ViroGame: a serious game for medical virology education - a feedback report

Abstract: Medical virology requires students to master complex concepts in a limited timeframe, yet traditional lectures often struggle to sustain engagement and ensure long-term retention. Serious games have emerged as promising tools to promote active learning. Building on the success of BacteriaGame, ViroGame was developed to reinforce virology knowledge through gamification. This study evaluated its effectiveness in enhancing student engagement, knowledge mobilization, and supervisor-perceived feasibility for curricular integration. A total of 318 learners participated in ViroGame sessions during the 2023-2024 academic year. Of these, 266 students/residents completed a structured questionnaire assessing with likert scale [1-5] gameplay fluidity, knowledge consolidation, perceived difficulty and potential integration with BacteriaGame. Nine supervisors also provided evaluations on rule clarity, session management and educational value. Data were analyzed using descriptive statistics, Mann-Whitney U tests and Chi-squared tests, with qualitative feedback examined thematically. Residents rated gameplay fluidity significantly higher than students (4.4/5 vs. 4.1/5; p = 0.039). Both groups reported high knowledge mobilization scores (students 4.5/5; residents 4.3/5; p = 0.378). Nearly half perceived some content as exceeding expected knowledge, despite alignment with national standards (47.4% vs. 41.8%; p = 0.482). A greater proportion of students than residents reported difficulties with virological concepts (78.9% vs. 60.3%; p = 0.021), particularly regarding diagnostic methods and viral structures. Supervisors rated the game positively, endorsing its use primarily as a revision tool. ViroGame is a well-received, effective and engaging tool for teaching medical virology. It promotes active learning, collaboration and knowledge retention while addressing the inherent complexity of virology. Further controlled studies are planned to evaluate its long-term impact on learning outcomes and exam performance.

Portet Sulla V
Marot S
Dutkiewicz M
Berti V
Grimal A
Ghelfenstein-Ferreira T
Solis M
Charre C
Salmona M
Thibault V
Pronier C
Pineros N
Lescat M
Besombes J
Vauloup-Fellous C

Humans
Virology
Students, Medical
Female
Male
Problem-Based Learning
Video Games
Surveys and Questionnaires
Curriculum
Adult
Education, Medical, Undergraduate
Educational Measurement


AI-based hardware and software tools in microscopy to boost research in immunology and virology

Abstract: The integration of computational advances in microscopy has enhanced our ability to visualise immunological events at scales. However, data generated with these techniques is often complex, multi-dimensional, and multi-modal. Data science and artificial intelligence (AI) play a key role in untangling the wealth of information hidden in microscopy data by enhancing image processing, automating image analysis, and assisting in interpreting the results. With this Review, we aim to inform the reader about the advances in the fields of fluorescence and electron microscopy with a focus on their applications to immunology and virology, and the AI approaches to aid image acquisition, analysis, and data interpretation. We also outline the open-source tools for image acquisition and analysis and how these tools can be programmed for an image-informed, AI-assisted acquisition.

Humans
Artificial Intelligence
Software
Image Processing, Computer-Assisted
Virology
Allergy and Immunology
Animals
Microscopy


A Fascination with Gastrointestinal Viruses

Abstract: My arrival into this world came quickly, according to my mother, and it feels like my life has mirrored that rapid beginning. I have enjoyed a rich, varied, and stimulating life and career that have gone through several phases. I credit genetics, my family, technological advances, and many environmental factors for shaping my career. Being a virologist allowed me to be curious and creative and to make several unexpected discoveries. This has been a fun and rewarding journey, but it wasn't always easy. I am not accustomed to talking about myself, but I am happy to share some scientific achievements and professional challenges with the hope that they illustrate the joy of research and the need for resilience and persistence to assure progress and acceptance of unexpected results.

Humans
History, 20th Century
History, 21st Century
Gastrointestinal Tract
Viruses
Virology

Research Support, U.S. Gov't, Non-P.H.S.


Scanning Transmission Electron Microscopy Tomography in Virology: 3D Imaging of High-pressure Frozen, Freeze-substituted Samples

Abstract: Electron microscopy (EM) and especially three-dimensional (3D) EM techniques have become established methods in structural virology. Investigation of virus-induced alteration of the cellular ultrastructure, such as Zika virus (ZIKV)-induced replication factories or coronavirus replication organelles, demands 3D imaging. Transmission electron microscopy (TEM) tomography is a widely used method, despite its limitation to samples with a thickness of up to 200 nm. Focused ion beam-scanning electron microscopy (SEM)-tomography can produce 3D data of larger volumes with isotropic, albeit typically lower resolution. Alternative techniques, such as block face-scanning electron microscopy (BF-SEM), SEM array tomography, or TEM imaging of serial sections are used for imaging of larger volumes. However, compared to the previously mentioned techniques, these techniques come at the cost of much lower resolution along the Z-axis of the sample. A technique that provides 3D information of samples up to 1 µm thickness with isotropic resolution of a few nanometers is scanning transmission electron microscopy (STEM) tomography. Here, we present a protocol for the preparation of high-pressure frozen, freeze-substituted, and resin-embedded virological specimens and their analysis using STEM tomography. This protocol benefits from the advantages of room temperature imaging while preserving the biological ultrastructure in a near-native state. We show two representative examples for questions that can be answered using STEM tomography. First, we apply the protocol for studying virion morphogenesis of a recombinant vesicular stomatitis virus (VSV). The STEM tomograms offer information on recombinant VSV budding that is otherwise not accessible by 2D imaging. Second, we show correlative light and electron microscopy (CLEM) using Foerster resonance energy transfer (FRET) imaging and STEM tomography (FRET-3D-CLEM) of EF-C peptide nanofibrils. This recently published combination gives new insights into the uptake and disassembly of infection-enhancing peptide nanofibrils, especially profiting from the large volume that is accessible by STEM tomography.

Journal of visualized experiments : JoVE

Wieland JG
La Roche J
Bergner T
Habisch R
Puschmann E
Soza-Ried J
Schütz D
Münch J
Walther P
Dass M
Read C

Microscopy, Electron, Scanning Transmission

Journal Article
Video-Audio Media
Research Support, Non-U.S. Gov't


The Emerging Role of Omics-Based Approaches in Plant Virology

Abstract: Virus infections in plants are a major threat to crop production and sustainable agriculture, which results in significant yield losses globally. The past decade has seen the development and deployment of sophisticated high-throughput omics technologies including genomics, transcriptomics, proteomics, and metabolomics, in order to try to understand the mechanisms underlying plant-virus interactions and implement strategies to ameliorate crop losses. In this review, we discuss the current state-of-the-art applications of such key omics techniques, their challenges, future, and combinatorial use (e.g., single cell and spatial omics coupled with super-resolution high-throughput imaging methods and artificial intelligence-based predictive models) to obtain new mechanistic insights into plant-virus interactions, which could be exploited for more effective plant disease management and monitoring.

Samarskaya V
Spechenkova N
Kalinina NO
Love AJ
Taliansky M

Plant Diseases
Plant Viruses
Proteomics
Genomics
Metabolomics
Plants
Host-Pathogen Interactions
Virology

Journal Article
Review
Research Support, Non-U.S. Gov't


The Frontier of Entomo-Virology: Applications and Tools for Virus and Vector Surveillance

Abstract: The term 'entomo-virology' arose because of the confluence of entomology and virology, focused on deepening the knowledge about the interactions between vectors and viruses and the aspects that involve hosts and the environment. Based on this, entomo-virological surveillance was proposed, aiming to develop tools that strengthen prevention for arboviral disease and vector control strategies. This review aims to present a narrative synthesis regarding the component elements of the concept of entomo-virology. In addition, the applications and tools for the surveillance of viruses and vectors, their implementation challenges, and perspectives are discussed.

Lemos PDS
Pacheco MMM
Nascimento BLSD
Coelho MS
Franco Filho LC
Dias DD
Sena L
Silva SPD
Sallum MAM

Animals
Insect Vectors
Humans
Virology
Entomology


Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) - General taxonomy proposals, 2025

Abstract: During the 56th annual meeting of the International Committee on Taxonomy of Viruses (ICTV), held in Bari, Italy, in August 2024, two technical proposals were presented. The first called for amended versions of accepted taxonomic proposals to be named in such a way to ensure that they are readily accessible on the ICTV website (2024.001G). The second proposed a substantial reformatting of the ICTV statutes and codes to produce a more unified text after the numerous changes made to both documents in previous years (2024.002G). Finally, the ICTV Executive Committee (EC) nominated Professor Stuart Siddell as a Life Member of the ICTV for his work over four decades on virus taxonomy, including 16 years as a member of the EC (2024.003G).

Zerbini FM
Crane A
Kuhn JH
Simmonds P
Lefkowitz EJ
Ictv Taxonomy Summary Consortium
ICTV Taxonomy Summary Consortium

Viruses
Classification
Terminology as Topic
Virology
Humans
Italy

Journal Article
Research Support, N.I.H., Extramural


Environmental Sampling of Photosynthetic Microbes and Their Viruses: From Field to Lab

Abstract: Environmental sampling of photosynthetic microorganisms and their viruses plays a critical role in understanding contemporary marine and freshwater biodiversity and ecosystem dynamics as well as the impacts of climate change-related factors (e.g., rising temperatures and acidification) on evolutionary trajectories of species and community composition. Unfortunately, the diversity of the virosphere does not support a single universal sampling and experimental workflow. Indeed, each virus system has unique features, which require modifications to standard protocols in virology to accomplish research goals. Although virus discovery and characterization require approaches that are specific to the target system, for all viruses, the research aims are similar: isolate the virus; determine host range; confirm productive infection; and characterize the virus, the host, and virus-host dynamics. Robust descriptions of virus-host systems consist minimally of elucidating morphology, physiology, biochemistry, and omics profiles. Further information may be obtained by manipulating the system by changing factors such as multiplicity of infection, temperature, pH, host-switch, directed evolution, or applying drugs to observe virus-host system response. Our laboratory studies viruses across domains of life (Archaea, Bacteria, and Eukarya). In this report, we detail methods for sampling photosynthetic microbes from the euphotic zone of freshwater and marine environments with focus on isolating bacteriophage (i.e., cyanophage) of cyanobacteria. Cyanobacteria are keystone species critical to primary production and nutrient cycling in these aquatic ecosystems. The described workflow extends from sampling waters at different depths to characterizing virus-host system features using liquid and solid media culture, advanced molecular/genetic methods, and analytical approaches. The methods described are adaptable to bacteriophage and virus discovery in virus-host systems across domains of life.


