BackgroundT-cell-engaging bispecific agents and related T-cell-engaging therapies are increasingly used across hematologic malignancies and selected solid tumors. Infection is a clinically important safety concern, but infection-focused post-marketing comparisons across the current product set remain limited. We evaluated infection-related adverse event reporting for T-cell-engaging agents using the FDA Adverse Event Reporting System/Adverse Event Monitoring System (FAERS/AEMS).MethodsPublic FAERS/AEMS quarterly ASCII files from 2022Q1 to 2026Q1 were analyzed. Reports were deduplicated by retaining the latest case version for each CASEID, and exposure was defined as a target T-cell-engaging agent recorded as the primary suspect drug. Infection-related events were identified with a prespecified MedDRA preferred-term dictionary and were summarized using a structured dominant-category framework. Disproportionality was assessed using reporting odds ratio (ROR) with 95% confidence interval (CI), with proportional reporting ratio (PRR) and information component (IC) as supportive metrics. Reporting followed the READUS-PV guideline for disproportionality analyses of individual case safety reports.ResultsAmong 6,102,203 deduplicated primary-suspect reports, 15,108 involved a target T-cell-engaging agent, of which 3,114 were infection-related (20.6%). The class-level infection-related reporting signal was significant (ROR 2.03 (1.95-2.11); IC025 0.80). The largest number of infection-related reports was observed for Teclistamab (Tecvayli) (829 reports), whereas the highest drug-level ROR was observed for Elranatamab (Elrexfio) (ROR 4.38 (3.94-4.87)). Prominent preferred-term signals included pneumonia (ROR 2.01 (1.84-2.21)), sepsis (ROR 3.76 (3.32-4.24)), septic shock (ROR 4.39 (3.71-5.19)), cytomegalovirus infection reactivation (ROR 27.19 (23.39-31.60)), and cytomegalovirus infection (ROR 12.60 (10.71-14.82)). The class-level signal persisted under the narrower infection definition (2,545 reports; ROR 1.95, 95% CI 1.87-2.03). Concordant DailyMed infection terms and FAERS/AEMS infection signals were found for 7 agents.ConclusionsFAERS/AEMS data showed a class-level reporting signal for infection-related adverse events with T-cell-engaging agents, particularly among BCMA x CD3 and CD20 x CD3 therapies. Cytomegalovirus-related events, pneumonia, and sepsis were prominent signal patterns. These findings are hypothesis-generating reporting patterns and should not be interpreted as incidence estimates, relative risks, or proof of causality.

BackgroundInflammation contributes to heart failure (HF) progression, and readily available inflammatory biomarkers may provide prognostic information. We evaluated the association and discriminatory performance of admission neutrophil-to-lymphocyte ratio (NLR) and neutrophil-and-monocyte-to-lymphocyte ratio (NMLR) for in-hospital mortality in acute HF.MethodsThis secondary analysis of a cross-sectional study included consecutive patients aged ≥14 years admitted with acute HF to Kilimanjaro Christian Medical Centre, Tanzania, between 1 May and 31 October 2024. Admission NLR and NMLR were calculated from routine hematological parameters and natural log-transformed for logistic regression because of skewed distributions. Univariable and multivariable binary logistic regression assessed associations with in-hospital mortality; variables with p<0.10 in univariable analysis were considered for multivariable inclusion. Receiver operating characteristic (ROC) analysis assessed discrimination and identified study-specific thresholds.ResultsAmong 290 patients, 228 (78.6%) were discharged and 62 (21.4%) died. Higher LN(NLR) was associated with mortality in univariable analysis (cOR: 1.47; 95% CI: 1.11-1.96; p=0.008) and remained independently associated after adjustment (aOR: 1.45; 95% CI: 1.04-2.01; p=0.028). Similarly, LN(NMLR) was associated with mortality (cOR: 1.47; 95% CI: 1.10-1.97; p=0.009) and remained independently associated after adjustment (aOR: 1.44; 95% CI: 1.03-2.02; p=0.032). NLR and NMLR demonstrated modest discrimination, with AUCs of 0.625 (95% CI: 0.544-0.705) and 0.624 (95% CI: 0.543-0.705), respectively. Thresholds were 5.35 for NLR and 6.47 for NMLR.ConclusionHigher admission NLR and NMLR were independently associated with in-hospital mortality and demonstrated modest discriminatory ability. These inexpensive biomarkers may complement clinical risk stratification, although the thresholds require external validation.

BackgroundChronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disorder in which bacterial and viral infections are established contributors to exacerbation, parasitic infection remains underexplored in COPD immunopathology.ObjectiveTo critically synthesize evidence that parasitic infections modify COPD immunopathology and to identify clinically relevant implications and research priorities.MethodsPubMed/MEDLINE, Embase, Scopus, and Web of Science were searched for publications from January 1985 to July 2026; Google Scholar and reference lists supplemented retrieval. Evidence was synthesized narratively and classified as direct COPD-specific clinical evidence, indirect human pulmonary evidence, animal-model evidence, or mechanistic evidence.ResultsInfections with helminths and protozoa may influence the pathophysiology of COPD by modulating the type 1 immune response through type 2 polarization, expansion of regulatory T cells, eosinophilia, systemic immune activation, and alterations to the microbiome. These mechanisms may influence inflammatory phenotypes and exacerbation susceptibility. Direct COPD-specific evidence is limited. Most support derives from pulmonary parasitic disease, observational studies, animal models, or mechanistic inference. Clinically, parasitic eosinophilia may confound COPD phenotyping, and occult Strongyloides stercoralis infection is particularly important when systemic corticosteroids are considered.ConclusionCurrent evidence supports a biologically possible role for parasitic infections as modifiers of COPD immunopathology, but does not establish causality or routine parasite-driven COPD. Prospective, phenotype-stratified studies integrating parasitological and immunological analyses are required, particularly in endemic populations.

The respiratory system is continuously exposed to environmental antigens, pathogens, and pollutants, requiring tightly regulated immunity to balance inflammation and host defense. Increasing evidence indicates that the microbiome-within the airways and through the gut-lung axis-plays a critical role in shaping pulmonary immune responses. Microbial metabolites such as short-chain fatty acids (SCFAs), tryptophan-derived indoles, and bile acid intermediates, influence the maturation and functional programming of alveolar macrophages, dendritic cells, and T lymphocytes. Using the emerging framework of microbiota dysbiosis-related disorders, this review distinguishes descriptive microbial alterations from functionally and clinically relevant dysbiosis involving microbial metabolites, barrier integrity, immune regulation, and respiratory outcomes. Nutritional and microbiome-targeted interventions-such as dietary fiber, probiotics, and antioxidant micronutrients including vitamin C-may help restore immune homeostasis and reduce inflammatory burden through microbiota-mediated and redox-regulatory pathways. By supporting epithelial barrier integrity, modulating oxidative stress, and promoting regulatory immune signaling, vitamin C may complement microbiome-directed strategies aimed at maintaining respiratory immune resilience. The review critically synthesizes mechanistic, observational, and clinical evidence linking microbiota dysbiosis to respiratory immune homeostasis and evaluates microbiome-targeted and vitamin C-related strategies according to their current level of evidentiary support.

IntroductionHypersensitivity reactions to carboplatin include type I reactions, mixed reactions, and delayed reactions.Case reportWe report a case of an atypical cytokine release syndrome induced by carboplatin in a patient with breast carcinoma.Management & outcomeThe patient developed clinical manifestations consisting of a delayed cytokine release syndrome following administration of carboplatin and paclitaxel. To establish the diagnosis, she underwent a double desensitization protocol over two consecutive days with paclitaxel and carboplatin. A delayed elevation of interleukin-6 after carboplatin supported the diagnosis of an isolated cytokine release syndrome. The patient subsequently continued treatment with paclitaxel through standard infusions and with carboplatin using a desensitization protocol.DiscussionCytokine release syndrome associated with carboplatin has been previously reported as occurring immediately after infusion and as part of a mixed phenotype (type I and cytokine release). A delayed-onset cytokine release syndrome induced by carboplatin, occurring outside the context of a mixed reaction, is reported.ConclusionCytokine release syndrome may present as an isolated, delayed reaction following carboplatin infusion. Measurement of interleukin-6 may be a valuable diagnostic tool for confirming the diagnosis of cytokine release syndrome.

