RESUMO
Dynamic treatment regimes (DTRs) are sequences of decision rules that recommend treatments based on patients' time-varying clinical conditions. The sequential, multiple assignment, randomized trial (SMART) is an experimental design that can provide high-quality evidence for constructing optimal DTRs. In a conventional SMART, participants are randomized to available treatments at multiple stages with balanced randomization probabilities. Despite its relative simplicity of implementation and desirable performance in comparing embedded DTRs, the conventional SMART faces inevitable ethical issues, including assigning many participants to the empirically inferior treatment or the treatment they dislike, which might slow down the recruitment procedure and lead to higher attrition rates, ultimately leading to poor internal and external validities of the trial results. In this context, we propose a SMART under the Experiment-as-Market framework (SMART-EXAM), a novel SMART design that holds the potential to improve participants' welfare by incorporating their preferences and predicted treatment effects into the randomization procedure. We describe the steps of conducting a SMART-EXAM and evaluate its performance compared to the conventional SMART. The results indicate that the SMART-EXAM can improve the welfare of the participants enrolled in the trial, while also achieving a desirable ability to construct an optimal DTR when the experimental parameters are suitably specified. We finally illustrate the practical potential of the SMART-EXAM design using data from a SMART for children with attention-deficit/hyperactivity disorder.
Assuntos
Projetos de Pesquisa , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: Limited information is available on the use of biologics in patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) in Japan. The types of biologics, treatment duration, treatment prior to biologics, concomitant treatment, and characteristics of patients receiving biologics were investigated. METHODS: We used a Japanese hospital claims database provided by Medical Data Vision Co. (2008-2021). RESULTS: In the database, 1186 of 34,207 SSc patients (3.5%) and 620 of 12,303 SSc-ILD patients (5.0%) received anti-interleukin-6 (anti-IL-6) drugs, anti-tumour necrosis factor (anti-TNF) drugs, abatacept, or rituximab. The most common were anti-IL-6 drugs [used in 35.5% of SSc patients and 38.5% of SSc-ILD patients (tocilizumab, 34.5% and 36.6%)], followed by anti-TNF drugs [31.3% and 26.5% (etanercept, 10.5% and 9.0%; others, <8%)], abatacept (17.5% and 20.6%), and rituximab (15.7% and 14.4%). Among SSc and SSc-ILD patients treated with anti-IL-6 drugs, anti-TNF drugs, or abatacept, the most common immunosuppressive drugs prior to initiation of biologics were methotrexate and tacrolimus. Approximately half of patients receiving anti-IL-6 drugs, anti-TNF drugs, or abatacept continued treatment beyond 1 year. CONCLUSIONS: Our study indicates that off-label biologics have been used in a certain number of SSc or SSc-ILD patients in Japan, with tocilizumab the most common.
Assuntos
Produtos Biológicos , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Rituximab/uso terapêutico , Abatacepte/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Produtos Biológicos/uso terapêutico , População do Leste Asiático , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Hospitais , PulmãoRESUMO
INTRODUCTION: We investigated the performance of the cobas® 6800 system and cobas SARS-CoV-2 & Influenza A/B, a fully automated molecular testing system for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This enabled an assay in a batch of 96 samples in approximately 3 h. METHODS: An assay was performed using the cobas SARS-CoV-2 & Influenza A/B on the cobas 6800 system for samples collected in four facilities between November 2019 and March 2020 in our previous study. The results were compared with those obtained using the reference methods. RESULTS: Of the 127 samples analyzed, the cobas SARS-CoV-2 & Influenza A/B detected influenza A virus in 75 samples, of which 73 were positive using the reference methods. No false negative results were observed. The overall positive and negative percent agreement for influenza A virus detection were 100.0% and 96.3%, respectively. There were no positive results for the influenza B virus or SARS-CoV-2. CONCLUSION: The cobas 6800 system and cobas SARS-CoV-2 & Influenza A/B showed high accuracy for influenza A virus detection and can be useful for clinical laboratories, especially those that routinely assay many samples.
