Detection of trichomonads in patients with lung cancer and transcription analysis on the response of human pulmonary epithelial cells to Trichomonas tenax invasion.

INTRODUCTION: Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis. METHODS: Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of Trichomonas tenax invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis. RESULTS: Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as Trichomonas tenax, while one was identified as Tetratrichomonas spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to T. tenax invasion. CONCLUSIONS: This study underscores the importance of recognizing the presence of trichomonads and the influence of T. tenax invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.

Navigating the challenges of invasive pulmonary aspergillosis in lung cancer treatment: a propensity score study.

Background: Invasive pulmonary aspergillosis (IPA) can negatively impact cancer patients' survival. It remains uncertain whether IPA's impact on patient outcomes varies by treatment approach in advanced lung cancer. Objectives: To explore the association between IPA and outcomes in patients with advanced lung cancer receiving different treatments. Design: A retrospective cohort study. Methods: We enrolled patients with advanced-stage lung cancer between 2013 and 2021 at a college hospital in Taiwan and used the 2021 European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium consensus for IPA diagnosis. Multivariable logistic regression was used to identify the IPA risk factors. We compared overall survival (OS) and postgalactomannan (GM) test survival between the IPA and control groups using multivariable Cox proportional hazards regression and the Kaplan-Meier method with propensity score matching (PSM). Results: Among 2543 patients with advanced-stage lung cancer, 290 underwent a GM test, of which 34 (11.7%) were diagnosed with IPA. Patients undergoing chemotherapy (HR = 4.02, p = 0.027) and immunotherapy [hazard ratio (HR) = 3.41, p = 0.076] tended to have IPA. Compared to the control group, the IPA group had shorter median OS (14.4 versus 9.9 months, p = 0.030) and post-GM test survival (4.5 versus 1.9 months, p = 0.003). IPA was associated with shorter OS (log-rank p = 0.014 and 0.018 before and after PSM, respectively) and shorter 1-year and 2-year survival post-GM test (HR = 1.65 and 1.66, respectively). Patients receiving chemotherapy or immunotherapy had a shorter post-GM test survival if they had IPA. Conclusions: IPA tended to be diagnosed more frequently in patients receiving chemotherapy or immune checkpoint inhibitors. Patients diagnosed with IPA are associated with shorter survival. Larger cohort studies are needed to verify the observations.

Mixed Mycobacterium kansasii and Mycobacterium smegmatis infection in an adult-onset immunodeficiency patient with anti-interferon-γ autoantibodies.

Anti-interferon-gamma autoantibody (AIGA) is a rare adult-onset immunodeficiency disease that increases the risk of occult infection. Nontuberculous mycobacteria (NTM) infections represent a diverse group of species and subspecies, and mixed infections with two or more NTM species have been reported. However, there is no consensus on the optimal antibiotics or immune modulator treatments for mixed NTM infections in AIGA patients. Here, we present the case of a 40-year-old female who initially presented with suspected lung cancer with obstructive pneumonitis. Tissue samples obtained through bronchoscopy, endoscopy, and bone marrow biopsy revealed disseminated mycobacterium infection. PCR-based testing confirmed a mixed pulmonary infection with Mycobacterium kansasii and Mycobacterium smegmatis, as well as M. kansasii bacteremia. The patient received 12 months of anti-NTM medications for M. kansasii, and the symptoms improved. Additionally, the images showed resolution after 6 months, even without the need for immune modulator treatment.

Cigarette smoke increases susceptibility of alveolar macrophages to SARS-CoV-2 infection through inducing reactive oxygen species-upregulated angiotensin-converting enzyme 2 expression.

Alveolar macrophages (AMs) are the drivers of pulmonary cytokine storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to investigate clinical-regulatory factors for the entrance protein of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) in AMs. Human AMs were collected from 56 patients using bronchoalveolar lavage. ACE2 expression in AMs was positively correlated with smoking pack-year (Spearman's r = 0.347, P = 0.038). In multivariate analysis, current smoking was associated with increased ACE2 in AMs (ß-coefficient: 0.791, 95% CI 0.019-1.562, P = 0.045). In vitro study, ex-vivo human AMs with higher ACE2 were more susceptible to SARS-CoV-2 pseudovirus (CoV-2 PsV). Treating human AMs using cigarette smoking extract (CSE) increases the ACE2 and susceptibility to CoV-2 PsV. CSE did not significantly increase the ACE2 in AMs of reactive oxygen species (ROS) deficient Cybb-/- mice; however, exogenous ROS increased the ACE2 in Cybb-/- AMs. N-acetylcysteine (NAC) decreases ACE2 by suppressing intracellular ROS in human AMs. In conclusion, cigarette smoking increases the susceptibility to SARS-CoV-2 by increasing ROS-induced ACE2 expression of AMs. Further investigation into the preventive effect of NAC on the pulmonary complications of COVID-19 is required.

