Search Results (3,432)

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are often complicated by immune-related adverse events, particularly colitis. With increasing ICI use, understanding the clinical course and management of ICI-induced colitis is essential. Objectives: To characterize the clinical, endoscopic, and histological features of ICI-induced colitis and evaluate treatment outcomes, focusing on the use of corticosteroids and second-line biologicals (infliximab and vedolizumab) in a real-world setting. Methods: A retrospective cohort study was conducted at Ghent University Hospital, including 77 adult patients diagnosed with ICI-induced colitis in between 2012 and 2023. Clinical, biochemical, endoscopic, and histological data were analyzed, along with treatment response and safety outcomes. Results: Patients with ICI-induced colitis received anti-PD-1/PD-L1 (64.9%), anti-CTLA-4 (9.1%), or combination of both (26.0%). In patients with normal endoscopic findings, histological signs of colitis were observed in 88.0%. Combination ICI therapy was associated with higher Mayo scores (p = 0.029) and increased need for biologicals (p = 0.011) compared to anti-PD-1/PD-L1 monotherapy. Clinical response rates were 79.6% with corticosteroids and 100.0% with biologicals. Rechallenge with ICIs lead to a 17.4% relapse rate. No colitis-related deaths were observed. Conclusions: In this retrospective study, we demonstrate that random colon biopsies reveal microscopic ICI-induced colitis in most patients with absence of endoscopic disease. Combination ICI therapy predicts a corticosteroid-refractory course, supporting the need for early escalation to biologicals. ICI rechallenge appears feasible, as relapse rates were relatively low and colitis morbidity remained manageable. Prospective studies are needed to refine therapeutic strategies and improve patient outcomes. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that affects women more frequently than men. This sex gap has widened over the past century, and appears to be shaped by lifestyle factors more than biological factors. This narrative review examines the evidence for sex-specific differences in lifestyle risk factors and their impact on both MS susceptibility and disease progression, with implications for diagnosis, monitoring, and treatment. Smoking, obesity, vitamin D deficiency, ultraviolet radiation exposure, and Epstein–Barr virus infection all interact with sex-related biological pathways to influence MS risk. Women appear to be more vulnerable to the pathogenic effects of smoking and obesity, both independently and in synergy with genetic risk alleles, while vitamin D and UV exposure confer stronger protective effects in females than in males. EBV infection also exhibits sex-dependent immune responses, shaped by hormonal regulation and host–virus genetic interactions. Sex-related lifestyle factors also modulate MS progression. Women experience more inflammatory activity and relapses, whereas men more often develop a progressive phenotype with greater neurodegeneration. Hormonal changes during female reproductive phases, such as pregnancy, breastfeeding, menopause, and hormone-based therapies, critically influence disease activity and progression in MS. Obesity, smoking, vitamin D status, diet, and gut microbiota further interact with sex hormones and genetic background, contributing to variable disease trajectories, also modulated by social determinants such as education level. These findings underscore the need to integrate into clinical practice the evaluation of lifestyle factors in a sex-specific way for diagnosis, monitoring, and treatment of MS. Full article

Acute myeloid leukemia (AML) accounts for 15–20% of childhood leukemia cases; however, it is characterized by very high aggressiveness and has the highest mortality rate among leukemias, with relapse rates ranging from 34% to 38%. It is a disease characterized by high molecular diversity, and the frequency of specific genetic alterations in children is different from that in adults. Furthermore, mutations and rearrangements vary with age within the pediatric population. To date, a wide spectrum of genetic alterations has already been studied, but the molecular landscape of each patient is unique. An analysis of rearrangements and mutations specific to children of different ages appears to be crucial in order to individualize diagnosis and therapy appropriately. The aim of the following review is to analyze the molecular landscape of pediatric AML by age in detail in order to prioritize therapeutic strategies dedicated to specific age groups. Full article

