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BACKGROUND/PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Proteinose Alveolar Pulmonar , Humanos , Idoso , Pessoa de Meia-Idade , Lactente , Proteinose Alveolar Pulmonar/epidemiologia , Proteinose Alveolar Pulmonar/terapia , Proteinose Alveolar Pulmonar/diagnóstico , Taiwan/epidemiologia , Estudos Prospectivos , Lavagem Broncoalveolar , Pulmão/patologiaRESUMO
Interstitial pneumonia with autoimmune features (IPAF) is a new disease entity proposed in 2015. Numerous questions regarding IPAF require clarification, including diagnostic criteria, standard managements for stable disease and exacerbation, and prognosis. We report a case of a 67-year-old Asian woman who presented with progressive dyspnea. Chest computed tomography (CT) scans revealed nonspecific interstitial pneumonia. Serologic testing indicated positive anti-Jo-1 without presence of extrathoracic manifestations. An IPAF diagnosis was made after a multidisciplinary discussion. The patient experienced a severe exacerbation requiring mechanical ventilation, and she was successfully salvaged with methylprednisolone pulse therapy and single-dose cyclophosphamide. During the one-year follow-up, she reported bilateral leg muscle weakness with noticeably elevated serum creatine kinase, suggesting polymyositis. The development of malignancy was also noted 15 months after the initial presentation, and the patient eventually died. This report demonstrated successful salvage treatment with glucocorticoid pulse therapy for IPAF with acute exacerbation. However, the maintenance therapy failed to control disease progression. The treatment strategies for exacerbation and stable disease in IPAF remain unknown and need further studies. Given the high risk of evolution into a defined connective tissue disease (CTD), regular evaluation of the clinical features and biomarkers of CTDs is essential for patients with IPAF.
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Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Polimiosite , Feminino , Humanos , Idoso , Doenças Pulmonares Intersticiais/etiologia , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Polimiosite/complicações , Tomografia Computadorizada por Raios X/métodos , PrognósticoRESUMO
Cancer remains a leading cause of death worldwide, despite many advances being made in recent decades. Changes in the tumor microenvironment, including dysregulated immunity, may contribute to carcinogenesis and cancer progression. The cysteinyl leukotriene (CysLT) pathway is involved in several signal pathways, having various functions in different tissues. We summarized major findings of studies about the roles of the CysLT pathway in cancer. Many in vitro studies suggested the roles of CysLTs in cell survival/proliferation via CysLT1 receptor (CysLT1R). CysLT1R antagonism decreased cell vitality and induced cell death in several types of cancer cells, such as colorectal, urological, breast, lung and neurological malignancies. CysLTs were also associated with multidrug resistance of cancer, and CysLT1R antagonism might reverse chemoresistance. Some animal studies demonstrated the beneficial effects of CysLT1R antagonist in inhibiting tumorigenesis and progression of some cancer types, particularly colorectal cancer and lung cancer. The expression of CysLT1R was shown in various cancer tissues, particularly colorectal cancer and urological malignancies, and higher expression was associated with a poorer prognosis. The chemo-preventive effects of CysLT1R antagonists were demonstrated in two large retrospective cohort studies. In summary, the roles of the CysLT pathway in cancer have been delineated, whereas further studies are still warranted.