BackgroundWD Repeat Domain 76 (WDR76) plays a potential role in cellular regulation; however, its comprehensive landscape across human malignancies and its specific biological function in hepatocellular carcinoma (HCC) remain largely unexplored.MethodsWe conducted a systematic pan-cancer analysis utilizing multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) atabases to evaluate WDR76 expression, subcellular localization, and its correlation with clinicopathologic features, genomic instability, and immune infiltration. Diagnostic and prognostic values were assessed via Receiver operating characteristic (ROC) and Kaplan-Meier analyses. Furthermore, the functional role of WDR76 in HCC was validated in vitro using Hep-3B and Huh7 cell lines through siRNA-mediated knockdown, followed by CCK-8, wound-healing, and transwell assays.ResultsWDR76 was significantly upregulated in the majority of tumor types, including LIHC, LUAD, and COAD, while exhibiting nuclear localization. Elevated WDR76 expression correlated with advanced tumor staging, metastasis, and poor clinical outcomes across multiple cohorts, particularly in ACC, KIRP, and LIHC. ROC analysis highlighted its exceptional diagnostic precision in cancers such as GBM and LIHC. Immunologically, WDR76 expression was intricately linked to immune cell infiltration, immune checkpoint markers, and genomic instability parameters, suggesting a role in shaping the tumor microenvironment. Drug sensitivity profiling revealed that high WDR76 levels correlate with resistance to specific chemotherapeutic agents. Experimentally, silencing WDR76 in HCC cells significantly suppressed cell proliferation, migration, and invasion capabilities.ConclusionOur study establishes WDR76 as a robust pan-cancer prognostic biomarker and a potential immunotherapeutic target. Specifically, we provide experimental evidence that WDR76 functions as an oncogenic driver in liver cancer, promoting malignant phenotypes and offering a novel avenue for targeted therapeutic intervention.

Infective endocarditis (IE) remains a severe condition associated with significant morbidity and mortality. Dental procedures involving manipulation of gingival tissue or the periapical region may cause transient bacteremia, making prevention strategies at the dental-medical interface clinically important. Current guidance emphasizes selective antibiotic prophylaxis (AP) for patients at the highest cardiac risk while prioritizing long-term oral health maintenance. This scoping review synthesizes contemporary evidence (2021-2025) and major international guidelines to clarify the relationship between invasive dental procedures (IDPs) and IE, identify patients who may benefit from AP, and outline practical prevention strategies in dental practice. A PRISMA-ScR-guided scoping review was conducted using PubMed/MEDLINE, Web of Science, and EMBASE (January 2021-October 2025), with citation tracking of key guidelines, including those from the American Heart Association (2021), European Society of Cardiology (2023), and National Institute for Health and Care Excellence. Thirty-four studies met the eligibility criteria and were included in the final evidence synthesis. The evidence base comprised international guidelines, systematic reviews, observational studies, registry analyses, and narrative reviews relevant to IE prevention and dental management. AHA and ESC recommend antibiotic prophylaxis for patients with high-risk cardiac conditions undergoing IDPs, defined as procedures involving gingival or periapical manipulation or mucosal perforation. NICE guidance does not recommend routine prophylaxis but supports individualized decision-making and informed consent. Contemporary data indicate the strongest short-term association between IDPs and IE following tooth extractions and oral surgical procedures in high-risk patients. In these groups, AP has been associated with reduced IE incidence, with estimated numbers needed to prevent one case of approximately 244 for all IDPs, 143 for extractions, and 71 for oral surgery. Evolving epidemiology underscores the need for accurate cardiac risk stratification. Prevention should focus on identifying high-risk patients, maintaining oral health, communicating procedural risks, and applying selective AP when indicated, although evidence remains largely observational.

Introduction/ObjectivesInborn Errors of Immunity (IEIs) are rare disorders in which delayed diagnosis leads to significant morbidity and mortality. Early recognition depends largely on primary care and non-immunology healthcare professionals; however, data on IEI awareness in Central Asia are limited. This study assessed the awareness of IEI among healthcare professionals in Kazakhstan and identified the association with higher diagnostic preparedness.MethodsA nationwide cross-sectional study was conducted from January to March 2025 using an online questionnaire distributed across multiple regions of Kazakhstan. Physicians and nurses affiliated with the immunology department were excluded. The survey was adapted from the Jeffrey Modell Foundation framework and demonstrated high internal consistency (KR-20 = 0.94). Descriptive analyses and multivariable logistic regression were performed.ResultsA total of 239 healthcare professionals participated (88.7% female; mean age, 38.3 ± 10.2 years). While 72.4% reported undergraduate exposure to immunology, only 30.5% received postgraduate or workplace-based training related to IEI. Overall, 40.6% of the respondents were familiar with the "10 warning signs" of IEI. Prior workplace-based training was independently associated with higher awareness (adjusted OR 12.6, 95% CI 6.43-24.65).ConclusionsAwareness of IEI among non-immunology professionals in Kazakhstan remains limited. Targeted workplace-based education and continuing medical education (CME) programs may improve early recognition and referral rates.

