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International Journal of Antimicrobial... Jun 2024Insufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance....
BACKGROUND
Insufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance. Measurement of drugs in biological samples, such as blood and saliva, can be used to assess adherence and make dose adjustments by therapeutic drug monitoring (TDM). Finger sweat testing is a convenient and non-invasive method to monitor patients.
OBJECTIVES
To assess the feasibility of finger sweat testing for medication adherence and as a semi-quantitative tool for TDM analysis.
METHODS
Ten patients provided finger sweat, blood and saliva samples following a controlled dose of isoniazid. Samples were analysed by liquid chromatography-mass spectrometry.
RESULTS
Isoniazid can be detected in finger sweat 1-6 h following administration at typically prescribed dosages. The normalisation of isoniazid to creatinine increases the correlation between finger sweat and serum isoniazid concentration and provides a means to account for inconsistent sample volumes.
CONCLUSION
We describe the time-course measurement of isoniazid (or drug-to-creatinine ratio) in finger sweat compared to the pharmacokinetic profile in blood for the first time. This technique, adaptable for other drugs, could reduce the burden on clinics and improve patient experience.
PubMed: 38918168
DOI: 10.1016/j.ijantimicag.2024.107231 -
Ecotoxicology and Environmental Safety Jun 2024Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods,...
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.
PubMed: 38917590
DOI: 10.1016/j.ecoenv.2024.116630 -
Microbiology Spectrum Jun 2024Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic...
UNLABELLED
Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic cycle. In this stage resides inside the host in a dormant and antibiotic-tolerant state. Latent TB infection can also lead to multisystemic diseases because invades virtually all organs, including ocular tissues. Ocular tuberculosis (OTB) occurs when the dormant bacilli within the ocular tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Histological evidence suggests that retinal pigment epithelium (RPE) cells play a central role in immune privilege and in protection from antibiotic effects, making them an anatomical niche for invading . RPE cells exhibit high tolerance to environmental redox stresses, allowing phagocytosed bacilli to maintain viability in a dormant state. However, the microbiological and metabolic mechanisms determining the interaction between the RPE intracellular environment and phagocytosed are largely unknown. Here, liquid chromatography-mass spectrometry metabolomics were used to illuminate the metabolic state within RPE cells reprogrammed to harbor dormant bacilli and enhance antibiotic tolerance. Timely and accurate diagnosis as well as efficient chemotherapies are crucial in preventing the poor visual outcomes of OTB patients. Unfortunately, the efficacy of current methods is highly limited. Thus, the results will lead to propose a novel therapeutic option to synthetically kill the dormant inside the RPE cells by modulating the phenotypic state of and laying the foundation for a new, innovative regimen for treating OTB.
IMPORTANCE
Understanding the metabolic environment within the retinal pigment epithelium (RPE) cells altered by infection with and mycobacterial dormancy is crucial to identify new therapeutic methods to cure ocular tuberculosis. The present study showed that RPE cellular metabolism is altered to foster intracellular to enter into the dormant and drug-tolerant state, thereby blunting the efficacy of anti-tuberculosis chemotherapy. RPE cells serve as an anatomical niche as the cells protect invading bacilli from antibiotic treatment. LC-MS metabolomics of RPE cells after co-treatment with HO and infection showed that the intracellular environment within RPE cells is enriched with a greater level of oxidative stress. The antibiotic tolerance of intracellular within RPE cells can be restored by a metabolic manipulation strategy such as co-treatment of antibiotic with the most downstream glycolysis metabolite, phosphoenolpyruvate.
PubMed: 38916325
DOI: 10.1128/spectrum.00788-24 -
Cureus May 2024is an uncommon nosocomial bacteria, typically dismissed as a contaminant. This case is a unique scenario in which bacteremia persisted despite appropriate treatment....
is an uncommon nosocomial bacteria, typically dismissed as a contaminant. This case is a unique scenario in which bacteremia persisted despite appropriate treatment. Further investigation revealed the presence of a right atrial thrombus believed to harbor a biofilm responsible for the sustained bacteremia. Clearance of the thrombus using the AngioVac system (AngioDynamics, Inc., Latham, NY) led to the resolution of blood cultures, and subsequently, the patient was discharged with a six-week course of intravenous (IV) antibiotics.
PubMed: 38915975
DOI: 10.7759/cureus.61046 -
BioRxiv : the Preprint Server For... Jun 2024Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we...
INTRODUCTION
Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer.
METHODS
Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pre-treatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons.
RESULTS
A total of 187 patients with non-small cell lung cancer (Black, 19; White, 168) were included in the analysis. There were no significant differences in baseline characteristics between Black and White patients. Compared to White patients, Black patients had significantly lower levels of CCL23 and CCL27, and significantly higher levels of CCL8, CXCL1, CCL26, CCL25, CCL1, IL-1 b, CXCL16, and IFN-γ (all <0.05, FDR<0.1). Black patients also exhibited greater populations of non-classical CD16+ monocytes, NKT-like cells, CD4+ cells, CD38+ monocytes, and CD57+ gamma delta T cells (all <0.05).
