Search Results (3,670)

Background: Multiple sclerosis (MS) is an immune-mediated neuroinflammatory disorder with a multifactorial etiology involving genetic susceptibility, environmental triggers, and vascular contributions. Carotid intima–media thickness (CIMT) is a significant marker of endothelial dysfunction. Endothelial cell-specific molecule-1 (endocan) and hyaluronic acid, key components implicated in endothelial and vascular remodeling, may significantly contribute to the inflammatory and vascular pathologies observed in MS. We aimed to investigate the relationship between CIMT and endothelial biomarkers, such as endocan and hyaluronic acid, in patients with MS. Methods: In this cross-sectional study, 100 patients with relapsing–remitting MS and 56 healthy controls were included. Demographic, clinical, laboratory, and imaging data were documented. CIMT was measured bilaterally using high-resolution B-mode ultrasonography. Serum endocan and hyaluronic acid levels were quantified via enzyme-linked immunosorbent assays. Results: MS patients exhibited significantly higher CIMT and serum endocan levels compared with controls (p < 0.001). CIMT values were significantly elevated in MS patients, with longer disease duration, higher expanded disability status scale scores, and an older diagnosis age (p < 0.05). However, serum endocan and hyaluronic acid levels did not significantly differ between MS subgroups based on disease duration, disability severity, and diagnosis age. Additionally, there was no correlation between CIMT and serum endocan and hyaluronic acid levels in MS patients (p > 0.05). Conclusions: Increased CIMT and serum endocan levels in MS patients may indicate endothelial dysfunction suggesting vascular involvement in MS. The lack of a correlation between CIMT and endocan and hyaluronic acid levels reveals the complexity of vascular and immune interactions in MS, which needs further research. Full article

Background/Objective: Insulin resistance (IR) during pregnancy, even in women with normal body mass index (BMI), may affect maternal and fetal metabolic and immune status. This study aimed to evaluate neopterin (NPT), leptin, insulin, and ghrelin concentrations in maternal blood (MB) and umbilical cord blood (CB) in normoglycemic women with and without IR, all with normal BMI. Methods: Peripheral and cord blood was collected from 36 Caucasian women with term, uncomplicated vaginal deliveries. The participants were classified into control (n = 16; age = 30.81 ± 4.875 years) and IR (n = 20; age = 31.95 ± 4.979 years) groups based on a professional medical diagnosis. Anthropometric parameters were recorded, and metabolic/hormonal markers were measured using ELISA and RIA. Results: NPT concentrations in CB were significantly higher in the IR group (p < 0.05), correlated positively with MB NPT levels (r = 0.3809, p < 0.05). A significantly higher concentration of both insulin and leptin was observed in the MB of women with IR compared to the control group (p < 0.0001), whereas in CB, only insulin concentration was significantly higher in the IR group than in healthy controls (p < 0.05). Ghrelin levels did not differ between the groups. Conclusions: Insulin resistance in non-obese pregnant women is associated with increased NPT concentration in CB, which may suggest fetal immune activation. However, defining the role of NTP as a metabolic “messenger” between mother and child requires further study. Full article

Background: Geographic information systems (GIS) are a promising tool for mapping vaccination coverage and identifying missed communities, yet their use in low- and middle-income countries (LMICs) remains limited. In settings without standardized addresses such as schools or outreach sites, innovative methods are needed to collect and analyse spatial data. Schools offer a unique platform for identifying under-vaccinated children missed by routine or campaign efforts. Methods: During a pilot school vaccination screening program in Zambia, GIS reference maps of health facility catchment areas were developed from hand-drawn sketch maps, catchment area shapefiles, and coordinates of prominent landmarks. These maps were iteratively refined with input from local health staff. In caregiver interviews, data collectors used the maps to identify the child’s zone of residence within the health facility catchment area. Vaccination status was extracted from paper registries used during screening. Geographic heat maps were generated in ArcGIS to visualize under-vaccination by zone. Results: Of 535 children screened across 25 zones, 29% were under-vaccinated. Under-vaccination varied by zone, with clusters of missed children identified, for example, 50% of children in Kabushi Zone 6 were under-vaccinated, compared with much lower rates elsewhere. Conclusions: Pairing school-based vaccination checks with GIS mapping offers a scalable approach to identifying missed communities in LMICs. This method enables spatial analysis without household visits, supporting targeted immunization planning where traditional data systems fall short. However, because the study was limited to children enrolled in five purposively selected schools, out-of-school children and those in other schools were not represented. This selection bias may underestimate the true extent of under-vaccination, and future evaluations should incorporate broader and more representative populations. Full article

