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Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied. Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed. Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [P = .03%] and 1.0% vs 3.8% [P = .05], respectively). Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD.
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OBJECTIVES: The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. METHODS: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites. RESULTS: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing. DISCUSSION: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.
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OBJECTIVES: Predicting progression of nontuberculous mycobacterial lung disease (NTM-LD) remains challenging. This study evaluated whether sputum bacterial microbiome diversity can be the biomarker and provide novel insights into related phenotypes and treatment timing. METHODS: We analyzed 126 sputum microbiomes of 126 patients with newly diagnosed NTM-LD due to Mycobacterium avium complex, M. abscessus complex, and M. kansasii between May 2020 and December 2021. Patients were followed for 2 years to determine their disease progression status. We identified consistently representative genera that differentiated the progressor and nonprogressor by using six methodologies. These genera were used to construct a prediction model using random forest with 5-fold cross validation. RESULTS: Disease progression occurred in 49 (38.6%) patients. Compared with nonprogressors, α-diversity was lower in the progressors. Significant compositional differences existed in the ß-diversity between groups (p=0.001). The prediction model for NTM-LD progression constructed using seven genera (Burkholderia, Pseudomonas, Sphingomonas, Candidatus Saccharibacteria, Phocaeicola, Pelomonas, and Phascolarctobacterium) with significantly differential abundance achieved an area under curve of 0.871. CONCLUSIONS: Identification of the composition of sputum bacterial microbiome facilitates prediction of the course of NTM-LD, and maybe used to develop precision treatment involving modulating the respiratory microbiome composition to ameliorate NTM-LD.
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BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.
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Bronquiectasia , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Bronquiectasia/fisiopatologia , Bronquiectasia/diagnóstico por imagem , Taiwan/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Volume Expiratório Forçado , Adulto , Pseudomonas aeruginosa/isolamento & purificaçãoRESUMO
BACKGROUND: Poor disease control in patients with chronic obstructive pulmonary disease (COPD) is associated with suboptimal inhaler use. PURPOSE: This study was designed to explore the accuracy of inhaler use and related factors in elderly patients with COPD. METHODS: A cross-sectional survey design was used to recruit patients with COPD from a medical centre in southern Taiwan who were over 65 years old and used inhalers regularly. All of the data as well as information on inhaler use accuracy were collected using a self-designed questionnaire and inhaler operation checklist. Multivariable logistic regression was used to analyse significant correlates of correct inhaler operation. RESULTS: The average age of the 150 participants was 75.0 years (SD = 7.5) years. Most used one type of inhaler only (86.0%). The rate of accurate inhaler operation was 40.7% (n = 61) for the sample, with dry powder inhalers associated with the highest accuracy (64%) and pressurized metered-dose inhalers associated with the lowest accuracy (1.6%). Multivariate logistic regression analysis showed that using a soft mist inhaler (adjusted odds ratio, AOR = 23.29; 95% confidence interval, 95% CI [2.84, 191.07]), using a dry powder inhaler (AOR =15.60, 95% CI [1.99, 122.26]), and higher satisfaction with the inhaler were positively and independently associated with accurate inhaler use (AOR = 1.94, 95% CI [1.09, 3.44]). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Important factors related to inhaler use accuracy include inhaler type and level of patient satisfaction with their inhaler. Healthcare professionals should regularly confirm that older patients are able to use their inhalers correctly and are satisfied with their inhalers.
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Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Masculino , Feminino , Estudos Transversais , Idoso de 80 Anos ou maisRESUMO
Epigenetic regulation and mitochondrial dysfunction are essential to the progression of idiopathic pulmonary fibrosis (IPF). Curcumin (CCM) in inhibits the progression of pulmonary fibrosis by regulating the expression of specific miRNAs and pulmonary fibroblast mitochondrial function; however, the underlying mechanism is unclear. C57BL/6 mice were intratracheally injected with bleomycin (5â¯mg/kg) and treated with CCM (25â¯mg/kg body weight/3 times per week, intraperitoneal injection) for 28 days. Verhoeff-Van Gieson, Picro sirius red, and Masson's trichrome staining were used to examine the expression and distribution of collagen and elastic fibers in the lung tissue. Pulmonary fibrosis was determined using micro-computed tomography and transmission electron microscopy. Human pulmonary fibroblasts were transfected with miR-29a-3p, and RT-qPCR, immunostaining, and western blotting were performed to determine the expression of DNMT3A and extracellular matrix collagen-1 (COL1A1) and fibronectin-1 (FN1) levels. The expression of mitochondrial electron transport chain complex (MRC) and mitochondrial function were detected using western blotting and Seahorse XFp Technology. CCM in increased the expression of miR-29a-3p in the lung tissue and inhibited the DNMT3A to reduce the COL1A1 and FN1 levels leading to pulmonary extracellular matrix remodeling. In addition, CCM inhibited pulmonary fibroblasts MRC and mitochondrial function via the miR-29a-3p/DNMT3A pathway. CCM attenuates pulmonary fibrosis via the miR-29a-3p/DNMT3A axis to regulate extracellular matrix remodeling and mitochondrial function and may provide a new therapeutic intervention for preventing pulmonary fibrosis.
