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4.
Int J Cancer ; 144(1): 190-199, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30255938

RESUMO

Tyrosine kinase inhibitors (TKI) have improved prognosis in metastatic anaplastic lymphoma kinase (ALK)-driven lung adenocarcinoma, but patient outcomes vary widely. We retrospectively analyzed the clinical course of all cases with assessable baseline TP53 status and/or ALK fusion variant treated at our institutions (n = 102). TP53 mutations were present in 17/87 (20%) and the echinoderm microtubule-associated protein-like 4 (EML4)-ALK variant 3 (V3) in 41/92 (45%) patients. The number of metastatic sites at diagnosis was affected more by the presence of V3 than by TP53 mutations, and highest with both factors (mean 5.3, p < 0.001). Under treatment with ALK TKI, progression-free survival (PFS) was shorter with either TP53 mutations or V3, while double positive cases appeared to have an even higher risk (hazard ratio [HR] = 2.9, p = 0.015). The negative effect of V3 on PFS of TKI-treated patients was strong already in the first line (HR = 2.5, p = 0.037) and decreased subsequently, whereas a trend for PFS impairment under first-line TKI by TP53 mutations became stronger and statistically significant only when considering all treatment lines together. Overall survival was impaired more by TP53 mutations (HR = 4.9, p = 0.003) than by V3 (HR = 2.4, p = 0.018), while patients with TP53 mutated V3-driven tumors carried the highest risk of death (HR = 9.1, p = 0.02). Thus, TP53 mutations and V3 are independently associated with enhanced metastatic spread, shorter TKI responses and inferior overall survival in ALK+ lung adenocarcinoma. Both markers could assist selection of cases for more aggressive management and guide development of novel therapeutic strategies. In combination, they define a patient subset with very poor outcome.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mutação , Proteínas de Fusão Oncogênica/genética , Proteína Supressora de Tumor p53/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Proteína Supressora de Tumor p53/metabolismo
5.
Clin Microbiol Infect ; 24 Suppl 1: e1-e38, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544767

RESUMO

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Gerenciamento Clínico , Anticorpos Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/complicações , Aspergilose/imunologia , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Biópsia/métodos , Lavagem Broncoalveolar , Diagnóstico Precoce , Flucitosina/farmacologia , Flucitosina/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Imagem por Ressonância Magnética , Mananas/análise , Testes de Sensibilidade Microbiana , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico
6.
Artigo em Inglês | MEDLINE | ID: mdl-29440884

RESUMO

Objective: Endoscopic valve therapy aims at target lobe volume reduction (TLVR) that is associated with improved lung function, exercise tolerance and quality of life in emphysema patients. So far, a TLVR of >350 mL was considered to be indicative of a positive response to treatment. However, it is not really known what amount of TLVR is crucial following valve implantation. Patients and methods: TLVR, forced expiratory volume in 1 second (FEV1), residual volume (RV) and 6-minute walk distance (6-MWD) were assessed before and 3 months after valve implantation in 119 patients. TLVR was calculated based on computed tomography (CT) scan analysis using imaging software (Apollo; VIDA Diagnostics). Minimal important difference estimates were calculated by anchor-based and distribution-based methods. Results: Patients treated with valves experienced a mean change of 0.11 L in FEV1, -0.51 L in RV, 44 m in 6-MWD and a TLVR of 945 mL. Using a linear regression and receiver operating characteristic analysis based on two of three anchors (ΔFEV1, ΔRV), the estimated minimal important difference for TLVR was between 890 and 1,070 mL (ie, 49%-54% of the baseline TLV). Conclusion: In future, a TLVR between 49% and 54% of the baseline TLV, should be used when interpreting the clinical relevance.


Assuntos
Broncoscopia/métodos , Pulmão/cirurgia , Enfisema Pulmonar/cirurgia , Broncoscopia/efeitos adversos , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Tomografia Computadorizada Multidetectores , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/psicologia , Qualidade de Vida , Recuperação de Função Fisiológica , Volume Residual , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Teste de Caminhada
7.
Pneumologie ; 72(1): 15-63, 2018 01.
Artigo em Alemão | MEDLINE | ID: mdl-29341032

RESUMO

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.


Assuntos
Pneumonia Associada a Assistência à Saúde/diagnóstico , Pneumonia Associada a Assistência à Saúde/terapia , Adulto , Estudos Transversais , Alemanha , Pneumonia Associada a Assistência à Saúde/epidemiologia , Humanos
12.
J Med Case Rep ; 11(1): 289, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-29047403

