Search Results (6,628)

Background: Cutaneous lichen planus (CLP) is a chronic inflammatory T cell-mediated disease driven by a mixed Th1 and Th2 lymphocyte population, for which many of the currently available treatments have poor efficacy. Aim: The aim of this study was to indicate the clinical success of dupilumab administration after two years of treatment in a case of longstanding CLP and to perform a review of the medical literature related to the use of dupilumab in different dermatologic settings and in CLP. Case presentation: One 26-year-old woman with a previous history of atopic dermatitis had a long-lasting skin condition, referred to as a suspected lichen, which started when she was 7 years old. Her disease exhibited a relapsing–remitting course with severe bouts of pruritus over a very long period. The final histological diagnosis of CLP was confirmed at the age of 26. Starting dupilumab (injected subcutaneously at a dose of 600 mg followed by a maintenance dose of 300 mg every two weeks) resolved the skin scenery of this patient, who is currently in full remission. Conclusions: The remarkable recovery from CLP obtained via treatment with dupilumab in this single-patient case study emphasizes the potential therapeutic implications of targeting the Th2 pathway in this skin disorder. Full article

Glucose metabolism reprogramming as a defining hallmark of cancer has become a pivotal frontier in oncology research. Recent technological advances in single-cell sequencing, spatial omics, and metabolic imaging have transformed the field from static bulk analyses to dynamic investigations of spatiotemporal heterogeneity at a single-cell resolution. This review systematically summarizes the current knowledge on tumor glucose metabolism dynamics, discussing spatial heterogeneity and temporal evolution patterns, metabolic subpopulation interactions revealed by single-cell metabolomics, the glucose metabolism–epigenetics–immunology regulatory axis, and therapeutic strategies targeting metabolic vulnerabilities. Recent technological advances in single-cell sequencing and spatial omics have transformed our understanding of tumor glucose metabolism by providing high-resolution insights into metabolic heterogeneity and regulatory mechanisms, contrasting with classical bulk analyses. Spatiotemporal heterogeneity critically influences therapeutic outcomes by enabling tumor cells to adapt metabolically under selective pressures (e.g., hypoxia, nutrient deprivation), fostering treatment resistance and relapse. Deciphering these dynamics is essential for developing spatiotemporally targeted strategies that address intratumoral diversity and microenvironmental fluctuations. By integrating cutting-edge advances, this review deepens our understanding of tumor metabolic complexity and provides a conceptual framework for developing spatiotemporally precise interventions. Full article

The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset. Biomarkers were quantified using single-molecule array and immunoblotting techniques, and CSF cell subsets were analyzed by flow cytometry. High sNfL z-scores and LS-OCMB positivity were independently associated with increased risk of RAW and aPIRA, collectively termed inflammatory-associated worsening (IAW), while elevated sGFAP levels predicted naPIRA. Patients with both high sNfL and LS-OCMB positivity had the highest risk of IAW. Among LS-OCMB–positive patients, higher regulatory T cell percentages were associated with lower sNfL levels, suggesting a protective role. Conversely, in LS-OCMB–negative patients, sNfL levels correlated with CSF C3 concentrations. These findings support the complementary role of sNfL, sGFAP, and LS-OCMB in identifying distinct mechanisms of disease worsening and may inform early personalized management strategies in MS. Full article

Obesity is a chronic, relapsing disease with multifactorial origins and significant global health implications. Historically, bariatric surgery has been the most effective intervention for achieving sustained weight loss and metabolic improvement, especially in individuals with moderate to severe obesity. However, the therapeutic landscape is rapidly evolving. Recent advances in pharmacotherapy—including GLP-1 receptor agonists, dual and triple incretin agonists, and amylin-based combination therapies—have demonstrated unprecedented efficacy, with some agents inducing 15–25% weight loss, approaching outcomes once exclusive to surgical intervention. These developments challenge the continued applicability of existing bariatric surgery criteria, which were established in an era of limited medical alternatives. In this narrative review, we examine the evolution of surgical eligibility thresholds and critically assess the potential role of novel pharmacotherapies in redefining treatment algorithms. By comparing the efficacy, safety, metabolic benefits, and cost-effectiveness of surgery versus next-generation drugs, we explore whether a more stepwise, pharmacotherapy-first approach may now be justified, particularly in patients with BMI 30–40 kg/m². We also discuss future directions in obesity management, including personalized treatment strategies, perioperative drug use, and the integration of pharmacologic agents into long-term care pathways. As the field advances, a paradigm shift toward individualized, minimally invasive interventions appears inevitable—necessitating a timely re-evaluation of current bariatric surgery guidelines to reflect the expanding potential of medical therapy. Full article

