Methods in molecular biology (Clifton, N.J.)Nadia Nasir, Maryalice Stetler-Stevenson, Hao-Wei Wang
Flow cytometry is the cornerstone for establishing the diagnosis of chronic lymphocytic leukemia (CLL), owing to its characteristic and well-defined immunophenotype that enables accurate distinction from other leukemias and lymphomas. Beyond diagnosis, flow cytometry provides essential prognostic information and allows sensitive detection of minimal residual disease (MRD), a strong predictor of clinical outcome. CLL MRD assessment is increasingly used to guide risk stratification, therapeutic decision-making, and treatment duration in the era of targeted therapies and immunotherapies. This chapter reviews best practices for specimen collection, processing, staining, and data analysis and summarizes the principles of flow cytometric MRD assessment in CLL.
Methods in molecular biology (Clifton, N.J.)Dana Delgado, Jolene L Cardinali, Joseph A DiGiuseppe
Immunophenotyping by flow cytometry is an important component in the diagnostic evaluation of patients with acute lymphoblastic leukemia. This technique further permits the detection of minimal residual disease after therapy, a robust prognostic factor that may guide individualized treatment. We describe here laboratory methods for both the initial characterization of lymphoblasts at diagnosis and the detection of rare leukemic lymphoblasts after treatment. In addition to antibody combinations suitable for diagnosis and detection of minimal residual disease, we describe procedures for peripheral blood and bone marrow sample preparation, procedures for labeling of cell-surface and intracellular proteins with fluorochrome-conjugated antibodies, and approaches to analysis of immunophenotypic data, including those obtained in patients following CD19-targeted therapies.
Methods in molecular biology (Clifton, N.J.)Pallavi Kanwar Galera, Raul Braylan
Immunophenotyping by multiparameter flow cytometry is a rapid and efficient technique to simultaneously assess and correlate multiple individual cell properties like size and internal complexity along with antigen expression in a population of cells. This method is utilized for rapid characterization of the blasts and classification of acute myeloid leukemia (AML) in both the peripheral blood (PB) and bone marrow (BM). This technique is not only useful in the initial diagnosis but also in monitoring and determining the prognosis of the disease through minimal residual disease (MRD) testing. This chapter provides an overview of procedures for specimen processing, staining, and immunophenotyping of AML and describes the principles of data analysis for AML classification and MRD testing.
Methods in molecular biology (Clifton, N.J.)Prashant R Tembhare, Nilesh Deshpande, Sitaram Ghogale
Measurable residual disease (MRD) serves as a critical biomarker of prognosis, treatment efficacy, and clinical outcome. It captures the presence of residual tumor cells below the detection threshold of conventional microscopy. Multiparametric flow cytometry (MFC) offers a rapid, cost-efficient, and widely applicable platform for MRD detection through leukemia-associated immunophenotypes (LAIPs) and deviation-from-normal (DfN) antigen maturation patterns. This technique underpins a wide range of clinical applications, including risk stratification, therapeutic decision-making, and post-transplant surveillance. This chapter outlines essential technical parameters for achieving high-sensitivity MRD detection across hematologic malignancies such as B-ALL, T-ALL, AML, MM, and CLL. Key topics covered include material required, reagent preparation, antibody panel design, sample processing and acquisition, gating strategies, and illustrative examples. Special emphasis is given to adaptations necessary for MRD monitoring following CD19-targeted therapies in B-ALL. By integrating rigorous methodology with evolving innovations, MFC continues to advance as a precise and expedient tool for MRD assessment, contributing significantly to personalized treatment strategies.
Journal of the peripheral nervous system : JPNSRuby F Ross, Jennifer A Langsdorf, Norman Latov
BACKGROUND AND AIMS: Chronic inflammatory demyelinating neuropathy (CIDP) is a rare, immune-mediated neuropathy that is distinct from other immune-mediated, paraneoplastic, and paraproteinemic neuropathies that may have overlapping clinical features. Identification of the specific diagnosis in each patient is important as each of these disorders has distinct pathophysiology and treatment response. CASE REPORT: Here, we present an atypical case of CIDP in which the patient developed an IgM monoclonal gammopathy with positive anti-ganglioside antibodies over 20 years into his disease course. INTERPRETATION: Patients with CIDP may be predisposed to develop IgM autoantibodies or monoclonal gammopathies. If a patient with CIDP experiences clinical worsening while on maintenance therapy, it may be helpful to test for anti-ganglioside antibodies and monoclonal gammopathies and reassess if alternative treatment would be useful.
Hematological oncologyElisa Suter, Martina Bertschinger, Inna Shaforostova, Marie-Noelle Kronig, Henning Nilius, Ulrike Bacher, Katja Seipel, Thomas Pabst
Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) is a highly effective treatment option for patients with relapsed refractory multiple myeloma (RRMM). However, reliable biomarkers predicting long-term treatment response remain elusive. Germline single-nucleotide polymorphisms (SNPs) in immune checkpoint regulators, including cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and lymphocyte activation gene 3 (LAG3) may affect CAR T-cell functionality and clinical efficacy. We conducted a retrospective analysis of 87 patients with RRMM treated with BCMA-directed CAR T-cells at a single academic center between May 2021 and September 2025, evaluating the impact of CTLA4 rs231775 and LAG3 rs870849 on relapse, progression-free survival (PFS), and overall survival (OS). The minor allele rs231775 of CTLA4 was present in 48%, while the minor allele of LAG3 rs870849 was observed in 87% of patients. Carriers of the CTLA4 rs231775 minor allele demonstrated lower relapse (40 vs. 53%) and mortality rates (31 vs. 44%) compared with major allele homozygotes, accompanied by significantly prolonged PFS and OS. Likewise, patients homozygous for the LAG3 rs870849 minor allele experienced reduced relapse (36 vs. 52%) and mortality rates (28 vs. 42%), significantly longer PFS, and a trend toward improved OS relative to carriers of the major allele. In conclusion, in our study, the minor alleles of CTLA4 rs231775 and LAG3 rs870849 were associated with superior clinical outcomes following BCMA-directed CAR T-cell therapy in RRMM patients. These findings suggest to further evaluate whether immune checkpoint SNPs could be biomarkers predicting response to BCMA-directed CAR T-cell therapy in MM which needs prospective studies and validation.
