Search Results (143)

Background: Asymmetrical brain oscillations may be characteristic of Parkinson’s disease (PD). We investigated differences in oscillation asymmetry between individuals with PD and healthy controls and explored associations between the asymmetry and clinical features. Methods: Clinical and resting-state EEG data from 37 patients and 24 controls were cross-sectionally analyzed. EEG asymmetry indices were calculated for the delta, theta, alpha, and beta frequencies in the frontal, central, and parietal regions. Independent t-tests and linear regression models were employed. Results: Patients exhibited lower alpha asymmetry than controls in the parietal region (t(59) = 2.12, p = 0.03). In the frontal alpha asymmetry models, there were associations with time since diagnosis (β = −0.042) and attention/orientation (β = 0.061), and with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRSIII)-posture (β = 0.136) and MDS-UPDRSIII-rest-tremor persistence (β = −0.111). In the central alpha model, higher asymmetry was associated with the physical activity levels (International Physical Activity Questionnaire) IPAQ-active (β = 0.646) and IPAQ-very active (β = 0.689), (Timed Up and Go) TUG dual-task cost (β = 0.023), MDS-UPDRSII-freezing (β = 0.238), and being male (β = 0.535). In the parietal alpha asymmetry model, MDS-UPDRSII-gait/balance was inversely associated with alpha asymmetry (β = −0.156), while IPAQ-active (β = −0.247) and being male (β = −0.191) were associated with lower asymmetry. Conclusions: Our findings highlight the potential role of alpha asymmetry as a neurophysiological marker of PD’s motor symptoms, mainly rest tremor, gait/balance, freezing, and specific cognitive domains such as attention/orientation. The models stressed the relationship between disease progression and reduced alpha asymmetry. Brazilian Registry of Clinical Trials (RBR-7zjgnrx, 9 June 2022). Full article

Breast cancer is a highly heterogeneous disease, with tumors capable of adapting to shifting conditions, making the development of effective personalized therapies particularly challenging. Patient-derived models, such as patient-derived organoids (PDOs) and circulating tumor cell (CTC) cultures, have emerged as powerful tools for investigating intra- and inter-tumor heterogeneity. These models largely retain the genetic, phenotypic, and microenvironmental features of the original tumors, providing valuable insights into disease progression, drug response, and resistance mechanisms. Furthermore, by enabling tumors’ spatiotemporal molecular profiling, PDOs and CTCs offer a dynamic approach to assess treatment efficacy over time. However, to fully capture the complexity of breast cancer heterogeneity, it is required to develop models from multiple tumor and blood samples collected throughout the course of treatment. This review explores the potential of integrating PDOs and CTC models to better understand intra-tumor heterogeneity while addressing key challenges in developing patient-derived models that accurately recapitulate patients’ tumors to advance personalized care. The integration of PDOs and CTCs could represent a paradigm shift in the personalized management of metastatic breast cancer. Full article

Background: Acute cellular rejection (ACR) remains a common complication following lung transplantation and is a major risk factor for chronic lung allograft dysfunction (CLAD). Although transbronchial biopsy (TBB) is the diagnostic gold standard, it is invasive and may be contraindicated in certain patients. This study aimed to assess the diagnostic utility of combining bronchoalveolar lavage fluid (BALF) lymphocyte counts with cytokine profiling—particularly interleukin-17A (IL-17A)—in lung transplant recipients with elevated peripheral blood eosinophil (EOS) counts. Methods: We retrospectively analyzed 108 BALF and matched TBB samples from 74 lung transplant recipients with EOS counts >200 cells/μL, collected between 2014 and 2020. BALF lymphocyte percentages and levels of cytokines (IL-4, IL-6, IL-10, IL-13, IL-15, IL-17A, IFN-γ, TNF) were quantified. Associations with histologically confirmed ACR were evaluated using generalized estimating equation models. Results: ACR was diagnosed in 57% of TBB samples. BALF lymphocyte percentages were significantly higher in ACR cases (median 8% vs. 4%, p < 0.001). Each 1% increase in lymphocytes was associated with a 10% increase in the odds of ACR (OR 1.102; 95% CI 1.076–1.129). IL-17A levels were also significantly elevated in ACR (OR 1.047; 95% CI 1.003–1.092; p = 0.032), but with moderate discriminative ability (AUC = 0.629). The combination of BALF lymphocyte counts and IL-17A levels improved diagnostic performance (AUC > 0.76). Conclusions: The combined assessment of BALF lymphocyte counts and IL-17A levels in recipients with elevated EOS offers a promising non-invasive strategy to support the diagnosis of ACR. Prospective studies are needed to validate these findings and further refine personalized diagnostic approaches to ACR. Full article