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) do not provide promising benefits to patients with advanced epithelial ovarian cancer (EOC). This study analyzed preoperative peripheral blood mononuclear cells (PBMCs) from these patients to evaluate the prognostic and therapeutic checkpoints. Methods: Preoperative PBMCs of 69 advanced EOC cases were collected to analyze the correlation between IC-expressing immune cells and survivals of patients. Co-expression of various ICs on the T lymphocytes from these patients was examined. Activation potential of programmed cell death 1 (PD-1)⁺herpes virus entry mediator (HVEM)⁺ T cells in PBMCs from the healthy donors and tumoricidal abilities of PMBCs treated with various ICIs were evaluated in vitro. Impact of respective ICIs on activation of T cells in PMBCs was investigated. Results: Percentages of PD-1⁺ CD4⁺ and CD8⁺ T cells in the PBMCs of patients could positively correlate with disease-free or overall survival. HVEM was highly co-expressed on these T lymphocytes. Prediction potential for overall survival of patients by the subpopulation of PD-1⁺ CD4⁺ or CD8⁺ T cells was higher than that by other parameters. The PD-1⁺HVEM⁺ CD4+ and CD8⁺ T cells showed characteristics of activated phenotype under activation signals. PBMCs receiving anti-B and T lymphocyte attenuator (BTLA) plus anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) or anti-PD-1 Ab had potent tumor-killing ability. Anti-BTLA Ab can drive T cells in the PBMCs toward an effector status. Conclusions: Percentages of PD-1⁺ T cells in the PBMCs could predict survival of EOC patients. Targeting HVEM-BTLA axis may be considered for ICI treatment of EOCs. Full article

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), represents a significant challenge in gastroenterology due to its chronic nature, unpredictable course, and impact on patients’ quality of life. The therapeutic landscape for IBD has evolved significantly with the advent of biologic agents targeting specific immune pathways. However, limitations, including partial efficacy, side effects, and development of resistance, highlight the ongoing need for innovative treatment approaches. This review explores emerging therapies in IBD, including novel biologics, small molecules, microbiome-based therapies, and gene and stem cell therapies. The article summarizes their mechanisms of action, clinical efficacy, safety profiles, and potential future directions in IBD management. Methods: This comprehensive narrative review synthesizes current knowledge and emerging developments in inflammatory bowel disease (IBD) therapeutics. Literature was identified through targeted selection of high-quality sources, including pivotal randomized controlled trials, systematic reviews and meta-analyses, regulatory approval documents, and clinical practice guidelines from major gastroenterology societies. Emphasis was placed on recent publications (2020–2024) to capture the rapidly evolving therapeutic landscape, with particular attention to FDA/EMA-approved therapies and promising late-stage investigational agents. Sources were prioritized based on clinical relevance, study quality, and regulatory status. This narrative approach was selected to provide comprehensive coverage of diverse therapeutic modalities spanning conventional treatments to cutting-edge techniques, including biologics, small molecules, microbiome-based therapies, gene therapy, and stem cell treatments. The review acknowledges the inherent limitations of non-systematic literature selection while prioritizing clinical utility and educational value for healthcare providers managing IBD patients in contemporary practice. Full article

Endothelial activation and cell adhesion molecules (CAMs) are exacerbated in the interaction of HIV infection and pre-eclampsia. This study compares the levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), and E-selectin (sE-selectin) in HIV-infected normotensive pregnant versus pre-eclamptic women. We investigated the plasma concentration of sVCAM-1, sICAM-1, and sE-selectin in normotensive pregnant women (n = 40) and pre-eclamptic women (n = 40) using an immunoassay procedure. The concentrations of both sVCAM-1 (p < 0.0083) and sE-selectin (p < 0.0260) were significantly different from sICAM-1 in pre-eclampsia compared to normotensive pregnant groups, irrespective of HIV status. In contrast to sVCAM-1, sICAM-1 (p = 0.0349) and sE-selectin (p < 0.0445) concentrations were significantly elevated in HIV-positive compared to HIV-negative groups, regardless of pregnancy type. In pregnancies complicated by HIV, statistically significant differences in ICAM-1 concentration were observed between pre-eclamptic HIV-positive versus pre-eclamptic HIV-negative groups (p < 0.0010). Similarly, sVCAM-1 levels differed significantly between pre-eclamptic HIV-negative and normotensive HIV-positive groups (p < 0.0139). In contrast, sE-selectin levels varied significantly between pre-eclamptic HIV-positive versus normotensive HIV-negative groups (p < 0.0485). We report a dysregulation of sICAM-1, sVCAM-1, and SE-selectin in the co-morbidity of pre-eclampsia in pregnant women living with HIV. This differential expression may be attributed to oxidative stress emanating from the hypoxic endothelial activation in both pre-eclampsia and HIV infection and exacerbated by the immune restorative action of antiretroviral therapy. Full article

