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1.
J Allergy Clin Immunol ; 153(5): 1268-1281, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38551536

RESUMO

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.


Assuntos
Asma , Biomarcadores , Vesículas Extracelulares , Galectinas , Sinusite , Humanos , Asma/sangue , Asma/fisiopatologia , Asma/imunologia , Asma/diagnóstico , Vesículas Extracelulares/metabolismo , Feminino , Masculino , Galectinas/sangue , Biomarcadores/sangue , Adulto , Pessoa de Meia-Idade , Sinusite/sangue , Sinusite/imunologia , Rinite/sangue , Rinite/imunologia , Rinite/fisiopatologia , Pólipos Nasais/imunologia , Pólipos Nasais/sangue , Eosinófilos/imunologia , Idoso , Doença Crônica
3.
Sci Rep ; 13(1): 8313, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221285

RESUMO

Minocycline is often administered prophylactically or therapeutically to non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for skin rash as an adverse event. We examined the effects of minocycline on the outcomes of EGFR-mutant NSCLC treated with first-line EGFR-TKIs based on a single-center retrospective analysis. In this retrospective cohort study, data were collected on NSCLC patients treated with first-line EGFR-TKIs between January 2010 and June 2021. The treatment efficacy of first-line EGFR-TKIs was compared between patients who received minocycline and those who did not. Median progression-free survival (PFS) with first-line EGFR-TKIs was significantly longer in the minocycline group (N = 32) than in the control group (N = 106); 714 (95% confidence interval CI 411-1247) days vs. 420 (95% CI 343-626) days, p = 0.019. A multivariate analysis including skin rash as a variable confirmed that the administration of minocycline for 30 days or longer correlated with good PFS and overall survival (OS) with first-line EGFR-TKIs (HR 0.44 [95% CI 0.27-0.73], p = 0.0014 and HR 0.50 [95% CI 0.27-0.92], p = 0.027, respectively). The administration of minocycline influenced good treatment efficacy with first-line EGFR-TKIs independently of skin rash.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exantema , Minociclina , Minociclina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , /uso terapêutico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Exantema/induzido quimicamente , Exantema/tratamento farmacológico , Estudos Retrospectivos , Intervalo Livre de Doença , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
4.
Sci Adv ; 9(20): eade0718, 2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37205755

RESUMO

Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non-small cell lung cancer (NSCLC) responded significantly better to anti-programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8+ T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Semaforinas , Animais , Humanos , Camundongos , Anticorpos Bloqueadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linfócitos T CD8-Positivos , Proliferação de Células , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Semaforinas/genética , Semaforinas/metabolismo , Microambiente Tumoral
5.
J Clin Microbiol ; 61(4): e0162622, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36946719

RESUMO

Because nontuberculous mycobacterial pulmonary disease is a considerable health burden, a simple and clinically applicable analytical protocol enabling the identification of subspecies and drug-resistant disease is required to determine the treatment strategy. We aimed to develop a simplified workflow consisting only of direct sequencing of mycobacterial growth indicator tube cultures (MGIT-seq). In total, 138 patients were prospectively enrolled between April 2021 and May 2022, and culture-positive MGIT broths were subjected to sequencing using MinION, a portable next-generation sequencer. Sequence analysis was conducted to identify species using core genome multilocus sequence typing and to predict macrolide and amikacin (AMK) resistance based on previously reported mutations in rrl, rrs, and erm(41). The results were compared to clinical tests for species identification and drug susceptibility. A total of 116 patients with positive MGIT cultures were included in the analysis. MGIT-seq yielded 99.1% accuracy in species-level identification and identified 98 isolates (84.5%) at the subspecies level. Macrolide and AMK resistance were detected in 19.4% and 1.9% of Mycobacterium avium complex (MAC) and Mycobacterium abscessus isolates. The predicted macrolide and AMK resistance was consistent with the results of conventional drug susceptibility tests, with specificities of 97.6% and 100.0%, respectively. Direct MGIT-seq has achieved comprehensive identification and drug resistance detection of nontuberculous mycobacteria, which could be applicable to determine the treatment strategy by a single test in clinical practice.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Micobactérias não Tuberculosas , Humanos , Estudos Prospectivos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/farmacologia , Amicacina , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana
6.
RMD Open ; 9(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36690385