Background/Objectives: We examined the in vivo effects of successive treatments with the histone deacetylase (HDAC) inhibitor romidepsin in patients with cutaneous T-cell lymphoma (CTCL), using changes in gene expression in peripheral blood mononuclear cells (PBMCs). Methods: Exploiting data from a highly responsive CTCL patient through 12 months of treatment, we identified a malignant cell predictor (MCP), a gene signature associated with the diminishing numbers of circulating malignant cells. Results: The MCP was successfully validated in the patient’s relapse sample 9 months after treatment was terminated and via an independent set of CTCL patient samples. Conclusions: The MCP set of genes contained novel CTCL markers, including membrane-associated proteins not normally expressed in lymphocytes. A subclass of those markers was also detectable in residual malignant cells undetected by flow cytometry in remission samples from a patient who relapsed 10 months later. We identified a subset of transcriptional regulators, miRNAs and methylation patterns associated with the effect of progressive treatments revealing potential mechanisms of transcriptional dysregulation and functional effects in the malignant cells. We demonstrate a role for transcriptional activator HLF, over-expressed in malignant cells, and downregulated transcriptional-suppressor and immune-modulator NFIL3, as regulators of CTCL-specific genes. Full article

Background/Objectives: Germ cell tumors are the most common neoplasia in males < 50 y. In two case series, thromboembolic events (TEs) were reported in 8% and 13% of patients undergoing chemotherapy, whereas arterial thromboembolic events (ATEs) in other types of cancer treated with cisplatin had a frequency of 2% in a retrospective series and 0.67% in a meta-analysis. Recent data found a frequency of 2.4% for ATE in a large cohort of testicular cancer patients. Risk factors are not clearly identified, and given the severity of these events, further exploration is needed to determine appropriate preventive measures. Methods: We performed a retrospective cohort study of 171 patients undergoing chemotherapy for germ cell tumors in two centers in Switzerland and recorded the occurrence of ATE or venous thromboembolic events (VTEs) during chemotherapy or in the 3 months after its completion. Results: of 171 patients, 33.3% underwent adjuvant chemotherapy for stage I disease. Overall, 32 patients had a TE (18.7%, 95% CI 13.3–25.5%), 26 (15.2%, 95% CI 10.3–21.7%) had VTEs, and 11 (6.4%, 95% CI 3.4–11.5%) had ATEs. Five patients had both a VTE and ATE. VTEs were associated with disease stage (II, III, or relapse, with OR 15.6, p = 0.0002), retroperitoneal lymph nodes ≥ 3.5 cm (OR 3.2, p = 0.012), LDH > 500 UI/L (OR 5.3, p = 0.0025), and age > 35 y (OR 3.4, p = 0.005). The Khorana Score (KS) varied between 1 and 2 in 96% of the patients. ATEs were associated with active smoking (OR 6.5 p = 0.010), KS of ≥2 (OR 6.4 p = 0.004), and age > 35 y (OR 6.3, p = 0.01). Conclusions: Our findings show that ATEs are more frequent in our cohort than previous reports. We found a strong association between smoking and ATEs, which should be further assessed. Platinum-induced endothelial damage may be amplified by smoking in young patients in the absence of other risk factors and preventive medication. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by intense pruritus and a significant impact on a patient’s quality of life. Despite advancements in understanding AD pathophysiology, there remains a critical need for innovative therapeutic options to better manage this debilitating disease. This review focuses on the evolving landscape of biological therapies for AD, offering insights into their role, mechanisms of action, and potential to revolutionize patient care. In this review, we explore the underlying immunological mechanisms of AD, particularly the role of cytokines and immune pathways implicated in the disease, and how targeted biological therapies modulate these pathways. Current FDA- and EMA-approved biologics, such as Dupilumab, are also discussed in terms of their mechanisms of action, efficacy, and safety. Additionally, we compare their effectiveness, highlighting the benefits and limitations observed in clinical practice. Emerging biological therapies currently under development offer new hope, with innovative targets like IL-13, IL-31, and thymic stromal lymphopoietin (TSLP) representing promising avenues for intervention. We also delve into personalized medicine, emphasizing the importance of biomarkers for predicting treatment response and stratifying AD patients to optimize therapeutic outcomes. Moreover, the synergistic potential of combining biologics with traditional therapies is reviewed, along with a discussion of the challenges involved, including safety, long-term efficacy, and patient adherence. We address the future direction of AD treatment, including microbiome-targeting biologics and the development of next-generation immune modulators. We highlight a new era of targeted treatment possibilities for this complex condition. Full article

