Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 139
Filtrar
1.
New Microbiol ; 47(1): 52-59, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700884

RESUMO

Monitoring Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection after transplantation is recommended to enable preemptive therapy. However, the most suitable sample type remains unclear. Patients who underwent hematopoietic stem cell or liver transplantation were included in this study. Viral loads in sequential whole-blood and plasma samples were retrospectively analyzed. EBV DNA was detected more frequently in whole blood (55%) than in plasma (18%). The detection rate of CMV DNA was similar between the two sample types. The correlation of viral loads between the two sample types were 0.515 and 0.688 for EBV and CMV, respectively. Among paired samples in which EBV DNA was detected in whole blood, the plasma EBV detection rate was significantly higher in patients who underwent hematopoietic stem cell transplantation than in those who underwent liver transplantation. The viral DNA load in whole blood and plasma showed similar trends. The EBV detection rate was higher in whole blood, and a high correlation was observed between CMV DNA loads and whole blood and plasma. These results indicate that whole blood is more sensitive for monitoring both EBV and CMV, whereas plasma is a potential alternative sample for monitoring CMV.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Carga Viral , Humanos , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/diagnóstico , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , DNA Viral/sangue , Adulto Jovem , Transplante de Células-Tronco Hematopoéticas , Idoso , Plasma/virologia , Transplante de Fígado , Adolescente
2.
J Ren Nutr ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38621434

RESUMO

OBJECTIVE: The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition in predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). METHODS: This single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and the incidence of all-cause mortality was evaluated using a multivariate Cox proportional hazards model. Malnutrition was defined as at least one phenotype (weight loss, low body mass index, or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). RESULTS: Multivariate Cox proportional hazards model showed that eGFR ≤29 (vs. eGFR: 60-89, adjusted hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.52-2.22), 30-59 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.20-1.64), and ≥90 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.14-1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18-1.62] and 2.18 [1.86-2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51-4.35) than in patients without malnutrition or eGFR 60-89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. CONCLUSION: Malnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

3.
J Clin Immunol ; 44(4): 103, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642164

RESUMO

Epstein-Barr virus (EBV) infection can lead to infectious mononucleosis (EBV-IM) and, more rarely, EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which is characterized by a life-threatening hyperinflammatory cytokine storm with immune dysregulation. Interferon-gamma (IFNγ) has been identified as a critical mediator for primary HLH; however, the detailed role of IFNγ and other cytokines in EBV-HLH is not fully understood. In this study, we used single-cell RNA sequencing to characterize the immune landscape of EBV-HLH and compared it with EBV-IM. Three pediatric patients with EBV-HLH with different backgrounds, one with X-linked lymphoproliferative syndrome type 1 (XLP1), two with chronic active EBV disease (CAEBV), and two patients with EBV-IM were enrolled. The TUBA1B + STMN1 + CD8 + T cell cluster, a responsive proliferating cluster with rich mRNA detection, was explicitly observed in EBV-IM, and the upregulation of SH2D1A-the gene responsible for XLP1-was localized in this cluster. This proliferative cluster was scarcely observed in EBV-HLH cases. In EBV-HLH cases with CAEBV, upregulation of LAG3 was observed in EBV-infected cells, which may be associated with an impaired response by CD8 + T cells. Additionally, genes involved in type I interferon (IFN) signaling were commonly upregulated in each cell fraction of EBV-HLH, and activation of type II IFN signaling was observed in CD4 + T cells, natural killer cells, and monocytes but not in CD8 + T cells in EBV-HLH. In conclusion, impaired responsive proliferation of CD8 + T cells and upregulation of type I IFN signaling were commonly observed in EBV-HLH cases, regardless of the patients' background, indicating the key features of EBV-HLH.


Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Transtornos Linfoproliferativos , Humanos , Criança , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Linfócitos T CD8-Positivos , Interferon gama/genética , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/complicações , Perfilação da Expressão Gênica
4.
Sci Rep ; 14(1): 5475, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443656

RESUMO

Congenital cytomegalovirus (cCMV) infection can damage the central nervous system in infants; however, its prognosis cannot be predicted from clinical evaluations at the time of birth. Urinary exosomes can be used to analyze neuronal damage in neuronal diseases. To investigate the extent of neuronal damage in patients with cCMV, exosomal miRNA expression in the urine was investigated in cCMV-infected infants and controls. Microarray analysis of miRNA was performed in a cohort of 30 infants, including 11 symptomatic cCMV (ScCMV), 7 asymptomatic cCMV (AScCMV), and one late-onset ScCMV cases, and 11 healthy controls (HC). Hierarchical clustering analysis revealed the distinct expression profile of ScCMV. The patient with late-onset ScCMV was grouped into the ScCMV cluster. Pathway enrichment analysis of the target mRNAs differed significantly between the ScCMV and HC groups; this analysis also revealed that pathways related to brain development were linked to upregulated pathways. Six miRNAs that significantly different between groups (ScCMV vs. HC and ScCMV vs. AScCMV) were selected for digital PCR in another cohort for further validation. Although these six miRNAs seemed insufficient for predicting ScCMV, expression profiles of urine exosomal miRNAs can reveal neurological damage in patients with ScCMV compared to those with AcCMV or healthy infants.


Assuntos
Líquidos Corporais , Infecções por Citomegalovirus , Exossomos , MicroRNAs , Criança , Lactente , Humanos , Exossomos/genética , MicroRNAs/genética , Sistema Nervoso Central , Infecções por Citomegalovirus/genética
5.
J Infect Chemother ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38552839

RESUMO

Salmonella enterica subspecies enterica serovar Choleraesuis (S. Choleraesuis) is a nontyphoidal Salmonella pathogen that causes swine paratyphoids. S. Choleraesuis is a zoonotic pathogen transmitted to humans via contaminated food and causes sepsis. Here, we report a rare case of pyelonephritis caused by S. Choleraesuis in a Japanese patient with a carcinoma of unknown primary origin. On the day of admission, the patient was diagnosed with pyelonephritis associated with ureteral stent obstruction. He had no history of raw pork consumption or gastrointestinal symptoms. Gram-negative rods were isolated from urine and blood cultures, identified as Salmonella enterica subsp. enterica using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The serological typing results were O7: -: 1 and 5; however, the serotypes could not be determined. The isolate was identified as S. Choleraesuis using multilocus sequence typing, nucleotide sequence analysis of the fliC gene, and biochemical examination. Four days after a 14-day course of intravenous piperacillin-tazobactam (9 g/day), the patient showed relapse of the condition. Subsequently, the patient was treated with intravenous ceftriaxone (2 g/day) and oral amoxicillin (1000 mg/day) for 14 days each; recurrence was not observed. This novel case of pyelonephritis with bacteremia was caused by S. Choleraesuis in Japan. Conventional testing methods could not identify the serotypes; however, the case highlights the importance of adopting advanced diagnostic techniques based on molecular biology to ensure accurate pathogen identification.

6.
Vaccine ; 42(11): 2927-2932, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38548526

RESUMO

BACKGROUND: The introduction of varicella vaccines into routine pediatric immunization programs has led to a considerable reduction in varicella incidence. However, there have been reports of varicella, herpes zoster, and meningitis caused by the vaccine strain of varicella-zoster virus (VZV), raising concerns. Establishing the relationship between the wild-type and vaccine strains in VZV infections among previously vaccinated individuals is crucial. Differences in the single nucleotide polymorphisms (SNPs) among vaccine strains can be utilized to identify the strain. In this study, we employed nanopore sequencing to identify VZV strains and analyzed clinical samples. METHODS: We retrospectively examined vesicle and cerebrospinal fluid samples from patients with VZV infections. One sample each of the wild-type and vaccine strains, previously identified using allelic discrimination real-time PCR and direct sequencing, served as controls. Ten samples with undetermined VZV strains were included. After DNA extraction, a long PCR targeting the VZV ORF62 region was executed. Nanopore sequencing identified SNPs, allowing discrimination between the vaccine and wild-type strains. RESULTS: Nanopore sequencing confirmed SNPs at previously reported sites (105,705, 106,262, 107,136, and 107,252), aiding in distinguishing between wild-type and vaccine strains. Among the ten unknown samples, nine were characterized as wild strains and one as a vaccine strain. Even in samples with low VZV DNA levels, nanopore sequencing was effective in strain identification. CONCLUSION: This study validates that nanopore sequencing is a reliable method for differentiating between the wild-type and vaccine strains of VZV. Its ability to produce long-read sequences is remarkable, allowing simultaneous confirmation of known SNPs and the detection of new mutations. Nanopore sequencing can serve as a valuable tool for the swift and precise identification of wild-type and vaccine strains and has potential applications in future VZV surveillance.