Background: Antimicrobial drugs are used to treat bacterial diseases in livestock production systems, including bovine respiratory disease (BRD) in feedlot cattle. It is recommended that therapeutic antimicrobial use (AMU) in food animals be informed by diagnostic tests to limit the emergence of antimicrobial resistance (AMR) and preserve the effectiveness of available drugs. Recent evidence demonstrates preliminary support for the pen as a prospective target for AMR testing-based interventions in higher-risk cattle. Methods: A previously reported agent-based model (ABM) was modified and then used in this study to investigate the potential for different pen-level sampling and laboratory testing-informed BRD treatment strategies to favorably impact selected antimicrobial stewardship and management outcomes in the western Canadian context. The incorporation of sample testing to guide treatment choice was hypothesized to reduce BRD relapses, subsequent AMU treatments and resultant AMR in sentinel pathogen Mannheimia haemolytica. The ABM was extended to include a discrete event simulation (DES) workflow that models the testing process, including the time at sample collection (0 or 13 days on feed) and the type of AMR diagnostic test (antimicrobial susceptibility testing or long-read metagenomic sequencing). Candidate testing scenarios were simulated for both a test-only control and testing-informed treatment (TI) setting (n = 52 total experiments). Key model outputs were generated for both the pen and feedlot levels and extracted to data repositories. Results: There was no effect of the TI strategy on the stewardship or economic outcomes of interest under baseline ecological and treatment conditions. Changes in the type and number of uses by antimicrobial class were observed when baseline AMR in M. haemolytica was assumed to be higher at feedlot arrival, but there was no corresponding impact on subsequent resistance or morbidity measures. The impacts of sample timing and diagnostic test accuracy on AMR test positivity and other outputs were subsequently explored with a theoretical “extreme” BRD treatment protocol that maximized selection pressure for AMR. Conclusions: The successful implementation of a pen-level sampling and diagnostic strategy would be critically dependent on many interrelated factors, including the BRD treatment protocol, the prevalences of resistance to the treatment classes, the accuracy of available AMR diagnostic tests, and the selected “treatment change” thresholds. This study demonstrates how the hybrid ABM-DES model can be used for future experimentation with interventions proposed to limit AMR risk in the context of BRD management. Full article

Background: The Comprehensive Geriatric Assessment (CGA) has proven to be a valuable tool for providing a more comprehensive health evaluation of allogeneic stem cell transplantation (allo-SCT) recipients. Methods: We prospectively developed and tested a new Simplified Geriatric Score-4 (SGS-4) on 135 consecutive patients aged ≥50 years who underwent allo-SCT between 2020 and 2023. Each CGA component was individually analyzed for its association with overall survival (OS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR). Then, we performed a two-factor analysis (FA) using oblimin rotation and Bartlett estimation on all CGA components and sex. Based on component weights, a simplified geriatric score-4 score (SGS-4) was created: [Gait Speed] + 2 × [Hand Grip] + Geriatric 8 + 1.5 × [Sex]. ROC analysis defined three fitness groups, frail (≤13), prefrail (>13–22.5), and fit (>22.5). Results: Reduced hand grip strength and impaired mini mental state examination (MMSE) were associated with worse OS and higher NRM. Vulnerable Elders Survey (VES-13) and Fondazione Italiana Linfomi (FIL) scores also indicated poorer OS, though with uneven group sizes. Other CGA domains and the Hematopoietic Cell Transplantation–Comorbidity Index (HCT-CI) showed no significant prognostic value. The SGS-4 effectively stratified patients into three fitness groups, with those in the frail category experiencing lower OS and an increased risk of relapse. Conclusions: The new Simplified Geriatric Score-4 (SGS-4) based on three CGA domains (gait speed, hand grip, Geriatric 8) and sex effectively predicts OS and CIR risk in patients aged ≥50 years undergoing allo-SCT. The study’s small sample size and disease heterogeneity warrant further validation in larger cohorts. Full article

