVE that was successfully managed using intravenous cyclophosphamide (IVCY). The recurrence of GAVE after discontinuation of IVCY was successfully managed using a combination of IVCY and endoscopic treatment, without blood transfusion. Long-term IVCY may be indicated for refractory GAVE associated with SSc.

Prognostic value of left ventricular dyssynchrony evaluated by gated myocardial perfusion imaging in patients with chronic kidney disease and normal perfusion defect scores.

BACKGROUND: This study aimed to investigate whether indices of left ventricular (LV) dyssynchrony by gated myocardial perfusion SPECT (GMPS) could be useful to predict prognosis in chronic kidney disease (CKD) patients with normal perfusion defect scores. METHODS: One hundred and sixty-seven CKD patients with normal perfusion defect scores on adenosine-stress 201Tl GMPS and no previous history of overt heart diseases were enrolled. Phase standard deviation (PSD) and bandwidth (BW) were automatically calculated from GMPS. The major adverse cardiac events (MACEs) for a mean of 560 days were defined as sudden cardiac death, fatal arrhythmias, and acute coronary syndrome requiring urgent coronary revascularization. Patients were divided into two groups according to the presence or absence of MACEs. RESULTS: The MACEs occurred in 12 patients (7.1%). Patients who experienced MACEs showed significantly higher PSD and wider BW than those who did not. In the Kaplan-Meier event-free survival analysis, cardiac event rate was significantly higher in the high-PSD and wide-BW group (n = 81) than in the low-PSD and narrow-BW group (n = 71) (P = .002). The multivariate regression analysis revealed that the PSD was associated with MACEs (odds ratio 1.33, 95% confidence interval 1.05-1.69, P = .01). CONCLUSION: The LV dyssynchrony indices from GMPS may be novel prognostic predictors in CKD patients with normal perfusion defect scores.

Analysis of relationships between polymorphisms in the genes encoding the pentameric complex and neutralization of clinical cytomegalovirus isolates.

INTRODUCTION: As congenital cytomegalovirus (CMV) infection is one of the major causes of birth defects and developmental abnormalities, it is essential to develop vaccines and therapeutic antibodies against CMV. Clinical trials demonstrated that the subunit vaccine based on glycoprotein B, which had been believed to be the major target for neutralization, did not induce sufficient protective immunity. On the other hand, it has been reported that the immunization of animals with the Pentamer, the pentameric complex of gH/gL/UL128/UL130/UL131A, induced strong neutralizing antibodies. Here, we sought to clarify whether any polymorphic alterations present in the Pentamer of clinical isolates affect neutralization by anti-Pentamer antibodies. METHODS: Sequences of the genes encoding the Pentamer components of 25 Japanese clinical isolates were determined. Neutralization of infection by two seropositive sera and by anti-Pentamer serum was measured using a CMV reporter cell line based on ARPE-19. RESULTS: Polymorphisms of the amino acid sequence of UL128, UL130, and UL131A ORFs were limited and clustered into two major groups. The identified alterations, except UL128 I140T, were mapped outside of the reported regions recognized by neutralizing antibodies. Anti-Pentamer serum neutralized infection with all isolates to a similar degree and had no correlation with the polymorphic groups. CONCLUSIONS: Our findings indicate that Pentamer antigens prepared from Merlin Fix strain induce antibodies that neutralize infection with all isolates to a similar level and that anti-Pentamer antibodies neutralize CMV infection better than do human sera, suggesting that vaccines and therapeutic antibodies based on Pentamer as an antigen have some promise.