RESUMO

BACKGROUND: Benign central airway tumors are very rare diseases. Their unspecific symptoms are responsible for late diagnosis. Endoscopic interventions with different techniques and tools are widely used for their treatment. However, in certain cases interventional endoscopy might be unsuccessful and therefore other methods such as high-dose-rate brachytherapy could be a therapeutic option. CASE PRESENTATION: A 76-year-old white German woman was referred to our clinic for an endoscopic treatment of a recurrent granulation polyp in her left main bronchus. She had dyspnea, coughing, and mucus retention. Three times resections via bronchoscopy were performed within less than a year. After each intervention the polyp regrew inside her left main bronchus causing a repeat of the initial symptoms. She presented to our clinic less than 1 month since the last intervention. Twice we performed a rigid bronchoscopy in total anesthesia where we resected the granulation polyp with a snare wire loop and did an argon plasma coagulation of its base. Due to the recurrent growing of the granuloma, we performed a high-dose-rate brachytherapy in conscious sedation after another interventional bronchoscopy with a resection of the polyp and argon plasma coagulation of the base. Three months after brachytherapy our patient came to our clinic for a follow-up with none of the initial symptoms. Only a small remnant of the polyp without a significant occlusion of her bronchus was visualized by bronchoscopy. Furthermore, 6 months after brachytherapy she was not presenting any of the initial symptoms. CONCLUSIONS: This case report shows that high-dose-rate brachytherapy is a therapeutic option for the treatment of benign airway stenosis when other interventional treatments are not or are less than successful. However, further investigations are needed to prove the effectiveness and reliability of the method.


Assuntos
Braquiterapia/métodos , Broncopatias/radioterapia , Granuloma/radioterapia , Pólipos/radioterapia , Idoso , Obstrução das Vias Respiratórias/etiologia , Broncopatias/complicações , Feminino , Granuloma/complicações , Humanos , Pólipos/complicações , Recidiva , Resultado do Tratamento
13.
Eur Radiol ; 27(8): 3275-3282, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28083695

RESUMO

BACKGROUND: Serial chest CT is the standard of care to establish treatment success in invasive pulmonary aspergillosis (IPA). Data are lacking how response should be defined. METHODS: Digital CT images from a clinical trial on treatment of IPA were re-evaluated and compared with available biomarkers. Total volume of pneumonia was added up after manual measurement of each lesion, followed by statistical analysis. RESULTS: One-hundred and ninety CT scans and 309 follow-up datasets from 40 patients were available for analysis. Thirty-one were neutropenic. Baseline galactomannan (OR 4.06, 95%CI: 1.08-15.31) and lesion volume (OR 3.14, 95%CI: 0.73-13.52) were predictive of death. Lesion volume at d7 and trend between d7 and d14 were strong predictors of death (OR 20.01, 95%CI: 1.42-282.00 and OR 15.97, 95%CI: 1.62-157.32) and treatment being rated as unsuccessful (OR 4.75, 95%CI: 0.94-24.05 and OR 40.69, 95%CI: 2.55-649.03), which was confirmed by a Cox proportional hazards model using time-dependent covariates. CONCLUSION: Any increase in CT lesion volume between day 7 and day 14 was a sensitive marker of a lethal outcome (>50%), supporting a CT rescan each one and 2 weeks after initial detection of IPA. The predictive value exceeded all other biomarkers. Further CT follow-up after response at day 14 was of low additional value. KEY POINTS: • CT evaluation offers good prediction of outcome for invasive pulmonary aspergillosis. • Predictive capability exceeds galactomannan, blood counts, and lesion count. • Any progression between day 7 and day 14 constitutes a high-risk scenario.


Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Aspergilose Pulmonar Invasiva/mortalidade , Masculino , Mananas/metabolismo , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Valor Preditivo dos Testes , Análise de Sobrevida , Tomografia Computadorizada por Raios X/estatística & dados numéricos
16.
Int J Chron Obstruct Pulmon Dis ; 11: 3093-3099, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27994448

RESUMO

INTRODUCTION: Valve implantation has evolved as a therapy for patients with advanced emphysema. Although it is a minimally invasive treatment, it is associated with complications, the most common being pneumothorax. Pneumothorax occurs due to the rapid target lobe volume reduction and may be a predictor of clinical benefit despite this complication. OBJECTIVE: The objective of this study was to conduct an exploratory data analysis of patients who developed a pneumothorax following endoscopic valve therapy for emphysema. MATERIALS AND METHODS: This study performed a retrospective evaluation of pneumothorax management and the impact of pneumothorax on clinical outcomes in 70 patients following valve therapy in 381 consecutive patients. RESULTS: Pneumothorax rate following valve therapy was 18%. Pneumothorax management consisted of chest tube insertion, valve removal, and surgical intervention in 87% (61/70), 44% (31/70), and 19% (13/70) of the patients, respectively. Despite pneumothorax, patients experienced modest but significant improvements in lung function parameters (forced expiratory volume in 1 second: 55±148 mL, residual volume: -390±964 mL, total lung capacity: -348±876; all P<0.05). Persistent lobar atelectasis 3 months after recovering from pneumothorax, which was associated with relevant clinical improvement, was observed in only 21% (15/70) of the patients. CONCLUSION: Pneumothorax is a frequent severe complication following valve therapy that requires further intervention. Nevertheless, the pneumothorax does not impair the clinical status in the majority of patients. Patients with lobar atelectasis benefit after recovering from pneumothorax in terms of lung function parameters.


