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1.
Cureus ; 15(10): e46733, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022050

RESUMO

Tracheal papillomatosis is a rare and challenging condition characterized by the development of benign tumors in the trachea and bronchial tree. This case report presents a 53-year-old female with refractory papillomatosis and mediastinal lymphadenopathy. Despite three previous resections, the papilloma recurred, causing moderate tracheal narrowing and symptoms mimicking severe persistent asthma. In June 2023, the patient underwent bronchoscopy with successful tumor debulking cryosurgery, significantly improving her symptoms.

2.
Cureus ; 15(8): e44226, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37645669

RESUMO

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) has proven to be highly accurate in lung cancer diagnosis and staging. However, its efficacy in diagnosing lymphoma, especially Hodgkin's lymphoma, remains controversial, mainly due to the need for larger biopsies for definitive diagnosis. This case study presents a 53-year-old HIV-positive man with a controlled viral load, who presented with a large left hilar mass and a left upper lobe nodule, both showing significant uptake on positron emission tomography scans. The patient underwent bronchoscopy with bronchoalveolar lavage, EBUS-TBNA using an Olympus™ Vizishot 2 needle (Center Valley, PA), and EBUS-guided transbronchial forceps biopsies (TBFB) of a left hilar lymph node using a 1.8 mm Boston Scientific™ forceps (Marlborough, MA). The EBUS-TBNA revealed granulomas, while the subsequent EBUS-guided TBFB revealed nodular lymphocyte-predominant Hodgkin's lymphoma. EBUS-TBFB may be a promising technique for obtaining larger tissue samples and enhancing diagnostic yield in cases of mediastinal lymphadenopathy with suspected lymphoma.

3.
South Med J ; 116(2): 202-207, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36724536

RESUMO

OBJECTIVE: The diagnostic accuracy and yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is not well established in lymphoma and other mediastinal-related diseases. The objective of this study was to examine the yield of a combined technique of EBUS-TBNA and endobronchial ultrasound-guided transbronchial forceps biopsies (EBUS-TBFB) compared with each modality alone in lymphoma and other mediastinal-related diseases. METHODS: This was a retrospective review of cases of mediastinal lymphadenopathy of unknown etiology accessed using TBNA and TBFB. The McNemar test was used to compare the diagnostic yield of TBNA, TBFB, and the combined technique. RESULTS: The combined approach yielded a definitive diagnosis in 31/35 cases (88.6%). In 9/10 cases (90%), Hodgkin's and non-Hodgkin's lymphomas were diagnosed and subtyped without further need for invasive testing. All of the granulomatous inflammation cases were confirmed using the combined technique. Two cases led to adequate whole-genome sequencing of lung cancer, and one patient was diagnosed as having dedifferentiated liposarcoma despite a nondiagnostic preprocedural mediastinoscopy. There was only one procedure-related complication, a pneumomediastinum that required no further intervention. There were no significant adverse events. CONCLUSIONS: The combination of EBUS-TBFB and EBUS-TBNA is safe and provides a high yield in the diagnosis of mediastinal adenopathy of unknown etiology, especially lymphoma. Furthermore, the larger samples obtained from TBFB increased its sensitivity to detect granulomatous disease and provided specimens for clinical trials of malignancy when needle aspirates were insufficient.


Assuntos
Neoplasias Pulmonares , Linfadenopatia , Linfoma , Humanos , Linfonodos/diagnóstico por imagem , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/etiologia , Linfoma/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Instrumentos Cirúrgicos , Estudos Retrospectivos , Broncoscopia/métodos , Sensibilidade e Especificidade
4.
Chest ; 162(3): e127-e131, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36088098

RESUMO

CASE PRESENTATION: A previously healthy 57-year-old man presented to the ED with altered mental status and severe shortness of breath. He was found to be in acute hypercapnic respiratory failure and required admission to the ICU. He reported the following: a 4-month history of progressive shortness of breath; left-sided chest pain; cough productive of brown, foul-smelling sputum; and weight loss. He had an extensive smoking history but had quit 1 year prior. The patient was born in Ethiopia but had been living in the United States for the last 20 years. His last visit to Ethiopia was in 2009, and he denied any other recent travel or exposure to TB. There was no history to suggest immune compromise. He had not seen a physician in many years and never established medical care in the United States.