Vulvar viral infections such as condyloma acuminata, genital herpes, molluscum contagiosum, and Lipschütz ulcers span both sexually and non-sexually transmitted diseases and affect patients across all age groups. Lesions may present as papules, verrucous growths, or painful ulcers, often causing functional impairment and significant psychosocial distress. A multidisciplinary strategy that integrates epidemiology, precise diagnostics, individualized therapy, and psychological support is essential to optimize outcomes. We performed a structured literature search in PubMed, Scopus, and Web of Science using terms “vulvar viral infection,” “HPV,” “HSV,” “molluscum contagiosum,” and “Lipschütz ulcers.” International guidelines from the UK, Europe, and Australia were reviewed, alongside reference lists of key articles. Particular attention was given to paradoxical presentations, pediatric considerations, and cost-effectiveness analyses. HPV vaccination programs have markedly reduced anogenital warts, while early PCR/NAAT for HSV accelerates targeted antiviral therapy. First-line treatments like oral acyclovir/famciclovir for HSV and topical imiquimod or podophyllotoxin (±cryotherapy) for HPV are supported by adjunctive measures for self-limiting conditions. Host factors (hormonal cycles, immune status) and local irritants modulate recurrence risk, informing anticipatory suppressive regimens and barrier-reinforcing care. Validated patient-reported outcome measures (VPAQ, DLQI, FSFI) capture pain, sexual function, and quality-of-life impacts. Health–economic evaluations underscore the long-term value of rapid diagnostics and broad vaccination. Personalized, multidisciplinary management that combines prevention, precision diagnostics, tailored therapy, psychosocial support, and economic considerations offers the greatest promise for improving clinical and quality-of-life outcomes in patients with vulvar viral infections. We aim to outline best practices for the diagnosis and management of common vulvar viral infections, providing practical guidance for clinicians to improve recognition and therapeutic decision-making. Full article

Background: Immune checkpoint inhibition (ICI) is the standard treatment for advanced melanoma patients. Despite its high efficacy compared to previous treatment options, immune-related adverse events (irAEs) occur frequently. While most of the patients experience mild to moderate irAEs, some patients develop severe to lethal irAEs under ICI treatment; hence, biomarkers are urgently required. Methods: In this retrospective single-center study, 157 advanced melanoma patients treated with ICI at the University Medical Center Hamburg–Eppendorf were included. IrAEs were correlated with clinico-pathological parameters, disease-related outcomes, and irAE-free survival. Results: In our cohort, 130 out of 157 patients receiving immunotherapy experienced irAE, of which more than half experienced irAE Grade ≥ 3. The most common irAE independent of its grade included cutaneous irAE, colitis, endocrine irAE, and hepatitis. Patients experiencing irAE had significantly longer progression-free survival (PFS) and overall survival (OS) compared to patients who did not experience irAE under ICI therapy. Stratification by irAE groups revealed that musculoskeletal irAEs are associated with the longest, whereas myocarditis is associated with the shortest OS and PFS. IrAE was a significant beneficial prognosticator for PFS in univariate, but not in multivariate Cox regression analysis. With respect to OS, the occurrence of irAE was an independent prognostic factor among ECOG status ≥ 2 and uveal melanoma. ROC analysis demonstrated that D-dimers have moderate predictive capability for irAE occurrence. Cox regression analysis demonstrated that elevated D-dimers and PD-1 monotherapy vs. CTLA-4 and PD-1 combination regimen are the only independent prospective prognostic markers for irAE-free survival. Conclusions: Our study demonstrates that different irAE across the irAE spectrum have a different impact on the PFS and OS of advanced melanoma patients. D-dimers may be used as a blood-based biomarker for irAE prediction, warranting future validation in multi-center studies. Full article

