Journal of Investigative Medicine

Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that tumors exploit to evade T-cell–mediated surveillance. While PD-L1 overexpression has been linked to advanced disease and poor prognosis in many cancers, its clinicopathological significance in differentiated thyroid cancer (DTC) remains unclear. We conducted a systematic review and meta-analysis by searching MEDLINE, Embase, the Cochrane Library, and PubMed from inception to 2 January, 2023. Eligible studies reported PD-L1 immunohistochemical positivity in DTC and its correlation with clinicopathological features. Data were extracted in duplicate, and study quality was assessed with a modified Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was evaluated by the I² value. Twelve retrospective studies met the inclusion criteria. All were retrospective and of moderate quality. High tumoral PD-L1 expression was significantly associated with the presence of lymphovascular invasion (LVI) (pooled OR 4.2, 95% CI 1.7–10.5), extrathyroidal extension (ETE) (pooled OR 1.7, 95% CI 1.2–2.4; p = 0.005) and distant metastases (pooled OR 4.6, 95% CI 1.6–13.0; p = 0.004). In other words, PD-L1–positive tumors were more likely to exhibit local invasion and distant metastasis. By contrast, PD-L1 status showed no significant association with tumor size, multifocality, lymph node metastasis, AJCC tumor stage, disease recurrence, or disease-specific mortality (p > 0.05 for all). Between-study heterogeneity was not significant for our key outcomes. PD-L1 overexpression in DTC is associated with a higher risk of local invasion and distant metastases, suggesting that PD-L1 may contribute to tumor progression via immune evasion.

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disorder with limited treatment options targeting its underlying pathophysiology. This study investigates the therapeutic effects of testosterone on lung function and inflammation in a male rat model of COPD, focusing on matrix metalloproteinase-9 (MMP-9) and fibroblast growth factor-23 (FGF-23), biomarkers linked to tissue remodeling and systemic inflammation. Sixty male Wistar rats were assigned to control, COPD, and testosterone-treated groups. COPD was induced by lipopolysaccharide instillation and cigarette smoke exposure; testosterone was administered via subcutaneous implants. Pulmonary function tests, histopathology, bronchoalveolar lavage fluid (BALF) analysis, and biochemical assays were performed. Testosterone significantly improved forced vital capacity, FEV100, and mid-expiratory flow compared to the COPD group. Histology showed reduced alveolar wall thickening and inflammatory infiltration. Testosterone-treated rats exhibited lower neutrophil counts and malondialdehyde levels in BALF, along with increased superoxide dismutase activity, indicating reduced oxidative stress. At the molecular level, testosterone suppressed MMP-9 and FGF-23 expression at both mRNA and protein levels and significantly decreased MMP-9 enzymatic activity, as confirmed by gelatin zymography. These results suggest that testosterone alleviates pulmonary damage and inflammation by modulating oxidative stress and inhibiting key molecular mediators of COPD progression. This study supports the potential of testosterone as an adjunct therapy in COPD by improving respiratory function and reducing inflammation.

This study aims to unravel the impact of anesthesia precision intervention on perioperative serum myocardial injury markers and major adverse cardiac events in high-risk cardiovascular patients undergoing non-cardiac surgery. One hundred and sixty high-risk cardiovascular disease patients were randomly allocated into two groups. The control group received conventional empirical management, while the observation group underwent precise anesthesia interventions. We compared the general data, the levels of myocardial injury markers, including cardiac troponin (cTn), creatine kinase isoenzyme (CK-MB), and myoglobin (Mb). Furthermore, the levels of cardiac function markers, such as brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as the levels of inflammatory factors and the incidence of adverse cardiac events were compared between the two groups. Postoperatively, the observation group exhibited significantly lower levels of cTn, CK-MB, Mb, BNP, NT-proBNP, C-reactive protein. Additionally, the total incidence of adverse cardiac events in the observation group was noticeably lower than that in the control group. The application of precise anesthetic intervention in the perioperative period of non-cardiac surgery for high-risk cardiovascular patients can further mitigate cardiac injury and reduce the incidence of adverse cardiac events, making it worthy of clinical application.

