We report a 14-year-old girl presenting with flank pain, microscopic haematuria, and polycythaemia. Imaging demonstrated a well-defined upper pole renal mass with minimal enhancement, while image-guided biopsy suggested metanephric adenoma but remained inconclusive. She underwent open partial nephrectomy, and histopathology confirmed metanephric adenoma despite atypical immunohistochemistry. Postoperative recovery was uneventful with preserved renal function, and polycythaemia resolved completely. This case highlights the diagnostic challenges of differentiating benign from malignant renal tumours in young patients and supports nephron-sparing surgery as an effective management approach.

Treatment for the classical Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET), has long relied on reducing thrombotic risk without a focus on underlying disease modification. The simplified framework of age and thrombosis history inadequately captures the biological complexity of these diseases with emerging data identifying leukocytosis, elevated neutrophil-to-lymphocyte ratio, and high JAK2 V617F variant allele frequency as independent predictors of thrombotic risk. Furthermore, prognostic models such as MIPSS-PV and MIPSS-ET incorporate somatic mutations to better predict survival. Despite these advances, real-world practice remains anchored to traditional risk categories, with over 30% of high-risk patients receiving no cytoreductive therapy. In this evidence-based review, we trace the evolution of risk stratification in PV and ET and examine the clinical evidence supporting current cytoreductive options, specifically hydroxyurea, interferons, ruxolitinib, and anagrelide. We argue for a paradigm shift away from binarily driven thrombosis-centric risk stratification toward a personalized, proactive approach that integrates molecular and inflammatory biomarkers, expands the population offered cytoreduction, and prioritizes disease-modifying therapies. Prospective studies are needed to validate the incorporation of these markers into risk-adapted algorithms and to define the long-term impact of early disease modification on transformation, survival, and quality of life.

Pruritus might be a debilitating symptom in myeloproliferative neoplasms (MPN). Since mast cells (MC) play a pivotal role, we hypothesized that bone marrow (BM) MC contribute to the cause of pruritus. In this exploratory study, untreated MPN patients were included. BM aspirate/biopsy/blood and MPN-SAF questionnaires were obtained. Thirty-two patients were included (Essential Thrombocythemia n=19, Polycythemia Vera n=7 and Primary Myelofibrosis n=6). Eleven had clinically significant pruritus (35%). The absolute MC count and proportion/total nucleated BM-cells were significantly higher in patients with pruritus compared to those without (mean 25.5 vs. 58.1 MC/mm2, p 0.032, and 0.59 vs 1.66%, p 0.041, respectively). The MC immunophenotype and serum levels of tryptase, IL-6, TNF-α and sCD117 were not correlated. The absolute and relative MC numbers are increased MPN patients with pruritus. Whether MC play a pathophysiological role in causing pruritus, or are bystanders remains to be determined.

Hypoxia is a prevalent pathophysiological condition. Prolonged exposure to hypobaric hypoxia can lead to maladaptation, increasing the risk of chronic hypoxic diseases such as high-altitude polycythemia (HAPC). Dauricine, an alkaloid derived from the root of Menispermum dauricum DC, has been demonstrated to possess anti-hypoxic properties; however, its underlying molecular mechanisms remain elusive. In this study, a potential multi-target anti-hypoxic mechanism of dauricine was proposed and computationally evaluated using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulations. Common targets between dauricine and hypoxia-related genes were identified through network pharmacology screening. A protein-protein interaction (PPI) network was constructed to identify core targets, followed by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Molecular docking was subsequently employed to evaluate the binding affinities between dauricine and the candidate core targets, while molecular dynamics simulations were performed to assess the dynamic stability of the resulting complexes. Additionally, the drug-likeness and safety profiles of dauricine were assessed. The results suggest that dauricine may exert its anti-hypoxic effects by modulating candidate core targets, including ESR1, PIK3CA, and MTOR, and by acting on key signaling pathways such as PI3K-Akt, MAPK, and mTOR. This study provides a theoretical foundation for the further investigation of dauricine as a multi-target candidate for intervention in hypoxia and establishes a bioinformatics basis for subsequent experimental validation.