Assuntos
Varicela , Herpes Zoster , Sequenciamento por Nanoporos , Humanos , Criança , Herpesvirus Humano 3/genética , Estudos Retrospectivos , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase/métodos , Vacina contra Varicela/genética , Herpes Zoster/prevenção & controle , DNA Viral/genética
7.
Sci Rep ; 14(1): 7412, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548914

RESUMO

Peritoneal membrane dysfunction in peritoneal dialysis (PD) is primarily attributed to angiogenesis; however, the integrity of vascular endothelial cells can affect peritoneal permeability. Hyaluronan, a component of the endothelial glycocalyx, is reportedly involved in preventing proteinuria in the normal glomerulus. One hypothesis suggests that development of encapsulating peritoneal sclerosis (EPS) is triggered by protein leakage due to vascular endothelial injury. We therefore investigated the effect of hyaluronan in the glycocalyx on peritoneal permeability and disease conditions. After hyaluronidase-mediated degradation of hyaluronan on the endothelial cells of mice, macromolecules, including albumin and ß2 microglobulin, leaked into the dialysate. However, peritoneal transport of small solute molecules was not affected. Pathologically, hyaluronan expression was diminished; however, expression of vascular endothelial cadherin and heparan sulfate, a core protein of the glycocalyx, was preserved. Hyaluronan expression on endothelial cells was studied using 254 human peritoneal membrane samples. Hyaluronan expression decreased in patients undergoing long-term PD treatment and EPS patients treated with conventional solutions. Furthermore, the extent of hyaluronan loss correlated with the severity of vasculopathy. Hyaluronan on endothelial cells is involved in the peritoneal transport of macromolecules. Treatment strategies that preserve hyaluronan in the glycocalyx could prevent the leakage of macromolecules and subsequent related complications.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Humanos , Animais , Camundongos , Ácido Hialurônico/metabolismo , Células Endoteliais , Diálise Peritoneal/efeitos adversos , Peritônio/metabolismo , Transporte Biológico , Soluções para Diálise/metabolismo , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/metabolismo
8.
Sci Rep ; 14(1): 2869, 2024 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311620

RESUMO

The direct impact of antimicrobial stewardship programs (ASP) and infectious disease (ID) consultations on patients' clinical diagnoses remains unknown. We assessed their influence on improving the diagnostic accuracy of blood culture-positive inpatients at a Japanese cancer center. Our single-center, retrospective observational study was conducted from April 1, 2018 to March 31, 2022 to evaluate two phases: pre-intervention (notification of antimicrobials by the infection control team) and post-intervention (ASP implementation and ID consultation service establishment). There were 42,514 inpatients: 22,096 during the pre-intervention and 20,418 during the intervention periods. A total of 939 blood culture-positive episodes (pre-intervention, n = 434; post-intervention, n = 505) were analyzed. During the pre-intervention period, 28.1% of the patients had an unknown diagnosis, which decreased significantly to 1.2% post-intervention. Furthermore, hepatobiliary tract and other infections increased significantly post-intervention, and the mortality rate due to Staphylococcus aureus infection decreased from 28.6% pre-intervention to 10.4% post-intervention. The trend and level of the total number of culture specimens submitted per 1000 patient days for all culture specimens increased significantly post-intervention. Notably, the two-set rate of monthly blood cultures increased significantly. In conclusion, improving the overall diagnostic process with ASP and ID consultations at cancer centers could lead to the optimization of patient care.