Navigating Virology's Frontiers in Africa: Global Virus Network 2024 Durban Meeting

Abstract: The Global Virus Network (GVN) is a voluntary consortium of virology laboratories and affiliated scientists that seek to prevent and control global viral threats. The meetings of the GVN are characterized by academic, health center, government, and industry participation, sharing information that is designed to further the mutual mission. In September 2024, the meeting in Durban, South Africa, highlighted diseases and investigators from Africa, and paid special attention to pandemic preparedness. Selected highlights from the meeting are presented here, along with a call-to-action in defense of global partnerships for research in the origins of human and animal viruses, the risk to humans from other animal sources, the pathogenesis of given viruses, and their prevention and treatment. Discussions of laboratory discovery science are juxtaposed with development of vaccines, antiviral drugs, immunotherapies, and innovative field strategies for control of viral diseases.

Bartlett ML
Perumal R
Vermund SH
Abdool Karim S

Humans
Virus Diseases
Africa
Virology
Animals
Viruses
Antiviral Agents
South Africa
Pandemics


A Fog-Delayed Flight and the Story of Sir Michael Anthony Epstein (1921-2024) and Yvonne Margaret Barr (1932-2016)

Abstract: The Epstein-Barr virus, was discovered in 1964, and was the first identified human oncogenic virus that can persist asymptomatically for life. It is associated with a broad spectrum of diseases in the pediatric population, including benign pathologies such as infectious mononucleosis or severe ones such as hemophagocytic lymphohistiocytosis, among others.Professor Sir Anthony Epstein (1921-2024), an English pathologist and virologist, was its co-discoverer with the Irish virologist Yvonne Barr (1932-2016). We will review the history, and the particularities of the serendipitous character that ended with the virus identification, together with the biography of both scientists who gave rise to this famous eponym, which endures to this day.

History, 20th Century
History, 21st Century
Virology
Herpesvirus 4, Human
Humans
Epstein-Barr Virus Infections


Reverse Genetics-Based Methodology for Molecular Virology Study

Abstract: Viral reverse genetics involves the process of generating synthetic viruses from purified DNA or RNA, enabling the artificial engineering of viral genes. In recent decades, viral reverse genetics has been effectively implemented for numerous viruses that pose significant threats to public health and the global economy. Viral reverse genetics techniques enable researchers to elucidate the molecular mechanisms of viral infection and transmission, trace viral evolution and replication, and study the impact of viral mutations on the virus life cycle. In this chapter, we describe a general reverse genetic strategy for rescuing DNA and RNA viruses.

Methods in molecular biology (Clifton, N.J.)

Reverse Genetics
RNA Viruses
DNA Viruses
Virus Replication
RNA, Viral
Humans
Virology
Genome, Viral


Isoquercitrin suppresses neuronal ferroptosis in ischemic stroke via SIRT1-mediated deacetylation of H3K9 at the RBM15 promoter

Abstract: Isoquercitrin (ISO), a neuroprotective flavonoid, alleviates ischemic stroke (IS) by inhibiting ferroptosis. In present study, we explored the mechanism of ISO attenuates neuronal ferroptosis in IS. HT22 cells and primary neurons underwent oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic in vitro IS. Dual‑luciferase reporter assays detected luciferase activity. H3K9 acetylation levels at the RBM15 promoter were assessed by ChIP. The m6A modification of SLC25A28 mRNA was analyzed by MeRIP. The binding of RBM15 and IGF2BP3 to SLC25A28 mRNA was examined via RIP. Lipid and intracellular ROS levels were measured by C11-BODIPY and DCFH-DA staining. The levels of ferroptosis-related indicators were determined with commercial kits. Cell viability was examined using the CCK-8 assay. In vivo, the middle cerebral artery occlusion (MCAO) rat model was used to explore the effect of ISO. ISO protected against OGD/R-induced ferroptosis and restored viability. ISO inhibited neuronal ferroptosis by reducing RBM15 expression. ISO suppressed RBM15 via SIRT1-mediated H3K9 deacetylation. Subsequently, RBM15 promoted m6A modification of SLC25A28 mRNA to enhance its stability. Reversal of ISO-mediated ferroptosis suppression by SLC25A28 overexpression was partly counteracted by RBM15 knockdown. In the MCAO model, ISO reduced infarct volume, lowered MDA levels, and restored GPX4 expression, which were partly reversed by RBM15 overexpression. ISO promoted SIRT1-mediated H3K9 deacetylation at the RBM15 promoter to suppress its transcription. RBM15 downregulation inhibited SLC25A28 stability by m6A-IGF2BP3-dependent, ultimately attenuating neuronal ferroptosis in IS.

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences

Cai S
Zhou S
Wang Y
Li Z
Long H
Chen Y
Wu M
Li X

Animals
Ferroptosis
Sirtuin 1
RNA-Binding Proteins
Quercetin
Neurons
Promoter Regions, Genetic
Ischemic Stroke
Rats
Neuroprotective Agents
Acetylation
Male
Mice
Histones
Rats, Sprague-Dawley
Cell Line
Cell Survival


Risk prediction of traumatic and non-traumatic subdural hematoma after ischemic stroke: a nationwide competing-risk model with external validation

Abstract: Subdural hematoma (SDH) represents a growing hemorrhagic concern among ischemic stroke survivors receiving long-term antithrombotic therapy. Although aging, multimorbidity, and antithrombotic exposure are all contributors to SDH, there is limited evidence on subtype-specific risk factors in stroke populations, and existing studies have often overlook competing mortality. Practical tools to guide individualized antithrombotic stewardship remain absent from contemporary guidelines. A nationwide retrospective cohort study was conducted using Korean National Health Insurance Service data from 2010 to 2023. Adults with incident ischemic stroke were followed for traumatic and non-traumatic SDH using Fine-Gray competing risk regression and cause-specific hazard models. Variables were selected using the Akaike information criterion to develop integer-based prediction scores. Internal validation used cross-validation, and external validation applied the models to an independent ischemic stroke cohort from the UK Biobank. A web-based calculator was employed to facilitate clinical use. Among 506,746 ischemic stroke survivors (median follow-up 57.9 months), 7,425 developed traumatic SDH and 1,705 developed non-traumatic SDH. The 10-year cumulative incidences were 1.94% for traumatic and 0.43% for non-traumatic SDH. Older age, multimorbidity, and antithrombotic exposure were independently associated with increased risk. Traumatic SDH demonstrated stronger associations with antiplatelet therapy and diabetes, whereas non-traumatic SDH was most strongly linked to warfarin use. Warfarin emerged as the only modifiable risk factor. Prediction models showed clear risk-gradient separation for both subtypes and maintained stratification performance in the UK Biobank cohort. A web-enabled platform provided individualized 10-year cumulative incidence estimates using routinely available clinical variables. This nationwide competing-risk analysis identified subtype-specific associations of aging, comorbidities, and antithrombotic exposure with SDH risk among ischemic stroke survivors. Because the models predict SDH specifically rather than overall intracranial hemorrhage, they are intended to support risk-stratified surveillance, monitoring, and patient counseling rather than to guide antithrombotic cessation in isolation, as such decisions require balancing ischemic recurrence against the full spectrum of major bleeding risk.

Humans
Hematoma, Subdural
Aged
Ischemic Stroke
Female
Risk Factors
Retrospective Studies
Male
Middle Aged
Aged, 80 and over
Republic of Korea
Risk Assessment
Incidence


Cross-population proteome-wide mendelian randomization study identifies likely causal proteins for cardiovascular diseases

Abstract: Blood proteins may play causal roles in cardiovascular diseases (CVDs) such as heart failure (HF) and peripheral artery disease (PAD). Proteome-wide Mendelian randomization (MR) has been widely used to prioritize drug targets for CVD in European populations, but its application to non-European populations remains limited. We conducted a proteome-wide MR analysis to evaluate the potential causal effects of 2,922 plasma proteins on five CVDs-atrial fibrillation (AF), coronary artery disease (CAD), HF, ischemic heart disease (IHD), and PAD. Analyses were performed across African (n = 931), East Asian (n = 262), and European (n = 10,840) populations using genetic instrument data from the UK Biobank cohort. Significant associations were further examined with genetic colocalization to strengthen causal inference. Using MR and colocalization analyses, we identified 53 significant protein-CVD associations across multi-populations, including 16 in African, six in East Asian, and 31 in European populations, respectively. Cross-population comparisons revealed four protein-CVD associations unique to African population and another four specific to East Asian population. Integration with clinical trial data prioritized 14 protein-disease pairs as promising candidates for therapeutic development or drug repurposing. Our findings highlight the value of proteome-wide MR in evaluating drug target applicability across populations. Several protein-disease associations were population-specific, emphasizing the need for inclusive genetic research to inform precision medicine in CVD prevention and treatment.