Early detection of the initial stages of LED light-triggered non-alcoholic fatty liver disease by wax physisorption kinetics-Fourier transform infrared imaging.

Light-emitting diodes (LEDs), particularly in the blue waveform range, are regarded as a major source of circadian rhythm dysregulation. A circadian rhythm dysregulation induced by blue LEDs is associated with non-alcoholic fatty liver disease (NAFLD). Hepatocellular accumulation of lipids is a key event in the early stages of NAFLD. Kupffer cells (KCs) have been reported to be lost in the early onset of NAFLD followed by an inflammatory reaction that alters the liver response to lipid overload. This study focused on the detection of the initial stages (subpathological stages) of LED light-triggered NAFLD. Mice were exposed to either blue or white LED irradiation for 44 weeks. Synchrotron radiation-based Fourier-transform infrared microspectroscopy (SR-FTIRM) and wax physisorption kinetic-Fourier transform infrared (WPK-FTIR) imaging were used to evaluate the ratio of lipid to protein and the glycosylation of glycoprotein, respectively. Immunohistopathological studies on KCs and circadian-related proteins were performed. Although liver biopsy showed normal pathology, an SR-FTIRM study revealed a high hepatic lipid-to-protein ratio after receiving LED illumination. The results of WPK-FTIR demonstrated that a high inflammation index was found in the high irradiance of the blue LED illumnation group. These groups showed a decrease in KC number and an increase in Bmal1 and Reverbα circadian protein expression. These findings provide explanations for the reduction of KCs without subsequent inflammation. A significant reduction of Per2 and Cry1 expression is correlated with the findings of WPK-FTIR imaging. WPK-FTIR is a sensitive method for detecting initiative stages of NAFLD induced by long-term blue LED illumination.

Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease.

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Acrolein plays a culprit role in the pathogenesis of diabetic nephropathy in vitro and in vivo.

Objective: Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an α,ß-unsaturated aldehyde, is a common dietary and environmental pollutant. Design: The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet/ streptozotocin-induced DN mice and in vitro DN cellular models. Methods: Acrolein-protein conjugates (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin-angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system. Results: We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathways, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function. Conclusions: These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.

Body-Weight Gain in Women During Smoking Cessation Is a Sex-Specific Predictor of 6-Month Abstinence: A Retrospective Cohort Study.

Background: Smoking behavior differs between the sexes. Weight control is one of the main reasons leading to tobacco abuse in women but not in men. Studies on the predictive factors of cessation failure between sexes are scarce. This study is aim to investigate whether there are sex differences in the effect of weight gain on smoking cessation rate. Methods: Participants in the smoking-cessation program at a Medical Center in Taiwan between 2018 and 2019 were included. Details of age, sex, comorbidities, depression screening, nicotine dependence, body weight, and cessation medications of the participants were collected. The participants were classified based on their sex, and multivariable logistic regression analyses were conducted. Multivariable logistic regression analyses were performed for sensitivity analysis after stratifying the participants according to their weight loss (weight loss ≥ 1.5 kg and weight loss ≥ 3.0 kg). Results: A total of 1,475 participants were included. The body-weight gain in women was associated with failed abstinence (adjusted odds ratio (OR): 3.10, 95% CI: 1.10-9.04). In contrast, body-weight gain in men was associated with successful 6-month prolonged abstinence (adjusted OR: 0.77, 95% CI: 0.61-0.98). The adjusted ORs for any body-weight loss, body-weight loss ≥1.5 kg, and body-weight loss ≥3.0 kg were 0.28 (95% CI: 0.09-0.88), 0.14 (95% CI: 0.03-0.55), and 0.03 (95% CI: 0.01-0.42), respectively. Conclusion: Body-weight gain in women during a hospital-based smoking-cessation program is associated with abstinence failure. Further multicenter studies, including participants of different races and cultural backgrounds, are warranted.

Multiple in-hospital counseling increases six-month smoking abstinence among individuals participating in a hospital-initiated smoking cessation program.

