Pulmonary alveolar proteinosis (PAP) is rare disease manifested as alveolar macrophage dysfunction and abnormal accumulation of surfactant protein in the alveoli. In this nationwide, population-based study, we investigated the epidemiology of PAP in Taiwan, and discovered the comorbidities and prognostic factors of PAP.From the National Health Insurance Research Database (NHIRD), we obtained comprehensive information about all patients of PAP in Taiwan between 1995 and 2013. The incidence, baseline characteristics comorbidities, and prognostic factors of PAP were investigated.The annual incidence rate of PAP was around 0.79 (range: 0.49-1.17) patients per million people after 2000, and the prevalence rate was 7.96 patients per million people by the end of 2013. In total, 276 patients of PAP were identified, including 177 (64%) and 99 (36%) patients with primary and secondary PAP, respectively. The median age of diagnosis was 53.8 years. The median survival was 9.6 years after the initial PAP diagnosis, and the 5-year survival rate was 65.96%. Twenty (7%) patients received whole lung lavage (WLL) within three months after the diagnosis had significantly better survival compared to the others. Multivariable Cox regression analyses showed that elder age, secondary PAP, and malignancy were associated with poorer survival, while WLL within 3 months of diagnosis might greatly improve the survival.We demonstrated the epidemiology of PAP in Taiwan, showing several poor prognostic factors and the potential effectiveness of WLL. Further prospective studies based on registry are warranted to improve the diagnosis and treatment of PAP.
Sonographic characteristics of various chest diseases in 154 cases were analysed according to margin of the lesion, internal echogenecity, posterior echo enhancement, air bronchogram etc. We intended to present the basic sonographic patterns of common chest diseases. The study included 10 normal cases, 10 cases with lung abscesses, 31 cases of pneumonia, 24 cases of tumors, 11 cases of obstructive atelectasis, 8 cases of pleuropericarcadial effusions, 10 cases of minimal effusions, 6 cases with pleural thickening, 32 cases of massive pleural effusion with simple compression atelectasis and 12 cases of pneumonia with parapneumonic effusion. Sonographically, normal lung showed hyperechoic zone beneath the chest wall. Identification of arc or ring-shaped wall favored lung abscess. Air bronchogram could only be found in pneumonia. Mass showed various internal echogenecity. The internal echogenecity in obstructive atelectasis was very homogeneous which could not be found in tumor. Pleural thickening showed linear hyperechogenecity beneath the chest wall. In minimal effusion, the line of the diaphragm could be easily identified. Pleuropericardial effusion could be easily diagnosed by chest sonography. The line of the pericarcadium could be clearly identified. The internal echogenecity of massive effusion were various. The internal echogenecity of simple compression atelectasis showed very homogeneous hyperdense internal echogenecity. The internal echogenecity of lung parenchyma in pneumonia with parapneumonic effusion was similar to that of pneumonia. Obstructive atelectasis, mass, consolidation and encapsulated effusion could be differentiated by chest sonography without much difficulty. Sonography could aid chest radiography by giving more morphologic information and was cheaper than computed tomography.
<i>Objective:</i> Detection of tumor-related mRNA in blood has become a potential cancer diagnostic approach. However, the sensitivity of single-marker assays is not high enough for clinical applications. The present study was aimed to evaluate the efficacy of a multimarker panel for molecular diagnosis of non-small cell lung cancer (NSCLC). <i>Methods:</i> Carcinoembryonic antigen (CEA), cytokeratin 19 (CK-19), c-met and heterogeneous nuclear ribonucleoprotein (hnRNP) B1 mRNAs were quantified by quantitative real-time reverse transcriptase polymerase chain reaction in 34 tumor tissues and 69 peripheral blood samples of NSCLC patients. <i>Results:</i> All four markers displayed high overexpression rates (range 82.3–97.1%) in NSCLC tumors. When used as single markers in blood for NSCLC diagnosis, CEA, CK-19, c-met and hnRNP B1 could only reach sensitivities of 52.2, 50.7, 42 and 17.4%, respectively. However, the sensitivity was enhanced up to 85.5% when CEA, CK-19 and c-met were combined in a 3-marker panel. Moreover, the expression of c-met and hnRNP B1 in blood was significantly correlated with patients’ pathological stages. <i>Conclusions:</i>The combined detection of CEA, CK-19 and c-met mRNAs in blood provided a valuable tool for molecular diagnosis of NSCLC. In addition, our results also suggested that hnRNP B1 was not a valuable diagnostic marker but a potential prognostic marker for NSCLC.
