Classic myeloproliferative neoplasms, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are chronic, clonal hematopoietic stem-cell disorders. These disorders are driven by gain-of-function mutations in the genes Janus kinase 2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (MPL) that activate cytokine signaling. These mutations arise decades before clinical disease develops and confer a clonal advantage that is further shaped by comutations in epigenetic, splicing, or signaling genes. Inflammation enhances clonal dominance, favoring the development of myelofibrosis and thrombotic complications. Disease evolution may culminate in secondary acute myeloid leukemia, which has a poor prognosis. Current therapies primarily aim to control symptoms, thrombosis, and splenomegaly, but they have limited disease-modifying effects, except for pegylated interferon alfa and JAK2 inhibitors in some patients. Emerging therapies that selectively target mutant CALR and JAK2 V617F using immunotherapy and selective inhibitors could be a breakthrough in the treatment of persons with myeloproliferative neoplasms, with the expectation of achieving durable disease modification and potentially clonal eradication.

The limited efficacy and tolerability of interferon (IFN)-based therapies make refining patient selection a critical step towards achieving a functional cure in chronic hepatitis B (CHB). The novel GOLDEN model, based on sequential changes in quantitative HBsAg (qHBsAg), accurately predicts hepatitis B surface antigen (HBsAg) loss in patients with CHB receiving nucleos(t)ide analogue (NA) therapy. However, it remains unvalidated in patients receiving sequential pegylated IFN α-2b (Peg-IFN α-2b)-based therapy. We aim to validate the GOLDEN model and the optimised cut-off value for the predictive index (Pi) to prospectively identify optimal candidates for clinical cure among patients receiving sequential Peg-IFN α-2b therapy using pre-IFN treatment qHBsAg kinetics across multiple centres.

Background Malignant melanoma (MM) arises from melanocytes, and vitiligo is an autoimmune condition targeting these cells. Although an association between MM and vitiligo has been proposed, underlying mechanisms remain unclear. Because several melanoma treatments modulate immune responses, this study evaluated the relationship between MM and vitiligo across commonly used systemic therapies. Methods In September 2025, using the TriNetX network, patients with MM receiving programmed cell death protein 1 (PD-1) inhibitors, interferon alpha-2b (IFN-α2b), B-Raf serine/threonine kinases (BRAF)/ mitogen-activated protein kinase kinases (MEK) inhibitors, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors were identified and 1:1 propensity score-matched to patients without MM receiving the same therapy. Demographics and vitiligo incidence were analyzed using risk ratios (RRs) and 95% confidence intervals (CIs) via Wald's method. Counts <10 were suppressed per platform guidelines. Results Baseline demographics were well balanced between MM and matched non-MM patients. MM was significantly associated with higher vitiligo risk among those treated with PD-1 inhibitors (RR: 24.84; 95% CI: 16.92-36.45), IFN-α2b (RR: 3.10; 95% CI: 1.53-6.30), and CTLA-4 inhibitors (RR: 32.04; 95% CI: 18.05-56.88). In the BRAF/MEK cohort, vitiligo occurred only in patients with MM, preventing RR calculation. Conclusions Across multiple therapeutic classes, MM consistently conferred a greater risk of developing vitiligo compared with matched non-MM patients. The strong associations observed with immune-modulating agents support vitiligo as a potential marker of antitumor immune activation rather than a coincidental adverse event. Even rare cases in BRAF/MEK-treated patients suggest that targeted therapy may also influence melanocyte-directed immunity. Further prospective studies are needed to characterize the clinical and immunologic significance of treatment-associated vitiligo.

Hepatitis D is common among immigrants in Canada, who account for approximately 23% of the population and tend to originate from high-endemic countries. Mortality rates are notably high among those with chronic infections, and immigrants are less likely to engage in screening and treatment services. This paper aims to assess the cost-utility of screening and treating Hepatitis D Virus (HDV)-positive immigrants in Canada compared with a scenario in which no screening is conducted. This analysis takes a public-payer perspective, uses a lifetime time horizon with a 1.5% annual discount rate, and expresses costs in 2023 Canadian dollars. A state-transition model representing the natural progression of chronic hepatitis B and hepatitis D was developed in TreeAge Pro and mapped onto three interventions: screening and treatment with bulevirtide; screening and treatment with pegylated interferon alfa-2a; and screening and treatment with both bulevirtide and pegylated interferon alfa-2a. The analysis was conducted in accordance with the guidelines of Canada's Drug Agency. The incremental cost-effectiveness ratio (ICER) was estimated for each intervention. Model sensitivity was performed using both univariate and probabilistic sensitivity analyses. All screening and treatment strategies resulted in a reduction in cases of decompensated cirrhosis, hepatocellular carcinoma and liver death, with combination therapy demonstrating the most favourable outcomes. Nevertheless, HDV screening and treatment with pegylated interferon alfa-2a monotherapy was the only cost-effective strategy (ICER: $23,177/QALY). While monotherapy with pegylated interferon alfa-2a proved cost-effective, combination therapy with bulevirtide is likely more clinically effective and may be cost-effective if treatment costs decrease significantly.