BACKGROUND: A cessation program for hospitalized smokers is an effective strategy to achieve smoking abstinence. The effects of multiple in-hospital counseling sessions on 6-month smoking abstinence require further investigation. METHODS: We retrospectively analyzed the data of smokers who participated in hospital-initiated cessation programs at a medical center between 2017 and 2019. Data on age, sex, comorbidities, daily number of cigarettes, cessation motivation, nicotine dependence, cessation medications, discharge diagnosis, length of hospitalization, and intensive care unit admission were collected. We conducted multiple logistic regression analysis to investigate the effect of multiple in-hospital counseling sessions on 6-month sustained smoking abstinence. Sensitivity analyses were carried out excluding participants who underwent post-discharge cessation programs and assuming that the loss to follow-up participants had failure in 6-month smoking abstinence. RESULTS: A total of 1943 participants aged ≥ 20 years were analyzed. Compared with single in-hospital counseling session, the adjusted odds ratios (ORs) for 2 and ≥ 3 counseling sessions were 1.44 (95% confidence interval [CI] 1.05 to 1.98) and 2.02 (95% CI 1.27 to 3.22), respectively, with a significant trend for increasing the number of counseling sessions (P < 0.001). The results remained significant after excluding participants who underwent a post-discharge cessation program or when assuming that lost to follow-up participants had failure in smoking abstinence. CONCLUSION: Multiple in-hospital counseling sessions were associated with a higher 6-month sustained smoking abstinence rate. This strategy could be used to reduce the prevalence of smoking.

Development and validation of a prediction index for recent mortality in advanced COPD patients.

The primary barrier to initiating palliative care for advanced COPD patients is the unpredictable course of the disease. We enroll 752 COPD patients into the study and validate the prediction tools for 1-year mortality using the current guidelines for palliative care. We also develop a composite prediction index for 1-year mortality and validate it in another cohort of 342 patients. Using the current prognostic models for recent mortality in palliative care, the best area under the curve (AUC) for predicting mortality is 0.68. Using the Modified Medical Research Council dyspnea score and oxygen saturation to define the combined dyspnea and oxygenation (DO) index, we find that the AUC of the DO index is 0.84 for predicting mortality in the validated cohort. Predictions of 1-year mortality based on the current palliative care guideline for COPD patients are poor. The DO index exhibits better predictive ability than other models in the study.

Baseline plasma KL-6 level predicts adverse outcomes in patients with idiopathic pulmonary fibrosis receiving nintedanib: a retrospective real-world cohort study.

BACKGROUND: Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. METHODS: We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. RESULTS: Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13-10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89-19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63-12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16-24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06-73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline. CONCLUSIONS: For patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.

Downstream Complications and Healthcare Expenditure after Invasive Procedures for Lung Lesions in Taiwan.

This study aimed to estimate the downstream complications and healthcare expenditure after invasive procedures for lung lesions, which in turn could be used for future cost-effectiveness analyses of lung cancer screening in Taiwan. We interlinked the Taiwan National Beneficiary Registry with the National Health Insurance Reimbursement databases to identify non-lung cancer individuals aged 50-80 years who underwent invasive lung procedures within one month after non-contrast chest computed tomography between 2014 and 2016. We directly matched one individual with 10 controls by age, gender, calendar year, residence area, comorbidities, and the past one-year healthcare expenditure to calculate incremental one-month complication rates and attributable costs. A total of 5805 individuals who underwent invasive lung procedures were identified and matched with 58,050 controls. The incremental one-month complication rates were 13.4% (95% CI: 10.9% to 15.8%), 10.7% (95% CI: 9.2% to 12.1%), and 4.4% (95% CI: 2.0% to 6.7%) for thoracic surgery, bronchoscopy, and needle biopsy, respectively. The incremental one-month healthcare expenditure for minor, intermediate, and major complications were NT$1493 (95% CI: NT$-3107 to NT$6092), NT$18,422 (95% CI: NT$13,755 to NT$23,089), and NT$58,021 (95% CI: NT$46,114 to NT$69,929), respectively. Individuals aged 60-64 years incurred the highest incremental costs. Downstream complications and the healthcare expenditure after invasive procedures for lung lesions would be substantial for non-lung cancer individuals 50-80 years of age. These estimates could be used in modeling the cost-effectiveness of the national lung screening program in Taiwan.

Dynamic Changes of Health Utility in Lung Cancer Patients Receiving Different Treatments: A 7-Year Follow-up.