Zhong H
Zhu J
Liu S
Wong HTH
Zhang Y
Luu HN
Wu Q
Wang X
Wu L

Humans
Mendelian Randomization Analysis
Cardiovascular Diseases
Proteome
Blood Proteins
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
European People


Hypertrophic cardiomyopathy-linked Tnnc1 variants are associated with distinct myopathic changes in slow skeletal muscle of mice

Abstract: Inherited hypertrophic cardiomyopathy (HCM) is considered a disease of the cardiac sarcomere and caused by pathogenic variants present in genes that encode sarcomeric proteins. The human TNNC1 gene is a designated HCM-susceptibility gene encoding the troponin C (TnC) protein, which is expressed in both cardiac and type I slow skeletal muscles and abbreviated as cTnC and ssTnC respectively. HCM patients have been reported to exhibit skeletal muscle weakness and reduced exercise tolerance. Patients bearing TNNC1 cardiac pathogenic variants also express it in type I fibers of their slow skeletal muscles. We hypothesized that the presence of TNNC1 HCM variants in type I fibers may decrease force generating capabilities and alter fatigue resistance of slow skeletal muscles. To address this, we examined the impact of HCM Tnnc1 variants in the soleus muscles of two HCM knock-in mouse models A8V+/-, A8V-/-, and C84Y+/- and their respective wild type (WT) controls. At high stimulation frequencies, we found that A8V-/- soleus muscles had lower tetanic force production than WT, however no differences in fatigue when comparing fatigue indices for either of the variants. The muscles were evaluated by comparing % specific force (N/cm2)-variant and both A8V-/- and C84+/- had increased responsiveness at low stimulation frequencies. Fiber type analysis uncovered an increase in abundance of type I fibers in A8V-/- soleus, however no other differences were observed in fiber-type percentage of either mouse model. Comparison of the cross-sectional areas (CSA) of type I fibers in soleus muscles revealed lower average values for A8V+/+ and A8V-/-, however an increase in C84Y+/- relative to controls. Examination of the CSA of type IIa fibers uncovered decreased values for both A8V+/- and A8V-/- with no changes in C84Y+/- soleus. Histological evaluation of A8V+/- and A8V-/- soleus muscles revealed central nucleation and the detection of embryonic myosin heavy chain by immunofluorescence suggested the presence of mild regeneration. In contrast, no histopathological changes were detected in the C84Y+/- soleus muscle. Serum myokines were also measured to assess systemic impacts of the pathogenic variants and alterations in the physical activity of the mice but no significant changes were found. Taken together our results suggest that the HCM A8V variant alters force production in soleus muscle that may be attributed to fiber atrophy and heightened pathophysiology.

Journal of muscle research and cell motility

Patel S
da Silva Santos GL
Florence J
Kahmini AR
Shi Y
Garcia MR
Gordon BS
Chase PB
Solís C
Laitano O
Pinto JR
Parvatiyar MS

Animals
Mice
Cardiomyopathy, Hypertrophic
Muscle Fibers, Slow-Twitch
Troponin C
Muscle, Skeletal
Humans
Male


Association Between Disruption of Blood Pressure Circadian Rhythm and Prognosis After Acute Anterior Myocardial Infarction

Abstract: To investigate the characteristics of blood pressure (BP) circadian rhythm disruption and its relationship with prognosis in patients with acute anterior ST-elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). A total of 330 patients with anterior STEMI who underwent emergency PCI were enrolled in this study (MI group). Additionally, 131 physical examination patients were selected as the control group. Based on 24-h ambulatory blood pressure monitoring (ABPM) results, BP rhythm in both groups was classified into Extreme dipper, Dipper, Non-dipper, and Reverse dipper. The characteristics of BP rhythm were compared between the two groups. Patients with anterior MI were followed up for 1 year postoperatively. The occurrence of major adverse cardiovascular events (MACE) was compared among subgroups with different BP rhythms. The proportion of dipper BP in the study group (11.21%) was significantly lower than that of the control group (63.36%) (p = 0.001). The proportions of non-dipper (43.03%) and reverse dipper (40%) BP in the MI group were higher than the control group (22.90% and 7.63%, respectively; all p < 0.001). Multivariate Cox regression analysis, using dipper BP as the reference, showed that reverse dipper BP was independently associated with MACE (HR = 6.417, p = 0.002). The cumulative risk of the primary endpoint event (Log Rank p = 0.021) was significantly higher in the reverse dipper group compared to the dipper group. Patients with anterior STEMI are still under the burden of disrupted BP circadian rhythm and reduced dipper BP rhythm. The reverse dipper BP rhythm may serve as an independent factor of MACE.

Humans
Circadian Rhythm
Blood Pressure
Male
Female
Percutaneous Coronary Intervention
Prognosis
Blood Pressure Monitoring, Ambulatory
ST Elevation Myocardial Infarction
Risk Factors
Middle Aged
Anterior Wall Myocardial Infarction
Time Factors
Follow-Up Studies
Retrospective Studies
Treatment Outcome
Aged


Association between perioperative D-dimer dynamics and post-treatment localized intravascular coagulation in venous malformations

Abstract: To investigate the association between the change in D-dimer levels (ΔD-dimer) and the development of localized intravascular coagulation (LIC) following surgical intervention in patients with venous malformations. This retrospective cohort study enrolled 267 patients with venous malformations who underwent surgical treatment at Fujian Maternity and Child Health Hospital between June 2021 and December 2025. The primary exposure variable was the preoperative-to-postoperative ΔD-dimer. The principal outcome was postoperative LIC. Multivariable logistic regression analysis was employed to estimate the effect size, adjusted for potential confounders. The incidence of LIC was 31.1% (83/267). Each unit increase in ΔD-dimer was significantly associated with a higher risk of LIC (adjusted odds ratio [aOR] = 2.51; 95% confidence interval [CI]: 1.93-3.26; p < 0.001). This association was consistent across stratified subgroups, including sex, age, number of lesions, tissue layer involvement, lesion volume, lesion location, surgical approach, and anticoagulation status (all P for interaction > 0.05), with a borderline interaction by head/neck involvement (P for interaction = 0.054). ΔD-dimer is independently associated with postoperative LIC in patients with venous malformations, with a monotonic dose-response relationship. A threshold near 4.8 mg/L FEU is suggested by exploratory segmented analysis but requires external validation before any clinical use. ΔD-dimer is independently associated with postoperative LIC in patients with venous malformations, demonstrating a significant dose-response relationship. Collectively, these findings suggest that ΔD-dimer is independently associated with postoperative LIC and may serve as a risk marker for perioperative coagulation monitoring.

Zhang R
Luo H
Jiang L
Jiang C
Cai T
He J
Chen K
Chen D
Zhan T

Humans
Fibrin Fibrinogen Degradation Products
Female
Male
Retrospective Studies
Vascular Malformations
Veins
Adult
Risk Factors
Child
Infant
Postoperative Complications
Perioperative Period
Child, Preschool
Adolescent


[Factor analysis and tempral distribution of postoperative lower limb deep venous thrombosis in patients with cervical spine fracture and paraplegia]

Abstract: To investigate the risk factors and tempral distribution of lower extremity deep vein thrombosis(DVT) formation after surgery in patients with cervical spine fracture and paraplegia. A total of 98 patients with cervical fracture and paraplegia admitted between January 2020 and January 2023 were enrolled in this study, including 50 males and 48 females. The age ranged from 18 to 80 years with a mean of (63.39±7.26) years, and the body mass index (BMI) ranged from 22.35 to 28.17 with a mean of (24.64±1.71) kg·m-2. Patients were divided into a DVT group (n=22) and a non-DVT group (n=76) based on the occurrence of postoperative DVT. General clinical data were compared between the two groups. The tempral distribution of DVT occurrence was analyzed in DVT patients at preoperation and on postoperative days 1,3,7, and 14, along with management strategies for different types of thrombus formation. Logistic regression analysis was performed to identify independent risk factors associated with postoperative DVT in patients with cervical fracture and paraplegia. A nomogram model was then constructed based on these identified independent predictors to estimate the risk of postoperative DVT in this patient population. Among the 98 patients who underwent surgical treatment for cervical fractures, 22 developed DVT, yielding an incidence rate of 22.45% (22/98). The peak onset of DVT occurred on the first postoperative day. The number of DVT cases detected preoperatively and on postoperative days 1,3,7, and 14 were 0,16,1,1, and 4, respectively. BMI≥25 kg·m-2, comorbid hypertension, elevated hemoglobin levels, high hematocrit, and the presence of large vascular atherosclerotic plaques were identified as independent risk factors for postoperative DVT in patients with cervical fracture and paraplegia (P<0.05). A nomogram model was constructed based on these indicators. Internal validation using Bootstrap resampling (1 000 replications) demonstrated that the model yielded an area under the curve (AUC) of 0.928, 95%CI(0.829, 0.990), with a specificity of 0.942 and a sensitivity of 0.872 for predicting postoperative DVT. Postoperative day 1 is the peak time for DVT occurrence. It is recommended that thromboprophylaxis measures be implemented as early as during or immediately after surgery. BMI, hypertension, hemoglobin, hematocrit, and atherosclerotic plaques in major vessels are independent risk factors for postoperative DVT. The nomogram constructed based on these factors can effectively predict the occurrence of postoperative DVT in patients with cervical spine fractures and paraplegia.