Pakistan journal of pharmaceutical sciencesYe Hui, Cao Lingli, Wang Hangsai, Panhuiying Panhuiying
BACKGROUND: Chemotherapy-induced leukopenia is a common dose-limiting toxicity that compromises treatment continuity and increases the risk of infection. Current pharmacological interventions are often associated with adverse effects, highlighting the need for safe and effective supportive strategies. Guiqi crucian carp decoction (GQCCD), a traditional dietary therapy derived from the concept of medicine-food homology, has been used to replenish qi and nourish blood; however, its hematopoietic protective effects have not been systematically evaluated. OBJECTIVES: This study aimed to investigate the hematopoietic and immunoprotective effects of GQCCD in a rat model of chemotherapy-induced leukopenia. METHODS: A leukopenia model was established in rats using 5-fluorouracil (5-FU). Rats were divided into a blank control group, model group, positive control group (batyl alcohol) and GQCCD-treated group. Peripheral blood parameters, including white blood cell (WBC), neutrophil (NE UT), lymphocyte (LYMPH) and monocyte (MONO) counts, were measured at different time points. Thymus and spleen indices were calculated and histopathological examinations of bone marrow, spleen and thymus were performed. RESULTS: 5-FU administration induced significant leukopenia, accompanied by reduced thymus and spleen indices and marked histopathological damage in immune organs and bone marrow. Compared with the model group, GQCCD treatment significantly increased WBC and NEUT counts and MONO percentage (P < 0.01), along with significant improvements in thymus and spleen indices (P < 0.01). Histopathological analysis revealed substantial restoration of bone marrow and immune organ structures. No statistically significant improvement in LYMPH counts was observed. CONCLUSION: GQCCD effectively alleviated chemotherapy-induced leukopenia in rats by restoring peripheral blood parameters, improving immune organ indices and ameliorating bone marrow and immune organ damage. These findings support the potential of GQCCD as a complementary dietary therapy for managing chemotherapy-related myelosuppression.
Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm with a high risk of leukemic transformation. Alternative polyadenylation (APA) is an important post-transcriptional mechanism, and its dysregulation is closely linked to the pathogenesis of hematological malignancies. This study aimed to clarify the regulatory role of the NUDT21-APA-SRSF2 axis in the progression of myelodysplastic syndrome (MDS). To this end, we established MDS cell models overexpressing or knocking down NUDT21 and SRSF2. The regulatory mechanism and functional impacts of this axis were systematically evaluated using RT-qPCR, Western blot, CCK-8 assay and flow cytometry; APA site analysis mediated by specific primers and transcriptome sequencing. The results showed that the expression of NUDT21 was negatively correlated with that of SRSF2 (p < 0.05). Overexpression of NUDT21 promoted the utilisation of distal polyadenylation sites on SRSF2, increasing the expression of its long 3'UTR variants; conversely, NUDT21 knockdown produced the opposite effect (p < 0.05). Functionally, NUDT21 enhanced MDS cell proliferation and inhibited apoptosis, though this effect was reversed by co-overexpression of SRSF2. Furthermore, SRSF2 could antagonize the regulatory effect of NUDT21 on the cell cycle. In summary, our in vitro data demonstrate that NUDT21 remodels SRSF2 isoform balance via alternative polyadenylation (APA) and regulates biological functions of MDS-derived cells. The NUDT21-APA-SRSF2 axis represents a key regulatory cascade with potential therapeutic implications.
Bioscience reportsShaopeng Sun, Jiabin Pan, Ning Zhang, Xianghong Jin, Tie-Nan Zhu, Zhijie Kang, Jihong Hao, Xiang-Dong Li
MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9 gene, which encodes the heavy chain of nonmuscle myosin IIA. Nearly all MYH9-RD patients present with macrothrombocytopenia, characterized by decreased platelet count and increased platelet size. In the present study, we collected blood samples from three MYH9-RD patients (R702S, D1424N, and R1464C) and unexpectedly found that the actin levels in the red blood cells (RBCs) from all three MYH9-RD patients are substantially lower than the healthy controls. We further revealed that the levels of two RBC membrane skeleton proteins, α-spectrin and tropomodulin, are also reduced in MYH9-RD RBCs. We showed that the membrane skeleton of MYH9-RD RBCs was more porous and that MYH9-RD RBCs produced more severe deformation under hyperosmotic pressure compared with healthy controls. We propose that defects in the membrane-skeleton network of RBCs may be an abnormal manifestation of MYH9-RD.
Biochemia medicaEmanuele Maria Coimbra Souza, Caroline Pereira Domingueti
INTRODUCTION: Concentration of glycated hemoglobin (HbA1c) may be influenced by different types of anemia. This systematic review and meta-analysis aimed to evaluate the effect of iron deficiency anemia (IDA) and latent iron deficiency (LID) on HbA1c concentrations. MATERIALS AND METHODS: A search was conducted in Medline/PubMed, Web of Science, Embase, and LILACS up to May 2026. Eligible studies included cross-sectional, cohort, case-control, non-randomized intervention studies and clinical trials assessing the impact of IDA or LID on HbA1c concentrations. Methodological quality was evaluated using the ROBINS-I V2 tool for intervention studies and the Newcastle-Ottawa Scale for cross-sectional studies. Meta-analyses were performed using Review Manager 5 (The Cochrane Collaboration, Copenhagen, Denmark). RESULTS: Among 43 studies evaluating IDA, 33 reported falsely elevated HbA1c concentrations. Of six studies assessing LID, two observed increased HbA1c concentrations. All four studies evaluating iron deficiency regardless of anemia status found elevated HbA1c. Among 19 intervention studies, 14 showed a reduction in HbA1c following iron supplementation. Meta-analyses including 30 studies confirmed increased HbA1c concentrations in patients with IDA (0.66% (0.31 to 1.00) or 7.21 mmol/mol (3.39 to 10.93), P < 0.001). Meta-analysis of four studies verified increased HbA1c in individuals with LID (0.66% (0.01 to 1.32) or 7.21 mmol/mol (0.11 to 14.43), P = 0.05). Meta-analysis of 14 intervention studies demonstrated a reduction in HbA1c following iron therapy (- 0.50% (- 0.92 to - 0.09) or 5.46 mmol/mol (- 10.05 to - 0.98), P = 0.02). Heterogeneity was mainly related to HbA1c assay methods and diagnostic criteria for anemia and iron deficiency. CONCLUSIONS: Iron deficiency anemia interferes with HbA1c measurement, leading to falsely elevated values, while LID may also increase HbA1c concentrations.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyKateřina Wolfová, Petra Otevřelová, Barbora Brodská
Acute myeloid leukemia (AML) is a heterogeneous disease with large spectrum of specific mutations and gene aberrations. Recently, the Bcl-2 inhibitor Venetoclax, in combination with hypomethylating agents (HMAs), was approved for older (> 65 years) AML patients, as well as for those unfit for intensive induction chemotherapy. In addition to Bcl-2 inhibition, Venetoclax also induces generation of reactive oxygen species (ROS). We demonstrated that distinct fraction exhibiting specific features arises during 24 h of sample exposure to Venetoclax. This fraction displays characteristic preapoptotic markers as mitochondria depolarization and partial Annexin V surface positivity. Moreover, monitoring of ROS showed negative correlation between signals detected using H2DCFDA and CellROX probes pointing to dynamic ROS changes induced by Venetoclax. The addition of HMA (Decitabine) had almost no effect on cell viability or ROS production but caused proliferation arrest in sensitive cells. In our panel of AML cell lines and primary AML samples we have found a correlation between ROS production, markers of apoptosis, and attenuation of Bcl-2 activity after Venetoclax treatment. Level of Mcl-1, another antiapoptotic protein from the Bcl-2 family, was reduced in sensitive cells, but increased in the resistant samples in response to Venetoclax. Moreover, the nucleolar protein nucleolin (NCL), which is frequently overexpressed in AML cells, was significantly deregulated in Venetoclax-treated cells. In particular, both NCL protein level and specific phosphorylation decreased in fractions sensitive to Venetoclax. Our findings suggest that Venetoclax targets distinct cell subpopulation, and that ability of a cell to follow increased ROS drives its response to Venetoclax.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsYujie Zhou, Xuelian Zhao, Xu Wang, Teng Hao, Shuaquan Li, Xiaojing Yao, Na'na Li, Wentao Zang, Xige Wang, Erfeng Yuan, Sibao Li
