The usefulness of several noninvasive assessments for evaluating liver fibrosis has been reported in Fontan-associated liver disease (FALD). However, no studies have reported on the usefulness of Mac-2 binding protein glycosylation isomer (M2BPGi) in FALD. Here, we investigated the usefulness of M2BPGi in identifying advanced FALD. This retrospective study included patients diagnosed with FALD. Based on the clinical signs of portal hypertension, we defined advanced FALD as a varices, ascites, splenomegaly, and thrombocytopenia (VAST) score ≥ 2, and we compared the cardiac parameters, liver parameters, and serological fibrosis markers, including M2BPGi. The Mann-Whitney U and Fisher exact test were used to compare variables. Spearman rank correlation coefficients (r) were calculated to evaluate correlations. The accuracy of outcome prediction was evaluated using the area under the receiver operating characteristic curve (AUROC). A total of 43 patients with FALD were enrolled. There were 22 cases (51%) diagnosed with advanced FALD. In the serological fibrosis markers, M2BPGi levels were significantly higher in cases with advanced FALD (median 0.65 vs 0.38 cutoff index [C.O.I], P = .003), similar to the fibrosis-4 (FIB-4) index and aspartate aminotransferase (AST) to platelet ratio index (APRI). Receiver operating characteristic analysis revealed that M2BPGi demonstrated moderate ability to predict the cases with advanced FALD (AUROC, 0.767), and the cutoff value was 0.64 C.O.I. Moreover, M2BPGi demonstrated a significant correlation with AST (r = 0.321, P = .036), albumin (r = -0.562, P < .001), FIB-4 index (r = 0.492, P = .001), APRI (r = 0.399, P = .008), and cardiac parameters such as central venous pressure (r = 0.413, P = .006) and brain natriuretic peptide (r = 0.431, P = .004). Esophagogastric varices (31% vs 3%, P = .024) and ascites (69% vs 27%, P = .016) were more prevalent in the higher M2BPGi group. Furthermore, there was a significant trend in increasing M2BPGi with worsening the VAST scores (P = .021). This study suggests that M2BPGi may be useful for identifying advanced FALD.

Myelodysplastic/myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T) is a genetically defined overlap entity integrating morphologic and molecular features. Assessment of ring sideroblasts may be unreliable in fibrotic marrows, creating diagnostic uncertainty under morphology-dependent systems. A 76-year-old man presented in 2021 with anemia, thrombocytosis, and splenomegaly. Bone marrow biopsy showed a hypercellular marrow with atypical megakaryocytic proliferation and MF-2 fibrosis; aspirate was a dry tap, precluding evaluation of ring sideroblasts. Next-generation sequencing identified JAK2 p.V617F (variant allele frequency 6.9%), SF3B1 p.D781G (16.5%), NRAS p.G12D (5.2%) and ASXL1 p.E635Rfs*15 (33%). Although findings strongly suggested MDS/MPN with ring sideroblasts and thrombocytosis, WHO 2017 criteria could not be met. After ruxolitinib therapy, he later developed leukocytosis and 2% circulating blasts. Repeat marrow demonstrated ≥ 15% ring sideroblasts. Retrospectively, the initial biopsy fulfills ICC 2022 criteria for MDS/MPN-SF3B1-T, highlighting the diagnostic value of genetics-integrated classification in fibrotic marrows.

Patients presented with jaundice and splenomegaly are easily diagnosed as having liver diseases. Actually, some atypical cases belong to hemolytic diseases leading to secondary hemochromatosis, which is easily misdiagnosed or never diagnosed. Here, we describe an atypical case in a 27 years old man presenting with unconjugated hyperbilirubinemia and splenomegaly since early childhood, who was hospitalized to check for any possible causes related to liver diseases. However, the probable etiology related to hemolytic diseases and liver disease was ruled out by negative traditional tests, which left a mystery to us. Fortunately, next-generation sequencing is becoming a suitable choice to determine the candidate genes responsible for rare or inherited disorders. A novel de novo mutation (c.5032delA) was firstly identified through whole exome sequencing which could induce an arginine to glycine substitution at residue 1678 (p.R1678Gfs*12), causing a premature termination codon in exon 38 of ANK1. ANK1 is involved in erythrocyte cytoskeleton formation, and contributes to one of the most common causes of hereditary spherocytosis (HS). Besides, homology-modeling analysis confirmed the loss-of-function of frameshift variant of ANK1 with bioinformatics methods. This work adds new knowledge in the etiology of hereditary spherocytosis. In addition, genetic testing can open up new perspectives for atypical and unknown diseases when traditional tests cannot be met.

Visceral leishmaniasis (VL) can present atypically in patients receiving immunosuppressive therapy, closely overlapping with autoimmune disease flares and posing a particular diagnostic challenge in non-endemic settings. We report a 57-year-old woman from Beijing, China, with a 2-year history of systemic lupus erythematosus (SLE) and Sjögren syndrome on long-term hydroxychloroquine and methylprednisolone. She had no known travel to leishmaniasis-endemic regions and no recognised sandfly exposure. She presented with anorexia, vomiting, and intermittent fever, and was found to have splenomegaly, marked hypergammaglobulinaemia (IgG 30.28 g/L), reduced complement C3, and patchy brown hyperpigmentation of all four limbs. Initial blood counts showed progressive pancytopenia (white blood cell count nadir 1.02 × 10[9]/L; haemoglobin 7.9 g/dl; platelets 64 × 10[9]/L). On hospital day 3, blood targeted next-generation sequencing (tNGS, 500+ pathogen panel) detected Leishmania genus at 425,566 specific reads (estimated concentration 10[5] copies/mL); a second tNGS platform identified the species as Leishmania donovani, a positive rK39 test provided serological support, and bone marrow smear subsequently demonstrated Leishmania amastigotes. Following antileishmanial therapy with sodium stibogluconate, systemic symptoms resolved, blood counts recovered, and the limb hyperpigmentation faded substantially. In immunosuppressed patients living in non-endemic areas, VL should be considered when fever, splenomegaly, and cytopenias cannot be fully explained by autoimmune activity. tNGS can deliver rapid pathogen identification when epidemiological clues are absent.