INTRODUCTION: This study aimed to estimate the utility values of all subtypes of lung cancer. The trajectories after different kinds of treatments and their major determinants were explored on the basis of real-world data and repeated measurements. METHODS: From 2011 to 2017, all patients with lung cancer who visited a medical center were invited to fill out the EuroQol Five-Dimension and WHO Quality of Life-Brief questionnaires at each visit. Utility values of quality of life (QoL) after diagnosis and treatments were depicted using a kernel smoothing method. We constructed linear mixed models to predict health utility in each time period and cross-validated them with domain scores of the WHO Quality of Life-Brief. RESULTS: A total of 1715 patients were enrolled, with 6762 QoL measurements. Utility values were lower in patients with advanced-stage disease and older patients. Patients receiving second-line targeted therapy showed higher utility values at 0 to 3 months, 3 to 6 months, and 6 months and beyond (0.89, 0.90, and 0.88, respectively) than did those undergoing chemotherapy (0.81, 0.85, and 0.80, respectively). After using mixed models to control confounders, including poor performance status and disease progression, patients receiving second-line chemotherapy showed health utility similar to that at quasi-baseline, whereas utility values related to second-line targeted therapy were higher at 3 to 6 months and 6 months and beyond (ß = 0.07, p = 0.010 and ß = 0.07, p < 0.001, respectively). There was convergent validity between the utility values and scores of the physical and psychological domains. CONCLUSION: Targeted therapy provided treated patients with a higher health utility value than was provided to those treated with chemotherapy. Development of the longitudinal trajectory may help predict changes in QoL and improve the care of lung cancer survivors.

Therapeutic efficacy of Traditional Chinese medicine, "Kuan-Sin-Yin", in patients undergoing chemotherapy for advanced colon cancer - A controlled trial.

BACKGROUND: Traditional Chinese Medicine (TCM) has been used increasingly as complementary medicine in cancer care. Kuan-Sin-Yin (KSY) is a TCM decoction containing seven herbs known to cause immunomodulation or anticancer activity, and which are associated with the TCM concept of Qi and energy supply. Kuan-Sin-Yin has cytostatic effects on cancer cells in animal models. OBJECTIVE: The aim of this study is to evaluate the level of improvement in meridian energy and heart-rate variability (HRV) and to assess whether these observations are compatible with TCM theory. METHOD: A non-randomized controlled trial was designed with monitoring of the meridian electro-conductivity and heart-rate variability (HRV) to compare the efficacy of Kuan-Sin-Yin in the control and experimental groups. 52 patients were enrolled in this study. We also measured cancer-related symptoms and quality of life as secondary outcomes. RESULTS: We found that colon cancer patients who received KSY as complementary therapy benefitted with enhancement of meridian energy (Yin meridian: 27.90:35.45µA; p=0.014; Yang meridian: 27.09:33.55µA; p=0.024) and increases in HRV activity (78.40:129.04ms; SDNN: p=0.001) and parasympathetic tone(HF:1644.80:3217.92 ms2; p=0.003; RMMSD:99.76:164.52ms; p=0.002). Cancer-related symptoms decreased (ECOG>1:46.2:7.7%; p=0.0001), and quality of life (KSY group: PCS 35.46:42.12, p=0.0001; MCS: 44.50:47.55, p=0.209) was improved with statistical significance. CONCLUSIONS: The correlation of positive results reflected in meridian energy and HRV activity confirms the positive role of complementary medicine of Kuan-Sin-Yin in cancer care.

High incidence and recurrence of transitional cell carcinoma in Taiwanese patients with end-stage renal disease.

AIM: This study examines the epidemiology of transitional cell carcinoma (TCC) in end-stage renal disease (ESRD) population from Taiwan, the area with the highest incidence and prevalence of ESRD. METHODS: A total of 98 out of 10,890 ESRD patients were referred for management of TCC between 2000 and 2008. Demographic, clinical and laboratory data were collected and patient mortality and tumour recurrence rates were analyzed. RESULTS: TCC patients were aged 61.4 ± 10.2 years and 66.3% were female. The average time from initiation of dialysis to tumour detection was 51.2 ± 36.4 months. Hypertensive nephrosclerosis, diabetes mellitus, chronic glomerulonephritis and unknown aetiology accounted for 25.5%, 20.4%, 22.4% and 31.6% of the causes of renal failure, respectively. The aetiology of renal failure for the 31.6% of patients was unclear, but chronic tubulointerstitial nephritis following long-term consumption of Chinese herbs (19.4%) or analgesic compounds (3.1%) was considered in some patients. Almost all (98.0%) patients presented with gross haematuria. Most TCC were in early stage (stage 0, 3.1%; stage I, 56.1%) during diagnosis. At the end of this study, 17 of 98 (17.3%) patients died. Multivariate Cox regression analysis found that age (odds ratio =1.140, 95% confidence interval = 1.049-1.239, P = 0.002) and tumour pain (odds ratio = 0.234, 95% confidence interval = 0.057-0.961, P = 0.044) were significant risk factors for all-cause mortality. Furthermore, 35.7% of TCC recurred during follow up. The 5 year patient and tumour-free survival rates were 72.4% and 14.4%, respectively. CONCLUSION: The data shows that Taiwanese patients with ESRD had high incidence (0.9%) and recurrence (35.7%) of TCC.