CONCLUSIONS
Black and White patients with lung cancer exhibit several differences in immune parameters, with Black patients exhibiting greater levels of numerous pro-inflammatory cytokines and cell populations. The etiology and clinical significance of these differences warrant further evaluation.
PubMed: 38915535
DOI: 10.1101/2024.06.07.597754 -
Journal of Surgical Case Reports Jun 2024Solitary fibrous tumor (SFT) of the lung is a rare neoplasm, usually originating from lung pleura. We present a case report of a 57-year-old male with no significant...
Solitary fibrous tumor (SFT) of the lung is a rare neoplasm, usually originating from lung pleura. We present a case report of a 57-year-old male with no significant medical history who was incidentally diagnosed with an SFT of lung parenchyma on chest computed tomography scan. Radiological imaging revealed a well-defined mass in the left lower lobe of the lung. Biopsy and histopathological examination confirmed the diagnosis of solitary fibrous tumor. This case highlights the importance of considering SFT in the differential diagnosis of lung masses, as its clinical presentation and radiological features can mimic those of more common pulmonary malignancies.
PubMed: 38915343
DOI: 10.1093/jscr/rjae426 -
Clinical Chemistry and Laboratory... Jun 2024Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to...
OBJECTIVES
Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to assess the current understanding and usage of metabolomics in laboratory medicine globally and evaluate the perception of its promise and future implementation.
METHODS
A survey was conducted by the IFCC metabolomics working group that queried 400 professionals from 79 countries. Participants provided insights into their experience levels, knowledge, and usage of metabolomics approaches, along with detailing the applications and methodologies employed.
RESULTS
Findings revealed a varying level of experience among respondents, with varying degrees of familiarity and utilization of metabolomics techniques. Targeted approaches dominated the field, particularly liquid chromatography coupled to a triple quadrupole mass spectrometer, with untargeted methods also receiving significant usage. Applications spanned clinical research, epidemiological studies, clinical diagnostics, patient monitoring, and prognostics across various medical domains, including metabolic diseases, endocrinology, oncology, cardiometabolic risk, neurodegeneration and clinical toxicology.
CONCLUSIONS
Despite optimism for the future of clinical metabolomics, challenges such as technical complexity, standardization issues, and financial constraints remain significant hurdles. The study underscores the promising yet intricate landscape of metabolomics in clinical practice, emphasizing the need for continued efforts to overcome barriers and realize its full potential in patient care and precision medicine.
PubMed: 38915248
DOI: 10.1515/cclm-2024-0550 -
Journal of Cardiothoracic Surgery Jun 2024Diabetes mellitus (DM) is a common comorbidity of lung cancer. We hypothesized that severe DM is associated with increased complications after surgical resection of...
PURPOSE
Diabetes mellitus (DM) is a common comorbidity of lung cancer. We hypothesized that severe DM is associated with increased complications after surgical resection of non-small-cell lung cancer (NSCLC).
METHODS
A review of our retrospective thoracic database identified 1139 consecutive surgical resections for NSCLC from 2002 to 2021. Our analysis included the exploration of clinicopathological features, perioperative variables, and surgical outcomes.
RESULTS
In addition to lung cancer, 170 patients (14.9%) had DM. The patients included 132 (77.6%) men and 38 (22.4%) women, with a median age of 72 (range, 51-93) years old. The median preoperative fasting blood glucose and HbA1c levels were 135 mg/dL (range, 57-303) and 6.9% (range, 5.1-14.8), respectively. Eighty-one patients had DM as a single comorbidity, and 89 patients had other comorbidities or a relevant medical history. A total of 144 patients were prescribed these drugs. There were 107 patients (62.9%) who consulted a specialist diabetes endocrinology department preoperatively and 118 patients (69.4%) who required sliding-scale insulin during the perioperative period. Forty-seven patients (27.6%) developed post-operative complications. No cases of bronchopleural fistula were noted. A univariate analysis showed that the sex (p = 0.017), body mass index (BMI) (p = 0.0032), surgical procedure (p = 0.017), surgical time (p = 0.002), and lymphatic invasion (p = 0.011) were significantly different among patients stratified by postoperative complications. A multivariate analysis showed that a low BMI (odds ratio [OR]: 0.413, 95% confidence interval [CI]: 0.196-0.870, p = 0.018), long surgical time (OR: 2.690, 95% CI: 1.190-6.082, p = 0.015), and presence of lymphatic invasion (OR: 2.849, 95% CI: 1.319-6.135, p = 0.007) were risk factors for postoperative complications. In contrast, severe preoperative DM did not have a significant negative effect on the incidence of postoperative complications.
CONCLUSION
In modern respiratory surgery, severe DM does not affect the short-term outcomes under strict preoperative treatment.