Assuntos
COVID-19 , Influenza Humana , Orthomyxoviridae , Humanos , Influenza Humana/diagnóstico , SARS-CoV-2/genética , Técnicas de Diagnóstico MolecularRESUMO
PURPOSE: We compared overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-amplified, treatment-refractory metastatic colorectal cancer (mCRC) receiving pertuzumab plus trastuzumab (PER-HER) in the phase IIa MyPathway multibasket study (ClinicalTrials.gov identifier: NCT02091141) with OS in those receiving routine clinical care in an electronic health record-derived external control arm. METHODS: A noninterventional study was conducted using patient-level data from MyPathway participants receiving PER-HER and real-world patients with HER2-amplified treatment-refractory mCRC receiving routine clinical care. This study used a deidentified US-based clinico-genomic database (CGDB). For patients in the CGDB who met study eligibility criteria at multiple index dates (treatment initiation dates in the treatment-refractory setting), all eligible index dates were used for the analysis. Standardized mortality ratio weighting on the basis of propensity score derived a pseudopopulation (postweighting population) balancing key prognostic variables between arms. Multivariate Cox proportional hazards models were used for estimation of the hazard ratio (HR) in the primary OS analysis. A series of sensitivity analyses were conducted to investigate the robustness and consistency of the primary analysis. RESULTS: The PER-HER arm comprised 57 patients enrolled in the MyPathway study by August 1, 2017 (data cutoff); the external control arm comprised 18 patients (27 index dates) with HER2-amplified mCRC who met the major MyPathway eligibility criteria in CGDB collected between 2011 and 2019. The estimated HR for OS from the multivariate Cox proportional hazards model in the postweighting population was 0.729 (95% CI, 0.184 to 3.900). The results of sensitivity analyses were consistent with the primary analysis in terms of the point estimate of HR. CONCLUSION: Despite a small sample size, these findings suggest that PER-HER could have a potential OS benefit for this population.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Receptor ErbB-2 , Trastuzumab/uso terapêuticoRESUMO
BACKGROUND: Current treatment for frequently relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome focuses on immunosuppressive therapies. Although the clinical guideline suggests the use of mycophenolate mofetil (MMF), limited information is available on patients with primary nephrotic syndrome who receive off-label treatment with MMF in Japan. METHOD: The dose, treatment duration, previous treatment, and characteristics of primary nephrotic syndrome patients receiving MMF were investigated using data from a Japanese hospital claims database (April 2008-September 2021). RESULTS: Data on 424 primary nephrotic syndrome patients receiving MMF (146 patients < 18 years old; 278 patients ≥ 18 years old) were captured. The most common initial daily doses of MMF capsules (% of patients < 18 and ≥ 18 years old) were 1000 mg (31.9%, 36.8%), 1500 mg (16.0%, 23.8%), and 500 mg (23.6%, 17.3%), and the most common maximum daily doses were 1000 mg (43.8%, 32.9%), 1500 mg (23.6%, 28.9%), and 2000 mg (6.3%, 16.2%). Most patients (97.9%, 99.3%) were treated with a daily dose of 2000 mg or less. Among patients < 18 years old, the younger the patient, the lower the dose. MMF was used for more than 1 year in 30.8% of patients < 18 years old and in 28.8% of patients ≥ 18 years old. CONCLUSIONS: Our study suggested that off-label use of MMF for primary nephrotic syndrome has increased since 2012 in Japan. The dose of MMF used in patients with primary nephrotic syndrome was generally within the approved dose range for lupus nephritis and transplant-related diseases in Japan.