OBJECTIVE: To summarize the early recognition clues, genetic characteristics, and short-term outcomes of children with Diamond-Blackfan anemia (DBA) in order to provide a reference for the differential diagnosis of severe anemia in early infancy. METHODS: A retrospective analysis was conducted on 11 children clinically diagnosed with DBA at the Department of Pediatric Hematology of the Third Affiliated Hospital of Zhengzhou University between May 2020 and December 2024. Their general condition, initial presentation, associated phenotypes, lab and bone marrow examination results, genetic testing results, treatment methods, and follow-up outcomes were collected and analyzed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2026-056). RESULTS: A total of 11 clinically diagnosed children were included, 6 of whom had onset in the neonatal period and 5 in infancy. Severe anemia in early infancy was a common feature, with hemoglobin levels ranging from 16 to 71 g/L (median value = 42 g/L), and mean corpuscular volume (MCV) being mostly normal or elevated. All 11 bone marrow examinations showed reduced erythroid lineage. Seven cases had confirmed structural malformations, and five cases had developmental delays. In terms of genetics, five DBA-related genes were involved, with RPS19 being the most common. Ten cases had pathogenic/likely pathogenic or DBA-related supportive variants detected, and one case had an RPS29 variant of uncertain significance related to the phenotype. All children had a history of blood transfusions. Among the 10 cases that could be followed up, glucocorticoid treatment was temporarily effective in six cases, three developed iron overload, two relapsed, and one underwent hematopoietic stem cell transplantation and survived. CONCLUSION: Early identification of DBA should focus on the core combination of severe anemia in early infancy, normal or increased MCV, reduced reticulocytes, and suppressed erythroid lineage in the bone marrow, while also considering the presence of congenital anomalies. Genetic testing has facilitated to clarify the molecular typing and explain the phenotypes. The absence of typical malformations does not rule out DBA, and infants with early severe anemia should undergo bone marrow and genetic evaluation as soon as possible.
Nature communicationsSemjon Willier, Julian Färber, Theodora Ispyrlidou, Jonas Wilhelm, Eileen Mayer, Dana Stenger, Jannika Seiferling, Annika E Brien, Sophia Nikolaides, Paulina F…
Currently, no immunotherapy is approved for T cell acute lymphoblastic leukemia (T‑ALL). High initial response rates to CD7‑directed chimeric antigen receptor (CAR) T cells are limited by profound T cell aplasia and CD7‑negative immune escape, underscoring the need for alternative targets. Here, we show that CD28 is overexpressed on T‑ALL blasts from children and adolescents compared with lymphoid progenitors from healthy donors and is uniformly upregulated in nodal T-follicular helper cell lymphomas (nTFHL-AI, nTFHL-F). Using CRISPR/Cas9-mediated CD28 knockout to prevent fratricide, we generate highly functional anti‑CD28 CAR T cells with selective cytotoxicity against CD28⁺ T‑ALL. Anti‑CD28 CAR T cells match anti‑CD7 CAR T cells in vitro and in vivo, but cause markedly less lymphodepletion, largely sparing CD8 T cells and NK cells while preferentially depleting CD4 T cells, particularly TH2 and TH17 subsets. These findings establish CD28 as an actionable target for CAR T cell therapy of T cell malignancies.
Science translational medicineAae Suzuki, Liang Zhao, Chelsea Thorsheim, Brittany Weiderhold, Changsong Yang, Valerie Tutwiler, Carla Casu, Jacob W Myerson, Elizabeth O Hexner, Narla Mohand…
Thrombotic events are the leading cause of death in myeloproliferative neoplasms (MPNs) driven by the JAK2 Val617→Phe (JAK2V617F) mutation. We investigated how JAK2V617F alters hemostasis and thrombosis in humans and in lineage-specific knockin mice to test whether red blood cell (RBC) mechanics contribute directly to clot pathology. Jak2F/+Vav-Cre knockin mice form structurally aberrant clots characterized by extended clot formation times and unstable hemostatic plug formation. Whole-blood clot contraction in vitro was impaired in humans and mice carrying the JAK2V617F mutation, even when Jak2V617F erythrocytes were resuspended in normal plasma with normal platelets. Thus, in addition to increasing the hematocrit, the JAK2V617F mutation imparted intrinsic changes in erythrocytes critical for mediating abnormal clot formation. Biophysical analysis showed that Jak2V617F erythrocytes had stiffened membranes, making them less compressible during clot contraction. Proteomic and lipidomic analysis of Jak2V617F erythrocytes revealed the loss of key membrane and cytoskeleton proteins, a sparse spectrin cytoskeletal network, increased membrane lipid content, and deep plasma membrane invaginations that were consistent with biaxial cytoskeletal stretching and altered lipid packing. These JAK2V617F-driven changes in erythropoiesis generated intrinsically rigid erythrocytes that impaired clot contraction and produced larger and more occlusive, yet mechanically unstable thrombi. This mechanism may explain the contradictory coexistence of thrombosis and hemorrhage in MPNs and why both complications improve when blood counts are lowered, suggesting that targeting erythrocyte mechanics may provide previously unidentified therapeutic opportunities.
The Journal of experimental medicineS Farshid Moussavi-Harami, Matt S Zinter, Marialetizia Motta, Luca Pannone, Paolo Calligari, Luca Mignini, Anne Slavotinek, Pierre-Marie Martin, Henry Sanchez,…
Severe inflammatory lung disease, including acute respiratory distress syndrome (ARDS), is life-threatening with diverse causes and few targeted therapies. Inborn errors of immunity (IEIs) underlie a subset of cases. We describe a novel IEI caused by biallelic loss-of-function variants in PTPN6, encoding the immunoregulatory phosphatase SHP1. Seven children from five families developed early-onset anemia and severe inflammatory lung disease, at times presenting as ARDS. The causative variants were shown to destabilize SHP1 and abolish its phosphatase activity. These findings expand the genetic landscape of inflammatory lung disease and suggest SHP1 activation as a potential therapeutic strategy for immune-mediated pulmonary pathology.
Journal of hematology & oncologyJennifer Marvin-Peek, Farhad Ravandi
The management of acute myeloid leukemia (AML) has undergone a remarkable transformation over the past decade, as advances in genomic profiling and drug development have expanded therapeutic options and enabled increasingly personalized treatment approaches. This review summarizes the evolving therapeutic landscape of AML, including current intensive and lower-intensity treatment backbones, approved molecularly targeted therapies, and emerging investigational strategies. We discuss the role of intensive cytarabine plus anthracycline-based regimens and venetoclax-based lower-intensity approaches, as well as targeted therapies directed against FLT3, IDH1/2, NPM1, and KMT2A-rearranged AML. We further examine efforts to optimize existing treatment paradigms through the incorporation of venetoclax into intensive chemotherapy, rational targeted combinations, and novel triplet regimens, in addition to the emerging use of highly active lower-intensity therapies in younger fit patients. Finally, we highlight promising future directions in AML, including therapies targeting RAS/MAPK signaling, emerging approaches for TP53-mutated disease, and immunotherapeutic strategies. AML treatment is rapidly evolving from broadly applied chemotherapy-based approaches toward increasingly molecularly informed and individualized therapeutic strategies. Continued advances in molecular diagnostics, targeted therapies, and synergistic combination regimens have the potential to further increase remission durability, reduce relapses, and improve long-term outcomes for patients with AML.