Topics: Humans; Male; Female; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Aged; Middle Aged; Postoperative Complications; Risk Factors; Glycated Hemoglobin; Aged, 80 and over; Pneumonectomy; Diabetes Mellitus; Preoperative Period; Blood Glucose
PubMed: 38915109
DOI: 10.1186/s13019-024-02912-7 -
Analysis of clinical characteristics of different types of lung function impaiement in TDL patients.BMC Pulmonary Medicine Jun 2024The clinical characteristics associated with pulmonary function decline in patients with Tuberculosis-destroyed lung (TDL) remain uncertain. We categorize them based on...
AIM
The clinical characteristics associated with pulmonary function decline in patients with Tuberculosis-destroyed lung (TDL) remain uncertain. We categorize them based on the pattern of pulmonary function impairment, distinguishing between restrictive spirometric pattern (RSP) and obstructive spirometric pattern (OSP). We aim to compare the severity of these patterns with the clinical characteristics of TDL patients and analyze their correlation.
METHOD
We conducted a retrospective analysis on the clinical data of TDL patients who underwent consecutive pulmonary function tests (PFT) from November 2002 to February 2023. We used the lower limit formula for normal values based on the 2012 Global Lung Function Initiative. We compared the clinical characteristics of RSP patients with those of OSP patients. The characteristics of RSP patients were analyzed using the tertiles of forced vital capacity percentage predicted (FVC% pred) decline based on PFT measurements, and the characteristics of OSP patients were analyzed using the tertiles of forced expiratory volume in 1 s percentage predicted (FEV% pred) decline.
RESULT
Among the RSP patients, those in the Tertile1 group (with lower FVC% pred) were more likely to have a higher of body mass index (BMI), spinal deformities, and C-reactive protein (CRP) compared to the other two groups (P for trend < 0.001, 0.027, and 0.013, respectively). Among OSP patients, those in the Tertile1 group (with lower FEV% pred) showed an increasing trend in cough symptoms and contralateral lung infection compared to the Tertile 2-3 group (P for trend 0.036 and 0.009, respectively).
CONCLUSION
For TDL patients, we observed that Patients with high BMI, a higher proportion of spinal scoliosis, and abnormal elevation of CRP levels were more likely to have reduced FVC. Patients with decreased FEV% pred have more frequent cough symptoms and a higher proportion of lung infections on the affected side.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Vital Capacity; Forced Expiratory Volume; Adult; Lung; Spirometry; Aged; Tuberculosis, Pulmonary; Respiratory Function Tests; C-Reactive Protein; Body Mass Index
PubMed: 38914991
DOI: 10.1186/s12890-024-03115-5 -
Scientific Reports Jun 2024Estimating the change rates in body size following the weight loss programs is very important in the compliance of those programs. Although, there is enough evidence on...
Estimating the change rates in body size following the weight loss programs is very important in the compliance of those programs. Although, there is enough evidence on the significant association of body weight change with the other anthropometric indices and/ or body composition, there is so limited studies that have depicted this relationship as mathematical formulas. Therefore, the present research designed to use a mathematical model to predict changes of anthropometric indices following a weight-loss diet in the overweight and obese women. In this longitudinal study, 212 overweight/obese women who received an individualized low-calorie diet (LCD) were selected and followed-up for five months. Anthropometric measurements such as weight, waist circumference (WC), hip circumference (HC), and body composition (lean mass and fat mass) were performed. Then, body mass index, waist to hip ratio (WHR), waist to height ratio (WHtR), a body shape index (ABSI), abdominal volume index (AVI), and body adiposity index (BAI) were calculated using the related formula. Following the LCD led to the substantial and consistent changes in various anthropometric indices over time. All of these anthropometric variations were significantly related with the percent change (PC) of body weight except than WHR. Moreover, according to the mathematical formulas, weight loss was closely related to the decrease of WC (PC-WC = - 0.120 + 0.703 × PC-WT), HC (PC-HC = - 0.350 + 0.510 × PC-WT), body fat percentage (PC-Body Fat = - 0.019 + 0.915 × PC-WT), WHtR (PC-WHtR = - 0.113 + 0.702 × PC-WT), and improvements in ABSI (PC-ABSI = - 0.112 + 0.034 × PC-WT) and AVI (PC-AVI = - 0.324 + 1.320 × PC-WT). The decreasing rates of WC, HC, body fat percentage, WHtR, ABSI, and AVI in relation to the weight loss were clinically and statistically significant. This means that a healthy weight lowering diet would be accompanied by decreasing the body fat, body size and also the risk of morbidities.
Topics: Humans; Female; Obesity; Adult; Weight Loss; Diet, Reducing; Middle Aged; Overweight; Anthropometry; Models, Theoretical; Longitudinal Studies; Body Mass Index; Waist Circumference; Waist-Hip Ratio; Body Composition; Caloric Restriction
PubMed: 38914732
DOI: 10.1038/s41598-024-65586-0