Zhongguo gu shang = China journal of orthopaedics and traumatology

Humans
Female
Venous Thrombosis
Spinal Fractures
Middle Aged
Lower Extremity
Male
Risk Factors
Paraplegia
Cervical Vertebrae
Adult
Aged
Postoperative Complications
Aged, 80 and over
Adolescent
Young Adult


Clinical Impact of Inherited Thrombophilia in Patients With Thrombosis: Evaluating the Real Risk of FVL, PTG20210A, and MTHFR Mutations in the Kurdistan Region of Iraq

Abstract: BackgroundInherited thrombophilia, particularly Factor V Leiden (FVL) mutation, globally, stands as a known contributing factor for venous thromboembolism (VTE). However, there are minimal case-control studies about the genetic composition and risk of these mutations within the Kurdistan Region of Iraq (KRI). This study's goal was to analyze the frequency and clinical significance of FVL, Prothrombin G20210A, and MTHFR C677T mutations in patients from Sulaymaniyah province.MethodsWithin this prospective case-control study, we analyzed 147 unselected patients (aged 18-49) with documented VTE (DVT, PE, or PVT) and 100 age and sex matched healthy controls. Molecular analysis was performed using multiplex PCR and reverse hybridization.ResultsIn the patient cohort, 55.8% had at least one prothrombotic mutation. The frequency of FVL was 14.3% in the patient cohort compared to 8% in the control group. FVL carriers showed a remarkably higher rate of recurrent thrombosis compared to non-carriers (71% vs. 40%; p = 0.041). Furthermore, FVL carriers had a five-fold increased risk for recurrent DVT (OR 5.4, 95% CI 0.778-37.505) and were significantly more likely to have a positive family history (p = 0.005). While MTHFR C677T was highly prevalent in both groups (48% patients, 49% controls), it was not identified to be an independent risk factor for VTE.ConclusionFVL is classified as a strong contributing factor for recurrent thrombosis in Sulaymaniyah. The high regional prevalence of FVL shows the need for targeted genetic screening in young patients, presenting with unprovoked or recurrent DVT, particularly when a family history is present.

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis

Abdulqader AMR
Noori AS
Noori AS
Mohammed NH
Abdalla HS
Mohammed RS
Mahmood SN


[Analysis of Risk Factors and Construction of Predictive Model for Iliac Vein Compression Syndrome Combined with Deep Vein Thrombosis of the Lower Extremities]

Abstract: To explore the risk factors of lower extremity deep vein thrombosis (DVT) in patients with iliac vein compression syndrome (IVCS) and to construct a risk prediction model. A total of 187 patients with IVCS admitted to The First Hospital of Lanzhou University from January 2023 to December 2024 were selected as the research subjects. Clinical data such as gender, age, underlying diseases, surgical history, anticoagulation history, body mass index (BMI), and laboratory test results of all patients were collected. According to whether the patients were combined with lower extremity DVT, they were divided into the DVT group (90 cases) and the non-DVT group (97 cases). Univariate and multivariate Logistic regression analyses were used to analyze the risk factors of lower extremity DVT in patients with IVCS. One hundred patients with IVCS admitted to our hospital from January 2025 to July 2025 were selected as the validation group for model validation. The Hosmer-Lemeshow test was used to evaluate the goodness-of-fit of the model, and the predictive performance of the model was evaluated based on the area under the receiver operating characteristic (ROC) curve (AUC). There were statistically significant differences between the DVT group and the non-DVT group in terms of age, BMI, lower extremity mobility disorder, postoperative infection, previous history of thrombosis, D-dimer levels, anticoagulation history, bed rest time, uric acid levels, prothrombin time, and fibrinogen levels (P < 0.05). Multivariate Logistic regression analysis revealed advanced age (OR =1.107, 95%CI : 1.033-1.187, P =0.004), plasma D-dimer >0.5 mg/L (OR =12.799, 95%CI : 1.124-145.782, P =0.040), BMI >25 kg/m2 (OR =5.695, 95%CI : 1.474-22.008, P =0.012), previous history of thrombosis (OR =40.453, 95%CI : 7.234-226.214, P < 0.001), no history of anticoagulation (OR =8.020, 95%CI : 2.274-28.279, P =0.001), bed rest time >72 hours (OR =38.500, 95%CI : 2.696-549.888, P =0.007), hyperuricemia (OR =1.026, 95%CI : 1.016-1.035, P < 0.001) and hyperfibrinogen (OR =3.786, 95%CI : 1.366-10.491, P =0.010) were independent risk factor for lower extremity DVT in patients with IVCS. The Hosmer-Lemeshow test showed that, χ2 =9.608, the P value was 0.294, the goodness-of-fit of the model was good. ROC curve analysis showed that the AUC of the model was 0.946 (95%CI : 0.914-0.978), the specificity was 0.918, and the sensitivity was 0.833. The prediction accuracy of this model was 90.00%, and the Kappa consistency coefficient was 0.780. Advanced age, elevated D-dimer, BMI >25 kg/m2, previous history of thrombosis, no anticoagulation prevention, bed rest time >72 hours, hyperuricemia and hyperfibrinogen are all independent risk factors for lower extremity DVT in patients with IVCS. In clinical work, these factors should be emphasized and active intervention measures should be taken to prevent the occurrence of lower extremity DVT, and improve the prognosis of diseases.

Zhu H
Xi YM
Ma HJ
Qin LN
Li SX
Xu WY
Bai YW

Humans
Venous Thrombosis
Risk Factors
May-Thurner Syndrome
Lower Extremity
Iliac Vein
Logistic Models
Female
Fibrin Fibrinogen Degradation Products


[Predictive Value of a Risk Assessment Model Based on Coagulation Biomarkers for Venous Thromboembolism after Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia]

Abstract: To construct a risk assessment model for venous thromboembolism (VTE) in children with acute lymphoblastic leukemia (ALL) after transplantation, and to explore the value of this new model in predicting the risk of post-transplant VTE in children with ALL. A total of 113 children with ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at Children's Hospital of Soochow University were enrolled. According to the occurrence of VTE within 30 days after transplantation, the children were divided into VTE group and non-VTE group. Differences in the levels of coagulation markers and the distribution of other thromboembolism-related clinical risk factors were compared between the two groups. Logistic regression analysis was used to screen independent risk factors for post-transplant VTE. Based on these factors, a new VTE risk assessment model was established, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the new model for VTE in children with ALL after transplantation, as well as to compare its advantages over traditional methods. In the VTE group, the plasma levels of tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer (DD) were significantly higher than those in the non-VTE group, while the fibrinogen (FIB) level was significantly lower (all P < 0.05). In the VTE group, the duration of ALL was generally longer, and the detection rates of granulocytopenia, agranulocytosis, and peripherally inserted central catheter (PICC)-related bloodstream infection (CRBSI) were significantly higher than those in the non-VTE group (all P < 0.05). Multivariate analysis showed that t-PAIC >4.3 ng/ml (OR =30.19, P =0.005) and APTT >31.8 s (OR =12.17, P =0.015) were independent risk factors for post-transplant VTE in children with ALL. A new VTE risk assessment model was established based on these two risk factors. The model showed significantly superior performance in predicting post-transplant VTE in children with ALL compared with individual coagulation and fibrinolysis indicators, as well as the traditional Caprini score and DIC score, with an AUC of 0.90 (P =0.001). The novel thrombotic marker t-PAIC has important clinical value in the early prediction of VTE in children with ALL after HSCT. Compared with the traditional thrombosis risk assessment models, the new model established based on t-PAIC and APTT exhibits superior diagnostic performance and clinical applicability in the pediatric ALL population.

Wei J
Chen F
Tan QX
Wang ZZ
Xue J
Shen HJ

Precursor Cell Lymphoblastic Leukemia-Lymphoma


[Validation of the Predictive Ability of IMWG, IMPEDE and SAVED Thrombosis Risk Stratification Systems for Venous Thromboembolism in Chinese Multiple Myeloma Patients]

Abstract: To validate the predictive ability of the International Myeloma Working Group (IMWG) venous thromboembolism (VTE) scoring system, the IMPEDE VTE scoring system, and the SAVED scoring system for VTE in Chinese multiple myeloma (MM) patients. A total of 415 patients with MM who visited The First Affiliated Hospital of Soochow University from January 1, 2019 to June 30, 2023 were included in the research cohort, and a retrospective analysis of their data was conducted. These patients were scored according to the IMWG, IMPEDE, and SAVED thrombosis risk models, respectively, and the predictive value of these three scoring models for VTE events was evaluated. The cumulative incidence of VTE events was 7.0% in the 415 patients. Both the IMWG score and the IMPEDE score demonstrated predictive value for VTE events. Each 1-point increase in the IMWG score was significantly associated with VTE events after treatment initiation (HR=3.41, 95%CI : 2.48-4.69, P < 0.001). Similarly, each 1-point increase in the IMPEDE score was also significantly associated with VTE events after treatment initiation (HR=2.46, 95%CI : 1.95-3.10, P < 0.001). In contrast, the SAVED score did not show significant predi- ctive value for VTE events in Chinese MM patients (P =0.693). However, according to the IMWG risk stratification, the vast majority of patients (97.3%) were classified into the high-risk group; in contrast, only 1 case (0.2%) was categorized into the high-risk group based on the IMPEDE risk stratification, indicating that these two risk stratification criteria are not suitable for Chinese patients. Therefore, patients were regrouped according to the IMWG score: ≤2 points as low-risk (163 cases), 3-4 points as intermediate-risk (214 cases), and ≥5 points as high-risk (38 cases); The 6-month cumulative incidence of VTE events in the high-risk group was 36.8%, which was significantly higher than that in the intermediate- and low-risk groups (P < 0.001, log-rank test). Patients were regrouped according to the IMPEDE score: ≤3 points as low-risk (265 cases), 4-5 points as intermediate-risk (131 cases), and ≥6 points as high-risk (19 cases); The 6-month cumulative incidence of VTE events in the high-risk group was 42.1%, which was significantly higher than that in the intermediate- and low-risk groups (P < 0.001, log-rank test). The IMWG score and the IMPEDE score have predictive value for VTE events in Chinese patients with MM, but restratification of patients based on these scores is required, while the SAVED score is not applicable to Chinese MM patients.