The objective of this study was mainly to evaluate the simultaneous detection of expression levels of a multiple mRNA marker panel in the peripheral blood of colorectal cancer (CRC) patients for use in complementary CRC diagnosis. Twenty-seven tumor tissue specimens and 80 peripheral blood specimens were collected from CRC patients. Firstly, the levels of multiple molecular markers in the tumor tissue and blood specimens were evaluated by using real-time quantitative PCR (RT-QPCR) and membrane array. The result of linear regression showed a high degree of correlation (r=0.954, P<0.0001) between the data of these two methods. CK-19 was the marker with the highest detection rate (87.5%) in the peripheral blood, followed by CEA (82.6%), REG4 (80.8%), and then uPA (80.0%) and TLAM1 (80.0%). The levels of the six markers in the peripheral blood were extensively explored. In the 80 patients, the frequency of CK-19, CK-20, CEA, REG4, uPA, and TIAM1 mRNA overexpression was 82.5% (66/80), 78.8% (63/80), 82.5% (66/80), 80.0% (64/80), 78.8% (63/80), and 80.0% (64/80), respectively. Then, a panel combining these 6 mRNA markers was evaluated for its utility in the clinical diagnosis of CRC. The sensitivity, specificity, and accuracy of membrane array-based diagnostic method were 88.8%, 87.8%, and 88.2%, respectively; much higher than those of examinations with single markers. Finally, lymph node metastasis (P=0.024) and TNM stage (P=0.009) were found to be significantly correlated with overexpression of the multiple mRNA marker panel. The detection rates of stage-I and -II CRC by using the multi-marker membrane array were 54.5% (6/11) and 92.0% (23/25), respectively. In conclusion, the results of the present study have shown that this innovative membrane array technique with a multiple mRNA marker panel can significantly improve the diagnosis rate of early colorectal cancer.
Abstract Background Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. Methods We prospectively obtained stool, blood, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. Results Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus , and Actinomyces and increase of Bacteroides, Alistipes , and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. Conclusions The study results suggest that gut microbiome composition may modulate host immunity relevant to TB susceptibility, and microbial signature might be a potential diagnostic biomarker and therapeutic target for LTBI in pDM patients.
Agyrophil staining was applied to nucleolar organizer regions (NOR) to differentiate cells of adenocarcinoma and histiomesotheliosis in pleural effusion. The smears were either nuclearly unstained, but cytoplasmically counterstained by Papanicolaou method or Papanicolaou-destained before agyrophil staining of nucleolar organizer regions (AgNOR). The purposes of this study were to assess the feasibility and usefulness of AgNOR staining in diagnostic cytology and to try to set up a procedure that could be used on prestained smears for retrospective study. All smears showed good background and cellular outline. The distribution of NOR was either intranuclearly or in the nucleoplasm diffusely. In previously nuclearly unstained smears, NOR showed granular to powder-like appearance. The mean number of NOR in adenocarcinoma (38.4 +/- 12.5) was significantly higher than that in histiomesotheliosis (15.6 +/- 2.9). In Papanicolaou-destained smears, the NOR showed confluent dots. The mean number of NOR was much lower as compared to that of previously nuclearly unstained smears. Furthermore, the mean number of NOR in adenocarcinoma (3.6 +/- 1.4) showed no significant difference with that of histiomesotheliosis (2.7 +/- 0.8). In conclusion, AgNOR staining is one of the methods to differentiate benign from malignant cells, but not in Papanicolaou-destained smears.
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