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1.
Acta Med Okayama ; 78(1): 63-70, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38419316

RESUMO

The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma.


Assuntos
Antineoplásicos , Carcinoma , Quinolinas , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Antineoplásicos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico
2.
J Orthop Sci ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39013755

RESUMO

BACKGROUND: The management of degenerative cervical myelopathy (DCM), which often impairs lower extremity function and increases the risk of falls, is gaining recognition for its importance in an aging society. Despite the significant overlap between frailty and locomotive syndrome (LS) in older adults, their interaction in older DCM patients remains unclear. We aimed to determine the characteristics of older DCM patients with frailty, focusing on the association between frailty and LS. METHODS: We retrospectively examined the clinical records and imaging data of consecutive patients aged 65 years and above who underwent surgery for DCM at a single facility. Frailty and LS stage were diagnosed using the modified frailty index-11 and the 25-question Geriatric Locomotive Function Scale (GLFS-25), respectively. RESULTS: A total of 114 subjects were analyzed, among whom approximately 30% were diagnosed with frailty. DCM patients with frailty had significantly worse Japanese Orthopaedic Association Cervical Myelopathy Assessment Questionnaire (JOACMEQ) and GLFS-25 scores at baseline than did those without frailty. Moreover, DCM patients with frailty had significantly more advanced LS stage at baseline than did those without frailty. Meanwhile, no significant difference in the improvement in JOACMEQ and GLFS-25 scores were observed between those with and without frailty after surgery. More precisely, DCM patients with frailty experienced better improvement in lower extremity function based on the JOACMEQ than did those without frailty. CONCLUSIONS: Our results demonstrated that older DCM patients had favorable outcomes following surgery regardless of frailty. Despite the significant association between frailty and LS in DCM patients, frailty did not negatively impact the improvement in LS in older DCM patients. These findings provide valuable information for both older DCM patients and their attending physicians that would help guide decisions about cervical spine surgery for DCM.

3.
BMC Neurol ; 23(1): 28, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653748

RESUMO

BACKGROUND: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused. METHODS: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized. RESULTS: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values. CONCLUSION: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS.


Assuntos
Convulsões Febris , Criança , Humanos , Lactente , Convulsões Febris/diagnóstico , Convulsões Febris/epidemiologia , Estudos Retrospectivos , Japão/epidemiologia , Convulsões/diagnóstico , Convulsões/epidemiologia
4.
BMC Geriatr ; 23(1): 169, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36964497

RESUMO

BACKGROUND: Polypharmacy is a growing public health problem occurring in all healthcare settings worldwide. Elderly patients with lumbar spinal canal stenosis (LSS) who manifest low back and neuropathic pain and have a high frequency of comorbidity are predicted to take many drugs. However, no studies have reported polypharmacy in elderly patients with LSS. Thus, we aimed to review the polypharmacy among elderly LSS patients with elective surgeries and examine how the surgical treatment reduces the polypharmacy. METHODS: We retrospectively enrolled all the patients aged ≥ 65 years who underwent spinal surgery for LSS between April 2020 and March 2021. The prescribed drugs of participants were directly checked by pharmacists in the outpatient department preoperatively and 6-month and 1-year postoperatively. The baseline characteristics were collected beside the patient-based outcomes including Roland-Morris Disability Questionnaire, Zurich Claudication Questionnaire, and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). The cutoff number of drugs for polypharmacy was defined as 6. The prescription drugs were divided into 9 categories: drugs for neuropsychiatric, cardiovascular, respiratory, digestive, endocrine metabolic, and urinary renal diseases; blood products; pain relief medication; and others. RESULTS: A total of 102 cases were finally analyzed, with a follow-up rate of 78.0%. Of the participants, the preoperative polypharmacy prevalence was 66.7%. The number of drugs 6-month and 1-year postoperatively was significantly less than the preoperative one. The proportions of polypharmacy at 6 months and 1 year after surgery significantly decreased to 57.8% and 55.9%, respectively. When the prescribed drugs were divided into 9 categories, the number of drugs for pain relief and digestive diseases was significantly reduced after surgery. The multi-variable analysis revealed that a higher score in the psychological disorder of JOABPEQ was associated with 3 or more drugs decreased 1-year postoperatively (OR, 2.5; 95% CI: 1.0-6.1). CONCLUSION: Polypharmacy prevalence was high among elderly LSS patients indicated for lumbar spinal surgery. Additionally, our data showed that lumbar spinal surgery was effective in reducing polypharmacy among elderly LSS patients. Finally, the multi-variable analysis indicated that better psychological condition was associated with the reduction of prescribed drugs after lumbar spinal surgery.