Background/Objectives: The treatment of multiple myeloma (MM) remains a challenge, as almost all patients will eventually relapse. Proteasome inhibitors are a cornerstone in the management of MM. Unfortunately, validated biomarkers predicting drug response are largely missing. Therefore, we aimed to identify genes associated with drug resistance or sensitization to proteasome inhibitors. Methods: We performed genome-wide CRISPR-Cas9 knockout (KO) screens in human KMS-28-BM myeloma cells to identify genetic determinants associated with resistance or sensitization to proteasome inhibitors. Results: We show that KO of KLF13 and PSMC4 induces drug resistance, while NUDCD2, OSER1 and HERC1 KO cause drug sensitization. Subsequently, we focused on top sensitization hit, NUDCD2, which acts as a co-chaperone of Hsp90 to regulate the LIS1/dynein complex. RNA sequencing showed downregulation of genes involved in the ERAD pathway and in ER-associated ubiquitin-dependent protein catabolic processes in both untreated and carfilzomib-treated NUDCD2 KO cells, suggesting that NUDCD2 depletion alters protein degradation. Furthermore, bortezomib-treated NUDCD2 KO cells showed a decreased expression of genes that have a function in oxidative phosphorylation and the mitochondrial membrane, such as Carnitine Palmitoyltransferase 1A (CPT1A). CPT1A catalyzes the uptake of long chain fatty acids into mitochondria. Mitochondrial lipid metabolism has recently been reported as a possible therapeutic target for MM drug sensitivity. Conclusions: These results contribute to the search for therapeutic targets that can sensitize MM patients to proteasome inhibitors. Full article

Polatuzumab vedotin (PoV) is a novel antibody-drug conjugate that targets CD79B for the treatment of Non-Hodgkin Lymphoma (NHL). This meta-analysis aimed to evaluate the efficacy and safety of PoV in patients with NHL. A systematic review and meta-analysis of clinical trials evaluating PoV in NHL were conducted. The primary outcomes were complete response (CR) rates, progression-free survival (PFS), and overall survival (OS). Safety outcomes were also assessed. Random-effects models were used for the pooled analyses. Thirteen studies with 1533 patients with NHL were included. PoV significantly improved CR rates compared to control treatments (OR 1.50, 95% CI 1.01–2.21, p = 0.04) and PFS (MD 4.17 months, 95% CI 2.18–6.15, p < 0.0001). OS was not significantly different (OR 0.97, 95% CI 0.47–2.01, p = 0.93). Adverse events were more common with PoV (RR 1.38, 95% CI 0.98–1.94, p < 0.0001). PoV improves CR rates and PFS in patients with NHL, particularly those with relapsed/refractory disease, but is associated with increased adverse events. Further research is needed on long-term survival outcomes and optimal patient selection. PoV appears to be a promising targeted therapy option for NHL, which warrants further investigation. Full article

Background/Objectives: Long-acting injectable antipsychotics (LAIs) represent a significant advancement in the treatment of schizophrenia (SCZ), particularly for improving adherence and long-term outcomes. This study aimed to assess the clinical outcomes of patients receiving atypical LAIs compared to those on various oral antipsychotics over a one-year follow-up in a naturalistic setting. Methods: Sixty patients with SCZ were subdivided in two groups, those receiving LAIs (n = 25) and those receiving oral antipsychotics (n = 35). The groups were comparable for age, gender, educational attainment, employment status, marital status, smoking habits, and baseline SCZ severity, with no differences in baseline chlorpromazine equivalent dosages. Results: Over the follow-up period, patients in the LAI group discontinued treatment less frequently (χ² = 4.72, p = 0.030), showed fewer suicide attempts (χ² = 5.63, p = 0.018), fewer hospitalizations (χ² = 4.95, p = 0.026), and fewer relapses (χ² = 6.61, p = 0.010). Significant differences also emerged on the Drug Attitude Inventory (DAI-10) scores (F = 8.76, p = 0.005) and Body Mass Index (BMI) values (F = 8.32, p = 0.007), with the LAI group showing more favorable outcomes. Conclusions: LAIs, compared to oral antipsychotics, may promote treatment adherence, as shown by decreased hospitalization; furthermore, their use is related with better outcomes, like fewer relapses and less suicide attempts in individuals with SCZ in real-world settings. Full article