RESUMO

OBJECTIVE: No studies have demonstrated the real-world efficacy of antifibrotics for progressive fibrosing interstitial lung disease (PF-ILD). Therefore, we evaluated the efficacy of antifibrotics in patients with PF-ILD. METHODS: We retrospectively reviewed the medical records of patients with ILD from January 2012 to July 2021. Patients were diagnosed with PF-ILD if they had ≥10% fibrosis on high-resolution CT (HRCT) and a relative forced vital capacity (FVC) decline of either ≥10% or >5% to <10% with clinical deterioration or progression of fibrosis on HRCT during overlapping windows of 2 years and with a %FVC of ≥45%. We compared FVC changes and overall survival (OS) between patients with and without antifibrotics. FVC changes were analysed using generalised estimating equations. We used inverse probability weighting (IPW) and statistical matching to adjust for covariates. RESULTS: Of the 574 patients, 167 were diagnosed with PF-ILD (idiopathic pulmonary fibrosis (IPF), n=64; non-IPF, n=103). Antifibrotics improved the FVC decline in both IPF (p=0.002) and non-IPF (p=0.05) (IPW: IPF, p=0.015; non-IPF, p=0.031). Among patients with IPF, OS was longer in the antifibrotic group (log-rank p=0.001). However, among patients with non-IPF, OS was not longer in the antifibrotic group (p=0.3263) (IPW and statistical matching: IPF, p=0.0534 and p=0.0018; non-IPF, p=0.5663 and p=0.5618). CONCLUSION: This is the first real-world study to show that antifibrotics improve the FVC decline in PF-ILD. However, among patients with non-IPF, we found no significant difference in mortality between those with and without antifibrotics. Future studies must clarify whether antifibrotics improve the prognosis of non-IPF.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Estudos Retrospectivos , Progressão da Doença , Fibrose Pulmonar Idiopática/diagnóstico , Prognóstico , Fibrose
7.
Sci Rep ; 12(1): 17461, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261600

RESUMO

Anti-programmed cell death-1 (PD-1) therapy exerts beneficial effects in a limited population of cancer patients. Therefore, more accurate diagnostics to predict the efficacy of anti-PD-1 therapy are desired. The present study investigated whether peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer (NSCLC) patients. Advanced NSCLC patients treated with anti-PD-1 monotherapy (nivolumab or pembrolizumab) were consecutively enrolled in the present study. Peripheral blood samples were subjected to an analysis of peripheral T cell cytotoxicity and flow cytometry prior to the initiation of anti-PD-1 therapy. Peripheral T cell cytotoxicity was assessed using bispecific T-cell engager (BiTE) technology. We found that progression-free survival was significantly longer in patients with high peripheral T cell cytotoxicity (p = 0.0094). In the multivariate analysis, treatment line and peripheral T cell cytotoxicity were independent prognostic factors for progression-free survival. The analysis of T cell profiles revealed that peripheral T cell cytotoxicity correlated with the ratio of the effector memory population in CD4+ or CD8+ T cells. Furthermore, the results of flow cytometry showed that the peripheral CD45RA+CD25+/CD4+ T cell ratio was higher in patients with than in those without severe adverse events (p = 0.0076). These results indicated that the peripheral T cell cytotoxicity predicted the efficacy of anti-PD-1 therapy for advanced NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T CD8-Positivos/metabolismo
8.
Transl Lung Cancer Res ; 11(9): 1835-1846, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36248332