Assuntos
Gestão de Antimicrobianos , Doenças Transmissíveis , Neoplasias , Humanos , Antibacterianos/uso terapêutico , Hemocultura , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/tratamento farmacológico , Encaminhamento e Consulta , Estudos Retrospectivos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico
9.
BMC Infect Dis ; 24(1): 180, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336644

RESUMO

BACKGROUND: Pseudomonas nitroreducens is a non-fermenting, gram-negative, rod-shaped bacterium commonly inhabiting soil, particularly soil contaminated with oil brine. To our knowledge, no cases of human infection with P. nitroreducens have been previously reported. Here, we present the first documented case of cholangitis caused by P. nitroreducens in a patient with bacteremia. CASE PRESENTATION: A 46-year-old Japanese man with an advanced pancreatic neuroendocrine tumor was hospitalized with fever and chills. Four days before admission, the patient developed right upper abdominal pain. Two days later, he also experienced fever and chills. Endoscopic retrograde cholangiopancreatography was performed on the day of admission, and the patient was diagnosed as having cholangitis associated with stent dysfunction. Gram-negative rods were isolated from blood cultures, but attempts to identify the bacteria using VITEK2 and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with VITEK MS ver. 4.7.1 (bioMérieux Japan Co. Ltd., Tokyo, Japan) were unsuccessful. Finally, the organism was identified as P. nitroreducens using MALDI-TOF MS with a MALDI Biotyper (Bruker Daltonics Co., Ltd., Billerica, MA, USA) and 16 S ribosomal RNA sequencing. Despite thorough interviews with the patient, he denied any exposure to contaminated soil. The patient was treated with intravenous cefepime and oral ciprofloxacin for 16 days based on susceptibility results, achieving a good therapeutic outcome. At the outpatient follow-up on day 28, the patient was in good general condition. CONCLUSIONS: This is the first reported human case of cholangitis with bloodstream infection caused by P. nitroreducens. This report provides clinicians with novel insights into the clinical manifestations and diagnostic methods necessary for the accurate diagnosis of P. nitroreducens, along with guidance on treatment.


Assuntos
Bacteriemia , Colangite , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Masculino , Humanos , Pessoa de Meia-Idade , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bactérias , Pseudomonas , Bactérias Aeróbias , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Colangite/tratamento farmacológico , Colangite/etiologia , Solo
10.
J Med Virol ; 96(2): e29450, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38304956

RESUMO

Primary Epstein-Barr virus (EBV) infection occasionally causes EBV-infectious mononucleosis (EBV-IM) and EBV-hemophagocytic lymphohistiocytosis (EBV-HLH). Although EBV-IM is mostly mild and self-limiting, EBV-HLH is a life-threatening disease characterized by excessive immune activation. However, the pathogenesis of EBV-HLH is yet to be fully elucidated. A diagnostic biomarker for EBV-HLH is desirable because early diagnosis and treatment are critical for the effective management of patients. In this study, the proteomic profiling of plasma was performed using liquid chromatography-mass spectrometry to identify proteins specific to EBV-IM and EBV-HLH. Furthermore, pathway analysis was performed for the proteins upregulated in patients with EBV-IM and EBV-HLH. Compared to healthy controls, 63 and 18 proteins were upregulated in patients with EBV-IM and EBV-HLH, respectively. Pathway and process enrichment analyses revealed that the complement system was the most enriched category of upregulated proteins in EBV-IM, whereas proteins related to immune effector processes were the most enriched in EBV-HLH. Among the 18 proteins upregulated in EBV-HLH, seven were exclusive to EBV-HLH. These specific proteins were associated with three pathways, and apolipoprotein E was commonly found in all the pathways. Proteomic analysis may provide new insights into the host response to EBV infection and the pathogenesis of EBV-related diseases.


Assuntos
Infecções por Vírus Epstein-Barr , Mononucleose Infecciosa , Linfo-Histiocitose Hemofagocítica , Humanos , Herpesvirus Humano 4/genética , Mononucleose Infecciosa/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Proteômica
11.
Sci Rep ; 13(1): 22697, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123633

RESUMO

We present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16-3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51-23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54-2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction.