Poor graft function (PGF) is a serious and life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Current therapeutic approaches show suboptimal clinical outcomes, with substantial variability in treatment efficacy across studies, which highlights the critical need for timely identification of PGF and appropriate preventive strategies to improve prognosis. To identify PGF risk factors and establish a nomogram-based predictive model of PGF, this real-world study analyzed 795 hematological malignancies patients underwent allo-HSCT. We identified lower CD34[+] cell dose in the graft, infection, cytomegalovirus activation, splenomegaly and anti-HLA antibody as independent risk factors for PGF. Severe graft-versus-host disease exhibited significant association with secondary PGF in subgroup analysis. Recipients with good graft function demonstrated higher 3-year overall survival (OS) rate compared to PGF cohorts (78.1% vs. 50.6%). Notably, secondary PGF cases exhibited superior 3-year OS relative to primary PGF cases (52.0% vs. 46.2%), and the primary PGF group showed a higher cumulative incidence of NRM than secondary PGF group. Restricted cubic spline analysis demonstrated a dose-dependent relationship between infused stem cell doses and the risk of PGF. Both CD34[+] cell dose and MNC dose showed inverse associations with the predicted probability of PGF. To assess the relative contribution of each covariate to PGF risk stratification, we constructed a predictive model based on the nomogram framework. Ten clinically relevant predictors were incorporated into the model, which demonstrated strong predictive performance and excellent calibration. The model also exhibited robust discriminative capacity (C-statistics = 0.782) and provided meaningful clinical utility. Importantly, this predictive tool facilitates identification of patients at high risk of PGF who could benefit from preventive measures.

Leprosy is a chronic granulomatous disease of the skin, peripheral nerves, and mucosal membranes caused by Mycobacterium leprae. Although curable with multidrug therapy (MDT), relapse, reinfection, or immunologic reactions can occur. Leprosy reactions are abnormal immune responses ranging from type IV hypersensitivity to immune-complex-mediated phenomena, such as erythema nodosum leprosum (ENL). We report a 23-year-old man who completed MDT for multibacillary leprosy 1 year prior and presented with a 2-week history of tender, erythematous subcutaneous nodules, systemic symptoms, and pre-existing hypopigmented patches. Imaging revealed lymphadenopathy and splenomegaly, suggesting systemic inflammation. Biopsies showed granulomatous collections of epithelioid to foamy histiocytes centered on dermal nerve bundles and adnexal structures, with focal early vasculitic changes and scattered neutrophils. Fite-Faraco staining demonstrated numerous weakly acid-fast bacilli. These findings were consistent with leprosy relapse and concurrent ENL. Treatment was initiated with monthly rifampin, moxifloxacin, and minocycline (RMM), alongside methotrexate and prednisone. This case highlights an unusual presentation of leprosy relapse with concurrent ENL following completion of MDT. Ongoing surveillance and follow-up are essential to monitor for relapse, reinfection, and reactions, particularly in high-risk patients.

Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, constitutional symptoms, cytopenias, and splenomegaly. Splenic enlargement, driven primarily by extramedullary hematopoiesis, represents a hallmark of MF and contributes substantially to symptom burden, portal hypertension, and worsening cytopenias through splenic sequestration. The identification of constitutive Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway activation as the central pathogenic mechanism in myeloproliferative neoplasms led to the development of JAK inhibitors, which have become the cornerstone of therapy for spleen volume reduction and symptom amelioration. Four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, and momelotinib-are currently approved by regulatory agencies, each exhibiting distinct pharmacological profiles suited to different clinical phenotypes. Ruxolitinib remains the first-line standard for patients with adequate platelet counts, pacritinib is preferred in severe thrombocytopenia, and momelotinib is the agent of choice in anemia-dominant disease. Fedratinib serves as an effective second-line option following ruxolitinib failure. Emerging combination strategies, including pelabresib plus ruxolitinib and navitoclax plus ruxolitinib, have demonstrated superior spleen volume reduction in phase III trials and represent a promising therapeutic frontier. Conventional agents such as hydroxyurea and immunomodulatory drugs retain a role in select patients. Non-pharmacologic interventions-including splenectomy, splenic irradiation, partial splenic artery embolization, and radiofrequency ablation-remain valuable for patients refractory to or ineligible for medical therapy. This review provides a comprehensive and updated overview of the management of splenomegaly in MF, integrating all four approved JAK inhibitors, emerging combination therapies, peri-transplant considerations, and procedural approaches, and proposes a practical phenotype-driven treatment framework.

Hypersplenism in adults with homozygous sickle cell disease (HbSS) is rare, as most patients undergo autosplenectomy during early childhood. However, phenotypic variants such as high fetal hemoglobin, coexisting hemoglobinopathies, and different globin gene haplotypes can lead to splenic preservation and altered disease progression. These patients often exhibit milder symptoms, delayed complications, and increased morbidity. We report a rare case of a 43-year-old female with HbSS and elevated fetal hemoglobin who presented with hypersplenism, characterized by massive splenomegaly, pancytopenia, and compensatory bone marrow proliferation. She underwent an open splenectomy with an uneventful postoperative course. This case highlights the importance of recognizing atypical presentations in adult patients with sickle cell disease, in whom splenomegaly may persist. Clinicians should maintain a high index of suspicion to facilitate timely diagnosis and appropriate management, which can significantly improve patient outcomes.