Background: Seborrheic dermatitis (SD) is a chronic, recurrent inflammatory dermatosis that primarily affects seborrheic areas such as the scalp, face, and upper trunk. Its etiology is multifactorial, involving sebaceous gland activity, immune dysregulation, skin barrier dysfunction, and alterations in the microbiome, particularly an overgrowth of Malassezia spp. Objective: This review provides an updated overview of the pathophysiological mechanisms of seborrheic dermatitis and critically examines current therapies and emerging treatments. Methods: A narrative review of the recent literature was conducted, including preclinical studies, clinical trials, and real-world evidence regarding SD pathogenesis and therapy. Special attention was paid to molecular pathways, microbiome-modulating strategies, and novel therapeutic agents. Results: Advances in transcriptomic and microbiome profiling have revealed a complex immunoinflammatory environment in SD, involving predominantly Th1, Th17, and Th22 axes. Conventional therapies are mainly based on antifungals, topical corticosteroids, and calcineurin inhibitors. However, new therapeutic approaches are under investigation, including PDE4 inhibitors (roflumilast, crisaborole, and apremilast), topical and oral JAK inhibitors, probiotics, and microbiome-targeted therapies. These agents offer promising results in selected patients, particularly those with refractory disease or facial involvement. Conclusions: SD remains a challenging condition due to its relapsing course and limited long-term therapeutic options. Emerging therapies represent a valuable opportunity to address unmet clinical needs, particularly in patients with severe, recurrent, or treatment-resistant forms. Full article

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet clinical need. The advent of bispecific monoclonal antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), dual affinity retargeting (DART) molecules and IgG-like bispecific antibodies, offers a novel promising therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R/R setting. BsAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against malignant cells and enhancing the immune response. Most BsAbs developed for the treatment of NHLs engage T-cells via CD3 and malignant B-cells via CD20, a surface antigen expressed on most lymphomatous cells. Engagement of malignant B-cells by BsAbs activates T-cells, leading to the release of multiple cytokines and potentially to two characteristic adverse events: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Epcoritamab and glofitamab have received FDA and EMA approval for R/R DLBCL after two or more systemic line of therapies. EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA. Odronextamab is approved by EMA for R/R DLBCL and FL in patients who have received at least two prior lines of therapy, but it has not been approved by FDA. Mosunetuzumab is approved by both agencies—but only for R/R follicular lymphoma (FL). BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL. Full article

Introduction: Fusobacterium nucleatum, a common oral microbe associated with periodontal disease, has emerged as a significant prognostic indicator in colorectal cancer (CRC). This organism is notably enriched in CRC tissues and is associated with reduced survival times and relapse. Fusobacterium is implicated in encouraging the development of chemoresistance through diverse tumor-promoting pathways that are increasingly being elucidated across molecular domains. Methods: This work uses a combined analysis of public data examining the role of F. nucleatum in CRC by investigating multiple transcriptomic datasets derived from co-culture infections in vitro. Results: In tandem with previously identified mechanisms known to be influenced by F. nucleatum, this analysis revealed that the bacterium activates multiple chemoresistance-associated pathways, including those driving inflammation, immune evasion, DNA damage, and metastasis. Notably, this study uncovered a novel induction of type I and type II interferon signaling, suggesting activation of a pseudo-antiviral state. Furthermore, pathway analysis (IPA) predicted altered regulation of several therapeutic agents, suggesting that F. nucleatum may compromise drug efficacy through transcriptional reprogramming. Conclusions: These findings reinforce the role of F. nucleatum in modulating host cellular pathways and support the hypothesis that bacterial association potentiates chemoresistance. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems, characterized by remissions and relapses. Musculoskeletal involvement occurs in up to 95% of patients and may present as the initial symptom in 50%. Such involvement is often subclinical, without obvious joint or tendon inflammation. Musculoskeletal ultrasound (US) has proven valuable for detecting pathological changes in joints and periarticular structures, including in SLE patients, and early detection, particularly in subclinical stages, supports optimal therapy, monitoring, and improved prognosis. This study aimed to determine the frequency of new clinical manifestations in patients with previously confirmed clinical and subclinical musculoskeletal inflammation after 2 and 5 years, and to evaluate associations with sex, age, BMI, smoking status, ESR, CRP, SLEDAI-2K, complement components C3 and C4, anti-dsDNA antibodies concentrations, and prior treatment. Methods: The study included 34 SLE patients with clinical and 22 with subclinical musculoskeletal inflammation, confirmed at baseline by history, examination, and US. Follow-up at 2 and 5 years recorded new clinical manifestations. Correlations with patient characteristics were assessed to identify predictors. Results: New clinical manifestations occurred in 34% of patients at 2 years and 48% at 5 years, most commonly cutaneous, musculoskeletal, and hematological. Summary analysis identified female sex, lower BMI, and lower baseline SLEDAI-2K scores as the strongest predictors. In the subclinical group, female sex, smoking, and lower SLEDAI-2K scores were predictive, while in the clinical group, female sex, lower SLEDAI-2K scores, lower ESR, and higher anti-ds DNA levels were associated with new manifestations. Conclusions: Female sex, lower BMI, and lower baseline SLEDAI-2K scores are key predictors of new clinical manifestations in SLE patients, highlighting the importance of early detection and individualized monitoring, particularly in patients with subclinical musculoskeletal inflammation. Full article