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Ácido Micofenólico , Síndrome Nefrótica , Adolescente , Adulto , Cápsulas/uso terapêutico , Criança , Quimioterapia Combinada , Hospitais , Humanos , Imunossupressores/uso terapêutico , Japão , Ácido Micofenólico/uso terapêutico , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/tratamento farmacológico , Esteroides/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: Limited information is available on patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) receiving mycophenolate mofetil (MMF) in Japan. The dose, treatment duration, and patient characteristics of SSc and SSc-ILD patients receiving MMF were investigated. METHODS: We used data from a Japanese hospital claims database (2008-2020). RESULTS: Data on 486 SSc patients ≥18 years old receiving MMF were captured; 314 had SSc complicated with ILD. The most common initial daily doses were 1000 mg (SSc, 39.5%; SSc-ILD, 38.1%) and 500 mg (SSc, 36.6%; SSc-ILD, 34.6%). The most common maximum daily doses were 1000 mg (SSc, 33.3%; SSc-ILD, 34.9%), 1500 mg (SSc, 24.4%; SSc-ILD, 23.1%), and 2000 mg (SSc, 23.8%; SSc-ILD, 24.4%). Doses ranged from 250 to 3000 mg/day and were similar for SSc and SSc-ILD patients. Over 27% of patients received treatment for >1 year. There was a gradual decrease in steroid doses during MMF treatment. CONCLUSIONS: Our study suggests that the off-label use of MMF for SSc and SSc-ILD has been increasing annually since 2015 in Japan. The doses used in patients with SSc and SSc-ILD were similar to the approved doses of MMF for lupus nephritis in Japan.
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Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Adolescente , Ciclofosfamida/uso terapêutico , Hospitais , Humanos , Imunossupressores/uso terapêutico , Japão , Pulmão , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/etiologia , Ácido Micofenólico/uso terapêutico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológicoRESUMO
Cationic magnetic hydrogel microparticles with high retention on cell surfaces were prepared using a two-step procedure. Using these magnetic hydrogel microparticles, cells were clustered with each other, and cell aggregates were prepared effectively. Cross-linked poly(vinyl alcohol) (PVA) hydrogel microparticles containing iron oxide nanoparticles were prepared. The diameter of the microparticles was in the range of 200-500 nm. Water-soluble cationic polymers containing both trimethyl ammonium (TMA) groups and phenylboronic acid (PBA) groups were synthesized for the surface modification of the microparticles. To regulate the composition, electrically neutral phosphorylcholine groups were introduced into the polymer. Covalent bonds were formed between the hydroxy groups of PVA microparticles and PBA groups in the polymer. The surface zeta potential of the microparticles reflected the composition of the TMA groups. The particles responded to an external magnetic field and clustered rapidly. Microparticles were adsorbed on the floating cell surface and induced cell aggregation quickly when a magnetic field was applied. Under the most effective conditions, the diameter of the cell aggregates increased to approximately 1 mm after 30 min. Denser cell aggregates were formed by the synergistic effects of the magnetic field and the properties of the microparticles. The formed cell aggregates continued to grow for more than 4 days under an applied magnetic field, indicating that the ability of the cells in the aggregate to proliferate was well maintained.
Assuntos
Hidrogéis , Polímeros , Fenômenos Magnéticos , Magnetismo , Álcool de PolivinilRESUMO
INTRODUCTION: Digital immunoassays (DIAs) and molecular point-of-care (POC) tests for influenza were recently developed. We aimed to evaluate and compare the positive rate with molecular POC tests and DIAs in detecting influenza virus A, B and respiratory syncytial virus (RSV). METHODS: A prospective observational study was conducted in 2019-2020. Nasopharyngeal swab samples were collected from adult outpatients with influenza-like illness who visited four hospitals and clinics in Japan. DIAs were performed at each facility. The clinical diagnosis was determined based on the findings of DIAs, history taking, and physical assessment. Molecular POC test and reverse transcription polymerase chain reaction (RT-PCR) were performed later. RESULTS: A total of 182 patients were evaluated. The positive rate for influenza virus with molecular POC test was significantly higher than that with DIAs (51.6% versus 40.7%, p = 0.046). In patients who tested positive for influenza virus with only molecular POC test, the presence of influenza virus was confirmed by RT-PCR. In a comparison between the patients who were positive for influenza virus with only molecular POC test and those with both molecular POC test and DIA, the percentage of patients who sought consultation within 18 h after the onset of symptoms was significantly higher in the molecular POC test only group than in the both methods group (70.0% versus 43.2%, p = 0.044). CONCLUSIONS: A molecular POC test could contribute to the accurate diagnosis of influenza in patients with influenza-like illness, especially those who visited a hospital immediately after the onset of symptoms.