BackgroundGastric cancer is a deadly disease with poor prognosis and unfavorable therapeutic outcomes. It is known that a major cause of treatment failure for gastric cancer is related to tumor heterogeneity. However, it is difficult to assess heterogeneity, as the composition of tumors is dynamic and cancer treatments reshape cell diversity and gene/protein expression profiles.ObjectiveWe utilized gastric cancer patient-derived tumor organoids to monitor tumor heterogeneity and the impacts of chemotherapy (FLOT and FOLFOX) on cancer stem cells (LGR5 and CD133) and cancer immune checkpoint molecules (MHC-I and PD-L1).MethodsSix tumor organoids were established from different patients or different regions of the same tumor. The tumor organoids were used to investigate the real-time profiles of cancer stem cell marker expression and cancer immune checkpoint molecule expression after chemotherapy treatment. Tumor suppression was monitored by the propidium iodide assay and measurements of tumor organoid diameter. Expression levels of cancer stem cell markers and immune checkpoint molecules were analyzed by flow cytometry.ResultsGrowth of all tumor organoids could be suppressed by chemotherapy. However, diverse impacts of FLOT and FOLFOX were observed in terms of the expression profiles of cancer stem cell markers and cancer immune checkpoint molecules. In particular, tumor organoids from different patients exhibited distinct expression profiles for cancer stem cell markers and immune checkpoint molecules after treatment with the same chemotherapeutic regimen. Similar observations were made with tumor organoids derived the same patient but different tumor regions.ConclusionOur findings demonstrated that spatial and temporal tumoral heterogeneity can be observed after treatment with chemotherapy, suggesting that repeated monitoring of tumor characteristics may be essential for clinical decision making. In addition, sampling of multiple sites at multiple time-points might be important when evaluating the impacts of chemotherapy on cancer stem cells markers and immune checkpoint molecules.

Persistent neurological symptoms such as cognitive impairment, fatigue, and neuropsychiatric disturbances are increasingly reported in patients with long COVID, with chronic neuroinflammation and neuronal injury proposed as potential contributors. To characterize inflammatory and neuroinjury-related biomarker patterns, we conducted a case-control study including 325 participants recruited at King Chulalongkorn Memorial Hospital between January 2022 and December 2023, comprising 265 individuals with persistent neurological symptoms following COVID-19 infection and 60 asymptomatic COVID-19 participants who did not develop long COVID symptoms. Blood samples were analysed for inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, IFN-α, IL-4) using multiplex immunoassays, and for neuroinflammatory and neurodegenerative biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, and beta-amyloid peptides (Aβ40, Aβ42) using SIMOA and ELISA platforms. Among 265 participants with complete data (critical = 7, severe = 22, moderate = 79, mild = 157), patients with severe and critical COVID-19 exhibited significantly higher concentrations of IL-6, IL-1β, TNF-α, and IL-8, together with elevated NfL, GFAP, and phosphorylated tau181 levels, and reduced Aβ42/40 ratios. Strong positive correlations between neurodegenerative biomarkers and pro-inflammatory cytokines were observed in critically ill patients, whereas these associations were weak or absent in mild and moderate cases. Older age was also associated with greater disease severity and increased risk of persistent neurological complications. These findings indicate that individuals with persistent neurological symptoms following COVID-19, particularly those with a history of severe or critical disease, exhibited higher inflammatory and neuroinjury-related biomarker levels, while blood-based biomarkers such as NfL, GFAP, and phosphorylated tau181 may serve as minimally invasive tools for characterizing neurological involvement and identifying patients at risk of long-term neurological sequelae.

Atherosclerosis (AS) is a chronic inflammatory disorder of the medium and large arteries, characterized by lipid accumulation within the arterial wall and a sustained inflammatory milieu, and it remains a leading cause of cardiovascular morbidity and mortality worldwide. Glycolysis and neutrophil extracellular traps (NETs) are both involved in the initiation and progression of AS in part through effects on endothelial function, platelet activation, lipid metabolism, and the inflammatory microenvironment. This article reviews the roles of NETs and glycolysis in AS, elucidates the mechanisms underlying NETosis, and discusses the association between glycolysis and NETosis. Finally, the article discusses the potential value of glycolytic inhibitors in the treatment of AS, with the aim of providing new perspectives for the diagnosis and treatment of AS and related cardiovascular diseases.