Assuntos
Derrame Pleural , Dor no Peito , Tosse , Dispneia/diagnóstico , Dispneia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia
5.
BMJ Case Rep ; 14(8)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373244

RESUMO

Diffuse alveolar haemorrhage (DAH) has been reported as a rare complication of clopidogrel use and is usually a diagnosis of exclusion. We describe the case of an 88-year-old Native American woman who presented with acute hypoxic respiratory failure with CT scan of the chest showing diffuse bilateral ground-glass opacities. She had been on clopidogrel for 6 months for a carotid artery stent. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsies revealed DAH. Infectious and autoimmune work-up were all negative. Clopidogrel was stopped and high-dose steroids were started. Her symptoms gradually improved until she was discharged from the hospital. The differential DAH is broad. Anticoagulant-induced DAH should be part of the differential diagnosis, and is usually a diagnosis of exclusion.


Assuntos
Pneumopatias , Idoso de 80 Anos ou mais , Lavagem Broncoalveolar , Broncoscopia , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Pneumopatias/diagnóstico , Pneumopatias/diagnóstico por imagem
6.
Clin Lung Cancer ; 22(4): e595-e601, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33526380

RESUMO

BACKGROUND: Thoracic vascular structures often preclude transbronchial access to central lung parenchymal lesions and lymph nodes, thereby necessitating either a surgical or transvascular needle aspiration (TVNA) approach for diagnostic sampling. The aim of this study was to evaluate the safety and efficacy of endobronchial ultrasound (EBUS) TVNA in the diagnosis and staging of mediastinal tumors. PATIENTS AND METHODS: We performed a retrospective analysis of 35 cases of EBUS-TVNA. Cases were reviewed in the Cerner electronic medical records between March 2013 and October 2018. Records were reviewed for patient comorbidities, smoking status, anticoagulation intake, procedural details, sample results, and postprocedural complications. RESULTS: Thirty-five EBUS-TVNA procedures were reviewed. Twenty-nine of them were performed by traversing the main pulmonary artery or its branches. Three involved transvascular access through the azygous vein, 2 via the brachiocephalic artery and 1 through the superior vena cava. Only 4 patients (11.4%) experienced postprocedural complications, which included mild hemoptysis, moderate hemoptysis requiring epinephrine and saline infusion, acute exacerbation of chronic obstructive pulmonary disease, and a rapid ventricular rate on top of preexisting atrial fibrillation. The yield of TVNA for malignancy was 22 (95.6%) of 23 patients. Overall yield was 31 (88.6%) of 35, with a need for additional intervention in 4 (11.4%) of 35 patients. Mutational analysis was adequate when ordered. CONCLUSION: In our single-center experience, the EBUS-TVNA procedure had a high diagnostic yield and was associated with low rates of postprocedural complications. Further trials are needed to assess its efficacy compared to more invasive procedures.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias do Mediastino/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos
8.
Clin Lung Cancer ; 20(3): 186-193.e3, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30711394

RESUMO

INTRODUCTION/BACKGROUND: Many patients with early stage non-small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. MATERIALS AND METHODS: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. RESULTS: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P < .001 and hazard ratio [HR], 1.02 per mL; P < .05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) - (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. CONCLUSION: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Progressão da Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Carga Tumoral
9.
Chest ; 155(2): 307-314, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29990479

RESUMO

BACKGROUND: Treatment of hepatic hydrothorax (HH) generally involves sodium restriction, diuretics, and serial thoracentesis. In more advanced cases, transjugular intrahepatic portosystemic shunt and liver transplantation may be required. Previously, indwelling tube drainage has been avoided due to concerns regarding high complication rates and overall poor outcomes. Recently, indwelling pleural catheters (IPCs) have been proposed as a novel treatment option for HH. METHODS: This study was a retrospective review of patients who had undergone IPC placement for HH over a 10-year period at a large liver transplant referral center. We tracked outcomes, including complication rates and liver transplantation, as well as biomarkers of nutritional status. RESULTS: Sixty-two patients underwent IPC placement between 2007 and 2017, with 33 IPCs (53%) placed as a bridge to liver transplantation. Complications were recorded in 22 patients (36%); empyema was the most common, diagnosed in 10 patients (16.1%). Ten patients evaluated for liver transplantation underwent successful transplantation following IPC placement. There were statistically significant decreases in both BMI and serum albumin levels following IPC placement. CONCLUSIONS: IPCs represent a potential treatment for refractory HH and should be used with caution in patients eligible for liver transplantation. Ideally, IPC use for these patients would be evaluated by a multidisciplinary team. IPC use may lead to small decreases in BMI and serum albumin levels in patients over time.