RESUMO

Background: There is no clear consensus regarding the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) and pre-existing interstitial lung disease (ILD). We aimed to elucidate the impact of ICIs on pre-existing ILD. Methods: We systematically queried PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science databases up to January 10, 2022. The pooled any-grade and grade 3-5 ICI-associated pneumonitis (ICIP) rate and objective response rate (ORR) in patients with pre-existing ILD were mainly evaluated. The relative risk (RR) was also evaluated for pre-existing ILD and usual interstitial pneumonia (UIP) patterns. Sensitivity and subgroup analyses were performed to assess the heterogeneity. Results: In total, 17 studies involving 5,529 patients were included in the meta-analysis. The pooled ICIP rate was 30% [95% confidence interval (CI): 24-36%]; it was found to be significantly higher in patients with pre-existing ILD relative to those without (RR =3.05, 95% CI: 2.53-3.69; I2=0.0%). The pooled grade 3-5 ICIP rate was 12% (95% CI: 9-15%); this was also significantly higher in patients with pre-existing ILD (RR =3.19, 95% CI: 2.32-4.38; I2=0.0%). According to subgroup analysis, these ICIP rates were not significantly different among the treatment lines (first, ≥ second, and mixed) (P=0.33) whereas the pooled ORR was 36% (95% CI: 24-48%; I2=53.7%) with a significant difference among the treatment lines (P=0.027). The pooled ICIP rate was independent of the UIP pattern (RR =1.06, 95% CI: 0.86-1.32; I2=0.0%). Conclusions: Overall, ICIs should be administered cautiously in patients with pre-existing ILD, regardless of the treatment line. Moreover, the risks of ICIP may outweigh ICI benefits, especially in second-or later-line treatment. These results need to be further confirmed by meta-analyses including more observational cohort studies in clinical setting.

9.
Int J Chron Obstruct Pulmon Dis ; 17: 1495-1506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35801120

RESUMO

Purpose: Pulmonary fibrosis and emphysema result in relatively maintained ventilation and reduced diffusing capacity. This pulmonary functional impairment complicates the evaluation of pulmonary function in patients with combined pulmonary fibrosis and emphysema (CPFE). Therefore, a single and easy-to-use pulmonary function index to evaluate patients with CPFE warrants further studies. Respiratory impedance can easily be provided by oscillometry and might be a candidate index to evaluate pulmonary function in patients with CPFE. As a preliminary study to assess the utility of respiratory impedance, we investigated the associations of physiological indices, including respiratory impedance, in patients with idiopathic pulmonary fibrosis (IPF) with and without emphysema. Patients and Methods: This retrospective study evaluated patients with IPF who did and did not satisfy the diagnostic criteria of CPFE. All patients underwent oscillometry, spirometry, and diffusing capacity for carbon monoxide (DLCO). Correlations of the obtained physiological indices were analyzed. Results: In total, 47 patients were included (18 and 29 patients with CPFE and IPF, respectively). Respiratory reactance (Xrs) at 5 Hz (X5) in the inspiratory phase was associated with forced vital capacity (FVC) % predicted in patients with CPFE (rS=0.576, P=0.012) and IPF (rS=0.539, P=0.003). Inspiratory X5 positively correlated with DLCO % predicted only in patients CPFE (rS=0.637, P=0.004). Conclusion: Emphysema might associate Xrs with ventilation and diffusing capacity in patients with IPF and emphysema. Given the multiple correlations of Xrs with FVC and DLCO, this study warrants further studies to verify the utility of oscillometry in a large-scale study for patients with CPFE.


Assuntos
Enfisema , Fibrose Pulmonar Idiopática , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Impedância Elétrica , Enfisema/complicações , Fibrose , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos
10.
BMC Infect Dis ; 22(1): 572, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35751044

RESUMO

BACKGROUND: The impact of SARS-CoV-2 infection on the gut fungal (mycobiota) and bacterial (microbiota) communities has been elucidated individually. This study analyzed both gut mycobiota and microbiota and their correlation in the COVID-19 patients with severe and mild conditions and follow-up to monitor their alterations after recovery. METHODS: We analyzed the gut mycobiota and microbiota by bacterial 16S and fungal ITS1 metagenomic sequencing of 40 severe patients, 38 mild patients, and 30 healthy individuals and reanalyzed those of 10 patients with severe COVID-19 approximately 6 months after discharge. RESULTS: The mycobiota of the severe and mild groups showed lower diversity than the healthy group, and in some, characteristic patterns dominated by a single fungal species, Candida albicans, were detected. Lower microbial diversity in the severe group was observed, but no differences in its diversity or community structure were detected between the mild and healthy groups. The microbiota of the severe group was characterized by an increase in Enterococcus and Lactobacillus, and a decrease in Faecalibacterium and Bacteroides. The abundance of Candida was positively correlated with that of Enterococcus in patients with COVID-19. After the recovery of severe patients, alteration of the microbiota remained, but the mycobiota recovered its diversity comparable to that of mild and healthy groups. CONCLUSION: In mild cases, the microbiota is stable during SARS-CoV-2 infection, but in severe cases, alterations persist for 6 months after recovery.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Microbiota , Enterococcus , Fezes/microbiologia , Humanos , SARS-CoV-2
11.
Emerg Infect Dis ; 28(7): 1437-1441, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35731181