Background: The detection of JAK2 exon 12 mutations is important for the differential diagnosis of myeloproliferative neoplasms (MPN) and is included in the World Health Organization's diagnostic criteria for polycythemia vera (PV). We developed and evaluated a pyrosequencing-based technique to detect somatic mutations in JAK2 exon 12 and tested the method in a group of PV patients. Methods: PCR and pyrosequencing primers were designed for region JAK2 exon 12; PCR conditions were optimized for subsequent qualitative and quantitative detection by pyrosequencing. Diagnostic specificity and sensitivity were determined using plasmid controls. Genomic DNA from 145 MPN patients was used to validate the method. Results: The analytical characteristics of the method were as follows: the limit of blank was 1.2-7.4% and the limit of detection was 3.4-9.9% depending on mutation type. DNA samples from Russian patients with clinical evidence of MPNs were analyzed. In 7 of 145 cases (4.8%) JAK2 exon 12 mutations were detected. One patient had the mutation I540-E543insdelTCAGAAATG<AAA. The A-homopolimer insertion in this complex mutation type could not be clearly identified by pyrosequencing, and Sanger confirmation was required. For another patient with N542-E543delAATGAA mutation, we observed the mutant allele burden growing from 15 to 55% between 2014 and 2018 and further reduction during treatment to 11%. Conclusions: The developed pyrosequencing-based method presents a simple solution to qualitative and quantitative JAK2 exon 12 mutations detection. However, some complex mutation types may require manual interpretation and Sanger confirmation.

Polycythemia is a condition with abnormal increase in red blood cell mass and number in circulation. Increased attenuation with diffuse involvement of Circle of Willis and cerebral venous sinuses mimicking a contrast enhanced study is one of the early noncontrast CT findings in polycythemia. It can mimic venous sinus thrombosis which is its complication and thus warrants further imaging studies. Further imaging studies are needed for the dense vessel appearance in NCCT where the CT number is above a threshold value.

BackgroundNeutrophil extracellular trap (NET) formation has emerged as a key driver of thrombosis in myeloproliferative neoplasms (MPNs). Its role in congenital bleeding disorders, however, remains unexplored.ObjectivesTo investigate circulating citrullinated histone H3 (cit-H3), a marker of NETosis, in thrombosis-prone MPNs and bleeding-prone severe hemophilia A.MethodsIn a cross-sectional study, plasma cit-H3 was quantified by ELISA in patients with JAK2-mutated polycythemia vera or essential thrombocythemia, patients with severe hemophilia A, and matched healthy controls. Clinical and laboratory data were analyzed for associations with cit-H3 levels.ResultsEighty-nine participants were included: 26 with myeloproliferative neoplasms (MPNs), 31 with severe hemophilia A, and 32 healthy controls. Demographic characteristics were comparable across groups, though comorbidities were more frequent in MPNs. Laboratory analyses confirmed expected disease-specific differences, including elevated leukocyte, neutrophil, and platelet counts in MPNs and prolonged activated partial thromboplastin time in hemophilia A. Circulating citrullinated histone H3 (cit-H3) levels differed significantly among groups (p < 0.001), being lowest in controls, intermediate in MPNs, and highest in hemophilia A. Within disease groups, cit-H3 levels were unaffected by clinical variables such as MPN subtype, aspirin use, phlebotomy history, or factor replacement regimen.ConclusionsElevated circulating cit-H3 levels, suggestive of increased NETosis activity, were observed in both thrombosis-prone MPNs and bleeding-prone hemophilia A. These exploratory findings suggest a possible association between NET formation and thromboinflammatory processes across distinct hemostatic disorders.

Budd-Chiari syndrome (BCS) is a rare hepatic vascular disorder frequently associated with prothrombotic conditions such as myeloproliferative neoplasms. Pregnancy and assisted reproductive technologies further increase thrombotic and portal-hypertensive risk. We report a successful in vitro fertilization-conceived pregnancy in a 35-year-old woman with chronic BCS secondary to JAK2-positive polycythemia vera. The pregnancy was complicated by ovarian hyperstimulation syndrome and severe intrahepatic cholestasis of pregnancy. Progressive portal hypertension with worsening esophageal varices prompted planned preterm delivery at 34 weeks' gestation. A multidisciplinary team performed cesarean delivery under epidural anesthesia with prophylactic perioperative terlipressin administration and thromboprophylaxis. Maternal and neonatal outcomes were favorable. With careful multidisciplinary management, pregnancy in women with stable BCS is feasible.