Assuntos
Cateteres de Demora , Empiema Pleural/terapia , Hidrotórax/terapia , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Toracentese/métodos , Idoso , Causas de Morte , Estudos de Coortes , Empiema Pleural/diagnóstico por imagem , Feminino , Humanos , Hidrotórax/diagnóstico por imagem , Hidrotórax/fisiopatologia , Falência Hepática/diagnóstico , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
10.
South Med J ; 111(8): 484-488, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30075474

RESUMO

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the primary method for the diagnosis and staging of lung cancer. The purpose of this study was to assess the yield of EBUS-TBNA in the subtyping and genotyping of lung adenocarcinoma. METHODS: Sixty-nine patients at Indiana University Hospital and Sidney and Lois Eskenazi Hospital with possible or confirmed lung adenocarcinoma underwent EBUS-TBNA using a 21-gauge Olympus needle without suction. Samples were sent for molecular testing after rapid onsite specimen evaluation. A total of 6 to 10 passes were placed in a cell block. RESULTS: Sixty-nine samples from patients with non-small-cell lung cancer were sent for molecular testing for epidermal growth factor receptor. Results were obtained in all of the patients. Mutations were found in three patients (4.3%). Fifty-eight samples were sent for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (100% yield), 10 of which had mutations (17.2%). Fifty-one samples were sent for proto-oncogene tyrosine-protein kinase ROS testing (1 [7.8%] mutant). Tissue samples were inadequate in three patients (94.1% yield). Sixty-three samples were sent for anaplastic lymphoma receptor tyrosine kinase testing (3 [4.8%] mutant, 6 [9.5%] inadequate, 90.5% yield). CONCLUSIONS: EBUS-TBNA with a 21-gauge needle is appropriate for the analysis of multiple mutations and the genotyping of lung adenocarcinoma.


Assuntos
Biópsia por Agulha/métodos , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Indiana , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proto-Oncogene Mas
11.
J Intensive Care Med ; 32(8): 500-507, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27251106

RESUMO

OBJECTIVE: In our academic intensive care unit (ICU), there is excess ordering of routine laboratory tests. This is partially due to a lack of transparency of laboratory-processing costs and to the admission order plans that favor daily laboratory test orders. We hypothesized that a program that involves physician and staff education and alters the current ICU order sets will lead to a sustained decrease in routine laboratory test ordering. DESIGN: Prospective cohort study. SETTING: Academic closed medical ICU (MICU). PATIENTS: All patients admitted to the MICU. METHODS: We consistently educated residents, faculty, and staff about laboratory test costs. We removed the daily laboratory test option from the admission order sets and asked residents to order needed laboratory test results every day. We only allowed the G3+I-STAT (arterial blood gas only) cartridges in the MICU in hopes of decreasing duplicative laboratory test results. We added laboratory review to the daily rounding checklist. MEASUREMENT AND MAIN RESULTS: Total number of laboratory tests per patient-day decreased from 39.43 to an average of 26.74 ( P <.001) over a 9-month period. The number of iSTAT laboratory tests per patient-day decreased from 7.37 to an average of 1.16 ( P < .001) over the same time period. The number of iSTAT/central laboratory processing duplicative laboratory tests per patient-day decreased from 0.17 to an average of 0.01 ( P < .001). The percentage of patients who have daily laboratory test orders decreased from 100% to an average of 11.94% ( P <. 001). US$123 436 in direct savings and US$258 035 dollars in indirect savings could be achieved with these trends. Intensive care unit morbidity and mortality were not impacted. CONCLUSION: A simple technique of resident, nursing, and ancillary staff education, combined with alterations in order sets using electronic medical records, can lead to a sustained reduction in laboratory test utilization over time and to significant cost savings without affecting patient safety.


Assuntos
Testes Diagnósticos de Rotina/estatística & dados numéricos , Educação Profissionalizante/métodos , Pessoal de Saúde/educação , Unidades de Terapia Intensiva/estatística & dados numéricos , Redução de Custos , Testes Diagnósticos de Rotina/economia , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Satisfação do Paciente , Estudos Prospectivos , Análise de Regressão
12.
Expert Rev Anticancer Ther ; 16(8): 869-75, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27279087