Assuntos
Diálise Peritoneal , Peritonite , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico , Função Ventricular Esquerda , Estudos Retrospectivos , Japão/epidemiologia , Disfunção Ventricular Esquerda/etiologia , Diálise Peritoneal/efeitos adversos , Fatores de Risco , Peritonite/epidemiologia , Peritonite/etiologia
12.
J Pediatric Infect Dis Soc ; 12(10): 525-533, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37738566

RESUMO

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is a leading cause of nonhereditary neurological complications. When considering antiviral treatment, it is important to differentiate between symptomatic and asymptomatic patients. This study aimed to identify candidate plasma biomarkers for neurological complications of cCMV infection using proteomic analysis. METHODS: This study retrospectively enrolled five patients with symptomatic cCMV infection, four with asymptomatic cCMV infection with isolated sensorineural hearing loss (SNHL), and five with asymptomatic cCMV infection. The plasma samples were collected during neonatal period. The peptides were analyzed using liquid chromatography-mass spectrometry. The concentrations of differentially expressed proteins were validated using an enzyme-linked immunosorbent assay. RESULTS: A total of 456 proteins were identified and quantified. The levels of 80 proteins were significantly different between patients with and without cCMV-related symptoms including isolated SNHL. The levels of 31 proteins were significantly different between patients with and without neuroimaging abnormalities. The plasma concentrations of Fms-related receptor tyrosine kinase 4 in patients with cCMV-related symptoms were significantly higher than those in patients with asymptomatic cCMV infection. Moreover, plasma peptidylprolyl isomerase A levels were significantly higher in patients with neuroimaging abnormalities than in those without. CONCLUSIONS: Proteomic analysis of patients with cCMV infection showed that Fms-related receptor tyrosine kinase 4 and peptidylprolyl isomerase A could be novel diagnostic biomarkers for neurological complications of cCMV infection.


Assuntos
Infecções por Citomegalovirus , Perda Auditiva Neurossensorial , Recém-Nascido , Humanos , Lactente , Citomegalovirus , Estudos Retrospectivos , Proteômica , Infecções por Citomegalovirus/congênito , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Biomarcadores , Peptidilprolil Isomerase , Proteínas Tirosina Quinases
13.
Rheumatol Adv Pract ; 7(3): rkad073, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37692053

RESUMO

Objective: Previous studies have identified the predictors of severe infections in ANCA-associated vasculitis. However, lymphopenia has not been fully evaluated as a predictor of subsequent severe infections in patients with microscopic polyangiitis (MPA). The aim of this study was to assess the association between lymphopenia and severe infections requiring hospitalization after receiving immunosuppressive therapy for MPA. Methods: This single-centre retrospective cohort study included 130 consecutive patients with newly diagnosed MPA from Aichi Medical University Hospital, Japan, who received immunosuppressive therapy between March 2004 and December 2020. The relationship between lymphopenia and subsequent severe infections was assessed using time-dependent multivariate Cox proportional hazard models adjusted for clinically relevant factors. Results: During the follow-up period (median: 38 months; interquartile range: 15-63 months), 56 severe infectious episodes occurred in 51 patients (39.2%). Time-dependent multivariate Cox proportional hazard analyses identified older age [adjusted hazard ratio (HR) = 1.74 per 10 years, 95% CI: 1.13, 2.67], methylprednisolone pulse therapy (adjusted HR = 2.04, 95% CI: 1.03, 4.02), moderate lymphopenia (vs normal, adjusted HR = 7.17, 95% CI: 3.10, 16.6) and severe lymphopenia (vs normal, adjusted HR = 36.1, 95% CI: 11.8, 110.9) as significant predictors of severe infection. Conclusion: Lymphopenia is a predictor of subsequent severe infections in patients with MPA who receive immunosuppressive therapy. These results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.

15.
J Matern Fetal Neonatal Med ; 36(1): 2207113, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37150592

RESUMO

BACKGROUND: Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. OBJECTIVE: The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. METHODS: Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. RESULTS: Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. CONCLUSION: Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings.


