Search Results (464)

Lymphomas are broadly categorized into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Despite treatment advances, they remain a major cause of cancer-related morbidity and mortality in Canada. This study examined temporal trends in socioeconomic inequalities in lymphoma mortality in Canada from 2000 to 2019. Using a unique census division level dataset (n = 280) constructed by pooling information from the Canadian Vital Statistics Death Database, the Canadian Census of Population and the National Household Survey, we measured mortality in HL and NHL in Canada. The age-standardized Concentration index (C) was used to quantify income and education inequalities in lymphoma. Time trend analyses were conducted to examine the changes in the observed socioeconomic inequalities. Crude HL mortality declined significantly over the study period. Crude NHL mortality remained largely unchanged in Canada overall, although modest declines were observed in the Prairies. The age-standardized C indicated persistent income and education inequalities for both lymphoma types. For NHL, mortality became increasingly concentrated among lower-income and lower-education populations over time. The persistent and widening socioeconomic inequalities observed in HL and NHL mortality, respectively, in Canada underscore the need for targeted public health interventions and more equitable distribution of resources to address systematic and avoidable differences in cancer outcomes associated with socioeconomic disadvantage. Full article

Background and Objectives: Relapsed/refractory non-Hodgkin lymphoma (R/R NHL) remains a major therapeutic challenge, particularly in patients with peripheral T-cell lymphomas (PTCL), who frequently exhibit poor responses to salvage therapy and inferior survival outcomes. Achieving adequate disease control before autologous stem cell transplantation (ASCT) is a critical determinant of long-term survival. The bendamustine, gemcitabine, vinorelbine, and prednisolone (BEGEV) regimen has demonstrated high efficacy and favorable tolerability in relapsed/refractory classical Hodgkin lymphoma; however, data regarding its role in NHL are extremely limited. Materials and Methods: We conducted a retrospective, single-center analysis of patients with R/R NHL who received the BEGEV regimen as salvage therapy. Clinical characteristics, response rates, transplantation outcomes, progression-free survival (PFS), overall survival (OS), and safety data were evaluated. Treatment responses were assessed according to standard radiologic response criteria. Survival analyses were performed using the Kaplan–Meier method. Results: A total of 68 patients with R/R NHL were included in the analysis. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype, accounting for 49 patients (72.1%). BEGEV was administered predominantly in later salvage settings. Response assessments were available for 56 patients. Among evaluable patients, the objective response rate (ORR) was 73.2%, whereas the ITT ORR was 60.3% (41/68). Following BEGEV therapy, 25 patients (36.8%) proceeded to autologous stem cell transplantation (ASCT), while 8 patients (11.8%) underwent allogeneic stem cell transplantation (allo-SCT). Exploratory analyses demonstrated longer overall survival (log-rank p = 0.012) and progression-free survival (log-rank p = 0.011) among patients who subsequently underwent transplantation; however, these findings should be interpreted with caution because of the retrospective study design and the potential for selection and immortal time biases. Median PFS and OS were 4 and 26 months, respectively. Adverse events were predominantly hematologic and generally manageable. Conclusions: BEGEV may represent a reasonable salvage regimen for selected patients with R/R NHL and may facilitate disease control allowing subsequent transplantation in selected patients, including selected PTCL patients. Full article

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, affecting approximately 50 million people worldwide. An estimated 15–30% of individuals with chronic HCV infection progress to cirrhosis, which may subsequently develop into hepatocellular carcinoma. Beyond liver disease, HCV is associated with a broad spectrum of extrahepatic manifestations, particularly mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Persistent viral infection induces chronic antigenic stimulation of B lymphocytes, a key pathogenic mechanism underlying the progression from MC to overt B-NHL. These observations have important therapeutic implications and support the use of antiviral therapy as a cornerstone of treatment. The efficacy of direct-acting antivirals (DAAs) has been well established in patients with HCV-related MC and cryoglobulinemic vasculitis. Several studies have shown that DAAs achieve sustained virologic response rates exceeding 90%, often approaching 100% in contemporary cohorts. Viral eradication is frequently associated with clinical and immunological improvement, as well as regression of cryoglobulinemia. Encouraging outcomes have also been reported in patients with HCV-associated indolent B-NHL, particularly marginal zone lymphoma, although confirmation in larger studies with longer follow-up is needed. In patients with HCV-positive aggressive lymphomas, DAAs have been safely administered in combination with immunochemotherapy, yielding promising results. This review summarizes the current evidence on HCV-associated MC and B-NHL and discusses the impact of DAA therapy on the clinical course and management of these disorders. Full article