Background: The rectal cancer treatment paradigm is rapidly changing with the advent of total neoadjuvant therapy and non-operative management approaches in responders. A good clinical response to neoadjuvant treatment documented by magnetic resonance imaging, endoscopy and clinical examination corresponds, to a large extent, to a pathologic complete response, as assessed in surgical specimens. Methods: We undertook a systematic review and meta-analysis on the MRI-based omics approach to predicting pathologic complete responses. Results: A total of 29 studies with relevant data available reporting on a total of 4486 patients were eligible for meta-analysis. The calculated values for the area under the curve in receiver operator curves of diagnostic accuracy for radiomics-only and radiomics-combined-with-clinical-data models were 0.80 and 0.88, respectively, for studies incorporating baseline imaging data only. The value for studies using delta radiomic data was 0.86, and those for studies using data from the post-neoadjuvant setting were 0.75 and 0.83, respectively, for the radiomics-only and radiomics-combined-with-clinical-data models. Conclusions: Radiomics-based prediction models for pathologic complete response assessment might further enable individualized treatment decisions to be made in patients with rectal cancer. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains among the most aggressive malignancies in the United States. Advances in treatments have slowly increased survival rates; however, outcomes remain dismal, largely due to the insidious onset of the disease and lack of screening tests leading to diagnosis at more advanced disease stages. As we better understand the molecular mechanisms that drive PDAC, we can leverage this technology for early detection of new PDAC or recurrences and find more effective methods to track treatment response. Liquid biopsies are increasingly common for the treatment of many malignancies, leveraging better technology to detect scant quantities of circulating tumor cells (CTCs) or byproducts of tumor biology (e.g., exosomes and microRNA [miRNA]) in the blood stream. When combined with existing biomarkers like CA 19-9, there is promising research that improved diagnostic modalities may be available in the future. Furthermore, these technologies are being leveraged to better prognosticate patients with PDAC and potentially monitor treatment responses not captured by cross-sectional imaging, which may allow for real-time changes in therapeutic strategy. This manuscript will review the molecular mechanisms that drive PDAC development and the biomarkers available for diagnosis and prognostication. Much of the data presented is still investigational, though many trials are ongoing to translate these studies for clinical use. Full article

Background: COVID-19, caused by SARS-CoV-2, has posed significant challenge to global healthcare systems, necessitating reliable biomarkers to predict disease severity and mortality. This systematic review and meta-analysis evaluated the prognostic value of novel biomarkers in COVID-19 patients. The aim of this study was to identify and prioritize the most prognostically relevant novel biomarkers associated with COVID-19 outcomes. Methods: We conducted a systematic review and meta-analysis of the available evidence. A systematic search of PubMed and Web of Science was performed to identify studies on the COVID-19 biomarkers. Observational studies that compared poor (severe disease/mortality) and good outcomes were included. For continuous measures, standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses for the biomarkers were used. The risk of bias was assessed using the Newcastle–Ottawa scale. Results: Of the 2907 screened studies, 38 were included (21 in the meta-analysis). MR-proADM showed higher levels of prediction for poor outcomes (SMD = 1.40, 95% CI: 1.11–1.69; AUC 0.74–0.96; sensitivity, 85%; specificity, 71%). The neutrophil-to-lymphocyte ratio (NLR) showed a high correlation with disease severity (SMD = 1.07, 95% CI: 0.79–1.35; AUC 0.73–0.98; sensitivity, 86%; specificity, 78%). Increased KL-6 levels were associated with lung injury (SMD = 1.22, 95% CI: 0.24–2.19; AUC 0.85–0.95). Other biomarkers (suPAR, miR-155, Galectin-3) showed promise but lacked sufficient data for pooled analysis. Heterogeneity was observed among the included studies in terms of diagnostic accuracy. These findings indicate that elevated levels of MR-proADM, NLR, and KL-6 are significantly associated with COVID-19 prognostic accuracy to guide patient management. Conclusions: MR-proADM, NLR, and KL-6 levels demonstrated strong prognostic value for COVID-19 severity and mortality. These biomarkers can enhance clinical decision-making. Full article

Background: Target trial emulation involves the application of design principles from randomised controlled trials (RCTs) to observational data, and is particularly useful in situations where an RCT would be unfeasible. Biomarker-guided trials, which incorporate biomarkers within their design to either guide treatment and/or determine eligibility, are often unfeasible in practice due to sample size requirements or ethical concerns. Here, we undertake a systematic review of methodologies used in target trial emulations, comparing treatment effectiveness, critically appraising them, and considering their applicability to the emulation of biomarker-guided trials. Methods: A comprehensive search strategy was developed to identify studies reporting on methods for target trial emulation comparing the effectiveness of treatments using observational data, and applied to the following bibliographic databases: PubMed, Scopus, Web of Science, and Ovid MEDLINE. A narrative description of methods identified in the review was undertaken alongside a critique of their relative strengths and limitations. Results: We identified a total of 59 papers: 47 emulating a target trial (‘application’ studies), and 12 detailing methods to emulate a target trial (‘methods’ studies). A total of 25 papers were identified as emulating a biomarker-guided trial (42%). While all papers reported methods to adjust for baseline confounding, 40% of application papers did not specify methods to adjust for time-varying confounding. Conclusions: This systematic review has identified a range of methods used to control for baseline, time-varying, and residual/unmeasured confounding within target trial emulation and provides a guide for researchers interested in emulation of biomarker-guided trials. Full article