Assuntos
Corioamnionite , Doenças do Recém-Nascido , Síndrome do Desconforto Respiratório do Recém-Nascido , Infecções por Ureaplasma , Gravidez , Recém-Nascido , Feminino , Humanos , Corioamnionite/microbiologia , Ureaplasma/genética , Antibacterianos/uso terapêutico , Doenças do Recém-Nascido/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Líquido Amniótico/microbiologia , Infecções por Ureaplasma/tratamento farmacológico
16.
Clin Nutr ESPEN ; 55: 167-173, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37202041

RESUMO

BACKGROUND & AIMS: Cardiovascular disease (CVD) is a significant cause of mortality and rising healthcare costs, involving numerous chronic and nutritional risk. Although several studies have reported that malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria is associated with mortality in patients with CVD, they have not evaluated this association in terms of malnutrition severity (moderate or severe). Furthermore, the relationship between malnutrition combined with renal dysfunction, a risk factor for death in CVD patients, and mortality has not been previously evaluated. Thus, we aimed to assess the association between malnutrition severity and mortality, as well as malnutrition status stratified by kidney function and mortality, in patients hospitalized due to CVD events. METHODS: This single-centre, retrospective cohort study included 621 patients with CVD aged ≥18 years admitted to Aichi Medical University between 2019 and 2020. The relationship between nutritional status based on the GLIM criteria (without malnutrition, moderate malnutrition, or severe malnutrition) and the incidence of all-cause mortality was evaluated by multivariable Cox proportional hazards models. RESULTS: Patients with moderate and severe malnutrition were significantly more prone to mortality than those without malnutrition (adjusted hazard ratio [HR] of patients without, with moderate, and with severe malnutrition: 1.00 [reference], 1.94 [1.12-3.35], and 2.63 [1.53-4.50], respectively). Furthermore, we found the highest all-cause mortality rate in patients with malnutrition and a lower estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m2) (adjusted HR, 10.1; confidence interval, 3.90-26.4) than in patients without malnutrition and normal eGFR (eGFR ≥60 mL/min/1.73 m2). CONCLUSIONS: The present study indicated that malnutrition according to the GLIM criteria was associated with increased all-cause mortality in patients with CVD, and malnutrition associated with kidney dysfunction was associated with a higher risk of mortality. These findings provide clinically relevant information to identify high mortality risk in patients with CVD and highlight the need for giving careful attention to malnutrition with kidney dysfunction among patients with CVD.


Assuntos
Doenças Cardiovasculares , Desnutrição , Humanos , Adolescente , Adulto , Doenças Cardiovasculares/complicações , Liderança , Estudos Retrospectivos , Desnutrição/complicações , Rim
17.
Int J Mol Sci ; 24(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37176037

RESUMO

High salt intake is a primary cause of over-hydration in chronic kidney disease (CKD) patients. Inflammatory markers are predictors of CKD mortality; however, the pathogenesis of inflammation remains unclear. Sodium storage in tissues has recently emerged as an issue of concern. The binding of sodium to tissue glycosaminoglycans and its subsequent release regulates local tonicity. Many cell types express tonicity-responsive enhancer-binding protein (TonEBP), which is activated in a tonicity-dependent or tonicity-independent manner. Macrophage infiltration was observed in the heart, peritoneal wall, and para-aortic tissues in salt-loading subtotal nephrectomized mice, whereas macrophages were not prominent in tap water-loaded subtotal nephrectomized mice. TonEBP was increased in the heart and peritoneal wall, leading to the upregulation of inflammatory mediators associated with cardiac fibrosis and peritoneal membrane dysfunction, respectively. Reducing salt loading by a diuretic treatment or changing to tap water attenuated macrophage infiltration, TonEBP expression, and inflammatory marker expression. The role of TonEBP may be crucial during the cardiac fibrosis and peritoneal deterioration processes induced by sodium overload. Anti-interleukin-6 therapy improved cardiac inflammation and fibrosis and peritoneal membrane dysfunction. Further studies are necessary to establish a strategy to regulate organ dysfunction induced by TonEBP activation in CKD patients.


Assuntos
Insuficiência Renal Crônica , Sódio , Camundongos , Animais , Inflamação/metabolismo , Fatores de Transcrição NFATC/metabolismo , Cloreto de Sódio , Cloreto de Sódio na Dieta/efeitos adversos , Água , Fibrose
18.
J Hum Genet ; 68(10): 671-680, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37217688

RESUMO

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.