Assuntos
Descompressão Cirúrgica , Estenose Espinal , Idoso , Humanos , Estudos Retrospectivos , Descompressão Cirúrgica/efeitos adversos , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Polimedicação , Vértebras Lombares/cirurgia , Estenose Espinal/tratamento farmacológico , Estenose Espinal/epidemiologia , Estenose Espinal/cirurgia , Canal Medular/cirurgia , Dor/etiologia , Resultado do Tratamento
5.
Eur Spine J ; 32(12): 4153-4161, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37837558

RESUMO

PURPOSE: It is still unclear how lumbar spinal surgery affects the lipid metabolism of patients with lumbar spinal disorders (LSDs) such as lumbar spinal canal stenosis and lumbar disk herniation. The present study aimed to assess the impact of lumbar spinal surgery on lipid metabolism in patients with LSDs and clarify the factors associated with changes in visceral fat (VF) accumulation before and after lumbar spinal surgery. METHODS: Consecutive patients with lumbar spinal surgery for LSDs were prospectively included. Abdominal computed tomography images and blood examination of the participants were evaluated before surgery and at 6 months and 1 year after surgery. The cross-sectional VF area (VFA) was measured at the level of the navel using computed tomography images. Blood examination items included triglycerides and high-density lipoprotein (HDL). RESULTS: The study enrolled a total of 138 patients. Female patients with LSDs had significantly increased VFA and serum triglyceride levels after lumbar spinal surgery. On multivariable analysis, the group with > 100 cm2 of preoperative VFA and a postoperative decrease in VFA had a significantly worse preoperative walking ability based on the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (relative risk 2.1; 95% confidence intervals 1.1-4.1). CONCLUSIONS: The present study demonstrated that patients with LSDs did not necessarily improve their lipid metabolism after lumbar spinal surgery. Instead, female patients with LSDs had significantly deteriorated lipid metabolism after lumbar spinal surgery. Finally, a worse preoperative walking ability was associated with the improvement in excess VF accumulation after lumbar spinal surgery.


Assuntos
Descompressão Cirúrgica , Estenose Espinal , Feminino , Humanos , Estudos Transversais , Descompressão Cirúrgica/métodos , Metabolismo dos Lipídeos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estenose Espinal/complicações , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Resultado do Tratamento , Estudos Prospectivos
6.
J Orthop Sci ; 28(3): 669-676, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35123844

RESUMO

BACKGROUND: Patients with lumbar spinal canal stenosis (LSS) often have peripheral arterial disease and aortic disease based on atherosclerosis. Oxidized LDL, which is clinically involved in the development of atherosclerosis, may also influence LF hypertrophy, but the function of the oxidized low-density lipoprotein (LDL)/lectin-type oxidized LDL receptor 1 (LOX-1) system in LF hypertrophy is unknown. We aimed to elucidate the potential involvement of oxidized LDL/LOX-1 system in ligamentum flavum (LF) hypertrophy. METHODS: A total of 43 samples were collected from LF tissues of the patients who underwent posterior lumbar spinal surgery. Immunohistochemistry for LOX-1 was performed using human LF samples. We treated the cells in vitro with inflammatory cytokines TNF-α and IL-1ß, oxidized LDL, and simvastatin. The expressions of LOX-1 and LF hypertrophy markers including type I collagen, Type III collagen, and COX-2 were assessed by real-time RT-PCR and immunocytochemistry. Phosphorylation of MAPKs and NF-κb was evaluated by Western blot after treatment with TNF-α, IL-1ß, oxidized LDL, and simvastatin. RESULTS: A significant weak correlation was observed between the number of positive cells of LOX-1 and cross-sectional area of LF on preoperative axial magnetic resonance imaging. In functional analysis, simvastatin treatment neutralized the oxidized LDL-mediated induction of mRNA expressions of LF hypertrophy markers. Western blot analysis showed that oxidized LDL as well as TNF-α and IL-1ß activated the signaling of MAPKs and NF-κb in LF cells, and that simvastatin treatment reduced the phosphorylation of all signaling. The TNF-α and IL-1ß treatments increased both mRNA and protein expression of LOX-1 in LF cells. CONCLUSION: We found a link between the oxidized LDL/LOX-1 system and LF hypertrophy. In addition, our in vitro analysis indicate that oxidized LDL may affect LF hypertrophy through signaling of MAPKs. Our results suggest that the oxidized LDL/LOX-1 system may be a potential therapeutic target for LSS.


Assuntos
Ligamento Amarelo , Estenose Espinal , Humanos , NF-kappa B/metabolismo , Ligamento Amarelo/patologia , Fator de Necrose Tumoral alfa/metabolismo , Lipoproteínas LDL/metabolismo , Estenose Espinal/patologia , Hipertrofia/patologia , RNA Mensageiro/metabolismo , Receptores Depuradores Classe E/metabolismo , Vértebras Lombares/patologia
7.
Medicina (Kaunas) ; 59(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36676735

RESUMO

Background and Objectives: Modic type 1 is known to be associated with lower back pain (LBP), but at present, a treatment has not been fully established. Meanwhile, platelet-rich plasma (PRP) has been used for tissue regeneration and repair in the clinical setting. There is no clinical PRP injection trial for the intervertebral disc of LBP patients with Modic type 1. Thus, this study aimed to verify PRP injection safety and efficacy in LBP patients with Modic type 1. As a preliminary experiment, two LBP cases with Modic type 1 are presented. Materials and Methods: PRP was administered intradiscally to two LBP patients with Modic type 1. PRP was obtained from the patients' anticoagulated blood. Primary endpoints were physical condition, laboratory data, and X-ray for safety evaluation. Secondary endpoints were pain scores using the visual analog scale (VAS), the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ) to evaluate PRP efficacy. The observation period was 24 weeks after the PRP injection. In addition, changes in Modic type 1 using MRI were evaluated. Results: This study assessed two LBP patients with Modic type 1. There were no adverse events in physical condition, laboratory data, or lumbar X-rays after injection. Follow-up MRI showed a decrease of high signal intensity on T2WI compared to before PRP administration. The pain scores tended to improve after the injection. Conclusions: PRP injection into the intervertebral disc of LBP patients with Modic type 1 might be safe and effective. This analysis will be continued as a prospective study to establish the efficacy.


Assuntos
Deslocamento do Disco Intervertebral , Disco Intervertebral , Dor Lombar , Plasma Rico em Plaquetas , Humanos , Dor Lombar/terapia , Dor Lombar/complicações , Estudos Prospectivos , Deslocamento do Disco Intervertebral/complicações , Imageamento por Ressonância Magnética , Vértebras Lombares , Resultado do Tratamento
8.
Medicina (Kaunas) ; 59(9)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37763688

RESUMO

Background and Objectives: There are several advantages of using lateral lumbar interbody fusion (LLIF) for correction surgeries for adult spinal deformity (ASD); however, we currently have unresolved new issues, including occasional anterior longitudinal ligament (ALL) rupture during the posterior correction procedure. When LLIF was initially introduced, only less lordotic cages were available and ALL rupture was more frequently experienced compared with later periods when more lordotic cages were available. We performed finite element analysis (FEA) regarding the mechanism of ALL rupture during a posterior correction procedure. Methods: A spring (which mimics ALL) was introduced at the location of ALL in the FEA and an LLIF cage with two different lordotic angles, 6 and 12 degrees (6DC/12DC), was employed. To assess the extent of burden on the ALL, the extension length of the spring during the correction procedure was measured and the location of the rotation center was examined. Results: We observed a significantly higher degree of length extension of the spring during the correction procedure in the FEA model with 6DC compared with that of 12DC. We also observed that the location of the rotation center was shifted posteriorly in the FEA model with 6DC compared with that of 12DC. Conclusions: It is considered that the posterior and rostral edge of the less lordotic angle cage became a hinge, and the longer lever arm increased the burden on ALL as the principle of leverage. It is important to use an LLIF cage with a sufficient lordotic angle, that is compatible with the degree of posterior osteotomy in ASD correction.

9.
J Infect Chemother ; 28(1): 35-40, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34620534

RESUMO

INTRODUCTION: Previous studies reported a dramatic decline in the incidence of varicella and varicella-related deaths after implementing universal varicella vaccination (VarV). Although previous studies reported the effectiveness and economic impact of VarV, they were unknown in the emergency department (ED) setting. METHODS: To determine the effectiveness and economic impact of VarV in the ED, Kobe, Japan, we retrospectively reviewed the clinical database of consecutive patients younger than 16 years presenting to our primary ED from 2011 to 2019. RESULTS: Of the 265,191 children presenting to our ED, 3,092 patients were clinically diagnosed with varicella. The number of patients with varicella was approximately 500 annually, before introducing the universal two-dose VarV for children aged 1 to <3 years in October 2014, in the Japanese national immunization program, and decreased to approximately 200 in 2019. The number of patients with varicella younger than 1 year (ineligible for the vaccination) also decreased. Regarding the economic impact, the medical cost in our ED reduced after the introduction of VarV was JPY 4.1 million (US$ 40,049) annually. From the central data, approximately 95% of children were vaccinated after October 2014; however, a relatively large percentage of infected unvaccinated children (59.0%) presented to ED in this study. After the implementation of the universal VarV, infection was mainly observed in older children (i.e., the unvaccinated generation). CONCLUSIONS: Our data showed the effectiveness and economic impact of VarV in the ED setting. Additionally, our data suggested that the public vaccination program should include older unvaccinated children and other unvaccinated individuals.


Assuntos
Varicela , Varicela/epidemiologia , Varicela/prevenção & controle , Vacina contra Varicela , Criança , Serviço Hospitalar de Emergência , Humanos , Japão/epidemiologia , Estudos Retrospectivos , Vacinação
10.
Cytokine ; 137: 155324, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33032108

RESUMO

Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1ß (IL-1ß), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.


Assuntos
Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Encefalopatias/sangue , Quimiocinas/sangue , Citocinas/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Choque Hemorrágico/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Encefalopatias/diagnóstico , Encefalopatias/terapia , Quimiocina CCL2/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/terapia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
11.
Pediatr Int ; 63(8): 918-922, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33260258

RESUMO

BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene. In 1984, Scheinberg and Sternlieb estimated the prevalence of WD to be 1:30 000. However, recent epidemiological studies have reported increasing prevalence rates in different populations. The carrier frequency of ATP7B variants and the prevalence of WD in the Japanese population have not been reported using multiple databases. METHODS: Multiple public databases were used. First, we included mutations in the ATP7B gene that were registered in the Human Gene Mutation Database (HGMD) Professional, where 885 ATP7B variants were identified as pathogenic. Next, we investigated the allele frequencies of these 885 variants in Japanese individuals using the Human Genetic Variation Database (HGVD) and the Japanese Multi Omics Reference Panel (jMorp). RESULTS: Of the 885 variants of ATP7B, 7 and 12 missense and nonsense variants, zero and three splicing variants, and zero and two small deletions were found in the HGVD and in jMorp, respectively. The total allele frequencies of the ATP7B mutations were 0.011 in the HGVD and 0.014 in the jMorp. According to these data, the carrier frequencies were 0.022 (2.2%) and 0.028 (2.8%), respectively, and patient frequencies were 0.000121 (1.21/10 000 individuals) and 0.000196 (1.96/10 000 individuals), respectively. CONCLUSIONS: This is the first study to report the carrier frequency of ATP7B variants and the prevalence of WD in Japan using multiple databases. The calculated prevalence of WD was comparatively higher than that of previous reports, indicating previous underdiagnosis or the existence of less severe phenotypes.


Assuntos
Degeneração Hepatolenticular , ATPases Transportadoras de Cobre/genética , Frequência do Gene , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/genética , Humanos , Japão/epidemiologia , Mutação , Prevalência
12.
J Orthop Sci ; 26(4): 560-565, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32753253

RESUMO

BACKGROUND: Although several causes of ligamentum flavum (LF) hypertrophy have been identified, the pathomechanisms underlying LF hypertrophy are not fully understood. Because collagen fibers are essential for the maintenance of LF tissues, characterization of the collagen composition of hypertrophied LF may help to elucidate the pathology of lumbar spinal canal stenosis (LCS). This study aimed to determine the association between the collagen composition and LF hypertrophy. METHODS: LF tissues were collected from 23 patients who underwent spinal decompression surgery for lumbar disorders. The cross-sectional area of LF was measured using the axial images of lumbar MRI. The expression of each collagen in human surgical samples was evaluated by real-time RT-PCR and immunohistochemical analysis. To investigate the impact of inflammatory cytokines on the expression of each collagen, we treated primary human LF cells with TNF-α or IL-1ß. RESULTS: Real-time RT-PCR analysis and immunohistochemistry showed that of the 28 types of collagen, collagen type I, III, V, VI, VIII were highly expressed regardless of LF hypertrophy. In addition, we found the moderate correlation between the cross-sectional area of LF and the mRNA expression level of collagen type I, III, and VI. In vitro analysis showed that the mRNA expression of collagen type I, III, V, VI, and VIII was up-regulated by treatment with TNF-α and with IL-1ß. CONCLUSION: Our results suggested that collagen type I, III, V, VI, and VIII were the main components of the LF extracellular matrix and that collagen type I, III, and VI may serve as useful markers of LF hypertrophy. These findings may contribute to the future development of diagnostic and treatment modalities for LF hypertrophy and even LCS.


Assuntos
Ligamento Amarelo , Estenose Espinal , Colágeno , Constrição Patológica , Humanos , Hipertrofia , Ligamento Amarelo/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Canal Medular , Estenose Espinal/cirurgia
13.
Kidney Int ; 98(6): 1605-1614, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32712167

RESUMO

Early kidney failure in the hereditary type IV collagen disease, Alport syndrome, can be delayed by renin-angiotensin inhibitors. However, whether all patients and all different genotypes respond equally well to this kidney-protective therapy remains unclear. Here, we performed a retrospective study on 430 patients with male X-linked Alport syndrome to examine the relationships among kidney prognosis, genotype, and treatment effect in a large cohort of Japanese patients. We analyzed the clinical features, genotype-phenotype correlation, and kidney survival period for patients treated with or without renin-angiotensin inhibitors. As a result, the median kidney survival period of patients in this cohort was found to be at 35 years with a strong genotype-phenotype correlation. The median age at the onset of end stage kidney disease (ESKD) significantly differed between patients treated with and without renin-angiotensin inhibitors (over 50 years versus 28 years, respectively). Moreover, these drugs delayed the onset of ESKD in patients with truncating variants for 12 years, extending the median age from 16 years to 28 years. Thus, our results confirmed a strong genotype-phenotype correlation in patients with male X-linked Alport syndrome. Additionally, it was suggested that renin-angiotensin inhibitors could significantly delay ESKD progression. Despite these therapies, patients with truncating variants developed ESKD at the median age of 28 years.


Assuntos
Angiotensinas , Nefrite Hereditária , Preparações Farmacêuticas , Colágeno Tipo IV/genética , Estudos de Associação Genética , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/tratamento farmacológico , Nefrite Hereditária/genética , Estudos Retrospectivos
14.
J Hum Genet ; 65(4): 355-362, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31959872

RESUMO

Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete negativity for laminin ß2 expression on glomerular basement membrane (GBM). In contrast, missense variants outside the laminin N-terminal (LN) domain in LAMB2 lead to milder phenotypes. However, we experienced cases not showing these typical genotype-phenotype correlations. In this paper, we report six PS patients: four with mild phenotypes and two with severe phenotypes. We conducted molecular studies including protein expression and transcript analyses. The results revealed that three of the four cases with milder phenotypes had missense variants located outside the LN domain and one of the two severe PS cases had a homozygous missense variant located in the LN domain; these variant positions could explain their phenotypes. However, one mild case possessed a splicing site variant (c.3797 + 5G>A) that should be associated with a severe phenotype. Upon transcript analysis, this variant generated some differently sized transcripts, including completely normal transcript, which could have conferred the milder phenotype. In one severe case, we detected the single-nucleotide substitution of c.4616G>A located outside the LN domain, which should be associated with a milder phenotype. However, we detected aberrant splicing caused by the creation of a novel splice site by this single-base substitution. These are novel mechanisms leading to an atypical genotype-phenotype correlation. In addition, all four cases with milder phenotypes showed laminin ß2 expression on GBM. We identified novel mechanisms leading to atypical genotype-phenotype correlation in PS.


Assuntos
Membrana Basal Glomerular , Laminina , Mutação de Sentido Incorreto , Síndromes Miastênicas Congênitas , Síndrome Nefrótica , Distúrbios Pupilares , Splicing de RNA , Substituição de Aminoácidos , Criança , Pré-Escolar , Feminino , Membrana Basal Glomerular/metabolismo , Membrana Basal Glomerular/patologia , Humanos , Lactente , Laminina/biossíntese , Laminina/genética , Masculino , Síndromes Miastênicas Congênitas/genética , Síndromes Miastênicas Congênitas/metabolismo , Síndromes Miastênicas Congênitas/patologia , Síndrome Nefrótica/genética , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Domínios Proteicos , Distúrbios Pupilares/genética , Distúrbios Pupilares/metabolismo , Distúrbios Pupilares/patologia
17.
J Pediatr Hematol Oncol ; 39(2): e92-e96, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27879539

RESUMO

Central nervous system involvement in hemophagocytic lymphohistiocytosis (HLH) is associated with a poor outcome. For such patients, it is unknown whether more aggressive therapies, such as intrathecal methotrexate or hydrocortisone, are inevitably required. We present a very rare case of 3-year-old Japanese girl who developed mild encephalitis/encephalopathy with a reversible splenial lesion, accompanied by Epstein-Barr virus-associated HLH, and review previous similar reports. Our case and previous reports suggest that mild encephalitis/encephalopathy with a reversible splenial lesion accompanied by Epstein-Barr virus-associated HLH has a relatively good prognosis, even in the absence of intrathecal treatments.


Assuntos
Corpo Caloso/patologia , Encefalite/etiologia , Infecções por Vírus Epstein-Barr/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Medula Óssea/patologia , Corpo Caloso/diagnóstico por imagem , Ciclosporina/uso terapêutico , Delírio/etiologia , Dexametasona/análogos & derivados , Dexametasona/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Quimioterapia Combinada , Encefalite/diagnóstico por imagem , Encefalite/tratamento farmacológico , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Etoposídeo/uso terapêutico , Humanos , Hiponatremia/etiologia , Linfo-Histiocitose Hemofagocítica/diagnóstico por imagem , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/virologia , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Neuroimagem , Prognóstico , Pulsoterapia
18.
Pediatr Int ; 58(7): 622-4, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26892675

RESUMO

The optimal timing of decompressive craniectomy in pediatric patients after presentation with malignant middle cerebral artery infarction is unknown. We report herein the case of a previously healthy 6-year-old Japanese girl who had good outcome after emergency decompressive craniectomy 116 h after malignant middle cerebral artery infarction. This case suggests that the timing of decompressive craniectomy can be delayed until deterioration of neurological findings and, compared with adults, a more prolonged time course for surgical intervention might be acceptable.


Assuntos
Craniectomia Descompressiva/métodos , Infarto da Artéria Cerebral Média/cirurgia , Angiografia Cerebral , Criança , Feminino , Seguimentos , Humanos , Infarto da Artéria Cerebral Média/diagnóstico , Imageamento por Ressonância Magnética , Fatores de Tempo , Tomografia Computadorizada por Raios X
19.
Hear Res ; 443: 108962, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295585

RESUMO

Nestin expression is associated with pluripotency. Growing evidence suggests nestin is involved in hair cell development. The objective of this study was to investigate the morphology and role of nestin-expressing cells residing in the early postnatal murine inner ear. A lineage-tracing nestin reporter mouse line was used to further characterize these cells. Their cochleae and vestibular organs were immunostained and whole-mounted for cell counting. We found Nestin-expressing cells present in low numbers throughout the inner ear. Three morphotypes were observed: bipolar, unipolar, and globular. Mitotic activity was noted in nestin-expressing cells in the cochlea, utricle, saccule, and crista. Nestin-expressing cell characteristics were then observed after hair cell ablation in two mouse models. First, a reporter model demonstrated nestin expression in a significantly higher proportion of hair cells after hair cell ablation than in control cochleae. However, in a lineage tracing nestin reporter mouse, none of the new hair cells which repopulated the organ of Corti after hair cell ablation expressed nestin, nor did the nestin-expressing cells change in morphotype. In conclusion, Nestin-expressing cells were identified in the cochlea and vestibular organs. After hair cell ablation, nestin-expressing cells did not react to the insult. However, a small number of nestin-expressing cells in all inner ear tissues exhibited mitotic activity, supporting progenitor cell potential, though perhaps not involved in hair cell regeneration.


Assuntos
Cóclea , Vestíbulo do Labirinto , Animais , Camundongos , Cóclea/metabolismo , Células Ciliadas Auditivas/metabolismo , Nestina/genética , Nestina/metabolismo , Sáculo e Utrículo/metabolismo , Vestíbulo do Labirinto/metabolismo
20.
Geriatr Gerontol Int ; 24(1): 116-122, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38140947

RESUMO

AIMS: With the aging society worldwide, lumbar spinal stenosis (LSS) has become common, and its incidence has been increasing worldwide. Frailty and locomotive syndrome significantly overlap as disorders in older people. The current study aimed to validate the association between frailty and locomotive syndrome in patients with LSS. In particular, the involvement of frailty in locomotive syndrome following surgery was examined. METHODS: We retrospectively reviewed the time-course data of consecutive patients aged ≥65 years who underwent lumbar spinal surgery for LSS. The locomotive syndrome stages were determined using the 25-Question Geriatric Locomotive Function Scale: stage 0, score ≤6; stage 1, score ≥7; stage 2, score ≥16; and Stage 3, score ≥24. Robust, pre-frailty, and frailty were defined as a modified frailty index-11 score of 0, <0.21, and >0.21, respectively. RESULTS: This study included 234 patients. All patients except one were diagnosed with locomotive syndrome preoperatively. Approximately 24.8% of participants were diagnosed with frailty. LSS surgery improved locomotive syndrome regardless of frailty severity. Meanwhile, multivariable analysis indicated that frailty could significantly inhibit improvement in locomotive syndrome after surgery in old patients with LSS (estimated relative risk: 0.6; 95% confidence interval: 0.4-0.9). CONCLUSIONS: This study first assessed the association between locomotive syndrome and frailty in patients with LSS. Locomotive syndrome could be managed effectively with surgery regardless of frailty severity in old patients with LSS. However, our findings emphasize the need to screen for frailty preoperatively in this patient group. Geriatr Gerontol Int 2024; 24: 116-122.


Assuntos
Fragilidade , Estenose Espinal , Idoso , Humanos , Estenose Espinal/complicações , Estenose Espinal/cirurgia , Estenose Espinal/diagnóstico , Estudos Retrospectivos , Fragilidade/complicações , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Vértebras Lombares/cirurgia , Envelhecimento
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