BMJ case reportsJennifer Khong, Alisa Liberman, Arabella Hammoudeh, Karthik Kailasam
A previously healthy woman in her early 30s developed rash, fever and arthralgia 3 weeks after SARS-CoV-2 infection, rapidly progressing to multiorgan failure. Laboratory studies revealed severe thrombocytopenia (23×109/L), microangiopathic haemolytic anaemia, acute kidney injury and ferritin >100 000 ng/mL. Kidney biopsy demonstrated thrombotic microangiopathy with negative antinuclear antibody, supporting atypical haemolytic uraemic syndrome (aHUS). Concurrently, low haptoglobin, elevated lactate dehydrogenase (2500 U/L), interleukin-2 receptor (18 644), triglycerides (425 mg/dL) and splenomegaly supported haemophagocytic lymphohistiocytosis (HLH). Despite plasmapheresis, corticosteroids, etoposide, eculizumab and continuous renal replacement therapy, she died 7 weeks after SARS-CoV-2 infection. Autopsy confirmed aHUS with extensive thrombotic microangiopathy and HLH with bone marrow haemophagocytosis. This case underscores the importance of recognising concurrent aHUS and HLH after COVID-19, as complement-mediated injury and hyperinflammation may produce catastrophic outcomes.
BMJ case reportsAboobacker Mohamed Rafi, Siju V Abraham, Susheela J Innah, Punchalil Chathappan Rajeev
Snakebite-associated coagulopathy is usually attributed to venom-induced consumption of clotting factors, but underlying mechanisms may be heterogeneous and not reliably detected by conventional coagulation tests. A man in his late 40s presented early after Russell's viper envenomation with local signs and a prolonged bedside modified Lee and White clotting time despite normal prothrombin time and activated partial thromboplastin time. Given this discordance, rotational thromboelastometry (ROTEM) was performed at admission. Extrinsically activated thromboelastometry (EXTEM) demonstrated rapid and complete clot lysis, while tranexamic acid-modified antifibrinolytic thromboelastometry (t-APTEM) showed restoration of clot stability with inhibition of fibrinolysis, supporting a hyperfibrinolytic component.The patient was managed with antivenom and supportive care, including plasma transfusion, with subsequent resolution of coagulopathy and an uncomplicated recovery. This report establishes a diagnostic and mechanistic framework for systematic evaluation of fibrinolysis in snakebite-associated coagulopathy and highlights that the role of antifibrinolytic therapy requires further exploration in patients demonstrating evidence of hyperfibrinolysis.
European journal of pediatricsNevzat Aykut Bayrak, Nihan Uygur Kulcu, Egemen Tural, Engin Aydin
The purpose of this study is to evaluate the association between follow-up regularity and dietary adherence, growth, and micronutrient status in children with celiac disease (CD). In this single-center, prospective observational study, children on a gluten-free diet (GFD) for ≥ 1 year were classified over a fixed 24-month window as regular follow-up (RFU; ≥ 4 visits) or irregular follow-up (IFU; < 4 visits) according to the number of outpatient visits. Adherence was assessed by parent- and child-reported modified Biagi scores and by anti-tissue transglutaminase IgA (TGA) normalization (< 20 RU/mL). Multivariable models were adjusted for age, sex, time since diagnosis, and socioeconomic status (SES). Of 345 children, 204 were RFU and 141 IFU; the median number of visits was 5 (IQR 4-5) versus 2 (1-3), respectively (p < 0.001). Children in the IFU group were older and more often of low SES. Non-normalization of TGA was independently associated with IFU (adjusted odds ratio (aOR): 3.16; 95% CI, 1.97-5.06); each additional visit lowered the odds of non-adherence (aOR, 0.66; 95% CI, 0.57-0.77). IFU was associated with non-strict parent-reported adherence (aOR, 2.20) and iron deficiency (aOR, 1.97). Parent-reported adherence correlated moderately with TGA status (κ = 0.46), whereas child self-report adherence was negligible (κ = 0.05). The lower BMI z-score in the IFU group lost significance after adjustment.Conclusion: More frequent follow-up improved GFD adherence, as reflected by normalized TGA levels; IFU was independently associated with poorer adherence and iron deficiency. Low GFD compliance is most likely among older and low-SES children. For children aged ≥ 10, self-reported adherence is unreliable; parental report with serology is preferable.
Journal of hematology & oncologyJan C Schroeder, Philipp Faustmann, Snjezana Janjetovic, Anna Ossami Saidy, Hanna K Zieger, Giuliano Filippini Velazquez, Thomas Melchardt, David Baden, Hristo…
Tagraxofusp (TAG), a CD123-directed protein-drug conjugate, is approved in front-line and relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN). Multicenter real-world outcomes and the contribution of up-front consolidation post-TAG remain less defined. We retrospectively analyzed 32 patients with BPDCN treated with frontline TAG (2019-2024) across 13 tertiary centers, contextualized against a historical cohort treated before TAG availability (n = 40). Patients were elderly (median age 71.5 years) with advanced disease, including skin (93.8%), bone marrow (84.4%), and peripheral blood involvement (53.1%). The overall response rate to TAG was 82.1%, with complete responses in 60.7%. Capillary leak syndrome occurred in 53.1% (grade ≥ 3 in 47.1%), with no unexpected safety signals. With a median follow-up of 18.4 months, 2-year overall survival (OS) and progression-free survival were 40.5% and 30.4%. Nearly half of patients proceeded to allogeneic stem cell transplantation post-TAG, associated with improved survival consistent with the primary analysis and landmark-adjusted analyses (HR 0.25 [0.06-1.14]; p = 0.073). Propensity score-matched comparison with the Non-TAG cohort showed comparable 2-year OS (59.4% vs 60.8%; p = 0.9). Frontline TAG was not associated with OS in pooled multivariable regression (HR 0.89 [0.37-2.15]; p = 0.803), while peripheral blood involvement remained associated with reduced OS (HR 2.63, 95% CI 1.1-6.27; p = 0.03). In this large multicenter real-world cohort, frontline TAG achieved high response rates with manageable toxicity. While unmeasured selection may contribute to the higher transplantation rate after TAG, durable remissions were achieved in patients undergoing post-TAG consolidation, supporting TAG as an induction and bridging strategy to allogeneic stem cell transplantation.