Triglyceride-deposit cardiomyovasculopathy (TGCV) is characterized by diffuse narrowing of the coronary arteries because of triglyceride-deposit atherosclerosis. However, the plaque characteristics and prognosis of TGCV in patients with diffuse coronary artery disease remain unclear. This study aimed to describe the morphology of coronary arteries in TGCV using integrated backscatter intravascular ultrasound (IB-IVUS) and assess the effects on clinical outcomes. This single-center, retrospective observational study compared the IB-IVUS findings and clinical outcomes of patients with native coronary lesions of TGCV with those of patients with non-TGCV, all of whom had diffuse coronary artery disease. TGCV was diagnosed as (1) a low washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP; <10%) on BMIPP single-photon emission computed tomography and (2) diffuse narrowing of the coronary arteries on coronary angiography. Thirty-one patients with diffuse coronary artery disease who underwent percutaneous coronary intervention were enrolled. Among these patients 10 (32%) were diagnosed with TGCV. IB-IVUS revealed that TGCV lesions had a significantly smaller ratio of the lipid area than non-TGCV lesions (20% ± 0.8% vs 23% ± 0.5%, p = 0.02). Conversely, the ratio of the calcification area tended to be larger. The Kaplan–Meier analysis revealed a significant increase in the rates of major adverse cardiovascular events in the TGCV group (p = 0.01). Patients with diffuse coronary artery disease present TGCV characterized by a smaller ratio of the lipid area. TGCV might be associated with worse clinical outcomes. The study findings may contribute to its early diagnosis and management.

The role of esophagogastroduodenoscopy (EGD) in evaluating patients with a positive fecal occult blood testing (FOBT) or fecal immunochemical testing (FIT) and normal colonoscopy findings remains uncertain, with current recommendations based on limited and low-quality evidence. This retrospective cohort study (2012–2022) included consecutive patients with positive FOBT or fecal FIT and normal colonoscopy, alongside asymptomatic controls referred for routine EGD prior to bariatric surgery. Demographic, clinical, and endoscopic data were collected and analyzed. Predictors of upper gastrointestinal malignancy and clinically significant findings (CSFs) were examined. Among 858 patients with positive FOBT/FIT and 2010 controls, significant differences in age and sex distribution were observed (p < 0.001). Hiatus hernia and reflux esophagitis were more common in controls (p < 0.01). CSFs were more frequent in the FOBT-positive group (11.3% vs 8.3%, p < 0.01). On multivariate analysis, male sex, older age, and endoscopist experience (>3 years) were independent predictors of CSFs, while positive FOBT was not independently associated with their presence. The diagnostic yield of EGD in patients with positive FOBT/FIT but normal colonoscopy is modest and comparable to that of asymptomatic controls. These findings suggest that universal EGD may not be routinely warranted in this setting, supporting instead a selective, risk-based approach. Prospective studies are warranted to confirm these findings and assess the cost-effectiveness of universal versus selective EGD in this population.

Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with early detection being vital for effective treatment and management. Traditional diagnostic methods often struggle with the difficulty of CKD datasets, leading to delays in diagnosis and intervention. Despite advancements in machine learning, there remains a need for more effective and accurate models that can manage the intricacies of CKD data. This paper proposes an advanced AI-based system for early detection and diagnosis of CKD by developing an AI-based system that can efficiently handle complicated healthcare data. The workflow begins with data collection, where the CKD dataset, including patient health features, is gathered. The data is then preprocessed, involving missing data imputation using Expectation Maximization and outlier removal with One-Class SVM. Feature extraction is performed using Principal Component Analysis to reduce dimensionality while retaining significant features. The extracted features are passed through the TabNet model for feature selection and the long short-term memory (LSTM) for capturing temporal dependencies. Finally, the system makes abnormality detections, providing predictions based on the extracted features and temporal patterns. The model achieves a performance of 98.58% accuracy, 98.89% precision, 98.24% recall, and 98.56% F1-score, outperforming existing models such as XGBoost, SVM, and KNN. This work presents an effective combination of TabNet for feature selection and LSTM for sequential pattern recognition, resulting in a robust system for early CKD detection with minimal false positives and false negatives.