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Curcumina , DNA Metiltransferase 3A , Matriz Extracelular , Fibroblastos , Camundongos Endogâmicos C57BL , MicroRNAs , Mitocôndrias , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Curcumina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , DNA Metiltransferase 3A/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Humanos , Camundongos , Masculino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Bleomicina , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are "non-atopic", lacking a clear etiology. METHODS: In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman's rank correlation coefficients, multiple logistic regression, and multinomial logistic regression. RESULTS: Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified. CONCLUSION: The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.
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Asma , Diabetes Mellitus Tipo 2 , Dietilexilftalato , Dietilexilftalato/análogos & derivados , Hipertensão , Ácidos Ftálicos , Adulto , Animais , Humanos , Dietilexilftalato/toxicidade , Dietilexilftalato/urina , Exposição Ambiental , Estudos de Casos e Controles , Asma/induzido quimicamente , Asma/diagnóstico , Asma/epidemiologia , CitocinasRESUMO
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 samples, 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 maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Tuberculose Latente , Humanos , Microbioma Gastrointestinal/imunologia , Imunidade , Tuberculose Latente/imunologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologiaRESUMO
BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.
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Poluentes Atmosféricos , Poluição do Ar , Asma , Diabetes Mellitus Tipo 2 , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Esfingolipídeos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/toxicidade , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental/métodosRESUMO
BACKGROUND: Systemic drug reaction (SDR) is a major safety concern with weekly rifapentine plus isoniazid for 12 doses (3HP) for latent tuberculosis infection (LTBI). Identifying SDR predictors and at-risk participants before treatment can improve cost-effectiveness of the LTBI program. METHODS: We prospectively recruited 187 cases receiving 3HP (44 SDRs and 143 non-SDRs). A pilot cohort (8 SDRs and 12 non-SDRs) was selected for generating whole-blood transcriptomic data. By incorporating the hierarchical system biology model and therapy-biomarker pathway approach, candidate genes were selected and evaluated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Then, interpretable machine learning models presenting as SHapley Additive exPlanations (SHAP) values were applied for SDR risk prediction. Finally, an independent cohort was used to evaluate the performance of these predictive models. RESULTS: Based on the whole-blood transcriptomic profile of the pilot cohort and the RT-qPCR results of 2 SDR and 3 non-SDR samples in the training cohort, 6 genes were selected. According to SHAP values for model construction and validation, a 3-gene model for SDR risk prediction achieved a sensitivity and specificity of 0.972 and 0.947, respectively, under a universal cutoff value for the joint of the training (28 SDRs and 104 non-SDRs) and testing (8 SDRs and 27 non-SDRs) cohorts. It also worked well across different subgroups. CONCLUSIONS: The prediction model for 3HP-related SDRs serves as a guide for establishing a safe and personalized regimen to foster the implementation of an LTBI program. Additionally, it provides a potential translational value for future studies on drug-related hypersensitivity.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Tuberculose Latente , Antituberculosos/efeitos adversos , Técnicas de Apoio para a Decisão , Quimioterapia Combinada , Humanos , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/prevenção & controle , Rifampina/análogos & derivadosRESUMO
BACKGROUND: Histologic diagnosis of granuloma is often considered clinically equivalent to a definite diagnosis of pulmonary tuberculosis (TB) in endemic areas. Optimal management of surgically resected granulomatous inflammation in lung with negative mycobacterial culture results, however, remains unclear. METHODS: From 7 medical institutions in northern, middle, and southern Taiwan between January 2010 and December 2018, patients whose surgically resected pulmonary nodule(s) had histological features suggestive of TB but negative microbiological study results and who received no subsequent anti-TB treatment were identified retrospectively. All patients were followed up for 2 years until death or active TB disease was diagnosed. RESULTS: A total of 116 patients were enrolled during the study period. Among them, 61 patients (52.6%) were clinically asymptomatic, and 36 (31.0%) patients were immunocompromised. Solitary pulmonary nodule accounted for 44 (39.6%) of all cases. The lung nodules were removed by wedge resection in 95 (81.9%), lobectomy in 17 (14.7%), and segmentectomy in 4 (3.4%) patients. The most common histological feature was granulomatous inflammation (n=116 [100%]), followed by caseous necrosis (n=39 [33.6%]). During follow-up (218.4 patient-years), none of the patients developed active TB. CONCLUSIONS: In patients with surgically resected culture-negative pulmonary granulomas, the incidence rate of subsequent active TB is low. Watchful monitoring along with regular clinical, radiological, and microbiological follow-up, instead of routine anti-TB treatment, may also be a reasonable option.