Therapeutic phlebotomy maintains hematocrit (Hct) <45% in patients with polycythemia vera (PV) and reduces thrombotic risks. However, frequent phlebotomy can induce iron deficiency. Ropeginterferon alfa-2b (ropeg) is a new-generation interferon therapy that induces durable complete hematologic and molecular responses through reduction of the Janus kinase 2 (JAK2)-mutated clone. Two dosing regimens have been investigated: the FDA-approved slow-titration regimen and a higher initial dose and accelerated titration (HIDAT) regimen. A cross-analysis of three prospective trials showed that ropeg achieved sustained Hct control and reduction of phlebotomy dependence in PV patients, including high-risk and hydroxyurea-resistant/intolerant patients. In exploratory cross-study comparisons, the HIDAT regimen was associated with more rapid phlebotomy-free Hct response rates, lower mean annualized phlebotomy frequency, higher overall hematologic response rates and deeper JAK2V617F allele burden reduction than slow titration. Both regimens were safe and well tolerated. Ropeg treatment provides durable Hct control and phlebotomy-independence in a broad PV population, including high-risk patients.

Chronic hepatitis delta is the most aggressive form of chronic viral hepatitis. Although pegylated interferon alfa (PegIFNα) has been the reference treatment for decades, the recent introduction of bulevirtide raises questions about its current role. To evaluate our real-world experience with PegIFNα, we conducted an observational, retrospective, single-centre study including patients with chronic hepatitis delta virus infection followed between 2014 and 2026. Fifteen patients were included, of whom 8 received PegIFNα. Toxicity was common, mainly due to haematological adverse effects, although flu-like symptoms and one serious neuropsychiatric event were also recorded. Of seven patients who completed treatment, two achieved a sustained virological response. Both patients also achieved HBV functional cure, being the only patients in the cohort to reach this endpoint. Our results confirm the considerable toxicity and limited efficacy of PegIFNα, but also its capacity to induce a sustained virological response and HBV functional cure in a subgroup of patients. In the bulevirtide era, PegIFNα remains a valid treatment option in selected patients given its curative potential.

HIV cure remains one of the major unsolved global health challenges. The persistence of the HIV reservoir is the key barrier to achieving viral eradication. The acute HIV infection (AHI) is crucial for reservoir establishment, making early intervention essential for long-term viral remission. Pegylated interferon-α (Peg-IFN-α) exhibits potent antiviral and immunomodulatory properties that may enhance reservoir clearance when combined with antiretroviral therapy (ART). This study aims to evaluate the efficacy and safety of Peg-IFN-α combined with ART in promoting reservoir reduction and immune reconstitution in individuals with AHI.

Chronic hepatitis B virus (HBV) infection remains a major global health concern due to the limited availability of curative treatment options. In this study, we investigate both analytically and numerically a spatiotemporal mathematical model of HBV infection incorporating pharmacological effects. The model consists of a system of three partial differential equations describing the dynamics and interactions between healthy hepatocytes (S), infected cells (I) and free viral particles (V). The model also considers spatial diffusion and dual-drug treatment of lamivudine and pegylated interferon alfa-2b (PEG-IFN alfa-2b). A general analytical expression is derived to determine the minimal drug dose required to effectively suppress viral replication and eliminate the infection. The basic reproduction number ([Formula: see text]) is calculated as a function of drug effectiveness and model parameters. To illustrate the relevance of the model, we apply it to clinical data from two HBV infected patients undergoing different therapeutic regimens. The first patient received 200 mg daily of lamivudine, while the second was treated with 200 mg of lamivudine daily and 0.2 mg weekly of PEG-IFN alfa-2b. Using nonlinear least squares, we fit the model to clinical data and estimate relevant parameters. In the absence of treatment, we find [Formula: see text]. Pharmacodynamic results show that after 4 weeks, the first patient experienced a [Formula: see text] copies/ml viral decline (64% effectiveness), while the second exhibited a [Formula: see text] copies/ml decline (69% and 64% effectiveness for PEG-IFN alfa-2b and lamivudine, respectively), corresponding to basic reproduction numbers of 185 and 58, respectively. To achieve sustained viral suppression ([Formula: see text]), we optimize the therapies. Lamivudine alone requires 99% effectiveness, which corresponds to a minimum dose of 565.92 mg daily over 350 days. For combination therapy, a PEG-IFN alfa-2b efficacy of 69% and lamivudine efficacy of 94.36% are sufficient to reach [Formula: see text] after 315 days. A Turing instability analysis reveals the emergence of diffusion-driven instabilities and allows the identification of a critical Turing wave number [Formula: see text]. Numerical simulations confirm the analytical predictions and show the formation of circular patterns. These patterns have been identified as having promising diagnostic and therapeutic value. Under treatment, the model predicts a progressive disappearance of infected patterns and a return toward spatial homogeneity. These findings highlight the crucial role of mathematical modeling in refining HBV treatment protocols and provide valuable insights for optimizing antiviral strategies.