MRI-guided focused ultrasound (MRgFUS) thalamotomy is an effective ablative procedure for medication-refractory essential tremor (ET). However, limited data exist regarding its safety in patients with coexisting intracranial disease such as cerebral cavernous malformations. We present a man in his late 60s with medication-refractory ET who underwent staged bilateral MRgFUS thalamotomy. Preoperative MRI demonstrated heterogeneously T1-hyperintense and T2-hyperintense lesions in the left caudate head and basal ganglia consistent with cavernous malformations, with an associated developmental venous anomaly and no prior haemorrhage. After individualised counselling regarding unknown procedural risks, the patient underwent right-sided thalamotomy, followed 1 year later by left-sided thalamotomy. MRI after each procedure demonstrated expected treatment-related changes without acute intracranial haemorrhage around the cavernous malformations. This case demonstrates successful staged bilateral MRgFUS thalamotomy in a patient with cerebral cavernous malformations, suggesting they may not uniformly preclude MRgFUS in carefully selected patients. Preoperative planning, counselling and MRI surveillance remain essential.
Science advancesEnrun Zheng, Qinghua Li, Xuelin Dou, Yiping Cao, Chao Ren, Feiya Suo, Lin Lin, Yan Zhao, Zhiwei Liao, Yang Liu, Zesen Shang, Sudun Guan, Chengying Zhang, Mengy…
Immunoglobulin heavy chain (IGH) enhancer translocations drive multiple myeloma (MM), but routine diagnostics resolve only 32 to 38% of cases. Here, we introduce TransFinder, a multiomic pipeline integrating SMRT long-read sequencing (LRS), Hi-C, H3K27ac ChIP-seq/CUT&Tag, and RNA-seq to systematically resolve cryptic translocations and their hijacked oncogenes by deconvoluting enhancer-promoter neo-loops at rearrangement breakpoints. Applied to MM, TransFinder identified that t(16;22)(q23;q11), a canonical translocation known to activate MAF, also hijacks enhancers to activate RAB36. It further uncovered previously unrecognized t(5;8)(q35;q24) and t(1;22)(q25;q13), which activate MYC and CBX7, respectively, through chromatin topology rewiring. CRISPR-Cas9-engineered t(1;22)(q25;q13) recapitulated CBX7 induction, and pharmacological inhibition of CBX7 suppressed myeloma cell proliferation. Beyond MM, TransFinder identified enhancer hijacking in chronic myeloid leukemia, where t(9;22)(q34;q11) repositioned an enhancer to activate BCR-ABL1, and pancreatic ductal adenocarcinoma, where t(2;12)(p24;q24) hijacked an enhancer to activate SDC1. Linking 3D genome architecture to oncogene activation, TransFinder decodes oncogenic structural variants and their trans-activities, establishing clinically actionable dependencies of noncoding drivers in malignancies.
Journal of hematopathologyGökhan Burul, Çagla Karaoglan, Erdem Bektaş, Cemal Bes, Leylagül Kaynar, İstemi Serin, Şeniz Öngören
BACKGROUND: VEXAS syndrome is a somatic autoinflammatory disorder caused by UBA1 mutations in hematopoietic progenitor cells, typically affecting older men and characterized by systemic inflammation and hematologic abnormalities. Early-onset cases are extremely rare. CASE PRESENTATION: We report a 25-year-old male patient presenting with recurrent fever, weight loss, arthralgia, and inflammation mimicking orbital cellulitis. Imaging demonstrated orbital soft tissue inflammation. Laboratory investigations revealed macrocytic anemia, leukopenia, thrombocytopenia, and elevated inflammatory markers; FDG-PET/CT showed splenomegaly and hypermetabolic lymphadenopathy. Bone marrow examination revealed hypercellularity, multilineage morphological abnormalities, and vacuolated blasts. Following exclusion of infectious and classical autoinflammatory diseases, the somatic UBA1 c.121A > G (p.Met41Val) mutation confirmed VEXAS syndrome. The patient initially responded to corticosteroids but subsequently developed refractory disease and progressive pancytopenia despite tocilizumab therapy. He underwent allogeneic hematopoietic stem cell transplantation from a 10/10 HLA-matched sibling donor using a myeloablative conditioning regimen. At 3 months post-transplantation, 99% donor chimerism and hematologic remission were achieved. CONCLUSION: VEXAS syndrome should be considered in young adults presenting with unexplained systemic inflammation and cytopenias, even with atypical manifestations such as orbital cellulitis. Early genetic evaluation is crucial for diagnosis, and allogeneic stem cell transplantation may provide effective disease control in refractory cases.
Renal anemia is a prevalent complication in patients undergoing peritoneal dialysis (PD). Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, but comparisons with erythropoiesis-stimulating agents (ESAs) require consideration of the specific regimens used. We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed from inception to December 2025 for randomized controlled studies comparing roxadustat-based regimens with ESA-based regimens in adults receiving PD. Eligible evidence was restricted to PD-only randomized studies after rechecking dialysis modality and study design. Nineteen studies involving 1,636 participants were included. The average post-treatment hemoglobin level was higher in the roxadustat-based groups than in the study-specific ESA comparator groups (mean difference = 7.30 g/L, 95% CI: 5.43 to 9.16; I2 = 62.6%). However, hemoglobin target-attainment data were not defined or reported consistently enough for quantitative synthesis. Post-treatment hematocrit and red blood cell count also differed between groups, with substantial heterogeneity. The pooled reported adverse-event rate yielded an RR of 0.45 (95% CI: 0.27 to 0.74), but definitions and ascertainment were not standardized. Effects on iron indices, inflammatory markers, lipid indices, and cardiovascular outcomes were exploratory. Grading of Recommendations Assessment, Development and Evaluation certainty was low for hemoglobin and low to very low for most secondary outcomes. Available evidence is insufficient to determine the comparative clinical superiority of roxadustat-based over ESA-based strategies in PD because final values were pooled and comparator regimens were heterogeneous. Evidence concerning hemoglobin target attainment, high-density lipoprotein cholesterol, and long-term safety remains insufficient.
A girl in the first decade of life presented with a 1.5 year history of gradually progressive bilateral upper eyelid swelling with bilateral proptosis, more prominent on the right side. She had a partial response to oral prednisolone, but symptoms recurred during tapering. Examination showed firm bilateral upper eyelid masses, preserved vision and mild restriction of upward gaze in the right eye. MRI demonstrated right preseptal/periorbital soft tissue thickening. Further evaluation excluded infection, vasculitis, sarcoidosis and malignancy; serum IgG4 level was normal. Biopsy of the right eyelid lesion showed concentric perivascular fibrosis with eosinophil-rich lymphoplasmacytic infiltrate, consistent with eosinophilic angiocentric fibrosis, supporting a diagnosis of possible organ-limited IgG4-related disease. The patient was treated with oral prednisolone and mycophenolate mofetil, resulting in sustained clinical improvement. This case highlights that paediatric IgG4-related disease may present as isolated orbital swelling with normal serum IgG4, making histopathology crucial for diagnosis.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerJamiel Reyes, Alexander Reyes
INTRODUCTION: Febrile neutropenia (FN) is an important complication of first-line immunochemotherapy for diffuse large B-cell lymphoma (DLBCL). Thresholds for primary granulocyte colony-stimulating factor (G-CSF) prophylaxis are risk-based, but the FN burden in routine practice is uncertain, and whether trial-derived estimates describe it is unknown. METHODS: Systematic review and meta-analysis of proportions. MEDLINE, CENTRAL, ClinicalTrials.gov, Europe PMC, Epistemonikos, Lens.org, Google Scholar, and citation tracking were searched from inception to 8 September 2026. Eligible studies reported FN incidence in adults with DLBCL receiving first-line R-CHOP or R-CHOP-like therapy. Analyses were stratified by design, because observational cohorts and trials measure FN under materially different conditions. Risk of bias and certainty were assessed using ROBINS-I/RoB 2 and GRADE. RESULTS: Fifteen studies (5440 patients; 885 FN events) were included. Across ten observational cohorts (4020 patients), pooled FN incidence was 19.0% (95% CI 17.1-21.1; I2 = 34.0%), prediction interval 15.3-23.3%, and was stable across all sensitivity and leave-one-out analyses. Five clinical trials (1,420 patients) reported 11.7% (95% CI 5.7-22.7) but were markedly heterogeneous (I2 = 79.4%; estimates 2.4-20.0%); the difference between designs was not significant (p = 0.051) and depended substantially on one trial. CONCLUSION: In routine practice, approximately one in five adults with DLBCL receiving first-line R-CHOP-based therapy develops FN-an incidence at, rather than below, the conventional 20% threshold for primary G-CSF prophylaxis. Trial-derived estimates should not be assumed to represent this burden.