RESUMO

Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP 111916T), Tsukamurella toyonakaense, from a patient given a misdiagnosis of nontuberculous mycobacterial pulmonary disease caused by unidentified mycobacteria. Genomic identification of this Tsukamurella species helped clarify its clinical characteristics and epidemiology.


Assuntos
Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Mycobacterium , Humanos , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Pneumopatias/microbiologia , Mycobacterium/genética , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-35604945

RESUMO

A slowly growing mycobacteria, identified as strain TY59T, was isolated from sputum of an elderly man with pneumonia. Sequencing of the 16S rRNA gene indicated that this strain was similar to members of the Mycobacterium avium complex and closely related species. Strain TY59T has highest 16S rRNA gene sequence similarities to the type strains of Mycobacterium colombiense (99.80 % sequence similarity), Mycobacterium vulneris (99.74 %), Mycobacterium timonense (99.54 %), Mycobacterium avium subsp. avium (99.54 %) and Mycobacterium avium subsp. silvaticum (99.54 %). Analysis of the internal transcribed spacer (ITS) and DNA-directed RNA polymerase subunit beta (rpoB) sequences gave similar results to the 16S rRNA gene analysis. The closest species to strain TY59T were M. colombiense and M. vulneris with 97.90-98.25 % identity in ITS and 96.4-96.6 % in rpoB. The strain's 65 kDa heat shock protein (hsp65) gene was different from those of M. vulneris, M. colombiense and M. avium subsp. silvaticum with 72.4-74.2 % identity. Average nucleotide identity results showed a 93.4 % match to M. vulneris as the maximum value. Phenotypically, the non-chromogenicity, rough colonies, growth at 42 °C, negative results for nitrate reduction, ß-glucosidase and Tween 80 hydrolysis, and positive results for catalase activity set this strain apart from closely related species. We propose that Mycobacterium senriense sp. nov. is a novel species of slowly growing mycobacteria. The type strain is TY59T (RIMD 1371001T=CIP 111917T).


Assuntos
Infecções por Mycobacterium , Mycobacterium , Idoso , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , RNA Polimerases Dirigidas por DNA/genética , Ácidos Graxos/química , Humanos , Masculino , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/microbiologia , Complexo Mycobacterium avium , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Escarro/microbiologia
14.
Respir Med Case Rep ; 36: 101619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251929

RESUMO

Pure red cell aplasia (PRCA), Good's syndrome (GS), and thymoma-associated multiorgan autoimmunity (TAMA) are associated with thymoma. Herein, we describe the case of a 56-year-old woman with PRCA, GS, and TAMA simultaneously. She was treated with cyclosporine, immunoglobulin supplementation, and prednisolone; however, she died of uncontrolled sepsis due to extreme immunosuppression. The combination of these three diseases is likely to lead to fatal infections, and to avoid such infections, it may be necessary to reduce or discontinue immunosuppressants and steroids as soon as possible if the diseases are controlled, as well as regular immunoglobulin supplementation.