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High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor mobility remains unclear. Therefore, we aimed to investigate whether HMGB1 affects mitochondria distribution and regulates dynamin-related protein 1 (DRP1)-mediated lamellipodia/filopodia formation to promote NSCLC migration. The regulation of mitochondrial membrane tension, dynamics, polarization, fission process, and cytoskeletal rearrangements in lung cancer cells by HMGB1 was analyzed using confocal microscopy. The HMGB1-mediated regulation of DRP1 phosphorylation and colocalization was determined using immunostaining and co-immunoprecipitation assays. The tumorigenic potential of HMGB1 was assessed in vivo and further confirmed using NSCLC patient samples. Our results showed that HMGB1 increased the polarity and mobility of cells (mainly by regulating the cytoskeletal system actin and microtubule dynamics and distribution), promoted the formation of lamellipodia/filopodia, and enhanced the expression and phosphorylation of DRP1 in both the nucleus and cytoplasm. In addition, HMGB1 and DRP1 expressions were positively correlated and exhibited poor prognosis and survival in patients with lung cancer. Collectively, HMGB1 plays a key role in the formation of lamellipodia and filopodia by regulating cytoskeleton dynamics and DRP1 expression to promote lung cancer migration.
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Dinaminas/metabolismo , Proteína HMGB1/metabolismo , Neoplasias Pulmonares/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Dinaminas/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Proteínas HMGB/metabolismo , Proteína HMGB1/fisiologia , Humanos , Neoplasias Pulmonares/genética , Masculino , Camundongos , Camundongos SCID , Microscopia Confocal/métodos , Mitocôndrias/genética , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Fosforilação , Pseudópodes/metabolismoRESUMO
BACKGROUND: Poor control of diabetes mellitus (DM) increases active tuberculosis (TB) risk. Understanding risk factors for latent TB infection (LTBI) in this population and intervention completion rates is crucial for policy making. METHODS: Under a collaborative multidisciplinary team consisting of public health professionals, endocrinologists, and pulmonologists, patients aged >45 years with poorly controlled DM (pDM), defined as having a glycated hemoglobin level of ≥9% within the preceding year, were enrolled by endocrinologists from 2 hospitals; these patients underwent LTBI screening by using QuantiFERON (QFT). Once-weekly isoniazid and rifapentine for 12 weeks (3HP) or daily isoniazid for 9 months (9H) was administered by pulmonologists. QFT-positivity predictors were evaluated using logistic regression. Completion rates and safety were also investigated. RESULTS: Among 980 patients with pDM (age: 64.2â ±â 9.7 years), 261 (26.6%) were QFT-positive. Age, DM duration, chronic kidney disease stage ≥3, and dipeptidyl peptidase-4 inhibitor use, not using metformin, were associated with QFT-positivity. Preventive therapy (3HP: 138; 9H: 62) was administered in 200 (76.6%) QFT-positive patients. The completion rates of 3HP and 9H were 84.1% and 79.0%, respectively (Pâ =â .494). Nine (6.5%) and zero patients in the 3HP and 9H groups, respectively, developed systemic drug reactions (Pâ =â .059); 78.3% and 45.2% had ≥1 adverse drug reactions (Pâ <â .001); and post-treatment QFT conversion rates were 32% and 20%, respectively (Pâ =â .228). CONCLUSIONS: LTBI prevalence exceeds 25% in elderly patients with pDM. Under care from a collaborative multidisciplinary team, the completion rate of preventive therapy, regardless of regimen could approach, or even exceed 80% in this population.