Background: Pediatric Crohn’s Disease (CD) affects more than physical health, influencing emotional well-being, social integration, and developmental milestones, with an impact on disease management. This study aimed to explore adolescents’ lived experiences with CD and identify factors influencing their motivation for self-management. Methods: A descriptive, cross-sectional qualitative study was conducted using a semi-structured, self-administered online questionnaire. Participants (n = 10) were adolescents with CD who had been diagnosed for over three years and were recruited from a tertiary pediatric gastroenterology center. Data included demographics, clinical characteristics, IMPACT-III (HRQOL), and PROMIS short forms. Open-ended responses underwent thematic analysis using the framework developed by Braun and Clarke. Results: Participants (80% female, median age 16.2 years, median disease duration 4.6 years) were all in clinical remission (median PCDAI = 2) and with good quality of life (median IMPACT-III = 80.7). Six themes emerged: (1) disease knowledge, (2) emotional responses, (3) coping and adaptation, (4) social support, (5) daily life and school impact, and (6) transition to adult care. Most participants demonstrated strong disease literacy and reported effective coping strategies. Emotional responses to diagnosis ranged from relief (60%) to distress (40%); relapses commonly triggered anxiety and fear. Therapeutic changes and disease monitoring were perceived as beneficial (100%) but with concern. Diagnostic procedures were viewed as burdensome by 70% of respondents. School performance and extracurricular participation were negatively affected in 40% during flares. Concerns regarding the future were reported by 40% of participants, with 30% believing that CD might limit life aspirations. While 60% managed their disease independently, 30% relied on parental support. All acknowledged the need for transition to adult care, though readiness varied. Conclusions: This study illustrates the overall impact of disease on pediatric CD patients. It reports significant emotional challenges and difficulties, as well as an impact on daily life, despite good disease knowledge. The findings underscore the importance of psychosocial well-being, ongoing mental health assessment, non-invasive monitoring, and holistic care, emphasizing the patient perspective, in managing pediatric CD. Full article

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the major subtype, accounting for more than 85% of all lung cancer cases. Recent advances in precision oncology have allowed NSCLC patients bearing specific oncogenic epidermal growth factor receptor (EGFR) mutations to respond well to EGFR tyrosine kinase inhibitors (TKIs). Due to the high EGFR mutation frequency (up to more than 50%) observed particularly in Asian NSCLC patients, EGFR-TKIs have produced unprecedented clinical responses. Depending on their binding interactions with EGFRs, EGFR-TKIs are classified as reversible (first-generation: gefitinib and erlotinib) or irreversible inhibitors (second-generation: afatinib and dacomitinib; third-generation: osimertinib). While the discovery of osimertinib represents a breakthrough in the treatment of NSCLC, most patients eventually relapse and develop drug resistance. Novel strategies to overcome osimertinib resistance are urgently needed. In Asian countries, the concomitant use of Western medicine and traditional Chinese medicine (TCM) is very common. Ganoderma lucidum (Lingzhi) and Coriolus versicolor (Yunzhi) are popular TCMs that are widely consumed by cancer patients to enhance anticancer efficacy and alleviate the side effects associated with cancer therapy. The bioactive polysaccharides and triterpenes in these medicinal mushrooms are believed to contribute to their anticancer and immunomodulating effects. This review presents the latest update on the beneficial combination of Lingzhi/Yunzhi and EGFR-TKIs to overcome drug resistance. The effects of Lingzhi/Yunzhi on various oncogenic signaling pathways and anticancer immunity, as well as their potential to overcome EGFR-TKI resistance, are highlighted. The potential risk of herb–drug interactions could become critical when cancer patients take Lingzhi/Yunzhi as adjuvants during cancer therapy. The involvement of drug transporters and cytochrome P450 enzymes in these herb–drug interactions is summarized. Finally, we also discuss the opportunities and future prospects regarding the combined use of Lingzhi/Yunzhi and EGFR-TKIs in cancer patients. Full article

Background/Objectives: The combination of venetoclax (VEN) and hypomethylating agents (HMA), such as azacitidine (AZA) or decitabine (DEC), has transformed the treatment landscape for acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy. However, optimal management of neutropenia and the impact of post-remission treatment interruptions (washouts) remain unclear. This study aimed to evaluate the safety and efficacy of post-remission washouts and their effect on clinical outcomes. Methods: We conducted a retrospective single-center study of 44 AML patients treated with HMA/VEN between 2020 and 2021. Clinical, molecular, and treatment-related data were collected, including treatment duration, post-remission washout duration, response rates, disease-free survival (DFS), and overall survival (OS). Statistical analyses included Fisher’s exact test and univariate and multivariate Cox models. Results: Overall, 61% of patients responded to therapy, with significantly higher response rates among those potentially eligible for the VIALE-A trial (86% vs. 39%, p = 0.002). Neither treatment duration nor post-remission washout length was associated with DFS or OS. DFS was significantly longer in patients treated with AZA compared to DEC (p = 0.006). Median OS was 7.7 months, with longer OS observed in patients who did not meet VIALE-A trial eligibility criteria (p = 0.021). Achieving complete remission (CR) was associated with improved OS (14.5 months). Conclusions: Post-remission treatment interruptions (washouts) did not negatively impact DFS or OS, suggesting they may be a safe strategy to support hematologic recovery. However, the choice of HMA appears to influence response duration, with AZA outperforming DEC in maintaining disease control. Full article