15.
Int Immunol ; 34(6): 327-340, 2022 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-35294531

RESUMO

Sarcoidosis is a complex, polygenic, inflammatory granulomatous multi-organ disease of unknown cause. The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. Extracellular vesicles (EVs) play important roles in intercellular communication. We subjected serum EVs, isolated by size exclusion chromatography, from seven patients with sarcoidosis and five control subjects to non-targeted proteomics analysis. Non-targeted, label-free proteomics analysis detected 2292 proteins in serum EVs; 42 proteins were up-regulated in patients with sarcoidosis relative to control subjects; and 324 proteins were down-regulated. The protein signature of EVs from patients with sarcoidosis reflected disease characteristics such as antigen presentation and immunological disease. Candidate biomarkers were further verified by targeted proteomics analysis (selected reaction monitoring) in 46 patients and 10 control subjects. Notably, CD14 and lipopolysaccharide-binding protein (LBP) were validated by targeted proteomics analysis. Up-regulation of these proteins was further confirmed by immunoblotting, and their expression was strongly increased in macrophages of lung granulomatous lesions. Consistent with these findings, CD14 levels were increased in lipopolysaccharide-stimulated macrophages during multinucleation, concomitant with increased levels of CD14 and LBP in EVs. The area under the curve values of CD14 and LBP were 0.81 and 0.84, respectively, and further increased to 0.98 in combination with angiotensin-converting enzyme and soluble interleukin-2 receptor. These findings suggest that CD14 and LBP in serum EVs, which are associated with granulomatous pathogenesis, can improve the diagnostic accuracy in patients with sarcoidosis.


Assuntos
Proteínas de Fase Aguda , Vesículas Extracelulares , Receptores de Lipopolissacarídeos , Sarcoidose , Proteínas de Fase Aguda/análise , Biomarcadores/análise , Vesículas Extracelulares/química , Humanos , Receptores de Lipopolissacarídeos/sangue , Glicoproteínas de Membrana/sangue , Proteômica/métodos , Sarcoidose/sangue , Sarcoidose/diagnóstico
16.
Clin Case Rep ; 10(2): e05463, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35223018

RESUMO

This is the first report of COVID-19 in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. HTLV-1 infection can cause immune dysfunction even in asymptomatic carriers. This case highlights the need for guidance on management of COVID-19-HTLV-1 coinfection, specifically on the appropriate use of corticosteroid treatment while considering secondary infection.

17.
Medicine (Baltimore) ; 101(1): e28476, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35029896

RESUMO

RATIONALE: Thymic carcinoma (TC) is a malignant mediastinal tumor, and there are no established treatments for pre-treated patients with advanced TC. Recently, lenvatinib was approved for such patients in Japan, ahead of other countries. Higher dose lenvatinib may be more efficacious than conventional treatments, although many patients experience grade 3 hypertension. Therefore, lenvatinib dose reduction remains controversial in terms of efficacy and tolerability. PATIENT CONCERNS: Case 1 involves a 72-year-old woman who underwent complete resection of TC and was taking cilnidipine and azilsartan for hypertension. Six years later, multiple lung metastases were observed, and lenvatinib was started. Case 2 involves a 60-year-old man with TC, and was taking amlodipine for hypertension. A chest computed tomography showed progression in primary and metastatic lesions, and the patient started lenvatinib. DIAGNOSES: In both patients, grade 3 hypertension was observed after the administration of lenvatinib. INTERVENTIONS: In Case 1, lenvatinib dose was reduced 3 times because lenvatinib was not interrupted despite grade 3 hypertension. In contrast, in Case 2, lenvatinib was interrupted when grade 3 hypertension occurred and was resumed after a decrease in blood pressure to baseline. OUTCOMES: In Case 2, higher tumor regression may have been achieved because of the maintenance of a high dose of lenvatinib compared with that in Case 1. LESSONS: Lenvatinib is a promising agent for advanced TC; however, hypertension should be addressed cautiously, especially at the outset of administration. Lenvatinib may have to be appropriately interrupted and resumed as soon as the blood pressure is controlled to maximize efficacy and minimize toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Idoso , Anti-Hipertensivos/uso terapêutico , Antineoplásicos/uso terapêutico , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Timoma/patologia , Neoplasias do Timo/patologia
18.
Microbiol Spectr ; 10(1): e0140621, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-34985326