KMT2A-rearranged (MLL-r) leukemias are highly aggressive hematological malignancies that require improved targeted therapies. DOT1L (histone H3K79 methyltransferase) functions as a critical oncogenic driver and represents an important therapeutic target in these high-risk leukemias. However, clinical responses to the first-in-class DOT1L inhibitor pinometostat (EPZ5676) have been modest, attributed to suboptimal pharmacokinetics and, more fundamentally, to the recognition that DOT1L possesses methyltransferase-independent functions that evade catalytic inhibition. This highlights the need for strategies that abrogate the full spectrum of DOT1L activity to effectively treat these high-risk leukemias. Proteolysis-targeting chimeras (PROTACs), which induce selective degradation of the DOT1L protein rather than inhibiting its catalytic activity, have therefore emerged as a promising approach. Notably, VHL-recruiting DOT1L PROTACs, such as DOT1L808, have demonstrated improved pharmacokinetic profiles and potent antileukemic activity in preclinical in vivo models. However, these findings remain preclinical, and significant challenges including oral bioavailability, potential toxicity, and lack of clinical validation must be addressed before clinical translation. In this review, we provide an overview of the evolving understanding of the biology of DOT1L, discuss existing MLL small molecule therapies, and evaluate current advances in therapeutically targeting DOT1L, with particular focus on the targeted degradation of DOT1L as a promising therapeutic strategy for high-risk KMT2A-r leukemia. Full article

Earthen plasters are attracting interest as low-impact, vapour-open finishing systems, yet most evidence still derives from laboratory characterization rather than from full-scale exposure. Their application in real buildings is still constrained by regulatory and material-related barriers, as national regulatory frameworks remain uneven and existing guidelines provide limited support for fibre-reinforced earthen mixtures. Moreover, natural soils vary in composition, making standardization and quality control difficult. In Mediterranean climates, vapour-open materials can support passive moisture regulation. However, seasonal changes in solar exposure and rainfall make full-scale assessment under real operating conditions necessary. This study assesses the in situ hygrothermal behaviour of an experimental circular earthen plaster, formulated with marble-processing dust and sisal fibres, against a natural hydraulic lime (NHL) reference. Two near-identical hollow-clay-block masonry test boxes were built near Catania (Southern Italy, Köppen Csa) and monitored under free-running conditions across winter, transition and summer campaigns in 2026, recording surface temperatures, indoor air temperature, relative humidity and CO₂. In winter, the earthen finish reduced the daily internal surface amplitude from 4.9 °C to 4.2 °C consistently on every paired monitoring day. During the transition period, surface differences were negligible, but relative humidity emerged as the discriminating variable, the earthen room remaining higher and more stable. In summer, the hygroscopic buffering became most evident, with the earthen room holding indoor humidity near 72% almost unchanged across a near-five-degree seasonal warming. A difference in solar absorptance between the two external finishes was identified and quantified, reducing the external surface peak of the earthen prototype by about 2 °C at maximum west-wall irradiance. The results support the use of full-scale monitoring for circular earthen plasters, advancing scientific understanding of circular earthen plasters under Mediterranean exposure and providing applied evidence for their performance-oriented use. Full article

Glyphosate-based herbicides are widely used agricultural chemicals. Concerns regarding carcinogenicity, particularly non-Hodgkin lymphoma (NHL), persist. We conducted a systematic review and meta-analysis to better evaluate glyphosate exposure and NHL risk. MEDLINE and EMBASE were searched for eligible cohort, case–control, and pooled studies. Risk of bias was assessed using recommended criteria. Random- and fixed-effects meta-analyses were performed, with sensitivity analyses addressing overlapping cohorts, hazard ratio inclusion, exposure definitions, and model overfitting. Evidence certainty was graded using GRADE. Ten primary datasets were analyzed. Ever-exposure was associated with an odds ratio of 1.11. Highest-exposure analyses demonstrated a significant association with NHL. Ever-exposure associations were modest, whereas a higher glyphosate exposure was consistently associated with an increased NHL risk. The findings were robust across sensitivity analyses. Full article

Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin’s lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain incompletely understood. Several therapeutic approaches, including topical therapies, conventional systemic drugs (e.g., methotrexate and cyclosporine), and biological agents have been investigated for their potential associations with malignancy risk. However, the available evidence is heterogeneous and influenced by disease severity, treatment duration, cumulative exposure, and patient-related confounding factors. While some epidemiological studies have reported associations between conventional therapies and selected skin or hematological malignancies, combined or sequential treatment regimens further complicate the interpretation of treatment-related cancer risk. Similarly, Janus kinase (JAK) inhibitors have been associated with higher reported rates of lymphoma and non-melanoma skin cancer than tumor necrosis factor α inhibitors (TNFi-α) in some observational studies. Recent studies also highlight the clinical utility of inflammatory markers, specifically the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) ratio, and systemic immune-inflammation index (SII), for monitoring systemic inflammation and treatment response, while certain therapies may additionally influence CVD risk. Despite these advances, substantial heterogeneity across observational studies, meta-analyses, and Mendelian randomization analyses preclude definitive conclusions regarding causality. Overall, this review synthesizes the current epidemiological and mechanistic evidence linking psoriasis, chronic inflammation, therapeutic interventions, cancer risk, and cardiovascular comorbidities, while highlighting the need for large prospective studies and standardized analytical approaches. Full article

Background/Objectives: Intracochlear electrocochleography (ECochG) is increasingly used to monitor cochlear function during cochlear implantation, particularly in patients with residual hearing. However, optimal acquisition parameters and interpretation of intraoperative ECochG patterns remain unclear. To (1) establish optimal stimulation and acquisition parameters for intracochlear ECochG, (2) evaluate the feasibility of signal acquisition in pediatric patients, and (3) characterize intraoperative ECochG response patterns in relation to surgical events. Methods: The study consisted of two phases: an optimization phase (n = 50) and a clinical observational phase (n = 28). In the optimization phase, various stimulation frequencies (500–2000 Hz), recording configurations, and acquisition modes were tested. Based on these findings, a standardized ECochG protocol was developed and applied in the clinical cohort. Results: Optimal ECochG recordings were obtained using 500 Hz and 1500 Hz tone bursts at 100 dB nHL, recorded from the apical electrode contact (ICE22) in continuous mode. In the clinical cohort, ECochG responses were detected in 11/28 patients (39%). Cochlear microphonics were observed even in patients without preoperative evidence of residual hearing. Intraoperative signal fluctuations were temporally associated with specific surgical events, including electrode manipulation and suctioning. Conclusions: Intracochlear ECochG enables real-time monitoring of cochlear function during implantation. However, interpretation of signal changes remains complex and requires standardized protocols as well as careful consideration of the surgical context. Full article

The literature on the qualitative experiences of patients with non-Hodgkin lymphoma (NHL) is limited. Qualitative interviews were conducted to investigate participants’ experiences with two types of NHL (diffuse large B-cell lymphoma [n = 20] and mantle cell lymphoma [n = 10]) and evaluate the comprehensiveness of patient-reported outcome (PRO) measures. Fatigue, tiredness, body aches, night sweats, lethargy, headache, appetite loss, altered taste, and weakness were the most frequent and bothersome symptoms. Key impacts were decreased physical performance, restricted activity, sadness, distress, fear of recurrence, and worry about future. Most participants expressed positive opinions about the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) (n = 22/28), EORTC QLQ-NHL-High Grade Module 29 (EORTC QLQ-NHL-HG29) (n = 12/16), EORTC QLQ-NHL-Low Grade Module 20 (EORTC QLQ-NHL-LG20) (n = 8/12), and Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) (n = 10/14), considering them relevant to their experiences (22/27, 13/15, 9/13, and 10/12, respectively). All measures adequately captured their experiences with NHL (QLQ-C30: n = 26/26, NHL-HG29: n = 14/14, NHL-LG20: n = 11/11, and FACT-Lym: n = 12/13). These findings provide a valuable framework for informing the selection of appropriate PRO measures in NHL clinical trials and identifying potentially meaningful trial endpoints. Full article

The degradation of the natural fibers in the hydraulic binder alkaline matrix is widely known. This study investigates the effect of two fiber treatments, namely immersion in sodium hydroxide (NaOH) solution and hornification, in two types of alkaline environmental ordinary Portland cement (OPC) and a mixture of OPC and natural hydraulic lime (NHL). After curing for 28 days, the specimens were subjected to 25 and 50 dry–wet aging cycles to evaluate their degradation behavior. Subsequently, the specimens underwent flexural and compressive strength tests. This study reveals that the specimens with the mixed binder of ordinary Portland cement (OPC) and natural hydraulic lime (NHL), after 50 aging cycles, reached toughness values in the descending branch compared to the total toughness obtained in the flexural–displacement diagram, of 17% and 27% for the treatment with NaOH and hornification fiber, compared to 3% and 10% obtained for the matrix with an OPC binder. Therefore, the inclusion of NHL as a matrix binder provided better softening behavior than those with only the OPC binder, providing better protection of the fibers against environmental alkalinity due to matrix alkalinity. In addition, the hornification treatment better preserved the fibers throughout the aging process. Full article

