ABSTRACT
El objetivo de esta revisión fue explorar algunos antecedentes en torno de la relación salud oral y migración en tanto tópico de investigación, en el contexto nacional e internacional. Se realizó una revisión bibliográfica de textos publicados entre 2009 y 2019 en bases de datos electrónicas. Se concluyó que existen interesantes cruces posibles de hacer entre ambos ámbitos y susceptible de abordar desde diferentes técnicas y acercamientos metodológicos. No es, sin embargo, un tema suficientemente explorado dentro de los tópicos sanitarios; lo cual debiera revertirse sobretodo considerando las necesidades de informar e insumar la política pública para nuestro país.
The aim of this review is to explore some records regarding the relationship between oral health and migration as a research topic, in the national and international context. A literature review was made between 2009 and 2019 in electronic databases. It was concluded that there are interesting possible crossovers between both areas, liable to be addressed from different techniques and methodological approaches. However, this matter has not been sufficiently explored within health topics; this should be reversed, especially considering the need to inform and implement public policies in our country.
ABSTRACT
La enfermedad celíaca y la sensibilidad al gluten no celíaca han tenido un aumento en su incidencia, esto las ha convertido en tema de interés en la búsqueda de enfoques terapéuticos innovadores que ayuden a mejorar los síntomas intestinales y extraintestinales. Esta revisión pretende determinar los efectos del uso de probióticos y prebióticos en la enfermedad celíaca y sensibilidad al gluten no celíaca. Se realizó una búsqueda en bases de datos HINARI, PubMed y Scopus en idioma español e inglés, se incluyeron artículos originales y de revisión con un máximo de cinco años desde su publicación. El uso de probióticos y prebióticos para la enfermedad celíaca ha mostrado beneficios restaurando la composición del microbiota intestinal, en especial con el uso de Lactobacilli y Bifidobacterium spp.; en la sensibilidad al gluten no celíaca, el uso se ve limitado al no conocer con exactitud su fisiopatología; no obstante, se propone como mejor pauta terapéutica una dieta libre de gluten. El uso de probióticos y prebióticos podría aliviar los síntomas gastrointestinales y mejorar la disbiosis en pacientes con enfermedad celíaca y sensibilidad al gluten no celíaca. Sin embargo, se necesitan más estudios que evidencien los beneficios de su uso como alternativa terapéutica
Celiac disease and non-celiac gluten sensitivity are entities that have shown an increase in incidence, making them a topic of interest to provide innovative therapeutic approaches and improve intestinal and extraintestinal symptoms. This review intends to determine the effects of the use of probiotics and prebiotics in celiac disease and non-celiac gluten sensitivity. A narrative review was undertaken by searching for original and review articles no older than five years since publication through data bases consulted: HINARI, PubMed and Scopus in Spanish and English. The use of probiotics and prebiotics in celiac disease has shown benefits by restoring the composition of the intestinal microbiota, especially with the use of Lactobacilli and Bifidobacterium spp.; in non-celiac gluten sensitivity, its use is limited as its pathophysiology is not exactly known, therefore, a gluten-free diet is currently considered to be the best therapeutic guideline. The use of probiotics and prebiotics could alleviate gastrointestinal symptoms and improve dysbiosis in patients with celiac disease and non-celiac gluten sensitivity. However, more studies are needed to demonstrate the benefits of its use as a therapeutic alternative
Subject(s)
El SalvadorABSTRACT
BACKGROUND: Thoracentesis and thoracoscopy are used to diagnose malignant pleural effusions (MPE). Data on how sensitivity varies with tumour type is limited. METHODS: Systematic review using PubMed was performed through August 2020 to determine the sensitivity of thoracentesis and thoracoscopy for MPE secondary to malignancy, by cancer type, and complication rates. Tests to identify sources of heterogeneity were performed. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and National Institutes of Health quality assessment tools. Publication bias was tested using funnel plots. RESULTS: Meta-analyses for sensitivity of thoracentesis for MPE secondary to malignancy, mesothelioma and lung and breast cancer included 29, eight, 12 and nine studies, respectively. Pooled sensitivities were 0.643 (95% CI 0.592-0.692), 0.451 (95% CI 0.249-0.661), 0.738 (95% CI 0.659-0.836) and 0.820 (95% CI 0.700-0.917), respectively. For sensitivity of thoracoscopy for MPE secondary to malignancy and mesothelioma, 41 and 15 studies were included, respectively. Pooled sensitivities were 0.929 (95% CI 0.905-0.95) and 0.915 (95% CI 0.871-0.952), respectively. Pooled complication rates of thoracentesis and thoracoscopy were 0.041 (95% CI 0.025-0.051) and 0.040 (95% CI 0.029-0.052), respectively. Heterogeneity was significant for all meta-analyses. Funnel plots were asymmetric. INTERPRETATION: Sensitivity of thoracentesis varied significantly per cancer type. Pooled complication rates were low. Awareness of how sensitivity of thoracentesis changes across cancers can improve decision-making when MPE is suspected.