Background/Objectives: Despite the high complete response (CR) rate to first-line therapy, approximately one-third of patients with advanced-stage Hodgkin lymphoma (HL) eventually relapse. In up to 30–50% of cases, relapses are subclinical, i.e., initially detected only by imaging procedures. However, there is no definitive consensus on the optimal surveillance strategy for high-risk HL patients. Methods: The purpose of this cohort study is to evaluate the long-term outcome of stage II-B/IV HL patients who relapsed under routine imaging surveillance (imaging cohort) compared to those who relapsed under conventional clinical monitoring (standard cohort). Follow-up in the imaging cohort systematically included FDG-PET/CT, ultrasonography, and/or chest X-ray. At relapse, patients were treated with the same approach (salvage therapy and autologous hematopoietic stem cell transplantation [AHSCT]) in both cohorts. Results: A total of 123 high-risk HL patients were assessed at their first relapse: 80 in the imaging cohort and 43 in the standard cohort. The 2-year event-free survival (EFS) was significantly higher in the imaging cohort compared to the standard cohort (70% vs. 37.2%, respectively; p = 0.001). Similarly, the CR rate following salvage treatment was greater in the imaging cohort as compared to the standard cohort (68.8% vs. 41.9%, respectively; p < 0.004). These differences were due to the capability of routine imaging surveillance to detect disease with more limited extension (early onset of clinically silent relapses) as compared to standard clinical monitoring, which was associated with relapsed disease in a more advanced stage. Conclusions: Our findings suggest that routine imaging surveillance in patients with high-risk HL leads to improved EFS detecting relapses, which were characterized by more favorable prognostic factors (low tumor burden), thus enabling the timely administration of salvage therapy. Full article

Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile similar to BCR::ABL1-positive leukemia, but lacking the BCR::ABL1 fusion gene. It is frequently associated with kinase-activating alterations, such as CRLF2 rearrangements, JAK-STAT pathway mutations, and ABL-class fusions. Patients with Ph-like ALL typically experience poor outcomes with conventional chemotherapy, underscoring the need for intensified and targeted therapeutic approaches. Methods: This review summarizes current evidence regarding the role of hematopoietic stem cell transplantation (HSCT) in patients with Ph-like ALL. We analyzed retrospective cohort studies, registry data, and ongoing clinical trials, focusing on transplant indications, molecular risk stratification, measurable residual disease (MRD) status, timing of transplant, and post-transplant strategies. Results: Retrospective data suggest that HSCT in first complete remission (CR1) may improve survival in patients with high-risk molecular lesions or MRD positivity at the end of induction. However, the lack of prospective data specific to Ph-like ALL limits definitive conclusions. Post-transplant relapse remains a challenge, and novel strategies, including the use of tyrosine kinase inhibitors or JAK inhibitors as post-HSCT maintenance therapy, are being explored. Emerging immunotherapies, such as chimeric antigen receptor (CAR) T cells, may reshape the therapeutic landscape and potentially alter the indications for transplantation. Conclusions: HSCT remains a crucial therapeutic option for selected patients with Ph-like ALL, particularly those with poor molecular risk features or persistent MRD. However, further prospective studies are needed to evaluate the indication for HSCT in CR1 and the potential integration of transplantation with targeted and immunotherapeutic strategies. Personalized treatment approaches based on genomic profiling and MRD assessment are essential to improve outcomes in this high-risk subset. Full article