The global burden of viral diseases in both humans and agricultural animals is exacerbated by dysregulated inflammatory cell death and cytokine storms. Pyroptosis, executed by gasdermin family proteins, is a key driver of this pathology, yet its functional conservation and therapeutic targeting in avian species remain critically unexplored. Here, we establish the first germline-edited heterozygous DFNA5-mutant chicken model using primordial germ cell mediated genome editing. We demonstrate that genetic disruption of DFNA5 markedly attenuates Raptinal-induced pyroptosis and reduces IL-1β and IL-18 secretion. Using an optimized adenoviral dual-sgRNA delivery system, we successfully generated chimeric chickens with stable germline transmission of a frameshift deletion in DFNA5. Notably, DFNA5 deficiency is associated with reduced expression of the viral gp85 gene following avian leukosis virus subgroup J (ALV-J) infection. Mechanistically, transcriptome analysis reveals that downregulated genes in ALV-J-infected DFNA5-mutant cells are enriched in apoptosis and NOD-like receptor signaling pathways, while upregulated genes are associated with cell adhesion, extracellular matrix organization, and homeostatic pathways, suggesting a possible shift from pyroptotic inflammation toward cellular integrity and repair. This work provides genetic evidence that a possible association between DFNA5-mediated pyroptotic responses and establishes a genetic strategy for poultry disease resistance research and for understanding host-virus evolution and viral-induced inflammatory pathologies across vertebrates.
BMJ case reportsPoshika Dhingra, Paige Shelemey, Rahima Bhanji
An adult male patient in his late teens presented with pruritus, nausea and progressive jaundice after travel to West Africa. He did not get a pre-travel hepatitis A vaccination or malaria chemoprophylaxis. Laboratory testing demonstrated hepatocellular injury with alanine aminotransferase (ALT) 4002 U/L (reference <60), marked hyperbilirubinaemia (total bilirubin 632 µmol/L, reference <20) and a mildly prolonged international normalised ratio (INR). Concurrently, he developed non-immune haemolysis with undetectable haptoglobin, elevated lactate dehydrogenase and reticulocytosis, as well as bite and blister cells on blood film with a negative direct antiglobulin test. Acute hepatitis A virus infection was confirmed and enzymatic testing showed glucose-6-phosphate dehydrogenase deficiency. Haemoglobin electrophoresis also identified sickle cell trait. He improved with supportive care, avoidance of oxidant medications and close monitoring without renal injury or need for transfusion. This case illustrates an approach to jaundice in a returning traveller, the recognition of oxidative haemolysis at the bedside and preventive opportunities.
Journal of visualized experiments : JoVEHumood Al Shmrany, Tareg M Belali, Mohammed H Abu-Alghayth, Abdulkarim S Binshaya, Amer Al Ali, Yara Alyahyawi, Osamah Mohammed Belali
Hereditary Factor VII (FVII) deficiency is associated with reduced F7 gene expression and impaired coagulation, and regulatory mechanisms controlling F7 transcription remain incompletely characterized. This study aimed to computationally explore whether restoration of predicted HNF4α binding at the F7 promoter, through transcription factor modulation, promoter motif correction, or CRISPR activation (CRISPRa)-mediated epigenetic regulation, could theoretically enhance predicted F7 transcription in hereditary FVII deficiency. An entirely in silico pipeline was developed to characterize the F7 promoter regulatory landscape by identifying conserved transcription factor binding motifs using JASPAR, FIMO, and UCSC Genome Browser datasets. Liver expression correlations were evaluated using GTEx transcriptomic data, while chromatin accessibility and regulatory context were assessed using ENCODE ChIP-seq, ATAC-seq, and ChromHMM/Segway annotations. A hepatic regulatory network was constructed in CellDesigner to simulate the predicted effects of HNF4α loss on F7 transcription over a 24-h period. Six high-confidence HNF4α binding motifs were identified within the proximal F7 promoter, including three regions overlapping known disease-associated variants. Liver expression analyses demonstrated positive correlations between F7 and HNF4A (r = 0.68) and HNF1A (r = 0.61). Computational modeling predicted that CRISPRa targeting of HNF4α-associated regulatory regions could increase simulated F7 transcription toward approximately 87% of wild-type levels under the modeled conditions, with predicted target specificity. Overall, this purely computational study presents an integrated multi-omic framework for prioritizing promoter-targeted regulatory strategies in hereditary FVII deficiency. By combining transcription factor motif analysis, chromatin annotation, transcriptomic correlation, regulatory network modeling, and CRISPR guide prioritization within a unified pipeline, the study generates experimentally testable hypotheses while providing a systematic approach that extends beyond previous single-variant or isolated experimental analyses.
Current treatment options in oncologyHaoping He, Bowei Chen, Xiaoqiang Hao, Haoyue Li, Jia Du, Weiwei Liu, Aijun Zhang
Mercaptopurine (6-MP) is a cornerstone drug for acute lymphoblastic leukemia (ALL) maintenance therapy. As a prodrug and purine analog, 6-MP is converted into the active cytotoxic product through a series of metabolic processes in the body. Its cytotoxic effects are mediated by the overactivation of deoxyribonucleic acid (DNA) mismatch repair mechanisms. The metabolism of 6-MP is influenced by multiple enzymes, and genetic polymorphisms encoding these enzymes affect drug tolerance and adverse reactions. Owing to significant individual variability, therapeutic drug monitoring (TDM) during 6-MP therapy has gained increasing attention, although no consensus has yet been established. Therefore, optimizing 6-MP maintenance regimens to mitigate adverse reactions and increase efficacy during this phase is critically important. Currently viable strategies include thiopurine enhanced ALL therapy (TEAM) and combination therapy with allopurinol. Finally, the issue of 6-MP resistance is attracting attention. Identifying methods for early detection of acquired resistance and developing corresponding strategies is important for improving the prognosis of ALL patients.