Huang Y
Wu XY
Shen HM
You HY
Yan Z
Zhai YY
Shi XL
Shang JJ
Jin S
Yan LZ
Wu DP
Fu CC

Humans
Multiple Myeloma
Venous Thromboembolism
Retrospective Studies
Risk Assessment
Risk Factors
East Asian People


[Analysis of Clinical Features of Newly Diagnosed Multiple Myeloma Complicated with Light Chain Amyloidosis]

Abstract: To analyze the clinical characteristics of patients with multiple myeloma (MM) complicated with light chain amyloidosis (AL), particularly those with cardiac amyloidosis (CA), in order to provide evidence for early identification. Clinical data were retrospectively collected from 359 newly diagnosed MM patients at the First Affiliated Hospital of Soochow University from August 2017 to December 2023. Based on histopathological results, patients were grouped to compare the clinical characteristics between the multiple myeloma with amyloid light-chain (MM-AL) group and the multiple myeloma without amyloid light-chain (MM without AL) group, as well as between the cardiac involvement and non-cardiac involvement subgroups within the MM-AL cohort. MM-AL patients accounted for 19.5% (70/359), of whom 30.0% had cardiac involvement. Compared with the MM without AL group, the MM-AL group had a higher proportion of λ light chain type (65.7% vs. 45.0%), a higher proportion of frail patients (45.7% vs. 29.1%), a lower proportion of DS stage III (84.3% vs. 93.4%), fewer patients presenting with bone pain as the initial symptom (45.7% vs. 69.2%), and higher proportions of patients with heart failure (12.8% vs. 4.2%) and non-hypoproteinemia polyserositis (27.2% vs. 5.9%) (all P < 0.05). Electrocardiogram abnormalities (low voltage, pseudo-infarction) were observed only in the MM-AL group. Compared with those without cardiac involvement, MM-CA patients had a higher proportion of light chain type (47.6% vs. 18.4%), a higher proportion of congestive heart-failure at onset (33.3% vs. 4.1%), a higher incidence of major adverse cardiovascular events during treatment (33.3% vs. 2.0%), and significantly elevated levels of NT-proBNP and hs-TnT, as well as a higher incidence of electrocardiogram abnormalities (all P < 0.05). Multivariate analysis showed that non-hypoproteinemia polyserositis (OR =7.66, P < 0.001) and λ light chain type (OR =2.40, P =0.017) were independent risk factors for MM complicated with AL. In terms of cytogenetics, the proportion of high-risk cytogenetic abnormalities was lower in MM-CA patients compared with those without cardiac involvement (14.3% vs. 36.7%, P =0.047). Patients with MM complicated by AL present with distinct clinical and cytogenetic features. The presence of λ light chain type and non-hypoproteinemic polyserous effusions are independent risk factors. Electrocardiographic findings of low voltage and pseudoinfarction patterns are suggestive of early recognition of AL and cardiac involvement.

Humans
Multiple Myeloma
Retrospective Studies
Immunoglobulin Light-chain Amyloidosis
Immunoglobulin Light Chains
Amyloidosis
Female


[The Clinical Significance and in vitro Experimental Study of hnRNP U in Multiple Myeloma]

Abstract: To analyze the expression level of heterogeneous nuclear ribonucleoprotein U (hnRNP U) and its correlation with prognosis in patients with multiple myeloma (MM), and explore the functional role as well as molecular mechanism of hnRNP U, thereby providing a theoretical basis for development of hnRNP U as a novel therapeutic target for MM. Based on Gene Expression Omnibus (GEO) database, the expression of hnRNP U in plasma cell diseases and healthy controls was compared. Based on the GSE9782 dataset (n =264), patients were divided into high expression group (n =114) and low expression group (n =150) according to the median expression level of hnRNP U . Overall survival (OS) between the two groups was compared. RPMI 8226, NCI-H929 and MM.1S cell lines were selected as tool cell lines. Following knockdown of hnRNP U by shRNA, the cell proliferation was detected by CCK-8. The apoptosis of MM cells was analyzed by Annexin V/7-AAD staining, and cell cycle was detected by BrdU/DAPI staining followed by flow cytometric analysis. The effect of hnRNP U on the biological characteristics of human MM cells was explored. The effect of knockdown of hnRNP U on DNA damage response pathways was analyzed by Western blot. Analysis of GSE5900 and GSE2113 datasets showed that the mRNA level of hnRNP U rose with the increased degree of malignancy of plasma cell diseases. Survival curve analysis of GSE9782 dataset showed that the high expression group of hnRNP U had a shorter OS than that of the low expression group. Down-regulation of hnRNP U in MM cell lines RPMI 8226, NCI-H929 and MM.1S could inhibit the cell proliferation, promote cell apoptosis and arrest the cell cycle. After knocking down hnRNP U, the expression levels of cleaved PARP and p-H2A.X, as the important markers of activated DNA damage pathway, were significantly increased in MM cells. hnRNP U is highly expressed in several plasma cell diseases including MM, and the high expression of hnRNP U in MM patients predicts poor prognosis. Knocking down hnRNP U can inhibit the malignant progression of MM cells, which is possibly associated with aggravated DNA damage.

Qi WH
Xu CL
Zhang LL
Tang KK
Lei L
Chu JH
Zhu TT


[Multi Model Study and Clinical Decision Analysis of Early Death Risk Warning in Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab]

Abstract: To retrospectively analyze the early death of patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab, build a risk warning model and verify its clinical decision-making benefits. The clinical data of 112 NDMM patients treated with daratumumab combination therapy in Tangshan Gongren Hospital from June 2018 to June 2022 were retrospectively collected as the training set, and the clinical data of 78 NDMM patients who received daratumumab combination therapy in the same period were collected as the validation set. According to whether early death occurred during regular follow-up (OS <24 months), the patients were divided into early death group (26 cases) and non-early death group (86 cases). The differences of clinical data between the two groups were analyzed, and Kaplan-Meier survival curves were used to analyze the survival difference of patients with different efficacy. Univariate and multivariate Cox regression analysis were used to analyze the independent risk factors affecting early death of NDMM patients treated with daratumumab. A warning nomogram model for the risk of early death was established, and the predictive performance was analyzed by receiver operating characteristic (ROC) curve and verified internally. According to whether the efficacy of daratumumab treatment achieved partial response (PR), the patients were divided into <PR group (32 cases) and ≥PR group (80 cases). Kaplan-Meier analysis found that the median OS of both groups were not reached, while the OS of patients with efficacy ≥PR was significantly longer than that of patients with efficacy <PR (log-rank χ2=14.225, P <0.001). Multivariate Cox regression analysis showed that older age, R-ISS stage Ⅲ, elevated hs-CRP, and efficacy <PR were independent risk factors for early death in NDMM patients (all P <0.05), and a nomogram model for early death risk in NDMM patients was constructed. ROC analysis and DeLong test showed that the AUC of the nomogram model was 0.894(95%CI : 0.828-0.959), which was higher than that of each individual model, and the differences were statistically significant (all P <0.05). Internal and external validation showed that the nomogram model was stable and had a positive net benefit. The OS of NDMM patients who did not reach PR after daratumumab treatment can be affected. Daratumumab treatment early death risk warning model for NDMM has good efficacy, and can be targeted at high-risk population for intensive treatment to improve prognosis.

Humans
Multiple Myeloma
Antibodies, Monoclonal
Retrospective Studies
Risk Factors
Clinical Decision-Making
Nomograms


[Correlation of CD269 Expression Patterns with Antigen Expression and Molecular Cytogenetics Abnormalities in Patients with Multiple Myeloma]

Abstract: To explore the correlation between CD269 expression patterns in multiple myeloma (MM) cells and the expression of other antigens and molecular cytogenetics. Flow cytometry was used to detect the expression level of CD269 in bone marrow plasma cells of 115 newly diagnosed MM patients. The patients were subsequently divided into CD269- group (<20%), CD269 partial expression group (20%-80%), and CD269 high expression group (>80%). The CD269 partial expression group and high expression group were combined as the CD269+ group. The immunophenotype of bone marrow plasma cells was analyzed by flow cytometry. Molecular cytogenetic analysis was performed using combined probe fluorescence in situ hybridization technology. There were 27 patients (23.5%) in the CD269- group, 42 patients (36.5%) in the CD269 partial expression group, and 46 patients (40.0%) in the CD269 high expression group. The expression rate of CD56 antigen was 72.7% in the CD269+ group, which was higher than 48.1% in the CD269- group (P <0.05). The expression rates of CD56 and CD117 antigen in the CD269 high expression group were 76.1% and 47.8%, respectively, which were higher than 69.0% and 16.7% in the CD269 partial expression group (both P <0.05). The CD56/CD117 co-expression rate in the CD269 high expression group was 39.1%, which was higher than 14.8% in the CD269- group and 14.3% in the CD269 partial expression group (both P <0.05). The positive rate of IgH/CCND1 gene fusion in the CD269- group was 63.0%, which was higher than 31.0% in the CD269 partial expression group, 19.6% in the CD269 high expression group, and 25.0% in the CD269+ group (all P <0.05). The IgH deletion rate was 13.0% in the CD269 high expression group, while no IgH deletion was observed in the CD269 partial expression group, with a statistically significant difference between the two groups (P <0.05). The expression of CD269 on bone marrow plasma cells in MM patients is significantly correlated with the expression of CD56 and CD117, as well as IgH/CCND1 gene fusion and IgH deletion. The high expression of CD269 is associated with better prognosis related biological indicators.