Infections with human herpesviruses are known to be associated with oral lesions and other oral complications. For example, herpes simplex virus 1 (HSV-1) is the causative agent for cold sores. Kaposi's sarcoma-associated herpesvirus (KSHV) causes oral Kaposi's sarcoma (KS) and other oral complications among immunocompromised patients, such as HIV-positive individuals. Novel antiviral strategies are needed to effectively treat oral infections caused by HSV-1 and KSHV, given the limitations of current FDA-approved anti-HSV-1 and anti-KSHV therapies. Nucleic acid-based gene-interfering molecules, such as antisense oligonucleotides, ribozymes, and small interfering RNA (siRNA), are promising gene-targeting agents for therapeutic applications. Ribozymes derived from the catalytic RNA subunit of RNase P in Escherichia coli represent a novel class of RNA-based gene targeting molecules for degrading target mRNAs and modulating gene expression. Methods have been developed to engineer RNase P ribozymes that more effectively suppress gene expression. In this review, we summarize the recent advances in using RNase P ribozymes to block the expression of HSV-1 and KSHV genes and inhibit the infection of HSV-1 and KSHV. Moreover, we discuss the potential of engineered RNase P ribozymes as therapeutics to treat infections and associated diseases caused by HSV-1 and KSHV in the oral cavity.

Cancer has become a major global health crisis and the second leading cause of death worldwide. With over 270 different types, it is estimated to claim 13 million lives by 2030. The complex pathophysiology of cancer, with its diverse genetic, epigenetic, and biochemical pathways, complicates the diagnostic criteria. Therapeutic approaches such as surgical interventions, radiotherapy, chemotherapy, and immunotherapy have been developed. However, the treatment is still challenging due to higher costs, toxicity, off-target effects, and comorbid conditions. Over the decades, liposomes, based on their particle size, surface charge, lipid composition, and lamellarity, have been explored for different therapeutic modalities for other cancers. They offer unique advantages, including improved drug efficacy, controlled site-specific release, enhanced cellular uptake, reduced systemic toxicity, and greater capacity to overcome tumor-induced resistance mechanisms. Researchers have explored liposomal treatment modalities for breast, lung, adenocarcinoma, ovarian, liver, fibrosarcoma, glioblastoma, and brain cancers. The tumor targeting drugs, for example, doxorubicin and paclitaxel, are delivered at the tumor microenvironment (TME) by passive and active transport, utilizing both the enhanced permeability and resistance (EPR) effect and cellular targets, for example, receptors, proteins, and organelles, in response to physical stimuli, for example, temperature, pH, fluid pressure, and nutrient and metabolic regulation. However, liposomes also face several limitations, including endosomal entrapment, heterogeneous targeting, suboptimal uptake by antigen-presenting cells (APCs), and storage instability. This review focuses on the advancements in liposomal nanocarriers for targeted cancer therapy. It emphasizes the evolution of their formulations to overcome potential limitations, making them highly tumor-specific and effective.

Epithelioid angiosarcoma (EA) is a malignant tumor of endothelium origin that most commonly arises in the deep soft tissues of extremities but may occasionally be primary in skin, adrenal gland, and bone. A 72-year-old male presented with a painless enlargement of his thyroid for more than 10 days before hospitalization. A walnut-sized mass in the right thyroid was found simultaneously by palpation and Color Doppler Ultrasound. After a total thyroidectomy was performed, a mass with a size of 4.5 cm × 3.5 cm was found at the lower pole of the right thyroid gland. Histologically, the tumor was diffusely distributed in a sheet-like pattern, with tumor cells being epithelioid. There was extensive coagulative necrosis while no components of papillary carcinoma, follicular carcinoma and insular poorly differentiated carcinoma were noticed. CD31 and vimentin were positive for immunostaining. The diagnosis of primary epithelioid angiosarcoma of right thyroid was then given to the patient. Eleven months after the operation, the patient died from brain metastasis. It is suggested that primary epithelioid angiosarcoma of thyroid, as an extremely rare tumor, have no characteristic clinical manifestations, laboratory and imaging examinations, and the diagnosis mainly depend on its unique clinical pathological features. Although extensive surgical resection is the preferred treatment, the prognosis is still very poor.