Background/Objectives: Granulomatous inflammation in tissue biopsies presents a diagnostic challenge, particularly in differentiating between Mycobacterium tuberculosis complex (MTB) and non-tuberculous mycobacteria (NTM) in high-HIV-prevalence areas. This study evaluates the prevalence and species distribution of mycobacteria in formalin-fixed, paraffin-embedded (FFPE) tissues from patients with granulomatous inflammation and correlates these findings with demographic and clinical data. Methods: Conducted at the NHLS-Dr George Mukhari Tertiary Laboratory, the retrospective descriptive study analysed 37 FFPE samples (January 2019–December 2020) after obtaining ethical approval and collecting clinicopathological data. Histopathological assessments using H&E and Ziehl–Neelsen (ZN) stains were carried out, and mycobacterial species were identified utilising multiplex PCR with reverse hybridisation (GenoType MTBC/CM/AS assays). Results: The cohort had an average age of 38.59 years, with a predominance of females (59.5%) and a high HIV positivity rate (62.2%). The most common biopsy site was lymph nodes (32.4%). All samples exhibited necrotising granulomas, but only 8.1% displayed acid-fast bacilli (AFB) on ZN staining. Molecular testing revealed mycobacterial DNA in 75.7% of samples, identifying NTM alone in 50.0%, MTB alone in 10.7%, and both in 28.6%. M. fortuitum was the most frequently recognised species. Importantly, there was no significant association between mycobacterial detection and HIV status (p > 0.05). Conclusions: The findings demonstrate that molecular methods substantially improve mycobacterial detection rates and speciation. This underscores the diagnostic limitations of ZN staining and highlights the importance of molecular diagnostics for accurately identifying bacterial aetiology, crucial for appropriate antimicrobial therapy in immunocompromised patients. Full article

The article critically examines the emergence of technofeudalism within the European Union’s legal framework, drawing on the theoretical contributions of Yanis Varoufakis, Alfred C. Yen, and Katrina Geddes. We argue that the EU’s historically market-oriented regulatory architecture contributed to conditions that facilitated the rise of dominant technology companies exercising quasi-governance functions over digital environments, extracting value from users while evading meaningful democratic accountability. Our analysis distinguishes between two categories of enabling legislation: structural rules, which govern corporate status, taxation, and market consolidation; and action-oriented rules, which regulate platform behavior, algorithmic governance, consumer relations, and data protection. We demonstrate how fragmented national tax regimes, ineffective merger control, under-regulated algorithms, asymmetric consumer protections, unclear liability frameworks for online content, exploitable private international law mechanisms, and inadequately enforced data protection standards collectively reinforce Big Tech’s dominance. While recent regulatory interventions such as the Digital Services Act and Digital Markets Act represent important steps, they remain embedded in a market-oriented paradigm that insufficiently addresses the broader social, cultural, and democratic implications of platform power. The article concludes by calling for a more coherent, democratically grounded approach to digital regulation—one that moves beyond fragmented, reactive policymaking toward a comprehensive framework capable of strengthening democratic accountability and public oversight within the digital sphere. Full article