Background. Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a complex inflammatory condition affecting the intestinal tract. Currently, immune-modulating treatments are inadequate for 30–50% of patients and often cause significant side effects, highlighting the urgent need for a personalized medicine approach. Real-world data and archived gut biological material from clinical repositories could be a resource for identifying new drug candidates and biomarkers. This study assesses the extent of stored formalin-fixed, paraffin-embedded (FFPE) gut biopsies from patients with IBD that could be leveraged for research efforts. Methods. Data from the Danish National Patient Register and the Danish Pathology Register were used to construct a cohort of patients diagnosed with IBD between 1 January 2005, and 30 June 2013, and followed for five years. Results. Among 14,512 IBD patients, 13,936 (96%) had at least one biopsy visit within five years after their initial diagnosis (CD 94%, UC 97%), and 13,598 (94%) had their first biopsy visit as part of the diagnostic process. Biopsies were taken from the colon (82%) or multiple locations (46%). Patients with severe disease had more biopsy visits than those with non-severe disease (IBD 3.3 vs. 2.0 visits, CD 2.9 vs. 1.9 visits, UC 3.6 vs. 2.0 visits). Conclusions. Thus, the vast majority of patients with IBD have biopsies taken. These findings demonstrate the feasibility and applicability of combining real-world data and archived gut biopsies for research, highlighting it as a valuable but underutilized resource for identifying new drug candidates and biomarkers, with huge potential for enhancing personalized medicine within IBD for the benefit of patients and society. Full article

Background/Objectives: Systemic and tissue inflammation play a crucial role in the pathophysiology of cardiometabolic disorders. Presepsin is a newly discovered marker of acute phase inflammation that is produced by monocytes or macrophages in response to bacterial infection and is a soluble fraction of the lipopolysaccharide (LPS) receptor. LPS is an endotoxin that, through the breakdown of the intestinal barrier, penetrates the systemic circulation and is an important bacterial mediator in the pathogenesis of sepsis and septic shock. Methods: A narrative review of the existing literature. Results: A growing body of evidence demonstrates that intestinal dysbiosis is involved in the pathogenesis of diabetes mellitus (DM) and cardiovascular (CV) disease, leading to increased circulating LPS concentrations in people with cardiometabolic disorders, even in the absence of infection. These data provide the theoretical background for a link between presepsin, DM, and CV pathology. Preliminary studies suggest that presepsin levels are downregulated in patients with well-controlled type 2 DM and correlate with continuous glucose monitoring metrics in infection-free individuals with type 1 DM. However, prospective data on the association between presepsin and the risk of diabetic complications are currently lacking. Presepsin has also been found to be elevated in infection-free individuals with myocardial infarction, heart failure, and myocarditis compared to controls and has been shown to correlate with mortality risk in subjects at high CV risk. Conclusions: The clinical utility of presepsin in the monitoring of patients with cardiometabolic disorders warrants further investigation by future studies. Full article

The appendix, an integral part of the large intestine, may serve two purposes. First of all, it is a concentration of lymphoid tissue that resembles Peyer’s patches. It is also the main location in the body for the creation of immunoglobulin A (IgA), which is essential for controlling intestinal flora’s density and quality. Second, the appendix constitutes a special place for commensal bacteria in the body because of its location and form. Inflammation of the appendix, brought on by a variety of infectious agents, including bacteria, viruses, or parasites, is known as appendicitis. According to a number of studies, the consequences of appendectomies may be more subtle, and may relate to the emergence of heart disease, inflammatory bowel disease (IBD), and Parkinson’s disease (PD), among other unexpected illnesses. A poorer prognosis for recurrent Clostridium difficile infection is also predicted by the absence of an appendix. Appendectomies result in gut dysbiosis, which consequently causes different disease outcomes. In this review, we compared the compositional differences between the appendix and gut microbiome, the immunological role of appendix and appendix microbiome (AM), and discussed how appendectomy is linked to different disease consequences. Full article