Wang XF
Shao M
Liang C
Wen JW
Shi YP
Liu YR

Humans
Multiple Myeloma
Female
Flow Cytometry
Dipeptidyl Peptidase 4
Middle Aged
Immunophenotyping
CD56 Antigen
Aged
In Situ Hybridization, Fluorescence
Male
Plasma Cells
Chromosome Aberrations


[Clinical Characteristics and Prognosis of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia]

Abstract: To explore the clinical features, treatment strategies, and prognostic factors of patients with new diagnosed Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), thereby enhancing the diagnostic and therapeutic understanding of this disease. Comprehensive clinical data were collected from 35 newly diagnosed LPL/WM patients at our hospital between December 2015 and June 2024. A systematic analysis was conducted on baseline characteristics, laboratory parameters, treatment regimens, and follow-up information. Survival analysis was performed using the Kaplan-Meier method, and a Cox regression model was applied to assess prognostic factors. A total of 35 LPL/WM patients were enrolled, with a male predominance (91.4%) and a median age at diagnosis of 69 years (range: 32-83). The most common clinical manifestations were fatigue (45.7%), lower limb edema (28.5%), and lymphadenopathy (62.9%). Laboratory findings revealed anemia in 88.6% of patients. The vast majority (94.3%) secreted monoclonal IgM, one patient secreted monoclonal IgG, and one patient had both monoclonal IgM and IgG. The light chain type was predominantly kappa (77.1%). Molecular genetic testing showed a MYD88 L265P mutation rate of 82.4% (28/34), while the CXCR4 mutation rate was lower (17.6%, 3/17). The overall response rate was 82.4% in the treatment group containing Bruton's tyrosine kinase inhibitors (BTKi) and 66.7% in the non-BTKi treatment group. With a median follow-up of 70 months, one patient was lost to follow-up and 14 patients died. The median overall survival (OS) for the entire cohort was 71 months. Univariate analysis identified β2-microglobulin ≥4 mg/L at diagnosis was associated with OS (P =0.036) and PFS (P =0.021). Multivariate analysis confirmed β2-microglobulin ≥4 mg/L at diagnosis as an independent adverse prognostic factor for OS (HR =3.854, P =0.025) and PFS (HR=3.201, P =0.030), while receiving BTKi-containing therapy was identified as a protective factor for OS (HR=0.312, P =0.047). This study confirms that elevated β2-microglobulin levels are an independent adverse prognostic factor in patients with LPL/WM. In our center's cohort, patients receiving BTKi therapy achieve higher response rates and longer OS.

Humans
Waldenstrom Macroglobulinemia
Prognosis
Male
Aged
Middle Aged
Adult
Female
Aged, 80 and over


Lymphatic therapies open the valve in Marfan syndrome

Abstract: Myxomatous degeneration of the mitral valve (MDMV) is a common cardiovascular manifestation of Marfan syndrome (MFS), yet the role of lymphatic vessels in the disease progression remains unknown. In this Commentary, we discuss the study by Tan, Kume, and colleagues, which identifies defective lymphangiogenesis as a previously unrecognized driver of MDMV. Their work demonstrates that impaired lymphatic development and drainage promote valve inflammation through reduced ZFP36-mediated antiinflammatory signaling, whereas restoration of lymphatic function or pharmacological activation of ZFP36 with the FDA-approved drug FTY720 ameliorates disease progression. These findings establish lymphatic vessels as critical regulators of mitral valve homeostasis and support exploration of lymphatic-targeted therapeutic opportunities for MFS-associated valvular disease.

Marfan Syndrome
Humans
Animals
Mitral Valve
Lymphangiogenesis
Fingolimod Hydrochloride
Lymphatic Vessels
Heart Valve Diseases


Neuroprotective Delivery of Dexmedetomidine Liposomes Mitigates Cerebral Energy Crisis by Modulating Calcium-Driven Aerobic Glycolysis in Cerebral Ischemia-Reperfusion Injury

Abstract: Cerebral ischemia-reperfusion injury (CIRI) involves complex pathogenesis with limited therapeutic options. This study investigated whether dexmedetomidine liposomes (Dex-lip) exert neuroprotective effects by modulating astrocytic aerobic glycolysis via calcium signaling. In vivo CIRI model mice received Dex-lip, with or without the aerobic glycolysis inhibitor 2-deoxy-D-glucose (2-DG). Neurological function, cortical calcium levels, aerobic glycolysis-related protein expression, lactate production, and hippocampal neuronal damage were assessed. In vitro, astrocytes were treated with the calcium channel blocker nifedipine to evaluate intracellular calcium, lactate levels, and glycolysis-related gene expression. Dex-lip treatment reduced cortical calcium overload, upregulated aerobic glycolysis key proteins, increased lactate production, and attenuated hippocampal neuronal injury. These neuroprotective effects were abolished by 2-DG. In vitro, nifedipine lowered astrocytic calcium concentration, which paradoxically increased lactate production, elevated ECAR, and upregulated HK1, HK2, and PFK1 mRNA expression, confirming that calcium reduction promotes aerobic glycolysis. Dex-lip ameliorates CIRI by reducing astrocytic calcium overload, enhancing aerobic glycolysis and lactate supply to neurons, thereby preventing apoptosis. This study provides a mechanistic basis and therapeutic strategy for CIRI.

Animals
Dexmedetomidine
Reperfusion Injury
Neuroprotective Agents
Glycolysis
Liposomes
Calcium
Mice
Astrocytes
Brain Ischemia
Male
Mice, Inbred C57BL
Hippocampus
Neurons
Lactic Acid


A machine learning-based risk prediction model for Hospitalized patients with deep vein thrombosis

Abstract: Deep vein thrombosis (DVT) is a common thrombotic condition with substantial morbidity when not identified early. Machine learning (ML)-based predictive models may improve early identification of patients at high risk for DVT, but few clinically applicable early-risk models exist. To develop and internally validate a ML model using routinely available clinical and laboratory indicators for early risk prediction of DVT, and to identify the most influential predictors using model explainability techniques. We retrospectively analyzed clinical data from 231 patients evaluated at the Fifth Affiliated Hospital of Southern Medical University between January 2017 and June 2024. Patients were labeled as DVT occurrence (n = 159) or non-occurrence (n = 72). Seven candidate predictors were selected by Least Absolute Shrinkage and Selection Operator (LASSO) regression. The dataset was split into training (70%, n = 162) and test (30%, n = 69) sets. Five ML algorithms were trained: XGBoost, CatBoost, Random Forest (RF), Logistic Regression, and Support Vector Machine, with hyperparameter tuning on the training set. Model performance was assessed by 5-fold cross-validation and on the held-out test set using Area Under the Receiver Operating Characteristic Curve (AUC), accuracy, recall, and F1 score. The best model was further interpreted via feature importance and Shapley Additive Explanations (SHAP). LASSO selected seven predictors: hemoglobin, platelet count, leukocyte count, fibrinogen, prothrombin time, D-dimer (DD), and glucose. The Random Forest model showed the best discrimination (test-set AUC = 0.874), with favorable accuracy, recall, and F1 compared with other classifiers (detailed metrics reported in the manuscript). In the RF model, D-dimer had the highest feature-importance contribution; SHAP analysis confirmed DD as the dominant risk driver and characterized the directions and relative effects of other features. We developed an internally validated ML model for early DVT risk prediction using seven routine clinical variables; Random Forest achieved the best performance and identified D-dimer as the most influential predictor. This model may support earlier identification and intervention for patients at risk of DVT, pending external validation and prospective evaluation.

Wang X
Chen X
Mao J
Liu M
Yan L
Sun W
Song J

Humans
Venous Thrombosis
Predictive Learning Models
Retrospective Studies
Female
Machine Learning
Random Forest
Boosting Machine Learning Algorithms
Risk Assessment
Male
Middle Aged
Risk Factors
Prediction Algorithms
Aged
Classification Algorithms
Fibrin Fibrinogen Degradation Products
ROC Curve
Hospitalization
Logistic Models


[Volontary poisoning with yew ( Taxus baccata) : a fatal case]

Abstract: Poisoning with Taxus baccata (common yew) is a life-threatening emergency due to its major cardiotoxicity. The taxines it contains block cardiac sodium channels, rapidly leading to severe arrhythmias, cardiogenic shock, and often cardiac arrest. Management is exclusively symptomatic and relies on intensive hemodynamic support, including advanced resuscitation and, in some cases, the use of extracorporeal circulatory support (ECMO). The administration of antidotes such as DigiFab®, although experimental and not formally validated for this indication, may be considered based on pharmacological analogies with digoxin.

Ait Moussa N
Delcour A
Morimont P
Lambermont B

Taxus
Humans
Plant Poisoning
Fatal Outcome
Shock, Cardiogenic

Case Reports
English Abstract
Journal Article


[Austrian Syndrome : when Pneumococcus strikes three times]

Abstract: Austrian syndrome is characterized by the triad of pneumonia, meningitis, and endocarditis due to Streptococcus pneumoniae («pneumococcus»). Endocarditis, often occurring in the background, is frequently diagnosed late and requires prompt medical and sometimes surgical management. We report the case of a 51-year-old man admitted for confusion. The initial evaluation revealed bacterial meningitis documented by purulent cerebrospinal fluid, associated with right basal pneumonia. Blood cultures and cerebrospinal fluid cultures identified Streptococcus pneumoniae. The clinical course was marked by hemodynamic deterioration with circulatory shock, multiorgan failure, and cardiac arrhythmias, prompting the performance of transoesophageal echocardiography. This revealed aortic valve endocarditis complicated by a mitro-aortic curtain abscess and severe aortic regurgitation due to valvular perforation. Intensive care management with targeted antibiotic therapy and urgent valve surgery was required. This case illustrates the importance of systematically investigating for endocarditis in any patient with pneumococcal meningitis, particularly when pneumonia is present, to avoid diagnostic delay with potentially fatal consequences.

Humans
Male
Middle Aged
Endocarditis, Bacterial
Meningitis, Pneumococcal
Syndrome
Streptococcus pneumoniae
Pneumonia, Pneumococcal
Pneumococcal Infections


[Pulmonary embolism following smoke inhalation]

Abstract: Carbon monoxide poisoning is one of the most common types of intoxication and is linked to a high mortality rate when not managed appropriately. We are discussing the case of a patient found unconscious after a house fire, presenting a smoke inhalation injury and particularly carbon monoxide poisoning. The clinical course was marked by the development of a massive bilateral pulmonary embolism despite thromboprophylaxis. This case highlights the increased thromboembolic risk, which can persist up to 90 days after carbon monoxide poisoning. We analyse the cardiovascular manifestations while focusing on the thromboembolic risks. Finally, we provide a brief overview of the pathophysiology and management of this condition.