Subject(s)
Mesothelioma, Malignant , Mesothelioma , Pleural Effusion, Malignant , Humans , Thoracentesis/adverse effects , Retrospective Studies , Pleural Effusion, Malignant/diagnosis , Pleural Effusion, Malignant/etiology , Mesothelioma/diagnosis , Mesothelioma, Malignant/complications , Thoracoscopy/adverse effectsABSTRACT
BACKGROUND: The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known. RESEARCH QUESTION: What diagnostic and staging strategies are most cost-effective for lung cancer? STUDY DESIGN AND METHODS: A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes. RESULTS: For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay. INTERPRETATION: The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.
Subject(s)
Decision Trees , Lung Neoplasms/diagnosis , Aged , Algorithms , Bronchoscopy , Endosonography , Female , Fluoroscopy , Humans , Image-Guided Biopsy , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Neoplasm StagingABSTRACT
BACKGROUND: Two models, the Help with the Assessment of Adenopathy in Lung cancer (HAL) and Help with Oncologic Mediastinal Evaluation for Radiation (HOMER), were recently developed to estimate the probability of nodal disease in patients with non-small cell lung cancer (NSCLC) as determined by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). The objective of this study was to prospectively externally validate both models at multiple centers. RESEARCH QUESTION: Are the HAL and HOMER models valid across multiple centers? STUDY DESIGN AND METHODS: This multicenter prospective observational cohort study enrolled consecutive patients with PET-CT clinical-radiographic stages T1-3, N0-3, M0 NSCLC undergoing EBUS-TBNA staging. HOMER was used to predict the probability of N0 vs N1 vs N2 or N3 (N2|3) disease, and HAL was used to predict the probability of N2|3 (vs N0 or N1) disease. Model discrimination was assessed using the area under the receiver operating characteristics curve (ROC-AUC), and calibration was assessed using the Brier score, calibration plots, and the Hosmer-Lemeshow test. RESULTS: Thirteen centers enrolled 1,799 patients. HAL and HOMER demonstrated good discrimination: HAL ROC-AUC = 0.873 (95%CI, 0.856-0.891) and HOMER ROC-AUC = 0.837 (95%CI, 0.814-0.859) for predicting N1 disease or higher (N1|2|3) and 0.876 (95%CI, 0.855-0.897) for predicting N2|3 disease. Brier scores were 0.117 and 0.349, respectively. Calibration plots demonstrated good calibration for both models. For HAL, the difference between forecast and observed probability of N2|3 disease was +0.012; for HOMER, the difference for N1|2|3 was -0.018 and for N2|3 was +0.002. The Hosmer-Lemeshow test was significant for both models (P = .034 and .002), indicating a small but statistically significant calibration error. INTERPRETATION: HAL and HOMER demonstrated good discrimination and calibration in multiple centers. Although calibration error was present, the magnitude of the error is small, such that the models are informative.
Subject(s)
Biopsy, Fine-Needle/methods , Carcinoma, Non-Small-Cell Lung/pathology , Endosonography/methods , Image-Guided Biopsy/methods , Lung Neoplasms/pathology , Lymphatic Metastasis , Neoplasm Staging/methods , Bronchoscopy/methods , Calibration , Carcinoma, Non-Small-Cell Lung/epidemiology , Female , Humans , Lung Neoplasms/epidemiology , Lymphatic Metastasis/diagnostic imaging , Lymphatic Metastasis/pathology , Male , Mediastinum/diagnostic imaging , Middle Aged , Patient Selection , Predictive Value of Tests , Prognosis , United States/epidemiologyABSTRACT
A 63-year-old male with non-small-cell lung cancer (NSCLC) developed a tracheomediastinal fistula after endobronchial ultrasound transbronchial needle aspiration while on treatment with bevacizumab. This vascular endothelial growth factor-specific angiogenesis inhibitor is a first-line treatment for unresectable or metastatic NSCLC and has been reported to cause fatal non-gastrointestinal fistulas. Respiratory tract fistulas are a known rare complication after bevacizumab therapy characterized by a high mortality rate.