European journal of clinical pharmacologyTuan Fauziah Tuan-Roslli, Mohd H Abdul-Aziz, Mohd Makmor-Bakry, Noraida Mohamed Shah, Shamin Mohd Saffian
INTRODUCTION: Multiple population pharmacokinetic (PopPK) models have been developed across diverse populations and disease groups for high-dose methotrexate (HDMTX), and published external evaluations of PopPK models have demonstrated limited transferability across populations. This study aims to develop a PopPK model describing HDMTX pharmacokinetics in Malaysian adults with hematological malignancies via routine clinical data. METHOD: Methotrexate (MTX) plasma concentrations at 48, 72, and 96 h were retrospectively collected from 91 HDMTX administrations with a total of 206 concentrations. Concentrations below the lower limit of quantification (BLQ) were handled using M3. Potential covariates evaluated included demographic factors (age, sex, body surface area), renal function, liver function parameters, hematocrit and treatment-related factors (protocol and infusion duration). Renal function was explored via the estimated glomerular filtration rate (eGFR), BSA-adjusted eGFR (GFR), and creatinine clearance derived from the Cockcroft-Gault equation, to assess their relative influence on clearance. Forward inclusion followed by backwards elimination was used for covariate selection. Model adequacy was assessed using goodness-of-fit plots and visual predictive check (VPC). RESULTS: A two-compartment model with literature-informed distribution parameters, first-order elimination and combined residual error best described the current data. Limited information during the distribution phase was mitigated by fixing V1, V2, and Q to the literature-derived values. Clearance (CL), normalized to the median covariate values was parameterized as: CL (L/h) = 11.13 × (Alb/39)0.7. Albumin was a significant predictor of CL (ΔOFV = -41.81 from 119.92 in base model). CONCLUSION: This model characterizes HDMTX pharmacokinetics in Malaysian adults with hematological malignancies, with albumin identified as a significant covariate on clearance. Simulation findings suggest that albumin may support risk stratification for delayed MTX elimination across different dosing scenarios.
BMJ case reportsLiran Shechtman, Carolyn M Tan, Christophe Langlois, David Nelson Juurlink
A man in his early 60s presented with dyspnoea superimposed on a 2-month to 3-month history of spontaneous mucocutaneous bleeding. Laboratory testing revealed unmeasurably elevated international normalised ratio (INR) and activated partial thromboplastin time. CT of the neck demonstrated supraglottic soft tissue swelling with severe airway narrowing, requiring intubation for airway protection. Further history revealed occupational exposure to rodenticides during pest control work without consistent use of personal protective equipment. Markedly reduced activity of vitamin K-dependent clotting factors (II, VII, IX and X) supported a presumptive diagnosis of superwarfarin toxicity. Treatment with 4-factor prothrombin complex concentrate and vitamin K1 rapidly corrected the coagulopathy, although prolonged high-dose oral vitamin K1 was required because of recurrent INR elevation. He was discharged after 9 days and completed a 3-week vitamin K1 taper. This case highlights a rare presentation of presumed transdermal superwarfarin toxicity causing life-threatening coagulopathy and airway compromise.
Cancer causes & control : CCCAtinuke G Oyinbo, Saif Al Amin, Matthew R LeBlanc, Staci A Keene, Sharon Peacock Hinton, Allison W Kurian, Sandi L Pruitt, Nicholas Pettit, Megan A Mullins, Ge…
PURPOSE: Non-specific presenting symptoms make multiple myeloma (MM) one of the most difficult hematologic cancers to diagnose, increasing the risk of late diagnosis and emergency presentation (EP). We examined the frequency of EP in MM, estimated associations between EP and patient-level factors, and MM symptom-related healthcare utilization in the year before diagnosis. METHODS: We studied Medicare beneficiaries age ≥ 66 years diagnosed with MM between 2008 and 2017. Emergency presentation (EP) was defined as diagnosis preceded by a recent ED visit, sub-classified as: inpatients (EP-IP) for subsequently admitted patients and outpatients (EP-OP) for those discharged for follow-up care. RESULTS: Among 20,437 patients, 52% were male, 75% non-Hispanic White (NHW), and the median age was 76. Overall, 37% were diagnosed through involvement with the ED (EP-IP: 30%; EP-OP: 7%). In iteratively adjusted models, oldest age, female sex, non-Hispanic Black, Hispanic, Asian American, Native Hawaiian or Other Pacific Islander race and ethnicity, unmarried status, dual eligibility for Medicaid and Medicare, lowest county SES, rurality, frailty, and higher healthcare use in the year pre-diagnosis were associated with higher frequency of ED involvement in diagnosis. Symptom-related healthcare utilization was comparable among EP and non-EP groups in the year preceding MM diagnosis but markedly increased for the EP group in the month before diagnosis. CONCLUSIONS: More than one-third of older US adults with MM are diagnosed through EP. Several socio-demographic, clinical and healthcare utilization factors are associated with EP. Similarities in healthcare utilization across EP status in the months preceding diagnosis suggest missed opportunities for earlier detection of MM.
BMJ case reportsBradley Loudon, Michael Joubert, David Owen-Conway, Shihaz Hussain, Trent Grundy, Montri Gururatsakul
IgA vasculitis (IgAV), a small-vessel systemic vasculitis characterised by arthritis, renal involvement and palpable purpura without thrombocytopenia, predominantly affects children and is rare in adults. Immunosuppressive treatment is typically reserved for significant renal involvement or refractory abdominal and joint pain. However, therapeutic targets for gastrointestinal involvement remain poorly defined. A man in his 20s with no medical history presented with weeks of abdominal pain, post-prandial vomiting, purpuric rash, arthralgia and hypertension. Urine studies showed subnephrotic range proteinuria and colonoscopy revealed ileal ulceration. Immunofluorescence of skin, ileal and renal biopsies demonstrated perivascular IgA deposition, confirming IgAV. Although renal involvement did not necessitate treatment, recurrent severe gastrointestinal symptoms and biochemical evidence of liver involvement prompted a 6-week course of oral prednisone following multidisciplinary consultation. His symptoms resolved, with complete normalisation of renal function and liver enzymes.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerAnna Fleischer, Carolin Burger, Magdalena Roll, Franziska Panther, Patrick-Pascal Strunz, Jessica Peter, Sofie-Katrin Kadel, Anja Gesierich, Julia Mersi, Johan…
The purpose of this study is to characterize patient-reported taste disturbances, recalled symptom course, nutritional changes, and quality of life in patients with relapsed/refractory multiple myeloma treated with talquetamab. This single-center cross-sectional study combined taste-strip testing with a study-specific questionnaire, EORTC QLQ-C30, and PHQ-4 in 32 patients. Analyses used recorded aggregate correct-identification counts without a normative hypogeusia classification. Symptom timing and changes since treatment initiation were recalled at one assessment. All patients reported taste disturbances during therapy. The median identification count was 2.5 (interquartile range 0.75-7.25); eight patients had no correct identifications. Twenty-three (71.9%) described onset within 14 days. Current appetite reduction was reported by 20 patients (62.5%), whose mean identification count was lower than that of the other 12 patients (2.45 versus 7.83; mean difference - 5.38, 95% confidence interval - 8.20 to - 2.57; p = 0.0006). Sixteen patients (50.0%) reported directional weight loss, with a median loss of 4.5 kg. Ten (31.3%) had considered stopping talquetamab; seven explicitly cited taste disturbance. Mean global health status was 50.5/100 and correlated with identification count (r = 0.406; p = 0.021). Taste disturbances co-occurred with substantial nutritional concerns. Lower taste-identification counts were associated with current appetite reduction and lower global health status. The findings support attention to taste-related burden but do not establish causality, sustained recovery, or effects on adherence. Prospective evaluations of supportive care are needed.