Humans
Pulmonary Embolism
Smoke Inhalation Injury
Carbon Monoxide Poisoning
Male


[Coronary artery anomalies associated with bicuspid aortic valve]

Abstract: Bicuspid aortic valve (BAV) is the most common congenital heart disease. It is often associated with aortic abnormalities and, more rarely, with coronary anomalies that may influence surgical strategy. We describe a 38-year-old patient with a Sievers type I BAV. Coronary CT angiography revealed an abnormally high proximal origin of the right coronary artery, with a 10 mm ectatic dilation at its origin followed by a return to normal caliber. This feature prompted a change in operative strategy: mechanical aortic valve replacement instead of a Ross procedure, more distal aortic clamping, and a «lazy-S» aortotomy. The procedure was completed without complications. Coronary anomalies are more frequent in patients with BAV than in the general population. Their preoperative identification is essential to prevent intraoperative complications. Multimodal imaging plays a key role in optimizing surgical planning in line with current recommendations. Coronary anomalies associated with BAV should be systematically screened for before any valve surgery. This case highlights the importance of thorough preoperative assessment and appropriate technical adaptation to ensure operative safety.

Damès S
Madani S
Durieux R
Tchana-Sato V
Radermecker M

Humans
Bicuspid Aortic Valve Disease
Aortic Valve
Coronary Vessel Anomalies
Heart Valve Diseases
Adult
Male


Idiopathic Intracranial Hypertension Masquerading as Cerebral Venous Sinus Thrombosis: A Diagnostic Challenge

Abstract: Idiopathic intracranial hypertension (IIH) is a syndrome identified by raised intracranial pressure (ICP), with absence of a mass lesion/hydrocephalus, typically affecting obese women of childbearing age.1 It may present with similar symptoms such as headache, visual disturbances, and papilledema, making clinical differentiation challenging.1 IIH primarily threatens vision, and treatment focuses on lowering ICP using medications like acetazolamide, serial lumbar punctures, or surgical interventions such as optic nerve sheath fenestration or CSF shunting in refractory cases.2 Misdiagnosing IIH as CVST can lead to unnecessary anticoagulation, which may prove to be harmful for the patient.

The Journal of the Association of Physicians of India

Humans
Sinus Thrombosis, Intracranial
Pseudotumor Cerebri
Diagnosis, Differential
Female
Adult


Profile of Philadelphia Chromosome Negative (Ph-) Myeloproliferative Neoplasm with Special Emphasis on Vascular Thrombotic Events and the Response to Cytoreductive Therapy in Polycythemia Vera and Essential Thrombocythemia Patients: A Single Center Study from Kerala

Abstract: Thrombotic events are a major morbidity among Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-MPN) patients. There is a lack of data from Kerala regarding the profile of Ph-MPN and the prevalence of thrombosis among these patients. To study the clinical profile, driver mutations, incidence of thrombotic events among Ph-MPN patients, and the response to hydroxyurea therapy. We reviewed the medical records of 84 Ph-MPN patients who were on follow-up from April 2019 to June 2023 in a tertiary care hospital in Kerala. There were 48 polycythemia vera (PV), 16 essential thrombocythemia (ET), 14 primary myelofibrosis (PMF), and six unclassifiable MPN (MPN-u) patients. The incidence of Janus kinase 2 (JAK2) mutation was 96, 62.5, and 79% among PV, ET, and PMF patients, respectively. The incidence of calreticulin (CALR) mutation was 37.5 and 21% among ET and PMF patients, respectively. The incidence of thrombotic events was 23/48 (48%), 7/16 (43.5%), and 6/14 (42.8%) among PV, ET, and PMF patients, respectively. All ET and PMF patients with thrombotic events were JAK2V617F-mutated. Eighty-seven percent of the evaluable patients on hydroxyurea for PV achieved freedom from therapeutic phlebotomies. ET patients who were on hydroxyurea achieved a median platelet count of 4.3 lakhs/µL (3.16-6.08). There is a higher incidence of thrombosis among Ph-MPN patients from Kerala, which needs to be ascertained in a population-based study. JAK2V617F mutation is the major determinant of thrombotic episodes in ET and PMF. Hydroxyurea is an effective cytoreductive therapy in PV and ET.

Prabhu RS
Nameera RS
Thangal K SML
Nair PR

Humans
Thrombocythemia, Essential
Polycythemia Vera
Male
Female
Janus Kinase 2
Middle Aged
Thrombosis
Hydroxyurea
Adult
Calreticulin
India
Aged
Mutation
Philadelphia Chromosome
Retrospective Studies
Incidence
Myeloproliferative Disorders
Cytoreduction Surgical Procedures
Primary Myelofibrosis


Gastric Antral Vascular Ectasia in a Patient with Chronic Myeloid Leukemia on Imatinib Treatment: A Rare Case Report

Abstract: Imatinib is the standard first-line therapy for chronic myeloid leukemia (CML) and is generally well tolerated. Gastrointestinal adverse effects are common; however, gastric antral vascular ectasia (GAVE) is an extremely rare complication. We report a 77-year-old woman with chronic-phase CML who developed severe upper gastrointestinal bleeding 1 month after the initiation of imatinib therapy. Endoscopy revealed classic features of GAVE, and no alternative etiology was identified. Discontinuation of imatinib resulted in complete clinical and endoscopic resolution. Clinicians should consider this rare complication in patients receiving imatinib who present with unexplained anemia or gastrointestinal bleeding.

Leukemia, Myelogenous, Chronic, BCR-ABL Positive


Acute Transverse Myelitis and Pulmonary Thromboembolism Following Scorpion Envenomation: A Rare Case Report

Abstract: Scorpion envenomation is common in India but rarely leads to neurovascular complications. We present a rare case of a 72-year-old male who developed acute transverse myelitis, subarachnoid hemorrhage, and pulmonary thromboembolism following a scorpion sting. The patient presented with sudden-onset paraparesis. Magnetic resonance imaging (MRI) of the spine revealed longitudinal hyperintensity from T5 to T12, suggestive of transverse myelitis, along with evidence of spinal subarachnoid hemorrhage. Computed tomography (CT) pulmonary angiography confirmed bilateral pulmonary thromboembolism. Cerebrospinal fluid analysis showed a hemorrhagic tap with elevated protein and lactate dehydrogenase (LDH), but no infectious or malignant cells. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. Nerve conduction studies showed bilateral sensorimotor axonal polyneuropathy. The patient was treated with corticosteroids and anticoagulants and showed gradual improvement. This case underscores the systemic toxicity of scorpion venom and highlights the importance of early recognition and multidisciplinary management of rare neurovascular complications.

Rijhwani P
Jain S
Gupta D
Agarwal P
Swami D
Agarwal A

Humans
Male
Aged
Scorpion Stings
Myelitis, Transverse
Pulmonary Embolism
Animals
Scorpion Venoms
Magnetic Resonance Imaging


A Complex Case of Systemic Sclerosis with Concurrent Breast Malignancy and Treatment-related Complications

Abstract: Systemic sclerosis (SSc) is a complex autoimmune disease marked by vasculopathy, fibrosis, and multisystem involvement. Interstitial lung disease (ILD) and pulmonary hypertension (PH) are major mortality contributors. Importantly, SSc is associated with an increased risk of malignancy. This report presents a challenging case of SSc with severe Raynaud's phenomenon (RP), digital gangrene, calcinosis cutis, extensive ILD, severe PH, and right heart failure. The patient underwent mesenchymal stem cell therapy (MST), following which she developed breast cancer and chemotherapy-related complications, ultimately leading to death. This case highlights the need for timely intervention, screening for malignancy, and awareness of potential therapy-related risks in SSc.

Humans
Female
Scleroderma, Systemic
Breast Neoplasms
Hypertension, Pulmonary
Raynaud Disease
Fatal Outcome
Lung Diseases, Interstitial
Mesenchymal Stem Cell Transplantation
Middle Aged


Bidirectional Ventricular Tachycardia Culminating in Cardiac Arrest: A Diagnostic and Management Conundrum

Abstract: Bidirectional ventricular tachycardia (BDVT) is a rare arrhythmia marked by beat-to-beat QRS axis alteration. We report a 36-year-old female with recurrent palpitations who presented with BDVT degenerating into polymorphic ventricular tachycardia and ventricular fibrillation. An extensive evaluation, including cardiac magnetic resonance imaging (MRI), stress and adrenaline provocation testing, and a comprehensive genetic arrhythmia panel, revealed no definitive etiology. Given the concern for proarrhythmic implantable cardioverter-defibrillator (ICD) shocks in a potential channelopathy and after shared decision-making, the patient was managed with high-dose beta blocker therapy. This case underscores the diagnostic and management challenges of BDVT in a structurally normal heart, particularly when balancing guideline recommendations against individualized patient factors.

Limaye SV
Anand AB
Nathani PJ
Lokhandwala YY

Humans
Female
Adult
Heart Arrest
Electrocardiography
Tachycardia, Ventricular
Tachycardia
Adrenergic beta-Antagonists
Defibrillators, Implantable
Ventricular Fibrillation


Ask-Upmark Kidney: A Rare Cause of Hypertension in Young Patients

Abstract: Ask-Upmark kidney was originally described as a congenital segmental hypoplasia of the kidney, but recent data suggest it to be a sequela of vesicoureteral reflux or pyelonephritis in early age. This segmental hypoplasia leads to hypertension in young people. This hypertension is treatable with a partial nephrectomy. This reported patient presented with hypertensive urgency in the OPD. On evaluation, he was found to have Ask-Upmark kidney. The patient was managed conservatively. In case of severe and progressive renal damage, surgical resection with or without transplant can be considered. If the disease is nonprogressive with normal kidney function, the patient can be managed with antihypertensive treatment alone. This is one of the rare causes of hypertension in young that should be kept in mind while evaluating such cases.