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Diabetes Mellitus , Tuberculose Latente , Idoso , Antituberculosos , Diabetes Mellitus/tratamento farmacológico , Quimioterapia Combinada , Humanos , Isoniazida/uso terapêutico , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Weekly rifapentine and isoniazid (3HP) is gaining popularity for latent tuberculosis infection treatment because of its short course and high completion rate. Prior to widespread use, comprehensive 3HP treatment assessment covering an all-age population is essential. METHODS: Participants receiving ≥1 3HP dose from September 2014 to December 2019 were stratified into elderly (≥65 years), middle-aged (>35 & <65 years), and younger (≤35 years) age groups. This study investigated the impact of age on treatment outcome, particularly systemic drug reactions (SDRs) and 3HP discontinuation. RESULTS: Overall, 134 of 579 (23.1%) participants were elderly. The completion rate was 83.1% overall and was highest and lowest in the younger group (94.5%) and elderly (73.9%) group, respectively. However, the 3HP discontinuation rate was not significantly different among the 3 groups in multivariate logistic regression analysis. In total, 362 (62.5%) participants experienced 1 or more adverse drug reactions (ADRs), of which 38 (10.5%) and 98 (27.1%) required temporary and permanent treatment interruption, respectively. The SDR risk was 11.2% in overall and 17.1% in the middle-aged group, 3.04-fold higher than that in the elderly group (P = .025). This finding was consistently observed in different clinical settings. Hypertensive events accompanied with flu-like symptoms occurred in 11.2% of elderly participants, and accounted for 50% of grade ≥3 ADRs. CONCLUSIONS: With proper medical support and programmatic follow-up, the 3HP completion rate is >70% even in elderly participants. In middle-aged and elderly individuals, 3HP should be employed with caution because of risk of SDRs and hypertensive events, respectively. Summary: Under programmatic medical support, widespread use of weekly rifapentine and isoniazid (3HP) for latent tuberculosis treatment is possible for its high completion rate. 3HP should be employed with caution for risk of systemic drug reactions and hypertensive events in middle-aged and elderly individuals, respectively.
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Tuberculose Latente , Idoso , Antituberculosos/efeitos adversos , Quimioterapia Combinada , Humanos , Isoniazida/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Pessoa de Meia-Idade , Rifampina/efeitos adversos , Rifampina/análogos & derivadosRESUMO
Lymph node metastasis is an aggressive condition characterized by poor treatment outcomes and low overall survival. Belinostat is a novel histone deacetylase (HDAC) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of relapsed peripheral T-cell lymphoma (PTCL). However, the major problem is that belinostat has a short half-life of 1.1 h. In this study, we successfully prepared 50 nm liposomal colloids, which showed a controlled release pattern and excellent pharmacokinetics. The results showed that the particle size of liposomes consisting of dioleoylphosphatidylcholine (DOPC) was larger than that of those consisting of dioleoylglycerophosphoserine (DOPS). In terms of release kinetics of belinostat, the free drug was rapidly released and showed lower area under curve (AUC) exposure for in vivo pharmacokinetics. When liposomal formulations were employed, the release pattern was fitted with Hixson-Crowell models and showed sustained release of belinostat. Moreover, HuT-78 cells were able to take up all the liposomes in a concentration-dependent manner. The safety assessment confirmed hemocompatibility, and the platelet count was increased. Furthermore, the liposomes consisting of DOPC or DOPS had different behavior patterns, and their delivery to lymphatic regions should be thoroughly investigated in the future.
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Osteosarcoma (OSA) is the most common type of cancer that originates in the bone and usually occurs in young children. OSA patients were treated with neoadjuvant chemotherapy and surgery, and the results were disappointing. Marine antimicrobial peptides (AMPs) have been the focus of antibiotic research because they are resistant to pathogen infection. Piscidin-1 is an AMP from the hybrid striped bass (Morone saxatilis × M. chrysops) and has approximately 22 amino acids. Research has shown that piscidin-1 can inhibit bacterial infections and has antinociception and anti-cancer properties; however, the regulatory effects of piscidin-1 on mitochondrial dysfunction in cancer cells are still unknown. We aimed to identify the effects of piscidin-1 on mitochondrial reactive oxygen species (mtROS) and apoptosis in OSA cells. Our analyses indicated that piscidin-1 has more cytotoxic effects against OSA cells than against lung and ovarian cancer cells; however, it has no effect on non-cancer cells. Piscidin-1 induces apoptosis in OSA cells, regulates mtROS, reduces mitochondrial antioxidant manganese superoxide dismutase and mitochondrial transmembrane potential, and decreases adenosine 5'-triphosphate production, thus leading to mitochondrial dysfunction and apoptosis. The mitochondrial antioxidant, mitoTempo, reduces the apoptosis induced by piscidin-1. Results suggest that piscidin-1 has potential for use in OSA treatment.