Assuntos
Vírus da Influenza A , Influenza Humana , Orthomyxoviridae , Infecções por Vírus Respiratório Sincicial , Adulto , Humanos , Imunoensaio , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Japão , Orthomyxoviridae/genética , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Randomized controlled trials (RCTs) enroll hundreds of millions of subjects and involve many human lives. To improve subjects' welfare, I propose a design of RCTs that I call Experiment-as-Market (EXAM). EXAM produces a welfare-maximizing allocation of treatment-assignment probabilities, is almost incentive-compatible for preference elicitation, and unbiasedly estimates any causal effect estimable with standard RCTs. I quantify these properties by applying EXAM to a water-cleaning experiment in Kenya. In this empirical setting, compared to standard RCTs, EXAM improves subjects' predicted well-being while reaching similar treatment-effect estimates with similar precision.
Assuntos
Experimentação Humana/ética , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Sujeitos da Pesquisa/psicologia , Causalidade , Humanos , Modelos Teóricos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Sujeitos da Pesquisa/estatística & dados numéricosRESUMO
A 44-year-old woman in the first remission phase of mixed-phenotype acute leukemia (T-lymphoid and myeloid lineages) suddenly exhibited thrombocytopenia (1.1×104/µl) with generalized petechiae approximately 150 days after bone marrow transplantation (BMT) from a one-locus (HLA-B) mismatched unrelated donor. Until then, the donor bone marrow had smoothly engrafted, and the platelet count had promptly normalized. Despite extensively searching for the triggering agent such as GVHD, graft failure, relapsed leukemia, or adverse drug effects, it could not be determined. Suspecting immune thrombocytopenia secondary to BMT, prednisolone (1 mg/kg/2 days) therapy was initiated, but its effects were unsatisfactory. Next, eltrombopag, a thrombopoietin receptor agonist (TPO-RA), was administered, which exhibited a marked effect on thrombocytopenia, resulting in the withdrawal of prednisolone. Even though the efficacy of eltrombopag against immune thrombocytopenia is well established, limited studies have reported the efficacy and safety of eltrombopag against immune thrombocytopenia after allogeneic stem cell transplantation. Herein we report a case in which thrombocytopenia occurred late after transplantation but was successfully treated with a TPO-RA. In addition, we discuss suspected causative mechanisms and review the literature.
Assuntos
Benzoatos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Hidrazinas/uso terapêutico , Púrpura Trombocitopênica Idiopática/terapia , Pirazóis/uso terapêutico , Trombocitopenia , Adulto , Feminino , Humanos , Resultado do TratamentoRESUMO
OBJECTIVES: The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. MATERIALS AND METHODS: Our analysis compared the 'EGFR testing strategy', in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the 'no-testing strategy,' in which genetic testing was not conducted and all patients were treated with standard chemotherapy. A three-state Markov model was constructed to predict expected costs and outcomes for each strategy. We included only direct medical costs from the healthcare payer's perspective. Outcomes in the model were based on those reported in the Iressa Pan-Asia Study (IPASS). The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life-years (QALYs) gained. Sensitivity and scenario analyses were conducted. RESULTS: The incremental cost and effectiveness per patient of the 'EGFR testing strategy' compared to the 'no-testing strategy' was estimated to be approximately JP¥122,000 (US$1180; US$1=JP¥104 as of February 2014) and 0.036 QALYs. The ICER was then calculated to be around JP¥3.38 million (US$32,500) per QALY gained. These results suggest that the 'EGFR testing strategy' is cost-effective compared with the 'no-testing strategy' when JP¥5.0 million to 6.0 million per QALY gained is considered an acceptable threshold. These results were supported by the sensitivity and scenario analyses. CONCLUSION: The combination use of gefitinib and EGFR testing can be considered a cost-effective first-line therapy compared to chemotherapy such as carboplatin-paclitaxel for the treatment for NSCLC in Japan.