RESUMO

Although serum anti-glycopeptidolipid (GPL)-core IgA antibody is a highly specific test for infection with Mycobacterium avium complex (MAC), Mycobacterium abscessus, and its subspecies abscessus, subsp. massiliense, and subsp. bolletii (MAB), its use for the definitive diagnosis of MAC pulmonary disease (PD) and MAB-PD are unknown. To clarify the diagnostic accuracy of the anti-GPL-core IgA antibody test among patients with radiologically suspected MAC-PD or MAB-PD who already have a single positive sputum culture test. The first isolations of MAC and MAB from patients with radiologically suspected MAC-PD or MAB-PD at the Osaka Toneyama Medical Center between January 2006 and December 2020 were collected. Patients were enrolled when their serum anti-GPL-core IgA antibody was measured during the 3 months before and after the first isolation. We retrospectively compared the results of anti-GPL-core IgA antibody testing with the final diagnoses based on the current guidelines. We included 976 patients for analysis. The serum anti-GPL-core IgA antibody was positive in 699 patients (71.6%). The positive predictive value of anti-GPL-core IgA antibody for the diagnosis of MAC-PD or MAB-PD was 97.4%. The median time required for the second positive culture after the first isolation was 51 days (interquartile range 12 to 196 days). The positive serum anti-GPL-core IgA antibody test allowed an early and definitive diagnosis of MAC-PD or MAB-PD in those who already had a single positive sputum culture test. IMPORTANCE To satisfy the microbiologic criteria of the current diagnostic guideline for nontuberculous mycobacterial pulmonary disease (PD), at least two positive sputum cultures of the same species of mycobacteria from sputum are required to avoid the casual isolation of mycobacteria. This study showed that the positivity of a serum anti-glycopeptidolipid (GPL)-core IgA antibody test has an excellent diagnostic ability among patients with radiologically suspected Mycobacterium avium complex (MAC)-PD or Mycobacterium abscessus (MAB)-PD who already had a single positive sputum culture test. The usage of single culture isolation plus anti-GPL-core IgA antibody as another diagnostic criterion has a time, cost, and effort-saving effect. Furthermore, it will facilitate the diagnosis of MAC-PD or MAB-PD in the early stage of disease because serum anti-GPL-core IgA antibody becomes high in these patients. Therefore, we proposed adding single culture isolation plus anti-GPL-core IgA antibody as "combined microbiological and serological criteria" to the diagnostic guidelines for MAC-PD and MAB-PD.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina A/sangue , Mycobacterium abscessus/imunologia , Complexo Mycobacterium avium/imunologia , Infecção por Mycobacterium avium-intracellulare/sangue , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicopeptídeos/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium abscessus/genética , Mycobacterium abscessus/isolamento & purificação , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos Retrospectivos
19.
Angiogenesis ; 25(2): 147-149, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34591203

RESUMO

We report a unique case of advanced non-small cell lung cancer that exhibited the opposite response to its unilateral choroidal metastases upon ramucirumab plus docetaxel treatment. A combination of cisplatin, pemetrexed, and pembrolizumab was administered as first-line treatment, resulting in shrinkage of all the lesions. However, although the patient was continued on a course of pembrolizumab, all the lesions had recurred approximately two months later. Ramucirumab plus docetaxel, administered as sequential treatment, resulted in maintained shrinkage of the choroidal lesions, yet all the other lesions progressed. Ramucirumab may be a suitable therapy for choroidal metastases, especially if administered immediately after immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Resultado do Tratamento , Ramucirumab
20.
Front Med (Lausanne) ; 8: 797171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901097

RESUMO

Mycolicibacterium mageritense (M. mageritense) is a rare species among rapidly growing mycobacteria, and M. mageritense pleurisy is very rare. Here, we report for the first time, an immunocompetent patient with pleurisy caused by M. mageritense. The patient had no history of immunodeficiency and no recurrence of lung cancer after surgery. However, 8 months after surgery, he developed a new lung shadow and pleurisy. Although whole-genome analysis of the colony cultured from the patient's pleural fluid revealed M. mageritense, we could not identify it in time, resulting in a poor outcome. M. mageritense pleurisy in this case might have occurred via a bulla rupture of the lung lesion because computed tomography of the patient's chest showed pneumothorax and a lung lesion in contact with thoracic cavity. This case emphasized that nontuberculous mycobacterial pleurisy should be considered in the differential diagnoses of pleural effusion even in immunocompetent patients. Advancement of comprehensive and rapid analyses of genomic data from clinical specimens will lead to better treatment strategies.

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