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antineoplásicos , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Proteínas de Peixes/farmacologia , Mitocôndrias/metabolismo , Osteossarcoma/patologia , Espécies Reativas de Oxigênio/metabolismo , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Bass , Proteínas de Peixes/química , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/enzimologia , Superóxido Dismutase/metabolismo , Tionucleotídeos/metabolismo , Células Tumorais CultivadasRESUMO
BACKGROUND: Paclitaxel is wildly used in chemotherapy, however, the adverse drug reactions (ADRs) occurred frequently. Various novel nano-based paclitaxel delivery systems were developed. The aim performed systemically review and meta-analyses to evaluate the effect adverse drug reactions (ADRs) of paclitaxel and its nano-based delivery systems. METHODS: Systematically searched PubMed, Embase, Web of Science, Cochrane, Clinicalkey, Clinicaltrial.com, ASCO and ESMO. Data of adverse effect were analyzed to odds ratio (ORs) with 95% confidence interval (CI). The quality of studies was assessed with CASP Randomised Controlled Trial Checklist. Statistical analysis was used WinBUGS software (version 1.4.3) with the NetMetaXL interface (version 1.6.1). RESULTS: Twenty-one studies, including 7011 patients and 6 paclitaxel formulations fulfilled the inclusion criteria. In all grade hypersensitivity reactions, comparing to SB-P, people with Lip-P had 0.19 times (95% CI= 0.02, 1.3) of chance, with Nab-P had 0.47 times (95% CI= 0.11, 1.40) of chance, with PPX had 0.44 times (95% CI= 0.03, 5.7) of chance for all grade adverse effect. In All grad neutropenia, comparing to Lip-P, people with SB-P had 0.83 times (95% CI= 0.15, 4.81) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.73 times (95% CI= 0.22, 2.42) of chance for all grade adverse effect. In leucopenia, comparing to Nab-P, people with SB-P had 0.66 times (95% CI= 0.50, 0.87) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.64 times (95% CI= 0.32, 1.16) of chance for all grade adverse effect. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations. CONCLUSION: Nano-based paclitaxel delivery resulted in fewer hypersensitivity reactions than solvent-based delivery. However, the incidence of neutropenia and leucopenia was higher in nano-based than solvent-based paclitaxel delivery. Dose-dependent ADRs were more frequent in paclitaxel anticancer treatment.
Assuntos
Sistemas de Liberação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Nanopartículas/química , Paclitaxel/uso terapêutico , Feminino , Humanos , Hipersensibilidade/etiologia , Masculino , Pessoa de Meia-Idade , Metanálise em RedeRESUMO
OBJECTIVES: A single isolate of nontuberculous mycobacterium (NTM) from bronchoscopic samples satisfies the microbiological criterion for diagnosing NTM-pulmonary disease (PD). Studies investigating patients with NTM-PD and multiple culture-negative sputum samples but culture-positive bronchoscopic samples are lacking. We investigated the clinical characteristics, outcome, and predictors of radiographic progression in this special population. METHODS: Patients with negative NTM culture from ≥2 expectorated sputum samples within the 3 months prior to bronchoscopy diagnosis of NTM-PD between 2009 and 2017 were included. Patient characteristics and clinical course were described. Predictors for radiographic progression of NTM-PD within 2 years were analysed by using multivariate logistic regression. RESULTS: Among 66 patients with bronchoscopy-diagnosed NTM-PD, radiographic progression occurred within 2 years in 17 (26%). Of the 60 patients not initially treated, radiographic progression occurred in 17 (28%). Among them, 10 never received treatment, with 6 deteriorating and 3 dying. Of the 6 and 7 patients who received treatment immediately after NTM-PD diagnosis and after radiographic progression, respectively, none had further radiographic progression. The independent predictors of radiographic progression were male sex, body mass index <18.5 kg/m2, use of inhaled corticosteroids, and acid-fast smear grade ≥2 of index bronchoscopic samples. CONCLUSIONS: Among patients with bronchoscopy-diagnosed NTM-PD, one fourth experienced radiographic progression within 2 years. The risk was even higher in those with the aforementioned predictors, immediate treatment or close monitoring is recommended. For others, conservative management by regular microbiological monitoring for sputum samples and image follow-up may be the optimal choice.