ABSTRACT
BACKGROUND: Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. RESEARCH QUESTION: Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? STUDY DESIGN AND METHODS: Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell's C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors' performances. RESULTS: The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P < .0001), pleural fluid lactate dehydrogenase (P = .029), and bilateral effusion (P = .002). DSMs for lung, breast, and hematologic malignancies showed C-statistics of 0.72, 0.72, and 0.62, respectively; the combined model's C-statistics was 0.67. LENT-D (C-statistic, 0.60) and LENT-C (C-statistic, 0.65) models underperformed. INTERPRETATION: EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.
Subject(s)
Clinical Decision Rules , Neoplasms , Patient Selection , Pleural Effusion, Malignant , Proportional Hazards Models , Thoracentesis , Analysis of Variance , Female , Humans , L-Lactate Dehydrogenase/analysis , Life Tables , Lymphocyte Count/methods , Male , Middle Aged , Neoplasm Metastasis/diagnosis , Neoplasm Staging , Neoplasms/blood , Neoplasms/classification , Neoplasms/diagnosis , Neoplasms/mortality , Neutrophils , Pleural Effusion, Malignant/diagnosis , Pleural Effusion, Malignant/metabolism , Pleural Effusion, Malignant/mortality , Pleural Effusion, Malignant/therapy , Prognosis , Retrospective Studies , Thoracentesis/methods , Thoracentesis/statistics & numerical data , United States/epidemiologyABSTRACT
BACKGROUND: Systematic endobronchial ultrasound (EBUS)-guided lung cancer staging starts with hilar N3 nodes, proceeding sequentially to mediastinal N3, N2, and N1 nodes, with sampling of all enlarged nodes (size, ≥ 5 mm) by EBUS. However, procedure time is limited by patient comfort when moderate sedation is used. It is unclear if EBUS staging should start with hilar N3 nodes or whether starting with mediastinal N3 nodes suffices. Knowing the probability of hilar N3 nodes with PET-CT scan negative findings harboring occult metastasis can inform this decision. RESEARCH QUESTION: What proportion of patients with hilar N3 nodes showing negative PET-CT scan findings have malignancy by EBUS? STUDY DESIGN AND METHODS: This retrospective observational, single-center cohort study included consecutive patients with clinical-radiographic T1-3, N0-3, M0 non-small cell lung cancer undergoing systematic EBUS staging with biopsy of hilar N3 nodes with negative PET-CT scan findings. The primary outcome was the proportion of patients with malignant hilar N3 nodes showing negative PET-CT scan findings. Based on expert opinion, a threshold probability of malignancy of less than 5% was considered sufficient to skip hilar N3 nodes. We used the binomial exact test to compare the observed proportion vs threshold probability of 5%. RESULTS: Of 1,737 consecutive patients undergoing EBUS staging, 1,567 showed negative PET-CT scan findings of the hilar N3 nodes. These nodes were enlarged by EBUS and were sampled in 739 patients. Malignancy was found in the hilar N3 nodes of 5 of 739 patients (0.68%; 95% CI, 0.22%-1.57%). The proportion was significantly less than the threshold probability (P < .001). Patients with positive PET scan results of the mediastinal N3 nodes were at higher risk of having occult hilar N3 nodal metastasis (P = .003), found in 3 of 46 patients (6.5%; 95% CI, 1.4%-17.9%) with positive PET scan results of the mediastinal N3 nodes. INTERPRETATION: When using moderate sedation, because time is limited, it is reasonable to start with the mediastinal N3 nodes if the hilar and mediastinal N3 nodes show negative PET scan results. Patients with positive PET scan findings of the mediastinal N3 nodes probably should undergo hilar N3 node sampling.