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Cisteína/metabolismo , Leucotrienos/metabolismo , Neoplasias/metabolismo , Transdução de Sinais/fisiologia , Animais , Apoptose/fisiologia , Proliferação de Células/fisiologia , Humanos , Estudos RetrospectivosAssuntos
Antituberculosos/uso terapêutico , Complicações do Diabetes/diagnóstico , Doenças Endêmicas , Prescrição Inadequada/prevenção & controle , Pulmão/patologia , Pneumonia/diagnóstico , Tuberculose Pulmonar/diagnóstico , Idoso , Biópsia , Diagnóstico Diferencial , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pneumonia/complicações , Radiografia Torácica , Taiwan , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Background: Malposition may occur during peripherally inserted central catheter insertion. Accurately measuring the length of a peripherally inserted central catheter is crucial to preventing malposition, including "long peripherally inserted central catheter placement," in which the tip of a peripherally inserted central catheter is deeper than the target position. The traditional method of measuring peripherally inserted central catheter length involves measuring from the insertion site to the parasternal notch and down to the third or fourth intercostal space, which may result in overestimation because of the thickness of the pectoralis major and anterior chest wall. To avoid this overestimation, the authors developed and tested a modified method for reducing long peripherally inserted central catheter placement. Methods: This study employed a retrospective design. Chest X-rays were used to examine the peripherally inserted central catheter tip positions in 48 patients in the medical intensive care unit who had undergone peripherally inserted central catheter insertion. The traditional and modified measurement methods were used to measure the peripherally inserted central catheter length in 17 and 31 patients, respectively. Fisher's exact test was used to examine between-group differences in the incidence of different types of peripherally inserted central catheter malposition. Results: The peripherally inserted central catheter tip position was near the target position in five patients (29.41%) in the traditional measurement group and 17 patients (54.84%) in the modified measurement group (p = 0.132), whereas long peripherally inserted central catheter placement occurred in six patients (35.29%) in the traditional measurement group and one patient (3.23%) in the modified measurement group (p = 0.006). However, the incidence of other types of peripherally inserted central catheter malposition did not differ significantly between the groups. Conclusions: The results of this study that the proposed modified measurement method may be able to reduce the incidence of long peripherally inserted central catheter placement among medical intensive care unit patients. The method must be further evaluated in prospective studies and studies with larger sample sizes in the future.
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Cancer cells harbor molecular alterations at all levels of information processing. Genomic/epigenomic and transcriptomic alterations are inter-related between genes, within and across cancer types and may affect clinical phenotypes. Despite the abundant prior studies of integrating cancer multi-omics data, none of them organizes these associations in a hierarchical structure and validates the discoveries in extensive external data. We infer this Integrated Hierarchical Association Structure (IHAS) from the complete data of The Cancer Genome Atlas (TCGA) and compile a compendium of cancer multi-omics associations. Intriguingly, diverse alterations on genomes/epigenomes from multiple cancer types impact transcriptions of 18 Gene Groups. Half of them are further reduced to three Meta Gene Groups enriched with (1) immune and inflammatory responses, (2) embryonic development and neurogenesis, (3) cell cycle process and DNA repair. Over 80% of the clinical/molecular phenotypes reported in TCGA are aligned with the combinatorial expressions of Meta Gene Groups, Gene Groups, and other IHAS subunits. Furthermore, IHAS derived from TCGA is validated in more than 300 external datasets including multi-omics measurements and cellular responses upon drug treatments and gene perturbations in tumors, cancer cell lines, and normal tissues. To sum up, IHAS stratifies patients in terms of molecular signatures of its subunits, selects targeted genes or drugs for precision cancer therapy, and demonstrates that associations between survival times and transcriptional biomarkers may vary with cancer types. These rich information is critical for diagnosis and treatments of cancers.
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OBJECTIVES: This study was conducted to explore the association between pneumoconiosis and pneumothorax. DESIGN: Retrospective cohort study. SETTING: Nationwide population-based study using the Taiwan National Health Insurance Database. PARTICIPANTS: A total of 2333 pneumoconiosis patients were identified (1935 patients for propensity score (PS)-matched cohort) and matched to 23 330 control subjects by age and sex (7740 subjects for PS-matched cohort). PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence and the cumulative incidence of pneumothorax. RESULTS: Both incidence and the cumulative incidence of pneumothorax were significantly higher in the pneumoconiosis patients as compared with the control subjects (p<0.0001). For multivariable Cox regression analysis adjusted for age, sex, residency, income level and other comorbidities, patients with pneumoconiosis exhibited a significantly higher risk of pneumothorax than those without pneumoconiosis (HR 3.05, 95% CI 2.18 to 4.28, p<0.0001). The male sex, heart disease, peripheral vascular disease, chronic pulmonary disease and connective tissue disease were risk factors for developing pneumothorax in pneumoconiosis patients. CONCLUSIONS: Our study revealed a higher risk of pneumothorax in pneumoconiosis patients and suggested potential risk factors in these patients. Clinicians should be aware about the risk of pneumothorax in pneumoconiosis patients.