Antiretroviral therapy (ART) is treatment for people infected with human immunodeficiency virus (HIV). We aimed to investigate the short-term effects of ART on T lymphocyte counts and the expression of activation markers, CD38 and HLA-DR, on CD4+ and CD8+ T cells. Thirty HIV patients (people with HIV (PWH) group), 30 patients who received 3 months of ART (PWH on ART group), and 20 HIV-negative controls were included in the study. Whole blood samples were collected in ethylenediaminetetraacetic acid-containing tubes. The percentages of CD38- and HLA-DR-expressing T cells were estimated by flow cytometric assay. Absolute counts were calculated by the double platform method. Viral load was analyzed by the PCR method. PWH showed a significant decrease in CD4+ T cells, with numerical recovery after 3 months of ART (p = 0.001), while CD8+ T cells increased (p = 0.011) and remained unchanged post-ART (p = 0.943), despite a percentage decrease (p = 0.031). After adjusting for CD4+ T cell counts, there was no significant difference in the percentage of CD4+CD38+ T cells among the groups. In contrast, CD8+CD38+ and CD8+HLA-DR+ T cells significantly increased in the PWH group (p < 0.001) and decreased after ART (p < 0.001, p = 0.003), even after adjusting for CD8+ T cell counts and other potential confounders. The percentage of CD4+CD38+ T cells was negatively (r = −0.578, p = 0.030), and CD8+CD38+ T cells were positively correlated with viral load (r = 0.530, p = 0.013). However, we observed no correlation between HLA-DR-expressing CD4+ and CD8+ T cells and viral load. These findings suggest that CD8+CD38+ T cells could serve as a useful marker for both immune activation and assessing the effectiveness of ART in HIV patients.

People experiencing homelessness (PEH) face significant barriers to primary care, compounded by stigma from healthcare professionals. Health professions education offers a critical window of time to shape attitudes, yet research suggests these attitudes can worsen during training. A cross-sectional survey at a multi-professional graduate institution assessed attitudes toward PEH among students and educators across seven health professions colleges. Attitudes varied significantly by profession, with osteopathic medicine and graduate nursing reporting more favorable views than pharmacy, veterinary medicine, dental medicine, physician assistant studies, and physical therapy. More positive attitudes were associated with greater physical comfort, more frequent prior experiences with PEH, and higher interest in learning about homelessness. Respondents who expressed interest in receiving more information afterwards also scored significantly higher on attitude measures. Findings suggest that targeted, profession-specific educational interventions that emphasize meaningful exposure to PEH may improve attitudes. Integrating experiential learning alongside didactic content could foster more holistic, equitable care across disciplines.

Preserved ratio impaired spirometry (PRISm) may be in the pre-stage of chronic obstructive pulmonary disease. However, little is known about peripheral eosinophils in PRISm. This study ultimately enrolled 7301 community-dwelling participants aged 20–79 years without airflow obstruction. Participants were categorized based on spirometry into two groups: normal spirometry and PRISm. Peripheral eosinophilia is defined by peripheral eosinophil counts ≥300 cells/µL. Multivariable logistic regression model was employed to examine the association between peripheral eosinophil counts and PRISm, as appropriate. Among the community adults finally recruited, 9.43% of participants exhibited PRISm, while 90.57% exhibited normal spirometry. Compared with the normal spirometry population, PRISm participants had a higher prevalence of peripheral eosinophilia in individuals aged 40–79 years (27.41% vs 21.37%, p = 0.01), non-Hispanic Whites (29.22% vs 21.32%, p = 0.01), those with a body mass index of 18.5–<25 kg/m² (25.01% vs 16.75%, p = 0.03), never smokers (23.47% vs 18.65%, p = 0.03), individuals without a history of asthma (26.81% vs 20.67%, p<0.001), and those with FeNO levels <50 parts per billion (p < 0.05). Multivariable regression analysis showed a significant association between participants with eosinophil counts ≥300 cells/µL and PRISm compared to those with counts <150 cells/µL, with an adjusted odds ratio of 1.39 (95% CI: 1.12, 1.72). Peripheral eosinophilia was associated with PRISm in individuals without airflow obstruction. It is necessary to focus on the characteristics of peripheral eosinophils in this population.

Biomedical review articles are important for education, evidence synthesis, and clinical decision-making. Large language models such as ChatGPT may contribute to a surge in the number of AI-written reviews, raising concerns about the quality and reliability of scientific content. We searched PubMed for open-access reviews in inflammatory bowel disease (IBD) published before ChatGPT (period 1), during the first year after ChatGPT’s release (period 2, 2023–2024), and the year after (period 3, 2024–2025), and randomly selected 60 articles for analysis from each period. Using an AI text detector, no articles were identified as AI-written in period 1, versus 1.7% and 6.7% in periods 2 and 3, respectively. None of the potentially AI-written articles disclosed AI use. None of them had an IBD expert as the first author; only one article from period 2 and one from period 3 had an IBD expert among the authors. While the absolute number of AI-written reviews remains relatively low at present, the growing trend is a cause for concern regarding the potential decline of the quality and trustworthiness of biomedical review articles. Safeguards should be established to maintain the values of review articles.