The major event that leads to death from breast cancer (BrCa) is the emergence of micrometastases into lethal growing metastases. While it is still uncertain what regulates the cell fate decision between remaining in dormancy and aggressive proliferative progression, accumulating evidence demonstrates a major role for the metastatic microenvironment. One area of interest is that of tissue and circulating mesenchymal stem cells (MSCs), which have been shown to alter the proliferative and metastatic potential of BrCa. Herein, we investigate how these cells impact the phenotype of metastatic BrCa. As the disseminated BrCa cells initially adopt an epithelial phenotype in ectopic organs, one that is dormant in having limited proliferation and being immune-silent, interactions that revert the disseminated metastatic BrCa to aggressive mesenchymal phenotypes, would be a driver of metastatic progression. BrCa cells exhibited phenotypic changes including increased E-cadherin expression, altered proliferation, and differential sensitivity to TRAIL-induced apoptosis when directly co-cultured with immortalized human MSCs, compared to the BrCa cells not co-cultured. These regulatory effects were dependent upon the BrCa cell’s epithelial–mesenchymal status and involved distinct juxtacrine and paracrine signaling mechanisms, as evidenced by differing responses in direct co-culture, conditioned medium, and Transwell systems. Our findings highlight the complex and context-dependent roles of MSCs in BrCa progression, improving our understanding of tumor-stroma interactions and laying groundwork for future therapeutic exploration. Full article

Background: The overall incidence of malignancy in patients with end-stage kidney disease (ESKD) is reportedly higher compared to the general population. Cancer remains one of the dominant causes of death in these patients, due in part to uremia-induced impairment of tumor immune surveillance. Malignancy is one of the major limitations in the evaluation of potential kidney transplantation. This study aimed to assess the prevalence of cancer in hemodialysis population, particularly in relation to the waiting list. Materials and Methods: From the population of 5879 prevalent hemodialysis patients (60% men), 757 of them had a history of malignancy. In this population, 449 patients were actively waitlisted, and 4619 were not considered for potential kidney transplantation. Only 54 patients had unclear status in relation to active waiting list (during evaluation/disqualification). We assessed demographic data, basal biochemical data, and comorbidities, including malignancy, in relation to age, sex, presence of metastasis, and being actively waitlisted. Results: Malignancy was reported in 13% of hemodialysis patients, 6% of which had metastatic disease. Patients with malignancy were older (p < 0.001). More cases of cancer were observed in males (p = 0.02), who also had higher Charlson Comorbidity Index scores. Moreover, in patients with cancer, cardiovascular diseases were more common. They were also more malnourished (lower albumin, hemoglobin, lean mass) and more inflamed (higher ferritin, lower phosphorus). Only 27 patients with cancer were actively waitlisted, representing only 3.8% of this population. Patients with prior cancer on the active waiting list constituted 6% of all the waitlisted patients. Patients with a history of malignancy on the active waiting list were significantly younger, healthier, with significantly lower Charlson Comorbidity Index score, significantly lower ferritin, lower prevalence of diabetes, and higher blood pressure when compared to patients with malignancy who not listed for kidney transplantation. Conclusions: As malignancy became a more common comorbidity in dialysis patients, the elderly in particular, standardized cancer screening protocols should be promoted in dialysis units. Modern oncology has made huge progress, enabling the treatment of previously incurable cancers, as malignancy after kidney transplantation is considerably increased either due to de novo cancers or the recurrence of previous malignancy. Therefore, the evaluation of potential kidney transplant recipients, with tailored cancer screening and multidisciplinary evaluation, is strongly recommended. Besides a history of malignancy, the cardiovascular status also determines the eligibility for transplantation in dialysis patients. It is of paramount importance as the main cause of death in transplant recipients is cardiovascular death followed by malignancy. Full article

Mold-active prophylaxis has reduced the incidence of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies (HMs), but breakthrough IPA (Bt-IPA) is increasingly encountered. Therefore, we studied determinants of Bt-IPA risk and its prognostic significance. We retrospectively reviewed culture-positive proven/probable IPA cases in HM patients at MD Anderson Cancer Center (2016–2021). Bt-IPA and non-Bt-IPA cases were compared to characterize risk factors, clinical presentation, and outcomes. Independent predictors of 42-day all-cause mortality were assessed using propensity score-adjusted Cox regression. Among 118 IPA cases, 50 (42.4%) were Bt-IPA. Bt-IPA was associated with acute leukemia/myelodysplastic syndrome, active HM, severe neutropenia (<100/mm³), and graft-versus-host diseases. Uncommon Aspergillus species (non-fumigatus, flavus, terreus, or niger) were more frequent in Bt-IPA than non-Bt-IPA (20.4% vs. 4.8%, p = 0.010). Forty-two-day mortality was higher in Bt-IPA (65.3% vs. 37.3%, p = 0.003), but Bt-IPA itself was not an independent predictor or mortality (p = 0.064), which was instead driven by neutropenia (p = 0.020) and hypoalbuminemia (p = 0.002). In conclusion, Bt-IPA accounted for nearly half of contemporary IPA cases and was linked to host-related risk factors and the recovery of uncommon Aspergillus species. Although not an independent prognostic predictor, Bt-IPA reflected poor host status. Thus, early diagnosis, immune enhancement strategies, and effective first-in-class antifungals may improve outcomes. Full article