Rheum tataricum L.fil., known for its high tolerance to drought, salinity, and nutritional deficiency, is the least studied species of wild rhubarb. Extract of roots and rhizomes of R. tataricum has been traditionally used for the treatment of different diseases such as liver, kidney, womb, and bladder diseases and also relapsing fever. An ethanol extract of the roots of R. tataricum was prepared and further successively fractionated by extraction with tert-butyl methyl ether (TBME) and ethyl acetate (EtOAc). The obtained extract fractions were subjected to a series of chromatographic separations on silica gel for the isolation of its individual compounds. A total of 12 individual compounds, 2-O-β-D-glucopyranoside of R-(4-hydroxyphenyl)-2-butanol (rhododendrin) 1, gallic acid 2, 2-O-β-D-glucopyranoside of S-4-(4-hydroxyphenyl)-2-butanol (epi-rhododendrin) 3, their aglycones (-)-(2R)-rhododendrol 4 and (+)-(2S)-rhododendrol 5, gallotannin β-glucogallin 6, chlorogenic acids (3,5-di-O-caffeoylquinic acid 7 and 5-O-caffeoyl-3-O-(p-coumaroyl) quinic acid 8), 4-(4-hydroxyphenyl)-2-butanon (raspberry ketone) 9 and three stilbenes (rhaponticin 10, desoxyrhaponticin 11 and resveratroloside 12), were isolated and characterized. The structure of desoxyrhaponticin 11 was confirmed by X-ray diffraction analyses. The results of in vitro biological assays (the MTT test) showed that ethanol extract Rheum tataricum was non-toxic against the normal epithelial VERO cells. The isolated compounds 1, 4, 11 and 12 exhibited cytotoxicity against a cervical cancer cell line (CaSki), breast adenocarcinoma (MCF7) and glioblastoma cell line (SNB-19) at low micromolar concentrations. Polyhydroxystilbenes 11 and 12 showed the best potency against adenocarcinoma cells (GI₅₀ = 7–8 μM). The inhibition activity towards cancer cells was comparable to those of the standard drug doxorubicin. The available from R. tataricum secondary metabolites may serve as new leads for the discovery of anticancer drugs. Full article

Background/Objectives: In this study, we aimed to evaluate probiotics’ clinical efficacy and safety in adults with chronic rhinosinusitis (CRS), and summarize mechanistic evidence related to mucosal immunity and microbiota modulation. Methods: We performed a systematic review and random-effects meta-analysis. MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched until May 2025. Eligibility: Randomized controlled trials (RCTs) and mechanistic studies investigating probiotics (any strain, dose, or administration route) in adults with CRS were eligible. Primary outcomes included changes in Sino-Nasal Outcome Test (SNOT-20/22) scores and CRS relapse rates. Secondary outcomes were adverse events and mechanistic endpoints. Results: Six studies (four RCTs, n = 337; two mechanistic studies) met the inclusion criteria. Probiotics did not significantly improve SNOT scores compared with the placebo, but trended in that direction (pooled mean difference—2.70; 95% CI −7.12 to 1.72; I² = 0%). Furthermore, probiotic use was associated with a non-significant trend towards fewer CRS relapses (risk ratio 0.41; 95% CI 0.16–1.04; p = 0.06; I² = 48%). Adverse events were mild and comparable to the placebo (risk ratio 0.87; 95% CI 0.33–2.34). Mechanistic data indicated that intranasal Lactococcus lactis W136 might downregulate type 1 inflammatory pathways and modestly increase microbiome diversity. Subgroup analyses (by route, duration, and CRS subtype) revealed no statistically significant effect modifiers, though mechanistic insights suggest possible differences in efficacy based on the CRS endotype and delivery method. Conclusions: Probiotics appear safe and may provide a small, non-significant improvement in CRS symptoms; emerging evidence of reduced relapse rates warrants further investigation through larger, endotype-stratified trials utilizing targeted probiotic strains and optimized delivery methods. Full article