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Endosonography/methods , Lung Neoplasms/pathology , Lymphatic Metastasis/pathology , Aged , Female , Humans , Male , Middle Aged , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Retrospective StudiesABSTRACT
BACKGROUND: Patients who have pleural effusions typically undergo thoracentesis with examination of pleural fluid in their initial assessment. However, limited data are available on the diagnostic yield of pleural fluid bacterial cultures and fungal and acid-fast bacilli (AFB) smear and cultures in patients with cancer. METHODS: We performed a retrospective cohort study of consecutive patients who had new onset pleural effusions and underwent an initial thoracentesis. The primary outcome was diagnostic yield of pleural fluid bacterial cultures and fungal and AFB smear and cultures. RESULTS: Of 1637 patients, 1547 (94%) had evidence of active malignancy and 1359 (83%) had evidence of metastatic disease. Of the 1637 patients, 542 (33%) had high clinical suspicion of pneumonia within 14 days prior to thoracentesis. Only 14 patients (1.1%) had positive pleural fluid bacterial cultures, and only 6 of these positive cultures met the criteria for true pleural space infection. CONCLUSIONS: The incidence of positive results from pleural fluid bacterial, fungal, and AFB in cancer populations is very low. Unless there is a suspicion for infection, microbiological analysis should be ordered selectively.
Subject(s)
Neoplasms/complications , Pleural Effusion, Malignant/microbiology , Aged , Bacteria/classification , Bacteria/isolation & purification , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , ThoracentesisABSTRACT
BACKGROUND: Registry trials have found radial endobronchial ultrasound (r-EBUS) sensitivity to vary between institutions, suggesting that in clinical practice, r-EBUS sensitivity may be lower than reported in clinical trials. We performed a meta-analysis to update the estimates of r-EBUS sensitivity and to explore factors contributing to heterogeneity of results. METHODS: A systematic review using PubMed was performed through July 2018 to determine the sensitivity of r-EBUS for lung cancer, and to construct a summary receiver operating characteristic curve. The DerSimonian and Laird method was used to weight results. Subgroup analysis and meta-regression was used to identify sources of heterogeneity. Study quality was assessed using the QUADAS tool, and publication bias was tested using funnel plots. RESULTS: Fifty-one studies with a total of 7,601 patients were included. r-EBUS pooled sensitivity was 0.72 (95% CI, 0.70-0.75), and area under the sROC curve was 0.96 (95% CI, 0.94-0.97). Significant heterogeneity was observed (I2 = 76%; heterogeneity P < .01). We failed to demonstrate an association between sensitivity and air bronchus sign, average nodule size, use of fluoroscopy, virtual bronchoscopy, guide sheath, cancer prevalence, multicenter status, or consecutive enrollment. Rapid onsite cytology was associated with increased sensitivity (P = .01). The pooled pneumothorax rate was 0.7% (95% CI, 0.3%-1.1%). Funnel plots were asymmetrical, demonstrating sample size-related effects and possible publication bias. CONCLUSIONS: r-EBUS has an excellent safety profile, but there is significant between-study heterogeneity. Sample size-related effects and possibly publication bias have led to overly optimistic estimates of the sensitivity of r-EBUS.
Subject(s)
Bronchoscopy , Endosonography , Image-Guided Biopsy , Lung Neoplasms/pathology , Bronchoscopy/methods , Bronchoscopy/standards , Endosonography/methods , Endosonography/standards , Humans , Image-Guided Biopsy/adverse effects , Image-Guided Biopsy/methods , Sensitivity and SpecificityABSTRACT
Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.
Subject(s)
Adenocarcinoma/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Lung Neoplasms/pathology , Lymph Nodes/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/radiotherapy , Aged , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/radiotherapy , Clinical Decision Rules , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Humans , Logistic Models , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Lymph Nodes/diagnostic imaging , Male , Mediastinum/diagnostic imaging , Middle Aged , Multivariate Analysis , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Radiosurgery , Reproducibility of Results , Risk AssessmentABSTRACT
BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.