RESUMO

INTRODUCTION: Stereotactic body radiation therapy (SBRT, also called stereotactic ablative body radiation SABR) is the treatment of choice for many patients with early-stage non-small cell lung cancer (NSCLC), including those who are unfit for surgery or refuse surgery. AREAS COVERED: In an effort to develop optimal staging for the evaluation of SBRT candidates, we review the performance of available lymph node staging methods, as well as risk factors for lymph node involvement. Pubmed was searched to identify relevant literature. Current staging methods for NSCLC, including Positron Emission Tomography/Computed Tomography(PET/CT) and endobronchial ultra sound (EBUS), have limited sensitivities. Expert commentary: There are several factors, including primary tumor location, tumor size, and histology that are possibly associated with the sensitivity of PET/CT to detect mediastinal lymph node metastasis. Small lymph node metastases typically remain undetected by PET/CT. Therefore invasive nodal staging procedures are indicated for most presumed early-stage NSCLC patients, but these also have limited sensitivity. Occult lymph node metastasis is associated with adverse outcome in NSCLC. Moreover, there is overwhelming evidence that certain patients who have lymph node metastases detected at the time of surgery derive an overall survival benefit from adjuvant therapies. It remains to be determined if improved detection of lymph node metastases in SABR candidates can indeed improve prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Taxa de Sobrevida
13.
J Bronchology Interv Pulmonol ; 23(3): 255-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27261934

RESUMO

BACKGROUND: The diffuse alveolar hemorrhage (DAH) syndrome is a life-threatening pulmonary complication related to systemic vasculitides, posthematopoietic stem cell transplantation, drugs, or toxins. Once DAH develops, the mortality rate is as high as 50% to 80%. Initial treatment consists of high-dose steroids and supportive measures, including mechanical ventilation. We present a case series of 6 patients treated with intrapulmonary recombinant factor VIIa (rFVIIa) to treat refractory DAH. METHODS: Six patients with DAH were treated with intrapulmonary instillation of rFVIIa. Doses were divided equally between the right and the left lungs. Doses were 30, 50, or 60 mcg/kg and frequencies varied from a single administration to repeated doses on subsequent days on the basis of the clinical response. All patients received high-dose steroids, and 4 also received an aminocaproic acid infusion. RESULTS: Intrapulmonary rVFIIa treated DAH effectively in 5 of 6 patients. Doses used were smaller and less frequent than those described previously. CONCLUSIONS: Intrapulmonary factor VII is an effective adjunctive treatment for DAH. We achieved treatment success with both smaller and less frequent doses than those described previously. This may be a good therapeutic option for DAH, particularly when standard therapies have failed or bleeding is immediately life threatening. It is possible that intrapulmonary rFVIIa could save costs, while improving the intensive care unit length of stay. Further prospective studies are needed to assess the optimal dose and frequency for adequate therapeutic efficacy.


Assuntos
Ácido Aminocaproico/administração & dosagem , Fator VIIa/administração & dosagem , Hemorragia/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ácido Aminocaproico/uso terapêutico , Quimioterapia Combinada , Fator VIIa/uso terapêutico , Evolução Fatal , Feminino , Hemorragia/etiologia , Humanos , Instilação de Medicamentos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Alvéolos Pulmonares/patologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Adulto Jovem
15.
BMJ Case Rep ; 20142014 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-25312888

RESUMO

Pulmonary arteriovenous malformations are uncommon communications between the pulmonary arteries and veins, most commonly associated with hereditary haemorrhagic telangiectasia. They can also be associated with a variety of other conditions, and can be single or multiple. We present a case of a female patient with a history of coronary artery bypass grafting and mitral valve repair, who presented to the hospital with severe hypoxia. She was found to have a large pulmonary artery to superior pulmonary vein fistula that was successfully repaired using a septal occluder. To our knowledge, this is the first case of a large pulmonary artery to superior pulmonary vein fistula following mitral valve repair.


Assuntos
Fístula Arteriovenosa/complicações , Hipóxia/etiologia , Complicações Pós-Operatórias , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Idoso , Fístula Arteriovenosa/terapia , Diagnóstico Diferencial , Feminino , Humanos , Estenose da Valva Mitral/cirurgia , Dispositivo para Oclusão Septal
16.
Case Rep Crit Care ; 2013: 832306, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24829830

RESUMO

This paper describes the case of a 75-year-old female who presented with significant hemoptysis over a 7-10 day period. She had a history of a left lower lobectomy 10 years prior for a "lung abscess." She subsequently had multiple episodes of cough, fevers, and possible pneumonia treated with multiple courses of Amoxicillin and Amoxicillin/Clavulanate. Review of her chest CT upon presentation to the hospital showed a large necrotic lingular infiltrate, which had been progressively increasing in size over at least one year. Bronchoscopy showed a yellowish, soft round body in the superior lingular subsegment. Endobronchial and transbronchial biopsies showed actinomyces species. This is a very interesting case of indolent actinomycosis which we suspect had a very slow progressive course secondary to the multiple courses of antibiotics that the patient was treated with.