Severe Factor V deficiency (parahaemophilia) is a rare autosomal recessive coagulation disorder with a highly variable clinical phenotype. We report the incidental detection of isolated severe Factor V deficiency (<1% activity) in a completely asymptomatic primigravida during routine preoperative evaluation prior to an elective caesarean section. Despite marked prolongation of prothrombin time and activated partial thromboplastin time, the patient had no prior bleeding history. Mixing studies and a normal thrombin time localised the defect to the common pathway, which was confirmed by factor assay. Management involved multidisciplinary planning, peri-operative fresh frozen plasma transfusion and avoidance of neuraxial anaesthesia. The patient underwent caesarean section under general anaesthesia and delivered a healthy neonate without maternal or neonatal complications. This case highlights the poor correlation between plasma Factor V levels and bleeding phenotype and underscores the diagnostic value of thrombin time in evaluating common pathway coagulation defects.
The American journal of case reportsQian Zhang, Wenjin Wu, Linrui Chen, Mingwei Xu, Jianhui Qiu, Qianwen Xiao, Qiong Wu, Yuan Yao, Tianyu Gong, Qin Zhang, Yulian Jin, Jun Yang, Qing Zhang, Mang X…
BACKGROUND Hemangiomas are relatively common in the head and neck but rarely involve the external auditory canal (EAC). Surgical approaches for EAC hemangiomas vary, and optimal surgical management remains unclear. CASE REPORT We present 2 cases of hemangioma involving the EAC. Case 1 involved a 68-year-old man who presented with a sensation of fullness in the left ear. Case 2 involved a 62-year-old woman who presented with right-ear fullness, hearing loss, and persistent tinnitus. Preoperative assessment included otologic examination, computed tomography, magnetic resonance imaging, and corresponding auditory evaluations. Imaging across both cases consistently revealed well-defined soft-tissue masses confined to the EAC, accompanied by localized bony irregularities but preserving the middle ear structures. Both patients underwent complete trans-canal excision with concurrent skin flap reconstruction. Histopathological analysis of the excised specimens confirmed the diagnosis of cavernous hemangioma in each case. At 1-year follow-up, both patients achieved full symptom resolution, intact canal anatomy, and no recurrence. CONCLUSIONS In our 2 cases, trans-canal resection combined with local flap reconstruction served as a practical approach for EAC cavernous hemangiomas, resulting in symptom resolution and preservation of canal integrity at the 1-year follow-up.
Journal of medical economicsSongkai Yan, Olof Mogard, Anna Tjärnlund-Wolf, Fredrik Sjöö, André Eid, Jack Ettinger, Douglass Drelich, Radovan Tomic, Stina Johansson
INTRODUCTION: Etranacogene dezaparvovec (EDZ), a novel one-time gene therapy for severe/moderately severe haemophilia B, provides sustained factor IX (FIX) activity, usually eliminating the need for lifelong replacement therapy. AIM: To evaluate cost-effectiveness of EDZ vs. prophylaxis with eftrenonacog alfa (rFIXFc) in adults with haemophilia B in Sweden. METHODS: A lifetime Markov model (age 41.5 up to 100 years) was developed based on four health states defined by stratified Pettersson scores, a measure of joint deterioration. Phase 3 trial results over 60-months informed efficacy parameters along with publicly available Swedish healthcare costs. Main outcomes were costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). A non-linear Bayesian model predicted FIX activity levels, projected to 60 years. A 3% discount was applied for costs and health outcomes. Uncertainty was assessed through sensitivity analyses. RESULTS: Accumulated QALYs were 20.41 EDZ vs. 18.66 rFIXFc. The QALY gain of 1.75 for EDZ was attributed to differential bleed rates, a utility increment for patients receiving EDZ, and disutility of administering rFIXFc regular infusions. EDZ resulted in total lifetime cost savings of ∼21.3 million SEK, driven by savings in drug costs (∼21.0 million SEK). The impact on other cost items was minimal. Results showed dominance of EDZ vs. rFIXFc and were consistent across sensitivity analyses. A scenario analysis starting at age 18 years with 0% discount showed total lifetime savings of ∼89.3 million SEK. CONCLUSION: EDZ is an effective and cost-saving treatment vs. rFIXFc for adults with severe/moderately severe haemophilia B, reducing clinical and economic burden.
Cancer chemotherapy and pharmacologyYi-Lun Wang, Tsung-Yen Chang, Shih-Hsiang Chen, Yi-Wen Hsiao, Yu-Chuan Wen, Tang-Her Jaing
INTRODUCTION: The use of intensified chemotherapy has significantly improved overall survival (OS) and relapse-free survival (RFS) in cancer patients. However, it also increases the risk of chemotherapy-induced neutropenia (CIN). Granulocyte colony-stimulating factor (G-CSF) is commonly used to hasten neutrophil recovery, but limited research has focused on the superiority of different routes of G-CSF administration. MATERIALS AND METHODS: This was a randomized, prospective, single-institution study. Twenty-eight participants were enrolled and randomly assigned to experimental and control arms in a 1:1 ratio. At the end of the study, 20 cases were eligible for statistical analysis. The primary endpoint was the duration from the onset of neutropenia to steady neutrophil recovery. Secondary endpoints included the safety profile, 7-day emergency return rate, and the occurrence of infectious or febrile events. RESULTS: The mean duration from CIN to neutrophil recovery was 6.2 days in the intravenous drip (IVD) group and 7.6 days in the intravenous injection (IVI) group (P = 0.0068). The mean difference between the two groups was 1.4 days. A significantly lower incidence of febrile neutropenia (FN) was observed in the IVD group compared to the IVI group (15% vs. 50%, P = 0.0407). Adverse effects (AEs) were comparable between the two groups. CONCLUSIONS: The IVD route of G-CSF administration leads to faster neutrophil recovery and reduces the risk of FN. All evaluable AEs are comparable between the two groups. These findings suggest that the IVD route may be a preferable option for optimizing supportive care in cancer patients with CIN.
Current cardiology reportsJan Habasko, Petr Kuchynka, Mayara Elisa Bonatto, Tomas Palecek
PURPOSE OF REVIEW: This review summarises recent advances in cardiac involvement in eosinophilia, with particular emphasis on pathophysiology, diagnostic challenges and therapeutic options. RECENT FINDINGS: Up to 43% of patients with histologically proven eosinophilic myocarditis (EM) have no evidence of peripheral blood eosinophilia. Aberrations in the interleukin-5 pathway are central to the pathophysiology of EM. In addition, other contributing factors for specific aetiologies are being recognised, such as susceptibility loci GPA33 and IRF1/IL5 in patients with ANCA-negative eosinophilic granulomatosis with polyangiitis. There is growing evidence for interleukin-5 pathway inhibition in disease management. EM carries a high mortality risk and thus, early identification of these patients, multidisciplinary collaboration and early initiation of targeted therapy are of utmost importance. Future studies are needed to investigate other therapeutic options, including long-acting anti-interleukin-5 inhibitors.