Background: Amino acid tracer positron emission tomography–magnetic resonance imaging (PET-MRI) was shown to be superior to MRI alone for evaluating central nervous system (CNS) tumours in adults. This study aimed to investigate the utility of amino acid PET-MRI in children with CNS tumours. Methods: We reviewed the amino acid PET-MRI findings of children with suspected or confirmed CNS neoplasms managed in a territory-wide referral centre in Hong Kong from 2022 to 2025. Maximal standardized uptake values (SUVmax) were captured, and tumour-to-background SUVmax ratios (TBRmax) were measured with reference to adjacent or contralateral normal brain structures. Comparisons were made among patients with clinical high-grade and low-grade/non-neoplastic lesions. Results: Thirty-seven patients were included, with 63 PET-MRIs performed. PET-MRI was performed as part of initial diagnostics in 41% of the cases, for response assessment in 48%, and evaluation of residual/relapsed disease in 11%. High-grade lesions had a significantly higher SUVmax and TBRmax compared to low-grade/non-malignant lesions (median SUVmax 3.7 vs. 1.6, p = 0.00006; median TBRmax 2.06 vs. 0.91, p = 0.00002). Optimal SUVmax and TBRmax cut-offs by ROC analysis were 2.38 and 1.62, respectively. Similar performance was reproduced by focusing on the subset of patients with suspected CNS germ cell tumours (CNS-GCT). The impact of amino acid PET availability is considerable, as clinical management was modified in 65% of patients. Conclusions: Our study demonstrates the performance and clinical utility of amino acid PET-MRI in the management of children with CNS pathologies. Amino acid PET-MRI contributes to the diagnosis, monitoring, and treatment guidance of these patients, providing crucial information for decision-making. Full article

Background: Chronic relapsing colitis involves immune dysregulation and oxidative stress, making monotherapies often insufficient. This study investigates a therapeutic strategy combining doxycycline (Dox), an immunomodulatory antibiotic, with Arthrospira platensis extracts to enhance anti-inflammatory and antioxidant effects, improving remission and controlling relapse. Methods: Ethanolic (ES) and aqueous (AS) extracts of A. platensis were chemically characterized by GC-MS after derivatization. Colitis was induced in mice using two intrarectal DNBS administrations spaced 7 days apart, with oral treatments (Dox, ES, AS, or combinations) given daily between doses. Disease progression was evaluated through clinical monitoring, histological scoring, and biochemical analysis, including MPO and CAT activities, as well as NO, MDA, and GSH levels. Results: GC-MS identified 16 bioactive compounds in each extract. ES contained mainly fatty acids and amino acids, whereas AS was rich in polysaccharides and phytol. Combined doxycycline and A. platensis extracts significantly enhanced recovery in reactivated DNBS colitis compared to monotherapies. Each treatment alone reduced disease severity, but their combination showed synergistic effects, significantly reducing disease activity index (p < 0.001), restoring mucosal integrity, and modulating inflammatory and oxidative markers (p < 0.001). Conclusion: Doxycycline potentiates the anti-colitic effects of A. platensis extracts via complementary mechanisms, offering a promising combination for managing relapsing colitis. Full article

Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. “Trained immunity”—the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors—maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut–bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome–immune–neuronal axis interactions, and host genetic variants modulating microbiome–immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions. Full article

This comprehensive review explores the distribution, diversity, and epidemiology of tick-borne borrelioses across Eurasia, focusing on Lyme borreliosis (LB) and other Borrelia-related infections. The genus Borrelia is categorized into three major groups, the Lyme Group (LG), the Relapsing Fever Group (RFG), and the Echidna–Reptile Group (REPG), each with distinct vectors, reservoirs, and pathogenic profiles. LB, caused by Borrelia burgdorferi sensu lato, is highly endemic in Europe and is increasingly reported in Asia, although it is underdiagnosed in Southeast Asia due to limited surveillance. This review details the ecological dynamics of tick vectors—primarily Ixodes spp.—and their vertebrate hosts, emphasizing the role of migratory birds and climate change in disease spread. It also highlights the presence of relapsing fever Borrelia species transmitted by soft ticks (Ornithodoros spp.) and the emergence of novel species such as Borrelia miyamotoi (RFG) and Borrelia turcica (REPG). This study underscores the need for harmonized surveillance systems, improved diagnostic tools, and integrated public health strategies to address the growing threat of borreliosis in Eurasia. Full article