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/economia , Quinazolinas/administração & dosagem , Quinazolinas/economia , Administração Intravenosa , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Carboplatina/administração & dosagem , Carboplatina/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/patologia , Análise Custo-Benefício , Análise Mutacional de DNA/economia , Análise Mutacional de DNA/métodos , Técnicas de Apoio para a Decisão , Farmacoeconomia , Receptores ErbB/antagonistas & inibidores , Gefitinibe , Humanos , Japão , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/patologia , Cadeias de Markov , Mutação , Paclitaxel/administração & dosagem , Paclitaxel/economia , Medicina de Precisão , Adulto JovemRESUMO
A 50-year-old man with a history of long-term corticosteroid treatment following adrenalectomy for Cushing's syndrome and uncontrolled diabetes mellitus was admitted for an examination of an abnormal thoracic shadow. Cryptococcal serum antigens were positive, and the histopathology of a lung biopsy showed encapsulated yeast resembling Cryptococcus neoformans. On admission, the serum ß-D-glucan level was approximately twice the cutoff value, several nodules were observed on both legs and magnetic resonance imaging revealed subcutaneous abscesses. Candida albicans was identified from needle aspirates, and the patient was successfully treated with fluconazole and flucytosine. We herein report the first case of concurrent C. albicans skin abscesses and pulmonary cryptococcosis.
Assuntos
Abscesso/etiologia , Candidíase Cutânea/etiologia , Criptococose/etiologia , Diabetes Mellitus Tipo 2/complicações , Glucocorticoides/administração & dosagem , Pneumopatias Fúngicas/etiologia , Abscesso/diagnóstico , Adrenalectomia , Candida albicans , Candidíase Cutânea/diagnóstico , Criptococose/diagnóstico , Síndrome de Cushing/complicações , Síndrome de Cushing/terapia , Humanos , Pneumopatias Fúngicas/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
Many clinical cases of acquired resistance to the BRAF inhibitor vemurafenib have recently been reported. One of the causes of this acquired resistance is the BRAF downstream kinase point mutation MEK1-C121S. This mutation confers resistance to not only vemurafenib, but also to the allosteric MEK inhibitor selumetinib (AZD6244). Here, we investigated the pharmacologic activities and effectiveness of the novel MEK inhibitor E6201 against BRAF (v-raf murine sarcoma viral oncogene homolog B1)-V600E mutant melanoma harboring the MEK1-C121S mutation. A cell-free assay confirmed that E6201 is an ATP-competitive MEK inhibitor, meaning it has a different binding mode with MEK compared with allosteric MEK inhibitors. E6201 is more effective against BRAF-V600E mutant melanoma compared with BRAF wild-type melanoma based on MEK inhibition. We found that the acquired MEK1-C121S mutation in BRAF-V600E mutant melanoma conferred resistance to both vemurafenib and selumetinib but not E6201. The effectiveness of E6201 in this preclinical study is a result of its binding with MEK1 far from the C121S point mutation so the mutation is unable to influence the MAPK pathway inhibitory activity. These results support further clinical investigation of E6201.
Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Indóis/farmacologia , Lactonas/farmacologia , MAP Quinase Quinase 1/genética , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Sulfonamidas/farmacologia , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Indóis/uso terapêutico , Lactonas/uso terapêutico , MAP Quinase Quinase 1/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/genética , Mutagênese Sítio-Dirigida , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/uso terapêutico , VemurafenibRESUMO
A 60-year-old woman was admitted with low fever, dry cough and occult hematuria with abnormality on her chest X-ray film showing patchy shadows in the apices of both lungs. The patient was seronegative for PR-3 ANCA and seropositive for MPO-ANCA and transbronchial lung biopsy showed inflammatory granulation tissue. We performed an open lung biopsy to achieve a definitive diagnosis. The lung specimen showed the typical findings of Wegener's granulomatosis. Renal biopsy revealed necrotizing glomerulonephiritis. A systemic form of Wegener's granulomatosis was diagnosed. Initilal treatment combined oral prednisolone at 30 mg daily with oral cyclophosphamide at 50 mg daily improved not only the clinical course, but also the radiographic findings. Finally, she became seronegative for MPO-ANCA.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Granulomatose com Poliangiite/diagnóstico , Feminino , Granulomatose com Poliangiite/imunologia , Humanos , Pessoa de Meia-IdadeRESUMO
An 83-year-old woman was admitted to our hospital because of fever and difficulty in walking with marked hypoxemia and diffuse ground glass opacities in bilateral lung fields by chest radiography and CT scanning. Treatment with antibiotics and corticosteroids resulted in improvement of the clinical findings and successful weaning from mechanical ventilation. At first, we diagnosed severe mycoplasma pneumonia because of a 2560 titer in a particle agglutiation (PA) test. Five days after discharge, she was given a second emergency admission, because of fever and difficulty in walking. Chest X-ray film revealed improvement after administration of methylprednisolone. Her detailed medical history proved that she had been treated with a Chinese herbal drug, Sai-rei-to, for several weeks before first admission. We finally diagnosed her disease as Sai-rei-to-induced pneumonitis. Despite intensive treatment, she finally died. The histopathological findings (H-E stain) of the autopsied lungs showed hyaline membrane formation and hyperplasia of type II alveolar epithelium cells, so-called, diffuse alveolar damage. This case and other referred in the literature suggest that Sai-rei-to-induced pneumonitis can become severe.
Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Medicina Kampo , Pneumonia/induzido quimicamente , Síndrome do Desconforto Respiratório/induzido quimicamente , Doença Aguda , Idoso de 80 Anos ou mais , Evolução Fatal , Feminino , Humanos , Pneumonia/patologia , Recidiva , Síndrome do Desconforto Respiratório/patologiaRESUMO
Cardiac fibrosis, characterized by excessive deposition of extracellular matrix proteins, is one of the causes of heart failure, and it contributes to the impairment of cardiac function. Fibrosis of various tissues, including the heart, is believed to be regulated by the signalling pathway of angiotensin II (Ang II) and transforming growth factor (TGF)-beta. Transgenic expression of inhibitory polypeptides of the heterotrimeric G12 family G protein (Galpha(12/13)) in cardiomyocytes suppressed pressure overload-induced fibrosis without affecting hypertrophy. The expression of fibrogenic genes (TGF-beta, connective tissue growth factor, and periostin) and Ang-converting enzyme (ACE) was suppressed by the functional inhibition of Galpha(12/13). The expression of these fibrogenic genes through Galpha(12/13) by mechanical stretch was initiated by ATP and UDP released from cardiac myocytes through pannexin hemichannels. Inhibition of G-protein-coupled P2Y6 receptors suppressed the expression of ACE, fibrogenic genes, and cardiac fibrosis. These results indicate that activation of Galpha(12/13) in cardiomyocytes by the extracellular nucleotides-stimulated P2Y(6) receptor triggers fibrosis in pressure overload-induced cardiac fibrosis, which works as an upstream mediator of the signalling pathway between Ang II and TGF-beta.