Subject(s)
L-Lactate Dehydrogenase/analysis , Neoplasms , Pleural Effusion, Malignant , Thoracentesis , Cohort Studies , Female , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasms/complications , Neoplasms/pathology , Palliative Care/methods , Pleural Effusion, Malignant/metabolism , Pleural Effusion, Malignant/pathology , Pleural Effusion, Malignant/physiopathology , Pleural Effusion, Malignant/therapy , Radiography, Thoracic/methods , Recurrence , Retrospective Studies , Risk Assessment/methods , Risk Factors , Thoracentesis/adverse effects , Thoracentesis/methodsABSTRACT
BACKGROUND: Thoracentesis with cytological examination of pleural fluid is the initial test of choice for evaluation of pleural effusions in patients with suspected malignant pleural effusion (MPE). There is limited data on the sensitivity of thoracentesis stratified by tumor type. A better understanding of stratified sensitivities is of clinical interest, and may guide early and appropriate referral for pleural biopsy. OBJECTIVE: The primary objective was sensitivity of thoracentesis with pleural fluid cytology stratified by tumor type. METHODS: This is a retrospective cohort study of consecutive patients with a solid tumor malignancy with proven or strong suspicion for metastatic disease with new pleural effusions that underwent an initial thoracentesis. Only patients with metastatic disease were included. RESULTS: Of the 725 patients examined, 63% had pleural fluid cytology positive for malignancy. Sensitivity of thoracentesis varied from a low of 0.38 (95% CI 0.13-0.68) in head and neck malignancy, 0.38 (95% CI 0.15-0.65) in sarcoma, and 0.53 (95% CI 0.34-0.72) in renal cancer to a high of 93 (95% CI 88-97) in breast cancer, and 100 (95% CI 0.82-100) in pancreatic cancer. Factors associated with an increased risk of MPE included larger amount of fluid drained (p = 0.014) and higher pleural fluid protein (p = 0.002). The only factor associated with decreased risk of MPE if first cytology was negative for malignancy was the presence of contralateral effusion (p = 0.005). CONCLUSIONS: Sensitivity of thoracentesis for solid tumors varies significantly depending on the type of tumor and is lowest in those with sarcomas, head and neck malignancies, and renal cell cancers.
Subject(s)
Pleural Effusion, Malignant/etiology , Pleural Effusion, Malignant/pathology , Thoracentesis/statistics & numerical data , Cohort Studies , Humans , Neoplasm Metastasis , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Mast cells (MCs) are involved in host defenses against pathogens and inflammation. Stimulated MCs release substances stored in their granules via regulated exocytosis. In other cell types, Munc13 (mammalian homolog of Caenorhabditis elegans uncoordinated gene 13) proteins play essential roles in regulated exocytosis. Here, we found that MCs express Munc13-2 and -4, and we studied their roles using global and conditional knock-out (KO) mice. In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and MC-specific Munc13-4 KO mice developed less hypothermia. This protection correlated with lower plasma histamine levels and with histological evidence of defective MC degranulation but not with changes in MC development, distribution, numbers, or morphology. In vitro assays revealed that the defective response in Munc13-4-deficient MCs was limited to regulated exocytosis, leaving other MC secretory effector responses intact. Single cell capacitance measurements in MCs from mouse mutants differing in Munc13-4 expression levels in their MCs revealed that as levels of Munc13-4 decrease, the rate of exocytosis declines first, and then the total amount of exocytosis decreases. A requirement for Munc13-2 in MC exocytosis was revealed only in the absence of Munc13-4. Electrophysiology and EM studies uncovered that the number of multigranular compound events (i.e. granule-to-granule homotypic fusion) was severely reduced in the absence of Munc13-4. We conclude that although Munc13-2 plays a minor role, Munc13-4 is essential for regulated exocytosis in MCs, and that this MC effector response is required for a full anaphylactic response.
Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Anaphylaxis , Animals , Disease Models, Animal , Exocytosis/physiology , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/physiology , Mast Cells/metabolism , Mast Cells/physiology , Membrane Proteins/genetics , Membrane Proteins/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/physiology , Protein Isoforms , Protein TransportABSTRACT
Antimicrobial proteins and peptides play an important role in the primary defence of epithelial barriers in vertebrates and invertebrates. Here we report the detection of the apolipoproteins A-I and A-II in the epidermis and epidermal mucus of the carp (Cyprinus carpio L.) by immunohistochemistry and Western blot analysis. Both apolipoproteins are major constituents of high density lipoprotein and have been shown to display antiviral and antimicrobial activity in mammals. Therefore the aim of this study was to evaluate if they could be part of the innate immune system of teleost fish. A cDNA clone containing most of the coding region for carp apoA-I was isolated and used as a probe to demonstrate the expression of apoA-I gene in the skin. In addition, mucus apoA-I was shown to be associated to small particles that could correspond to nascent HDL. Finally, affinity purified plasma HDL displayed bactericidal activity in vitro against a non-pathogenic Escherichia coli strain, suggesting a defensive role for HDL and its associated proteins in the carp epidermis and mucus.