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Pneumoconiose , Pneumotórax , Estudos de Coortes , Comorbidade , Humanos , Incidência , Masculino , Pneumoconiose/complicações , Pneumoconiose/epidemiologia , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
An increased incidence of temporomandibular disorders (TMD) among patients with sleep apnea (SA) has been reported. However, the association between TMD and SA has not been demonstrated in a large-scale study. This population-based cohort study with the Taiwan National Health Insurance (NHI) Research Database aimed to understand the association between SA and TMD. We identified adult patients with suspected SA (identified with diagnostic codes) and excluded those diagnosed with TMD prior to SA. Patients with SA diagnosis after polysomnography were also identified as probable SA patients. The index dates were the dates of their initial SA diagnosis. Ten control subjects were matched, by age and sex, to each SA patient, and were assigned the same index dates as the SA patients. In total, 10,408 suspected SA patients (including 4105 probable SA patients) matched to 104,080 control subjects (including 41,050 subjects matched to the probable SA patients) in this study. The TMD incidence rate was significantly higher in the SA patients than in the control subjects (2.8 vs. 1.0 per thousand-patient-year in probable SA patients vs. the corresponding control subjects, with an adjusted incidence rate ratio [95% confidence interval] = 2.5 [2.3-2.7], p < 0.0001). SA patients significantly showed a higher cumulative incidence of TMD than the corresponding control subjects (p < 0.0001). Multivariable Cox regression analysis revealed SA as an independent risk factor for the development of TMD (adjusted hazard ratio = 2.5 [1.7-3.7], p < 0.0001). In summary, this study confirmed an increased TMD incidence in the SA patients. While treating TMD patients, dentists should pay careful attention to the potential underlying SA.
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Síndromes da Apneia do Sono , Transtornos da Articulação Temporomandibular , Estudos de Coortes , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndromes da Apneia do Sono/epidemiologia , Taiwan/epidemiologia , Transtornos da Articulação Temporomandibular/epidemiologiaRESUMO
Apoptosis is an essential part of normal embryonic development in vertebrates, and it is involved in sculpturing organs and controlling cell populations. In previous studies, we identified two novel proteins, zfBLP1 and zfMcl-1a, which are similar to those of the Bcl-2 family as a group of evolutionarily conserved proteins that regulate cellular anti-apoptosis. To evaluate the effect of dysregulated hepatocyte apoptosis during zebrafish hepatogenesis, we demonstrate the transgenic overexpression of either zfBLP1 or zfMcl-1a in zebrafish larval liver. Results showed that 18%-43% of larvae overexpressed zfBLP1 and that 16%-37% of larvae overexpressed zfMc1-1a in the liver leading to liver hyperplasia in 5-day postfertilization (dpf) zebrafish larvae. Histologically, zebrafish larvae exhibiting liver hyperplasia displayed a normal type of hepatocyte and the same cell numbers in their two liver buds compared with only one liver bud of wild-type larvae. Of interest, the expression of cyclin genes (A2, B, D1, and E), hepatocyte nuclear factor genes (HNF-1alpha, beta, -3beta, and 4alpha), and oncogenic markers (P53, c-myc, beta-catenin, N-ras, and gankyrin) were up-regulated, while the expression of C/EBP-alpha was down-regulated in a zfMcl-1a-mediated anti-apoptotic process of the liver. Increased cell death and proliferation was found in both hepatic cells of zebrafish larvae overexpressing either zfBLP1 or zfMcl-1a. However, those zebrafish larvae with liver hyperplasia only lived approximately 10 days. (This finding may have been due to liver abnormalities that led to failure of liver function.) In conclusion, transgenic overexpression of zfBLP1 or zfMcl-1a in zebrafish larvae interrupts regulation of the homeostatic balance between cell proliferation and programmed cell death during hepatogenesis and leads to liver hyperplasia.