Assuntos
Fibrose Cística , Humanos , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Mutação , Japão/epidemiologia , Genótipo
19.
Nutrients ; 15(7)2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37049433

RESUMO

Previous cohort studies have reported conflicting associations between alcohol consumption and chronic kidney disease, characterized by proteinuria and low glomerular filtration rate (GFR). This systematic review, which included 14,634,940 participants from 11 cohort studies, assessed a dose-dependent association of alcohol consumption and incidence of proteinuria and low estimated GFR (eGFR) of <60 mL/min/1.73 m2. Compared with non-drinkers, the incidence of proteinuria was lower in drinkers with alcohol consumption of ≤12.0 g/day (relative risk 0.87 [95% confidence interval 0.83, 0.92]), but higher in drinkers with alcohol consumption of 36.1-60.0 g/day (1.09 [1.03, 1.15]), suggesting a J-shaped association between alcohol consumption and the incidence of proteinuria. Incidence of low eGFR was lower in drinkers with alcohol consumption of ≤12.0 and 12.1-36.0 than in non-drinkers (≤12.0, 12.1-36.0, and 36.1-60.0 g/day: 0.93 [0.90, 0.95], 0.82 [0.78, 0.86], and 0.89 [0.77, 1.03], respectively), suggesting that drinkers were at lower risk of low eGFR. In conclusion, compared with non-drinkers, mild drinkers were at lower risk of proteinuria and low eGFR, whereas heavy drinkers had a higher risk of proteinuria but a lower risk of low eGFR. The clinical impact of high alcohol consumption should be assessed in well-designed studies.


Assuntos
Consumo de Bebidas Alcoólicas , Proteinúria , Humanos , Taxa de Filtração Glomerular , Incidência , Fatores de Risco , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Coortes , Proteinúria/epidemiologia , Proteinúria/etiologia
20.
Lab Invest ; 103(4): 100050, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870292

RESUMO

Long-term peritoneal dialysis (PD) is often associated with peritoneal dysfunction leading to withdrawal from PD. The characteristic pathologic features of peritoneal dysfunction are widely attributed to peritoneal fibrosis and angiogenesis. The detailed mechanisms remain unclear, and treatment targets in clinical settings have yet to be identified. We investigated transglutaminase 2 (TG2) as a possible novel therapeutic target for peritoneal injury. TG2 and fibrosis, inflammation, and angiogenesis were investigated in a chlorhexidine gluconate (CG)-induced model of peritoneal inflammation and fibrosis, representing a noninfectious model of PD-related peritonitis. Transforming growth factor (TGF)-ß type I receptor (TGFßR-I) inhibitor and TG2-knockout mice were used for TGF-ß and TG2 inhibition studies, respectively. Double immunostaining was performed to identify cells expressing TG2 and endothelial-mesenchymal transition (EndMT). In the rat CG model of peritoneal fibrosis, in situ TG2 activity and protein expression increased during the development of peritoneal fibrosis, as well as increases in peritoneal thickness and numbers of blood vessels and macrophages. TGFßR-I inhibitor suppressed TG2 activity and protein expression, as well as peritoneal fibrosis and angiogenesis. TGF-ß1 expression, peritoneal fibrosis, and angiogenesis were suppressed in TG2-knockout mice. TG2 activity was detected by α-smooth muscle actin-positive myofibroblasts, CD31-positive endothelial cells, and ED-1-positive macrophages. CD31-positive endothelial cells in the CG model were α-smooth muscle actin-positive, vimentin-positive, and vascular endothelial-cadherin-negative, suggesting EndMT. In the CG model, EndMT was suppressed in TG2-knockout mice. TG2 was involved in the interactive regulation of TGF-ß. As inhibition of TG2 reduced peritoneal fibrosis, angiogenesis, and inflammation associated with TGF-ß and vascular endothelial growth factor-A suppression, TG2 may provide a new therapeutic target for ameliorating peritoneal injuries in PD.


Assuntos
Fibrose Peritoneal , Camundongos , Ratos , Animais , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/prevenção & controle , Fibrose Peritoneal/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína 2 Glutamina gama-Glutamiltransferase , Actinas/metabolismo , Clorexidina/efeitos adversos , Clorexidina/metabolismo , Células Endoteliais/metabolismo , Peritônio/patologia , Fator de Crescimento Transformador beta1/metabolismo , Fibrose , Inflamação/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Camundongos Knockout
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA