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1.
Cancer Sci ; 112(1): 72-80, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33084148

RESUMO

CD24, a heavily glycosylated glycosylphosphatidylinositol-anchored surface protein, inhibits phagocytosis as potently as CD47. The relationship between such anti-phagocytic factors and the immune response with immune-checkpoint inhibitors (ICI) remains unexplored. We evaluated CD24 and CD47 tumor proportion scores (TPS) in 68 of the 106 patients with advanced non-small-cell lung cancer who participated in a prospective observational study of ICI treatment. We also explored the impact of CD24 TPS and CD47 TPS on ICI efficacy and serum cytokine changes. CD24 positivity (TPS ≥ 1) was negatively associated with progression-free survival (PFS) of ICI when PD-L1 TPS was < 50 (median PFS; 37 vs 127 d, P = .033), but there was no association when PD-L1 TPS was ≥ 50 (median PFS; 494 vs 144 d, P = .168). CD24 positivity was also related to significantly higher increase of CCL2 from baseline to 4-6 wk later, and such increase was notably observed only when PD-L1 TPS < 50 (P = .0004). CCL2 increase after ICI initiation was negatively predictive for survival after initiation of ICI (median survival time; not reached vs 233 d; P = .028). CD47 TPS high (≥60) significantly suppressed the increase in vascular endothelial growth factor (VEGF)-A, D and PDGF-AB/BB after ICI initiation. There was no association, however, between CD47 tumor expression and the efficacy of ICI. In conclusion, CD24, not CD47, is a candidate negative predictive marker of ICI in advanced, non-small-cell lung cancer with PD-L1 TPS < 50. Tumor expression of both CD24 and CD47 was associated with changes in factors related to monocytes and angiogenesis after ICI initiation (UMIN000024414).


Assuntos
Antígeno B7-H1/metabolismo , Antígeno CD24/metabolismo , Antígeno CD47/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Pontuação de Propensão , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular/metabolismo
2.
Oncologist ; 25(4): e679-e683, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32297443

RESUMO

BACKGROUND: Although predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been suggested by several studies, their assessments were insufficient because patients were categorized only by the occurrence of irAEs. It has not been elucidated whether irAEs also play a significant role even in responders. MATERIALS AND METHODS: Between December 2015 and September 2018, 106 patients with advanced non-small cell lung cancer treated with ICIs were enrolled in our prospective biomarker study. Twenty-three of these were responders, defined as those with complete or partial response. We investigated the proportion of irAEs among overall and responders. For responders, progression-free survival (PFS) and overall survival of ICIs were compared between those with and without irAEs. As an exploratory analysis, we measured 41 proteins from peripheral blood before and after ICI treatment. RESULTS: The proportion of irAEs was significantly higher in responders than nonresponders (65.2% vs. 19.3%, p < .01). Among responders, clinical characteristics did not differ regardless of the occurrence of irAEs. However, there was a significant difference in PFS among responders (irAE group 19.1 months vs. non-irAE group 5.6 months; hazard ratio: 0.30 [95% confidence interval: 0.10-0.85]; p = .02). Of 41 protein analyses, fibroblast growth factor-2 at baseline and monocyte chemoattractant protein fold change showed significant differences between them (p < .04). CONCLUSION: Although this is a small sample-sized study, irAE might be a predictive factor of durable efficacy, even in patients who responded to ICIs. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI. IMPLICATIONS FOR PRACTICE: Although the predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) has been suggested by several studies, it has not been elucidated whether irAEs also play a significant role even in responders. This study showed that more than 60% of responders had irAEs. It demonstrated the strong correlation between irAEs and efficacy even in responders. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Pulmonares , Neoplasias , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos
3.
J Pediatr Gastroenterol Nutr ; 71(3): 333-339, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32487952

RESUMO

OBJECTIVES: Causes of early-onset refractory diarrhea include exudative diarrhea associated with very early-onset inflammatory bowel diseases, osmotic or secretory diarrhea, and protein-losing enteropathy. Monogenic disorders are included in these diseases, yet a comprehensive genetic analysis has not been fully established. METHODS: We established targeted gene panels covering all responsible genes for early-onset diarrhea. In total, 108 patients from 15 institutions were enrolled in this study. We collected clinical data from all patients. Seventy-three patients with exudative diarrhea, 4 with osmotic or secretory diarrhea and 8 with protein-losing enteropathy were subjected to genetic analysis. RESULTS: A total of 15 out of the 108 enrolled patients (13.9%) were identified as monogenic. We identified 1 patient with RELA, 2 with TNFAIP3, 1 with CTLA4, 1 with SLCO2A1, 4 with XIAP, 3 with IL10RA, 1 with HPS1, 1 with FOXP3, and 1 with CYBB gene mutations. We also identified 1 patient with NFKB2 and 1 with TERT mutations from the gene panel for primary immunodeficiency syndromes. The patient with refractory diarrhea caused by heterozygous truncated RelA protein expression is the first case identified worldwide, and functional analysis revealed that the mutation affected nuclear factor kappa B signaling. Genotypes were significantly associated with the clinical and pathological findings in each patient. CONCLUSIONS: We identified variable monogenic diseases in the patients and found that genes responsible for primary immunodeficiency diseases were frequently involved in molecular pathogenesis. Comprehensive genetic analysis was useful for accurate molecular diagnosis, understanding of underlying pathogenesis, and selecting the optimal treatment for patients with early-onset refractory diarrhea.An infographic for this article is available at: http://links.lww.com/MPG/B853.


Assuntos
Diarreia , Transportadores de Ânions Orgânicos , Diarreia/genética , Heterozigoto , Humanos , Mutação , Fenótipo , Sequenciamento do Exoma
4.
Digestion ; 100(3): 210-219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30540997

RESUMO

BACKGROUND/AIMS: Behçet's disease (BD) with intestinal lesions and Crohn's disease (CD) share clinical features. However, no report has compared the 2 diseases with regard to lesions of the upper gastrointestinal tract (UGT). We aimed to evaluate endoscopic and histologic findings of UGT in CD and BD. METHODS: We retrospectively assessed the endoscopic records and biopsy samples of 84 Helicobacter pylori-negative patients (50 CD, 34 BD). In duodenal samples, MUC5AC immunohistochemical analysis was performed to identify gastric foveolar metaplasia. RESULTS: In endoscopic findings, bamboo joint-like appearance (17/50 CD, 0/34 BD) and erosions (14/50 CD, 2/34 BD) were significantly more frequent in CD gastric lesions (p < 0.001, and p = 0.012). In histologic findings of stomach, focal neutrophil infiltration in lamina propria (15/48 CD, 1/34 BD) was significantly more frequent in CD (p < 0.001). In that of duodenum, wide gastric foveolar metaplasia (19/49 CD, 1/34 BD) was significantly more frequent in CD duodenal lesions (p = 0.013). The mean maximum width of the gastric foveolar metaplasia was 114.0 ± 10.6 and 29.5 ± 4.5 µm for CD and BD respectively (p = 0.003). CONCLUSIONS: In H. pylori-negative patients, gastric focal neutrophil infiltration and wide duodenal gastric foveolar metaplasia were important for distinguishing CD from BD.


Assuntos
Síndrome de Behçet/diagnóstico , Doença de Crohn/diagnóstico , Duodeno/patologia , Mucosa Gástrica/patologia , Infiltração de Neutrófilos/imunologia , Adolescente , Adulto , Síndrome de Behçet/imunologia , Síndrome de Behçet/patologia , Biópsia , Criança , Doença de Crohn/imunologia , Doença de Crohn/patologia , Diagnóstico Diferencial , Duodeno/diagnóstico por imagem , Endoscopia Gastrointestinal , Feminino , Mucosa Gástrica/citologia , Mucosa Gástrica/diagnóstico por imagem , Humanos , Masculino , Metaplasia/diagnóstico por imagem , Metaplasia/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
5.
Mod Rheumatol ; 29(4): 708-713, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28271948

RESUMO

Here we describe a 20-year-old man with ankylosing spondylitis and gut inflammation, who was successfully treated with adalimumab. Capsule endoscopy and ileocolonoscopy showed multiple erosions and aphthoid ulcers in the ileum and the ileocecal valve. Immunohistochemical analysis of the terminal ileum demonstrated that the number of IL-23p19 expressing macrophages was increased. Adalimumab was administered, and his back pain and abdominal symptoms improved. Adalimumab might be an effective treatment for gut inflammation related to ankylosing spondylitis.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Endoscopia por Cápsula , Doenças Inflamatórias Intestinais/tratamento farmacológico , Espondilite Anquilosante/complicações , Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Adulto Jovem
6.
Nihon Ronen Igakkai Zasshi ; 55(1): 143-147, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29503358

RESUMO

An 84-year-old man, who had received artificial pneumothorax for pulmonary tuberculosis 67 years previously, complained of severe chest pain. Chest CT revealed chronic pyothorax with multiple heterogeneously enhanced cavity lesions in the wall of the right intrathoracic space. 18FDG-PET revealed that the lesions showed an abnormal uptake. CT-guided biopsy was performed and he was diagnosed with pyothorax-associated lymphoma (PAL); the histological diagnosis was diffuse large B cell lymphoma (DLBCL). Furthermore, immunohistochemical staining revealed that the tumor cells were positive for EBNA-2 and LMP-1, suggesting that the latent gene products of Epstein-Barr virus were associated with the development of PAL. The patient was treated with chemotherapy, including rituximab; however, the treatment was discontinued due to the development of severe delirium after chemotherapy. We should keep in mind that elderly patients with a long history of chronic pyothorax are at risk of developing malignant lymphoma. We report the present case with a brief review of the literature.


Assuntos
Empiema Pleural/etiologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Linfoma Difuso de Grandes Células B/etiologia , Idoso de 80 Anos ou mais , Regulação Viral da Expressão Gênica , Humanos , Masculino
7.
J Clin Immunol ; 37(1): 67-79, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27747465

RESUMO

PURPOSE: Pediatric inflammatory bowel disease (IBD) is a heterogeneous disorder caused by multiple factors. Although genetic and immunological analyses are required for a definitive diagnosis, no reports of a comprehensive genetic study of a Japanese population are available. METHODS: In total, 35 Japanese patients <16 years of age suffering from IBD, including 27 patients aged <6 years with very early-onset IBD, were enrolled in this multicenter study. Exome and targeted gene panel sequencing was performed for all patients. Mutations in genes responsible for primary immunodeficiency diseases (PID) and clinical and immunological parameters were evaluated according to disease type. RESULTS: We identified monogenic mutations in 5 of the 35 patients (14.3 %). We identified compound heterozygous and homozygous splice-site mutations in interleukin-10 receptor A (IL-10RA) in two patients, nonsense mutations in X-linked inhibitor of apoptosis protein (XIAP) in two patients, and a missense mutation in cytochrome b beta chain in one patient. Using assays for protein expression levels, IL-10 signaling, and cytokine production, we confirmed that the mutations resulted in loss of function. For each patient, genotype was significantly associated with clinical findings. We successfully treated a patient with a XIAP mutation by allogeneic cord blood hematopoietic stem cell transplantation, and his symptoms were ameliorated completely. CONCLUSIONS: Targeted sequencing and immunological analysis are useful for screening monogenic disorders and selecting curative therapies in pediatric patients with IBD. The genes responsible for PID are frequently involved in pediatric IBD and play critical roles in normal immune homeostasis in the gastrointestinal tract.


Assuntos
Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Imunidade/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Adolescente , Alelos , Criança , Pré-Escolar , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Padrões de Herança , Interleucina-10/genética , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-10/deficiência , Subunidade alfa de Receptor de Interleucina-10/genética , Subunidade alfa de Receptor de Interleucina-10/metabolismo , Japão , Masculino , Mutação , Fenótipo , Transdução de Sinais , Sequenciamento do Exoma , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/deficiência , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
8.
J Org Chem ; 81(16): 7262-70, 2016 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-27187207

RESUMO

We report an efficient method for the synthesis of pyrrolo[2,1-a]isoquinoline derivatives using sequential [3 + 2] cycloaddition/oxidative aromatization reactions catalyzed by methylene blue with fluorescent light irradiation under an oxygen atmosphere. The products were obtained in moderate to good yields.

9.
Pediatr Int ; 57(1): e18-22, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25711270

RESUMO

Collagenous sprue (CS) is a severe malabsorption disorder, the etiology of which has not been well defined. Herein, we report the case of a 3-month-old infant with CS who responded to steroid and immunomodulator treatment and presented a thick subepithelial collagen band. A 3-month-old Japanese girl presented with severe watery diarrhea that lasted for 2 weeks. She was admitted to the referring hospital, but symptomatic improvement was not achieved with fasting and rehydration. Gastroduodenal endoscopy showed an edematous duodenal mucosal surface. Duodenal biopsy indicated severe villous atrophy with infiltration of mostly CD8-positive T cells; and deposition of subepithelial collagen was confirmed. The subepithelial collagen deposits, however, had disappeared after treatment. Historically, child-onset CS is extremely rare and this case is likely to be the youngest case of infantile CS. The present case suggests that CS should be considered as a differential diagnosis for intractable diarrhea, even in infants.


Assuntos
Doença Celíaca/diagnóstico , Espru Colágeno/diagnóstico , Mucosa Intestinal/patologia , Biópsia , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Feminino , Humanos , Lactente
10.
Rinsho Ketsueki ; 55(1): 130-2, 2014 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-24492046

RESUMO

Tyrosine kinase inhibitors (TKIs) are highly effective in the treatment of chronic myelogenous leukemia (CML), but there have been a few adverse event reports describing gastrointestinal bleeding. We clinically analyzed two patients who developed intestinal bleeding during the administration of TKIs for CML. Platelet counts of both patients were normal. The patients showed endoscopic findings characterized by mildly hemorrhagic mucosa. The imatinib patient was diagnosed by capsule endoscopy of the small intestine, and required frequent blood transfusions. The dasatinib patient showed occult bleeding due to CD8-positive colitis. We should adequately recognize that gastrointestinal bleeding may occur during the administration of TKIs.


Assuntos
Benzamidas/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/efeitos adversos , Idoso , Benzamidas/administração & dosagem , Endoscopia por Cápsula , Dasatinibe , Substituição de Medicamentos , Endoscópios Gastrointestinais , Feminino , Hemorragia Gastrointestinal/patologia , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Tiazóis/administração & dosagem
11.
Nihon Shokakibyo Gakkai Zasshi ; 111(10): 1983-9, 2014 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-25283227

RESUMO

A 48-year-old man with colorectal cancer and right inguinal lymph node metastasis had previously undergone radiotherapy and chemotherapy (uracil/tegafur/leucovorin) after a colostomy in another hospital before being referred to us. Esophagogastroduodenoscopy (EGD) revealed the presence of a gastric metastatic lesion. After three courses of treatment with a modified regimen of leucovorin plus 5-fluorouracil plus oxaliplatin-6 (mFOLFOX6), EGD revealed that the gastric lesion had disappeared; computed tomography revealed that the size of the primary tumor and inguinal lymph node metastasis were markedly reduced. Subsequently, he underwent rectal resection of the primary tumor and continued treatment with mFOLFOX6 in combination with bevacizumab. We reviewed 29 similar cases from the literature, and determined that surgical resection of the tumor and appropriate chemotherapy can lead to long-term survival for patients with gastric metastases from colorectal cancer. Furthermore, positive CK20 and CDX2 expression and negative CK7 expression were useful adjuncts in the immunohistochemical diagnosis of gastric metastases from colorectal adenocarcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Gástricas/secundário , Tomografia Computadorizada por Raios X
12.
Respir Med ; 231: 107721, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38972608

RESUMO

BACKGROUND AND OBJECTIVE: Acute exacerbation of fibrosing interstitial lung disease (AE-FILD) is a serious condition with a high mortality rate. We aimed to comprehensively analyze cytokines in bronchoalveolar lavage fluid and their association with the clinical course of AE-FILD. METHODS: We retrospectively enrolled 60 patients with AE-FILD who underwent bronchoalveolar lavage. We comprehensively measured 44 cytokines and chemokines in the obtained bronchoalveolar lavage fluid using a Luminex analyzer. Patients were grouped into those who died within 90 days (non-survival group) and survived beyond 90 days (survival group) to investigate the association of the levels of cytokines and chemokines with mortality. RESULTS: The levels of matrix metalloproteinase 1 (p = 0.003), granulocyte-macrophage colony-stimulating factor (p = 0.040), interleukin 6 (p = 0.047), interleukin 8 (p = 0.050), monocyte chemoattractant protein-1 (p = 0.043), and eotaxin (p = 0.044) were significantly higher in the non-survival group than in the survival group. In the receiver operating characteristic analysis, their areas under the curve were 0.80, 0.68, 0.71, 0.70, 0.70, and 0.72, respectively. Using machine learning with these six cytokines and chemokines, the predictive accuracy for the survival group was 0.94. CONCLUSIONS: Our study demonstrated that several cytokines and chemokines in bronchoalveolar lavage fluid could be prognostic predictors in patients with AE-FILD.


Assuntos
Líquido da Lavagem Broncoalveolar , Quimiocinas , Citocinas , Progressão da Doença , Doenças Pulmonares Intersticiais , Humanos , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Masculino , Prognóstico , Citocinas/metabolismo , Idoso , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/metabolismo , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Quimiocinas/metabolismo , Quimiocinas/análise , Pessoa de Meia-Idade , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/análise , Interleucina-6/metabolismo , Interleucina-6/análise , Interleucina-8/metabolismo , Interleucina-8/análise , Quimiocina CCL11/metabolismo , Quimiocina CCL11/análise , Biomarcadores/metabolismo , Biomarcadores/análise
13.
Cancer Med ; 13(4): e6839, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38457231

RESUMO

BACKGROUND: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. METHODS: This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. RESULTS: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). CONCLUSIONS: Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.


Assuntos
Flebite , Neoplasias Torácicas , Humanos , Cisplatino/efeitos adversos , Furosemida/efeitos adversos , Manitol/efeitos adversos , Flebite/induzido quimicamente , Flebite/tratamento farmacológico , Estudos Prospectivos
14.
J Pain Symptom Manage ; 67(3): 204-211.e1, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37992848

RESUMO

CONTEXT: The efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. OBJECTIVES: The primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. METHODS: In this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). RESULTS: Between February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21-1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3-10). Median survival time was 19 days (range, 3-657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8-1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. CONCLUSION: To our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea.


Assuntos
Neoplasias , Insuficiência Respiratória , Humanos , Cânula , Estudos Prospectivos , Dispneia/etiologia , Dispneia/terapia , Oxigênio , Neoplasias/complicações , Neoplasias/terapia , Oxigenoterapia , Insuficiência Respiratória/terapia
15.
Digestion ; 88(3): 153-60, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24051473

RESUMO

The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme 'Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, 'Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by 'Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care.


Assuntos
Gastroenteropatias/patologia , Gerenciamento Clínico , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Humanos , Japão
16.
J Infect Chemother ; 19(2): 208-10, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23053499

RESUMO

There are conflicting views about the association between type A gastritis with pernicious anemia (PA) and infection with Helicobacter pylori, and currently, no definite conclusion has been reached. In this study, we evaluated H. pylori infection in patients with type A gastritis who developed PA. The study included a total of 25 Japanese patients (13 males and 12 females) who had been diagnosed with PA at our department, with a mean age of 71.2 years. We diagnosed infection with H. pylori by measuring serum H. pylori-IgG antibodies in all 25 patients, and we performed gastric biopsy in 17 patients. They were all negative for H. pylori-IgG antibody (0/25) and H. pylori on gastric biopsy (0/17). Although the prevalence of H. pylori infection (70-80 %) in our age-matched controls in Japan is higher than the prevalence in similar populations in western countries, we believe that type A gastritis with PA is very poorly associated with H. pylori infection.


Assuntos
Anemia Perniciosa/microbiologia , Gastrite/sangue , Gastrite/microbiologia , Infecções por Helicobacter/sangue , Helicobacter pylori/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade
17.
Pain Med ; 13(4): 541-51, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22360795

RESUMO

OBJECTIVES: The present study aimed to develop a Japanese version of the Short-Form McGill Pain Questionnaire (SF-MPQ-J) that focuses on cross-culturally equivalence to the original English version and to test its reliability and validity. DESIGN: Cross-sectional design. METHOD: In study 1, SF-MPQ was translated and adapted into Japanese. It included construction of response scales equivalent to the original using a variation of the Thurstone method of equal-appearing intervals. A total of 147 undergraduate students and 44 pain patients participated in the development of the Japanese response scales. To measure the equivalence of pain descriptors, 62 pain patients in four diagnostic groups were asked to choose pain descriptors that described their pain. In study 2, chronic pain patients (N=126) completed the SF-MPQ-J, the Long-Form McGill Pain Questionnaire Japanese version (LF-MPQ-J), and the 11-point numerical rating scale of pain intensity. Correlation analysis examined the construct validity of the SF-MPQ-J. RESULTS: The results from study 1 were used to develop SF-MPQ-J, which is linguistically equivalent to the original questionnaire. Response scales from SF-MPQ-J represented the original scale values. All pain descriptors, except one, were used by >33% in at least one of the four diagnostic groups. Study 2 exhibited adequate internal consistency and test-retest reliability, with the construct validity of SF-MPQ-J comparable to the original. CONCLUSION: These findings suggested that SF-MPQ-J is reliable, valid, and cross-culturally equivalent to the original questionnaire. Researchers might consider using this scale in multicenter, multi-ethnical trials or cross-cultural studies that include Japanese-speaking patients.


Assuntos
Dor Crônica/diagnóstico , Dor Crônica/etnologia , Comparação Transcultural , Cultura , Medição da Dor/normas , Adulto , Idoso , Povo Asiático/psicologia , Dor Crônica/psicologia , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição da Dor/psicologia
18.
Rinsho Ketsueki ; 53(2): 240-5, 2012 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-22450586

RESUMO

In this paper we report our clinical investigation of three cases with acquired hemophilia A treated in our department. These patients were all elderly males (79, 77, and 68 years old), and presented with subcutaneous bleeding, a prolonged activated partial thromboplastin time (APTT), and anemia. On the basis of these findings as well as decreased factor VIII activities (0.9~3.1%) and the presence of factor VIII inhibitors (57.1~173 BU/ml), we made a diagnosis of acquired hemophilia A. In cases 1 and 2, a recombinant activated factor VII was used to achieve hemostasis. The factor VIII inhibitor disappeared with prednisolone (PSL) alone in case 1 and a combination of PSL and cyclophosphamide in case 2. In case 3, treatment involving five courses of weekly rituximab (RTX) reduced the activity of factor III inhibitor to 3.5 BU/ml (and subsequently to zero). During this time, the patient achieved hemostasis without using a specific hemostatic agent, and was again referred to the previous hospital for the treatment of hepatocellular carcinoma. Although PSL is often chosen as a first-line therapy to suppress the production of factor VIII inhibitor, which may cause acquired hemophilia A, RTX may be another therapeutic option in some patients.


Assuntos
Hemofilia A/tratamento farmacológico , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Fator VIII/antagonistas & inibidores , Evolução Fatal , Hemofilia A/sangue , Hemofilia A/diagnóstico , Hemofilia A/etiologia , Humanos , Masculino , Prednisolona/uso terapêutico , Rituximab , Resultado do Tratamento
19.
Respirol Case Rep ; 10(9): e01019, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35992553

RESUMO

A 70-year-old man with no history of pleural diseases had a dumbbell-shaped chest wall mass extending from the thoracic cavity to the spinal canal at the intervertebral foramen without bone destruction. Computed tomography revealed a positive a 'pleural sandwich sign', where the intercostal artery was enveloped by the mass. A high maximum standard uptake value was noted on fluorodeoxyglucose-positron emission tomography. No lesions were found in areas other than the chest wall. CT-guided biopsy was performed and he was diagnosed with primary chest wall lymphoma. This case report suggests that these radiographic findings may be helpful for diagnosing chest wall lymphomas even in patients without prior pleural disease.

20.
J Clin Med ; 11(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36233400

RESUMO

Physical activity is decreased in patients with chronic obstructive pulmonary disease, and decreased physical activity leads to a poor prognosis. To determine an individual's target step count from the measured step counts and predicted step counts, simple and detailed prediction equations for step count were developed. To verify the validity of the simple prediction equation, the validity of the simple equation was evaluated in a different cohort and the correlation between the step counts calculated by the simple equation and those by the detailed prediction equation were evaluated. When the step counts calculated by the simple prediction equation for all participants were compared with the measured step counts, a significant correlation was obtained among them, and the calculated values were found to be reproducible with the measured values in patients with a measured step count of <6500 by Bland−Altman plots. Furthermore, the values calculated by the simple prediction equation and those calculated by the detailed prediction equation showed a significant correlation. In conclusion, the simple prediction equation was considered reasonable.

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