Assuntos
Broncoscopia/efeitos adversos , Broncoscopia/instrumentação , Pulmão/cirurgia , Tomografia Computadorizada Multidetectores , Pneumotórax/etiologia , Enfisema Pulmonar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tubos Torácicos , Remoção de Dispositivo , Feminino , Volume Expiratório Forçado , Nível de Saúde , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Pneumotórax/diagnóstico por imagem , Pneumotórax/terapia , Valor Preditivo dos Testes , Desenho de Prótese , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
Radiologe ; 56(10): 910-916, 2016 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-27659711

RESUMO

CLINICAL/METHODICAL ISSUE: Pulmonary complications are frequent in patients with collagen vascular diseases (CVD). Frequent causes are a direct manifestation of the underlying disease, side effects of specific medications and lung infections. STANDARD RADIOLOGICAL METHODS: The standard radiological procedure for the work-up of pulmonary pathologies in patients with CVD is multidetector computed tomography (MDCT) with thin-slice high-resolution reconstruction. PERFORMANCE: The accuracy of thin-slice CT for the identification of particular disease patterns is very high. The pattern of usual interstitial pneumonia (UIP) representing the direct pulmonary manifestation of rheumatoid arthritis (RA) can be identified with a sensitivity of 45 % and a specificity of 96 %. ACHIEVEMENTS: Both direct pulmonary manifestations, drug-induced toxicity and certain infections can have a similar appearance in thin-slice MDCT in various forms of CVD. Knowledge of the patterns and causes contributes to the diagnostic certainty. PRACTICAL RECOMMENDATIONS: At first diagnosis of a CVD and associated pulmonary symptoms thin-slice MDCT is recommended. Clinical, lung function and imaging follow-up examinations should be performed every 6-12 months depending on the results of the MDCT. In every case the individual CT morphological patterns of pulmonary involvement must be identified. The combination of information on the anamnesis, clinical and imaging results is a prerequisite for an appropriate disease management.


Assuntos
Doenças do Colágeno/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Doenças Vasculares/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Radiografia Torácica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Radiologe ; 56(10): 874-884, 2016 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-27638826

RESUMO

CLINICAL/METHODICAL ISSUE: Granulomas as signs of specific inflammation of the lungs are found in various diseases with pulmonary manifestations and represent an important imaging finding. STANDARD RADIOLOGICAL METHODS: The standard imaging modality for the work-up of granulomatous diseases of the lungs is most often thin-slice computed tomography (CT). There are a few instances, e. g. tuberculosis, sarcoidosis and silicosis, where a chest radiograph still plays an important role. METHODICAL INNOVATIONS: Further radiological modalities are usually not needed in the routine work-up of granulomatous diseases of the chest. In special cases magnetic resonance imaging (MRI) and positron emission tomography (PET)-CT scans play an important role, e. g. detecting cardiac sarcoidosis by cardiac MRI or choline C­11 PET-CT in diagnosing lung carcinoma in scar tissue after tuberculosis. PERFORMANCE: The accuracy of thin-slice CT is very high for granulomatous diseases. ACHIEVEMENTS: In cases of chronic disease and fibrotic interstitial lung disease it is important to perform thin-slice CT in order to diagnose a specific disease pattern. Thin-slice CT is also highly sensitive in detecting disease complications and comorbidities, such as malignancies. Given these indications thin-slice CT is generally accepted in the routine daily practice. PRACTICAL RECOMMENDATIONS: A thin-slice CT and an interdisciplinary discussion are recommended in many cases with a suspected diagnosis of pulmonary granulomatous disease due to clinical or radiographic findings.


Assuntos
Granuloma/diagnóstico por imagem , Infecções por Micobactéria não Tuberculosa/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Tuberculose Pulmonar/diagnóstico por imagem , Diagnóstico Diferencial , Humanos
19.
Zentralbl Chir ; 141 Suppl 1: S35-42, 2016 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-27607887

RESUMO

Patients with diffuse airway instability due to tracheobronchomalacia or excessive dynamic airway collapse are typically highly symptomatic, with marked dyspnoea, recurrent bronchopulmonary infections and excruciating intractable cough. Silicone stents achieve immediate symptom control, but are - due to the typical complications associated with stent treatment - usually not an option for long-term treatment. The aim of surgical intervention is definitive stabilisation of the trachea and of both main bronchi by posterior splinting of the Paries membranaceus with a polypropylene mesh. This operation is an appropriate treatment option for patients with documented severe tracheobronchomalacia or excessive dynamic airway collapse and is ultimately the only therapy that can achieve permanent symptom control. The success of the operation, however, depends on many factors and requires close interdisciplinary collaboration.


Assuntos
Brônquios/cirurgia , Traqueia/cirurgia , Traqueobroncomalácia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Broncoscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tireoidectomia , Tomografia Computadorizada por Raios X , Traqueobroncomalácia/diagnóstico , Traqueobroncomegalia/diagnóstico , Traqueobroncomegalia/cirurgia
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