Background: Breast cancer is the most common malignancy affecting women worldwide and continues to pose significant challenges despite progress in early detection and personalized therapies. While its pathogenesis has traditionally been associated with genetic, hormonal, and environmental factors, recent studies have highlighted the potential role of dysbiosis—an imbalance in gut and systemic microbiota—in breast cancer development and progression. This article aims to examine the mechanisms through which systemic dysbiosis may contribute to breast cancer risk and explore its therapeutic implications. Methods: This study seeks to analyze and compare the fecal microbiota profiles of breast cancer patients and healthy individuals from a single center in Craiova, Romania, in order to identify microbial signatures linked to breast cancer and BRCA mutation status. Special attention is given to the gut–liver axis and its influence on estrogen circulation, a key factor in hormone-sensitive breast cancers. Results: Evidence suggests that dysbiosis can influence breast cancer progression by promoting chronic inflammation, impairing immune regulation, and altering estrogen metabolism through the gut–liver axis. These effects may contribute to tumor development, immune evasion, and therapeutic resistance. Interventions aimed at restoring microbial balance show promise in preclinical studies for mitigating these effects. Conclusions: Systemic dysbiosis represents a potentially modifiable risk factor in breast cancer. Microbiota profiling may serve as a useful biomarker for risk stratification and therapeutic response. Future research into microbiome-based interventions could offer novel approaches for prevention and treatment in breast cancer care. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raced around the world across different populations; there needs to be a consolidated effort to understand the divergence of the epidemiology of SARS-CoV-2. Population-based epidemiological characteristics studies measure the extent of SARS-CoV-2 infection in a country. The current research study was designed to report epidemiological data from Pakistan. For this purpose, 246 SARS-CoV-2-infected patients were included in the study. For SARS-CoV-2 confirmation, viral samples were collected from all the study participants; SARS-CoV-2 infection was confirmed by viral nucleic acid detection using a nucleic acid detection kit. After SARS-CoV-2 confirmation, all the study participants were interviewed for epidemiological data through a detailed questionnaire. The study results showed that the disease ratio was higher between 30 and 59 years (51.21%) of age. The male ratio (55.28%) was higher compared to the female ratio (44.71%). The patients’ illiteracy and low socioeconomic status were 32.52% and 59.75%, respectively. The majority of the patients (97.56%) had cough, smell or taste disturbance (79.67%), or fever (76.42%), and 70.73% had fatigue. For comorbidities, a higher ratio was observed for diabetes (38.61%), hypertension (36.17%), and respiratory disease (16.26%). The vaccination status analysis revealed that 51.21% of patients had not received routine immunizations, and 65.5% were un-vaccinated against SARS-CoV-2. Notably, not a single patient was vaccinated for influenza vaccine. The current research study concluded that SARS-CoV-2 was more prevalent in individuals who were middle aged, male, and had low socio-economic status. The most common symptoms were cough, smell or taste disturbance, and fever. The patients’ vaccination status highlights a critical gap in preventive healthcare and shows the need to strengthen vaccination awareness and accessibility in the population to reduce vulnerability to future outbreaks. Future research should focus on investigating the impact of COVID-19 outcomes on comorbidities such as diabetes and hypertension. Full article

Sanitary challenges (SCs) may alter the health status, growth performance, and pigs’ welfare. Changes in amino acid (AA) plasma concentrations have been observed in inflammatory-challenged pigs which may be associated with key factors, such as: (1) the synthesis of immune components to support innate and/or adaptive immune responses, (2) the redistribution of nutrients from growth and production functions toward cells and tissues involved in inflammatory and immune responses, and (3) decreased anabolism and/or increased catabolism of skeletal muscle to increase the availability of nutrients, often as a consequence of reduced feed intake. Due to their health-promoting effects, nutritional strategies involving AA may help mitigate the negative impacts of SC. Methionine, tryptophan, and threonine, beyond serving as protein building blocks, are considered functional AA because they support immune system function, enhance intestinal barrier integrity, modulate inflammatory responses, and limit oxidative stress. Additionally, the review highlights the influence of individual variability, such as differences in body weight, on nutritional requirements and responses to AA supplementation for pigs under SC. The integration of nutritional strategies tailored to immune-challenged pigs offers promising avenues to improve productivity and animal welfare in commercial swine production systems with increasing restrictions on antibiotic use. Full article