17.
Biol Blood Marrow Transplant ; 18(12): 1827-34, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22766224

RESUMO

Nonmyeloablative conditioning before allogeneic hematopoietic cell transplant (HCT) is an alternative to conventional conditioning in older patients and those with comorbidities. It is not known whether the decreased tissue injury associated with nonmyeloablative conditioning lowers the risk of pulmonary complications. The medical records of patients who underwent transplantation were reviewed and all pulmonary complications documented. Sixty-two consecutive patients with hematologic malignancies who underwent minimally intensive HCT (subjects) were compared to 48 consecutive patients who received conventional myeloablative allogeneic peripheral blood HCT (controls) over the same period at Indiana University Hospital. Pulmonary complications were categorized according to the type of complication and the time of onset after transplantation. Median follow-up times were similar between groups (P = .70). The study population (minimal intensity recipients) was older (P < .01), and the incidence of chronic graft-versus-host disease (cGVHD) was higher in subjects than controls (P = .02). Sixty-nine percent of subjects and 73% of controls developed pulmonary complications (P = .70). There was a trend in the minimally conditioned patients towards a lower incidence of pulmonary complications in older patients in the early posttransplantation period and a higher incidence of infectious pneumonias and bronchiolitis obliterans syndrome at later time points. The frequency of pulmonary complications seems to be similar after minimally intensive or myeloablative conditioning and allotransplantation. There was no difference in overall mortality or pulmonary-related mortality between the 2 groups.


Assuntos
Bronquiolite Obliterante/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Pneumopatias/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Bronquiolite Obliterante/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade
18.
Am J Respir Crit Care Med ; 181(4): 344-52, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19965812

RESUMO

RATIONALE: Vascular endothelial growth factor receptor (VEGFR) inhibition increases ceramides in lung structural cells of the alveolus, initiating apoptosis and alveolar destruction morphologically resembling emphysema. The effects of increased endogenous ceramides could be offset by sphingosine 1-phosphate (S1P), a prosurvival by-product of ceramide metabolism. OBJECTIVES: The aims of our work were to investigate the sphingosine-S1P-S1P receptor axis in the VEGFR inhibition model of emphysema and to determine whether stimulation of S1P signaling is sufficient to functionally antagonize alveolar space enlargement. METHODS: Concurrent to VEGFR blockade in mice, S1P signaling augmentation was achieved via treatment with the S1P precursor sphingosine, S1P agonist FTY720, or S1P receptor-1 (S1PR1) agonist SEW2871. Outcomes included sphingosine kinase-1 RNA expression and activity, sphingolipid measurements by combined liquid chromatography-tandem mass spectrometry, immunoblotting for prosurvival signaling pathways, caspase-3 activity and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assays, and airspace morphometry. MEASUREMENTS AND MAIN RESULTS: Consistent with previously reported de novo activation of ceramide synthesis, VEGFR inhibition triggered increases in lung ceramides, dihydroceramides, and dihydrosphingosine, but did not alter sphingosine kinase activity or S1P levels. Administration of sphingosine decreased the ceramide-to-S1P ratio in the lung and inhibited alveolar space enlargement, along with activation of prosurvival signaling pathways and decreased lung parenchyma cell apoptosis. Sphingosine significantly opposed ceramide-induced apoptosis in cultured lung endothelial cells, but not epithelial cells. FTY720 or SEW2871 recapitulated the protective effects of sphingosine on airspace enlargement concomitant with attenuation of VEGFR inhibitor-induced lung apoptosis. CONCLUSIONS: Strategies aimed at augmenting the S1P-S1PR1 signaling may be effective in ameliorating the apoptotic mechanisms of emphysema development.


Assuntos
Alvéolos Pulmonares/efeitos dos fármacos , Enfisema Pulmonar/tratamento farmacológico , Receptores de Lisoesfingolipídeo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Western Blotting , Células Cultivadas , Ceramidas/biossíntese , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cloridrato de Fingolimode , Indóis/farmacologia , Lisofosfolipídeos/biossíntese , Lisofosfolipídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Reação em Cadeia da Polimerase , Propilenoglicóis/farmacologia , Alvéolos Pulmonares/fisiopatologia , Enfisema Pulmonar/fisiopatologia , Pirróis/farmacologia , Receptores de Lisoesfingolipídeo/fisiologia , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Receptores de Fatores de Crescimento do Endotélio Vascular/fisiologia , Transdução de Sinais/efeitos dos fármacos , Esfingosina/análogos & derivados , Esfingosina/biossíntese , Esfingosina/farmacologia
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