Most studies on circular mineral-based materials report short-term mechanical properties without providing predictive frameworks that link chemical degradation to long-term mechanical performance. This study develops and validates a leaching-index-driven chemo-mechanical framework for predicting the degradation of a natural hydraulic lime (NHL)–pozzolan mortar exposed to sulfuric acid. A normalized ionic-release index was used to drive all parameters of a trilinear continuum damage mechanics (CDM) model, enabling the prediction of complete stress–strain responses from leachate chemistry alone. The framework was calibrated using an extensive experimental dataset comprising accelerated acidic exposure at pH 1.5, 2.0, and 3.0 for durations up to 6000 h. Iron release was identified as the most suitable degradation indicator based on its monotonic evolution and strong correlation with mechanical deterioration. Power-law relationships linking the normalized leaching index to elastic modulus, peak strength, transition strain, and post-peak energy were established and validated against independent exposure groups, yielding prediction errors generally below 20%. Validation was performed against three independent blind exposure groups withheld from calibration, yielding mean deviations of approximately 18% in the elastic modulus and 13% in the peak strength, so that the quantitative validation rests on this limited three-group set, whereas the extension to circular mineral binders is presented only on a prospective, non-validated basis. A kinetic sub-model was further introduced to relate exposure conditions to the leaching index, enabling a complete predictive chain from environmental exposure to mechanical response and service-life estimation. Sensitivity analysis showed that post-peak energy dissipation degrades approximately 1.3–1.5 times faster than stiffness and strength, indicating that ductility-related parameters govern long-term reliability. The methodological architecture is further discussed, on a prospective and non-validated basis, in relation to circular mineral binders relevant to Baltic industrial and municipal by-product streams, including municipal-waste bottom ash, slag, fly ash, and recycled glass. Although experimental validation is limited to the NHL–pozzolan system, the proposed framework provides a physically grounded and data-efficient pathway for durability assessment and future durability-oriented design of circular mineral binders in the Baltic region. Full article

Background/Objectives: Relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs) remain a major therapeutic challenge, particularly in patients with aggressive subtypes and limited treatment options after multiple lines of therapy. The ViPOR regimen, a multi-targeted combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide, has demonstrated promising activity in early-phase studies; however, real-world data are limited. Methods: We conducted a retrospective, two-center study including patients with R/R B-NHL treated with the ViPOR regimen between January 2024 and April 2026. Clinical characteristics, treatment responses, survival outcomes, and safety data were analyzed. Results: A total of 14 patients were included, with a median age of 45 years and a median of 3.5 prior lines of therapy. Most patients had advanced-stage disease (71% stage IV), and 36% had primary refractory disease. The interim overall response rate (ORR) was 62%, including 31% complete response (CR) and 31% partial response. At the end of treatment, the ORR was 54%, with a CR rate of 54%. Radiotherapy was incorporated in selected patients with residual disease and contributed to response deepening. Six patients (43%) were successfully bridged to allogeneic stem cell transplantation, all in CR. Responses were notably more favorable in the activated B-cell (ABC) subtype compared to the germinal center subtype. The most common adverse events were neutropenia (57%) and diarrhea (36%), and the regimen demonstrated a manageable safety profile. During follow-up, 57% of patients remained alive. Conclusions: The ViPOR regimen demonstrated promising efficacy and acceptable safety in heavily pretreated R/R B-NHL, particularly in the ABC subtype. Its ability to induce deep responses and enable bridging to allogeneic stem cell transplantation highlights its potential role in real-world clinical practice. Larger prospective studies are warranted to confirm these findings. Full article

Background: Lymphoma is the most common hematologic malignancy diagnosed in active-duty service members (ADSMs). Service members treated for lymphoma often face uncertainty regarding their fitness for duty, which carries implications for individual careers and force readiness. In this retrospective, exploratory study we aimed to (1) determine the proportion of previously deployed ADSMs who deployed after a lymphoma diagnosis, and (2) characterize those deployments. Methods: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) cases diagnosed between 2001 and 2022 were identified from the Defense Health Agency Cancer Registry using International Classification of Diseases for Oncology, Third Edition histology codes. Deployment variables were obtained from the Defense Manpower Data Center. Analysis was restricted to service members who were on active duty at diagnosis and had a history of deployment; those who had never deployed were excluded. This study was exempt from full institutional review board review. Results: A total of 866 previously deployed ADSMs with lymphoma were identified (455 HL, 411 NHL). Of these, 119 (13.7%; 95% CI 11.6–16.2) deployed after their lymphoma diagnosis, including 86 of 455 with HL (18.9%; 95% CI 15.6–22.8) and 33 of 411 with NHL (8.0%; 95% CI 5.8–11.1). HL survivors were significantly more likely than NHL survivors to deploy after diagnosis (p < 0.001). The mean interval from diagnosis to deployment was 5.1 years (SD 3.7) for HL and 4.5 years (SD 2.3) for NHL. As of 2022, all 119 individuals were alive at last follow-up. Conclusions: Among previously deployed ADSMs with lymphoma, roughly one in six deployed after their diagnosis and treatment, typically within five years. These findings indicate that deployment after lymphoma treatment is achievable for a significant subset of service members, highlighting both the success of cancer care in military treatment facilities and the favorable impact of modern oncologic care on operational readiness. Full article