Assuntos
Pressão Sanguínea , Fibrose , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Receptores Purinérgicos P2/fisiologia , Transdução de Sinais , Trifosfato de Adenosina/metabolismo , Animais , Moléculas de Adesão Celular/biossíntese , Fator de Crescimento do Tecido Conjuntivo/biossíntese , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Peptidil Dipeptidase A/biossíntese , Antagonistas do Receptor Purinérgico P2 , Ratos , Fator de Crescimento Transformador beta/biossíntese , Difosfato de Uridina/metabolismoRESUMO
A 20-year-old woman, with systemic lupus erythmatosus complicated by steroid-and immunosuppressant-resistant bilateral pleural effusion, was admitted to the emergency room because of dyspnea and fever. Chest Xray film revealed bilateral massive pleural effusion. Bilateral thoracocentesis yielded fluid with chyle. Conservative treatment including intravenous hyper-alimentation and continuous drainage were performed but with no remarkable improvement. She underwent thoracoscopy-aided ligation of the thoracic duct. After the operation, bilateral pleurodesis was performed by intrathoracic injection of OK-432, because of uncontrolled pleural effusion. There have been no signs of recurrence at 10 months in this case of SLE with steroid-and immunosuppressant-resistant pleural effusion.
Assuntos
Quilotórax/etiologia , Lúpus Eritematoso Sistêmico/etiologia , Derrame Pleural/complicações , Adulto , Quilotórax/terapia , Drenagem , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores , Ligadura , Picibanil/administração & dosagem , Derrame Pleural/terapia , Pleurodese , Prednisolona , Ducto Torácico/cirurgia , Toracoscopia , Resultado do TratamentoRESUMO
A 48-year-old man with diabetes mellitus and alcholic chronic pancreatitis was admitted to our hospital with fever and dyspnea. Chest x-ray film showed infiltration of the right upper lung field and blood exam demonstrated marked increase in CPK and renal dysfunction. Intravenous ceftriaxone sodium was started, but the next day, we started intravenous ciprofloxacin because the urine sample was positive for the Legionella antigen. Hemodialysis was started for acute renal failure due to rhabdomyolysis, and mechanical ventilation was introduced due to worsening of acute respiratory failure. Despite these treatments, bilateral infiltration on chest x-ray worsened, resulting in acute respiratory distress syndrome (ARDS). After administration of intravenous pulse methylpredonisolone and sivelestat (neutrophil elastase inhibitor), the patient was successfully weaned from mechanical ventilation. He was also removed from hemodialysis, and discharged from hospital with a good performance status 28 days later. The outcome in this case suggested that treatment with pulse steroid and sivelestat sodium in addition to antibiotics may be effective for Legionella pneumonia complicated by ARDS and acute renal failure.
Assuntos
Injúria Renal Aguda/etiologia , Glucocorticoides/uso terapêutico , Glicina/análogos & derivados , Doença dos Legionários/complicações , Doença dos Legionários/tratamento farmacológico , Metilprednisolona/uso terapêutico , Síndrome do Desconforto Respiratório/etiologia , Sulfonamidas/uso terapêutico , Glicina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Case 1 was a 62-year-old man who had performance status (PS) of 1 and stage IIIB adenocarcinoma of the lung. Because he showed progressive disease after induction chemoradiotherapy, he started to receive best supportive care alone. Three months after initial diagnosis, he complained of abdominal pain. As a result of computed tomography of the abdomen. He was diagnosed with abdominal pain probably caused by ileal perforation. An operation was undertaken and the surgical findings showed perforation by small intestine metastasis from lung adenocarcinoma. After the operation, he survived more than ten months. Case 2 was a 54-year-old man who had a PS of 3 and stage IV large cell carcinoma. After chemotherapy and sequential cranial radiotherapy, he developed anemia of unknown cause. He also complained of an abdominal pain during hospitalization and digestive tract perforation was diagnosed by a CT scan of the abdomen. He underwent surgery and the surgical findings showed a metastasis of large cell carcinoma in the small intestine. He died in a hospice two months after the operation. In the Japanese literature from 1983 to 2006. 48 operated cases with perforation caused by small intestine metastasis of lung cancer have been reported in full-length papers. Although the postoperative median survival time was 48 days, only one surgery-related death occurred. Patients who had a history of prior cancer treatment before surgery tended to achieve more prolonged survival compared to those who had not cancer treatment, probably due to poor PS. The preoperative PS may be one important prognostic factor in these patients.