Background/Objectives: Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting up to 15% of reproductive-age women, characterized by hyperandrogenism, chronic oligo-ovulation, and metabolic dysfunction. This study aims to evaluate serum sortilin levels in women with PCOS for the first time and investigate their potential associations with metabolic and hormonal alterations. Material and Methods: Eighty PCOS patients and 80 healthy controls were included; serum sortilin levels were measured using ELISA kits, with documented intra-assay and inter-assay variations below 6% and 8%, respectively, ensuring high specificity and sensitivity. Results: Serum sortilin levels were significantly elevated in PCOS patients (69.51 ± 27.75 pg/mL) versus controls (48.60 ± 21.20 pg/mL) (p < 0.001). PCOS patients exhibited higher mean HOMA-IR, free androgen index values, serum glucose, insulin, triglycerides, high-sensitivity C-reactive protein, luteinizing hormone, total testosterone, and DHEA-S levels, alongside reduced high-density lipoprotein cholesterol and sex hormone-binding globulin levels (all, p < 0.05). Notably, inverse correlations were observed between sortilin and low-density lipoprotein cholesterol levels in both groups (p = 0.028 and 0.033). Conclusions: This pioneering study indicates that serum sortilin may be implicated in PCOS pathogenesis and serves as a potential biomarker for metabolic dysfunction in PCOS. Larger, diverse studies with longitudinal designs are needed for further validation. Full article

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk > 0.63 and ≤0.84, High Risk > 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p < 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p < 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization. Full article

Background/Objectives: Mismatch repair (MMR) status is an important prognostic and predictive indicator in cancer, distinguishing proficient (pMMR) tumors from deficient (dMMR) ones. This study aimed to determine the prevalence of dMMR in colorectal (CRC) and selected non-CRC solid tumors (gastric, esophageal, and endometrial cancers). Methods: This retrospective study was conducted at a private health institution in Mexico City, analyzing patients diagnosed with colorectal, gastric, esophageal, or endometrial cancer from January 2017 to December 2020. dMMR prevalence was assessed using available status information and tissue samples for immunohistochemistry (IHC). Data were analyzed via SPSS, presenting results in frequencies and percentages. Results: Most solid tumors exhibited MSH2, MSH6, and MLH1 expression above 90%, with slightly lower levels in endometrial cancer. Esophageal cancer showed 100% pMMR. dMMR prevalence was found to be 12.7% for CRC, 8.3% for gastric, and 18.5% for endometrial cancers. Prevalence rates were similar across genders (11.1% in women and 12.9% in men), with the highest prevalence in the 41–50 age group (20%) and the lowest in the 31–40 age group (7.7%). Conclusions: This study offers valuable insights into the frequency of dMMR mutations in a cohort of the Mexican population, providing a basis for further research on their prevalence in Mexico. Full article

Background/Objectives: Chronic graft-versus-host disease (cGVHD) and oral lichen planus (LPO) are chronic inflammatory conditions with similar oral manifestations. This study aimed to assess whether serum and salivary cytokines (IL-1α, IL-6, IL-17) could serve as reliable biomarkers for cGVHD. Methods: A prospective cohort study was conducted involving cGVHD patients, LPO patients, and healthy controls. Cytokine levels in serum and saliva were measured by ELISA and compared across the groups using the Kruskal–Wallis test. Results: IL-17 levels were significantly elevated in the serum of cGVHD patients compared to LPO patients and controls (p < 0.05). However, IL-6 and IL-1α did not show significant differences among the groups. A comparison of salivary samples between the three groups did not reach statistical significance (p > 0.05). Conclusions: This study suggests that IL-17 could be a potential biomarker for cGVHD-related inflammation, warranting further investigation. Salivary samples do not seem to be a reliable biological marker for the diagnosis of cGVHD. The findings underline the need for larger studies to validate these preliminary results. Full article

Background/Objectives: COVID-19 is characterised by a wide variety of clinical manifestations, and clinical tests and genetic analysis might help to predict patient outcomes. Methods: In the current study, the expression of genes related to immune response (CCL5, IFI6, OAS1, IRF9, IL1B, and TGFB1) was analysed in the upper airway and paired-blood samples from 25 subjects infected with SARS-CoV-2. Relative gene expression was determined by RT-qPCR. Results: CCL5 expression was higher in the blood than in the upper airway (p < 0.001). In addition, a negative correlation was found between IFI6 and viral load (p = 0.033) in the upper airway, suggesting that the IFI6 expression inhibits the viral infection. Concerning sex, women expressed IL1B and IRF9 in a higher proportion than men at a systemic level (p = 0.008 and p = 0.049, respectively). However, an increased expression of IRF9 was found in men compared to women in the upper airway (p = 0.046), which could be due to the protective effect of IRF9, especially in men. Conclusions: The higher expression of CCL5 in blood might be due to the key role of this gene in the migration and recruitment of immune cells from the systemic circulation to the lungs. Our findings confirm the existence of sex differences in the immune response to early stages of the infection. Further studies in a larger cohort are necessary to corroborate the current findings. Full article