Humans
Hypertension
Male
Kidney
Antihypertensive Agents
Nephrectomy


An Unusual Case Report of Pseudothalamic Pattern of Sensory Loss in Lateral Medullary Syndrome

Abstract: Lateral medullary syndrome is a collection of different neurological symptoms after ischemic/hemorrhagic insult to either the posterior inferior cerebellar artery/vertebral artery or rarely the anterior inferior cerebellar artery, causing infarction of ipsilateral cerebellum and posterolateral medulla (Tiedt and Weidauer, 2013). Dizziness, nausea, vertigo, vomiting, nystagmus, ataxia, dysphagia, hoarseness of voice, ptosis, and sensory impairment of face and body are typical. Here we report an unusual presentation of a 47-year-old female who was hypertensive and diabetic and who complained of vertigo, nausea, vomiting, slurring of speech, facial deviation toward the left, and loss of pain and temperature over the right side of the face and body without any difficulty in swallowing or nasal regurgitation. The patient was eventually diagnosed with left lateral medullary syndrome, drawing attention to the rare and unusual presentation of the same.

Ballabh R
Chakraborty A
Kumar S
Maraskole PA
Rohatgi A
Kumar N

Humans
Female
Lateral Medullary Syndrome
Middle Aged
Magnetic Resonance Imaging
Medulla Oblongata


Diffuse Alveolar Hemorrhage in a Case of Granulomatosis with Polyangiitis: A Case Report

Abstract: Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary condition characterized by widespread bleeding into the alveoli, leading to respiratory failure. It can result from various etiologies, including autoimmune disorders, drug reactions, and infections. Here is a rare case of a 37-year-old male who presented with progressive dyspnea, hemoptysis, and hypoxemia. Chest imaging and bronchoscopy confirmed the diagnosis of DAH, while laboratory tests revealed ANCA-associated vasculitis. On diagnosis, the patient with granulomatosis with polyangiitis was initiated on corticosteroids and cyclophosphamide. Early initiation of immunosuppressive therapy and supportive care plays a crucial role in disease management, reducing morbidity in such cases.

Shaily KP
Mandadi M
Navothna S
Barthwal M

Humans
Male
Granulomatosis with Polyangiitis
Adult
Hemorrhage
Lung Diseases
Pulmonary Alveoli
Immunosuppressive Agents
Cyclophosphamide
Hemoptysis


Successful Management of Milroy's Disease: A Rare Condition Complicated by Tuberculous Pericardial Effusion

Abstract: Milroy's disease is a rare hereditary primary lymphedema, typically presenting at birth or early infancy with chronic lower limb swelling due to mutations in the FLT4 gene encoding VEGFR-3. While congenital lymphedema is the hallmark, its association with tubercular pericardial effusion leading to tamponade is extremely rare. We report an 18-year-old female with longstanding bilateral lower limb lymphedema who presented with progressive dyspnea and fever. Evaluation revealed tubercular pericardial effusion, and genetic testing confirmed an FLT4 mutation. The patient improved with antitubercular therapy and supportive care. This case emphasizes the need to consider rare systemic complications in congenital lymphedema syndromes to optimize early diagnosis and management.

Khan K
Quazi T
Jalgaonkar P
Bhrushundi M
Quazi S

Vascular Endothelial Growth Factor Receptor-3


A Study on Prehospital Factors Determining the Timely Arrival for Thrombolysis among Patients Presenting with Acute Ischemic Stroke at a Tertiary Care Center in South India

Abstract: Among ischemic stroke patients, prehospital delay is the most common reason for underutilization of thrombolysis. The study assessed prehospital factors contributing to delay and timely arrival among study participants. A cross-sectional study was carried out at the casualty department of Government Stanley Medical College and Hospital, South India. We selected 212 study participants by consecutive sampling. Data were collected by interviewing patients or accompanying family members using a semistructured questionnaire. Univariate analysis was followed by multivariate logistic regression to examine prehospital factors contributing to delay and timely arrival. Follow-up of eligible study participants for thrombolysis was performed using the National Institutes of Health Stroke Scale (NIHSS) and American Heart Association (AHA)-2019 checklist. The most common factors contributing to prehospital delay and timely arrival were found to be "unawareness regarding benefits of timely arrival among patients/relatives (48.7%)" and "apprehension of some serious health issue (50%)," respectively. The distance between the hospital and the place of onset of symptoms, stroke during sleep, mode of transport, National Institutes of Health Stroke Scale (NIHSS), and slurring of speech were found to have significant odds for timely arrival for intravenous thrombolysis (IVT). Among those who arrived on time (n = 60), 13 study participants could not undergo thrombolysis. The most common reason for this was refusal of thrombolysis (4, 6.7%), and other criteria, such as minor neurological deficits (4, 6.7%), rendered them ineligible for it. The study highlights factors associated with timely arrival at the hospital and further reasons for not undergoing IVT despite timely arrival among cases of acute ischemic stroke (AIS). There is also a need to generate awareness and disseminate information on the benefits of IVT, timely arrival, and prehospital factors; provide training in stroke preparedness; and strengthen the referral system to ensure maximum eligibility and utilization.

P S NS
Vadanere NP
Mugundhan K
Velayudham S
Jeyaraj M
Sowmini PR

Humans
Male
Cross-Sectional Studies
India
Thrombolytic Therapy
Tertiary Care Centers
Female
Middle Aged
Time-to-Treatment
Ischemic Stroke
Treatment Delay
Aged
Emergency Medical Services
Adult
Time Factors
Fibrinolytic Agents
Stroke


Colorectal Cancer Risk Factors in Adults in Nigeria

Abstract: Colorectal cancer (CRC) incidence is increasing in sub-Saharan Africa, including Nigeria, where more than half of patients die within 1 year due to late diagnosis and limited treatment. Without ready access to screening, identifying risk factors is critical. However, regional data are scarce, and it is unclear whether risk factors from high-income populations apply to Nigerians, who may have distinct clinicodemographic patterns and tumor characteristics. To assess whether 13 CRC risk factors identified in high-income populations are associated with CRC in adults in Nigeria. This multicenter case-control study was conducted in 6 hospitals across 3 of Nigeria's 6 geopolitical zones, with recruitment from April 2020 to September 2024. Participants were patients newly diagnosed with CRC and cancer-free controls matched on age, sex, location, education, and recruitment site. Data were analyzed from April 2023 to November 2025. Family history of cancer, anthropometric factors (adult height, body mass index [BMI], and somatotype or body size over the life course), physical activity, and dietary and lifestyle factors (processed meat, red meat, fruit, vegetables, fiber, alcohol, smoking, and diabetes). The associations of risk factors with CRC were assessed using odds ratios (ORs) and 95% CIs, estimated using multivariable unconditional logistic regression. Among 2063 participants (1103 [53.5%] male; median [IQR] age, 54 [42-64] years) enrolled, most had secondary education or higher (1756 participants [85.2%]), lived in urban areas (1817 participants [88.1%]), and were Yoruba (1524 participants [73.9%]). Cases were older than controls (median [IQR] age, 56 [45-66] vs 52 [41-63] years) but were otherwise similar. Family history of cancer (OR, 1.55; 95% CI, 1.06-2.26), adult height (OR per 5-cm increase, 1.09; 95% CI, 1.00-1.20), body size or type over the life course (tertile 3 vs tertile 1: OR, 1.88; 95% CI, 1.30-2.72), and processed meat intake (lowest vs highest tertile of intake: OR, 1.43; 95% CI, 1.07-1.91) were positively associated with CRC risk, and an inverse U-shaped association was identified between physical activity and CRC risk (OR vs first quartile of activity, quartile 2: 0.63; 95% CI, 0.44-0.88; quartile 3: 0.52; 95% CI, 0.34-0.79; quartile 4: 0.77; 95% CI, 0.58-1.02), consistent with data from high-income populations. BMI was inversely associated with CRC risk (OR vs BMI 18.5-24.9, BMI <18.5: 2.63; 95% CI, 1.79-3.86; BMI ≥30: 0.42; 95% CI, 0.28-0.63), likely reflecting prediagnostic weight loss. No associations with diabetes, smoking, or intakes of red meat, fruit, vegetables, fiber, or alcohol were observed, likely due to low prevalence or variability. This case-control study of CRC risk factors in adults in Nigeria found CRC risk patterns similar to those observed in high-income populations. These insights offer immediate opportunity to tailor education, prevention, and early detection in the region, especially as economic development leads to lifestyles more similar to high-income populations. These data provide a foundation for prospective research and investigations in other African populations.

Alatise OI
Peeri NC
Abdulkareem FB
Badejo OA
Gali BM
Oludara M
Okereke CE
Olatoke SA
Ademakinwa OR
Alabi A
Aderounmu A
Adeomi A
Mohammed T
Adegboyega O
Adisa A
Ajewole O
Famurewa OC
Agodirin SO
Ariyibi O
Nggada HA
Babatunde OJ
Badmos K
Balogun OS
Bamidele CO
Batta CS
Betiku OA
Bojuwoye MO
Choonawala NR
Cookey C
Daji FY
Egberongbe A
Esan O
Folaranmi OO
Fasiku OK
Fatusi A
Fodero R
Francis AO
Gallagher G
Habeeb MYM
Shittu HA
Iasonos A
Ige OE
Ikujenlola AV
Igetei R
Jackman JM
Kahn R
Katung A
Koiki MA
Komolafe AO
Lawrence AP
Lawal A
Lawal NOO
Makanjuola A
Mobolaji J
Omodele F
Na'aya HU
Nganjiwa US
Njokanma I
Nuhu A
Nwachukwu E
O'Connell K
Odunafolabi T
Ogunleye SO
Olaofe OO
Olcese C
Ologunagba PO
Olokoba A
Olasehinde O
Olajide TO
Osinowo AO
Omoyiola OZ
Omisore AD
Onyekwere C
Owoade IA
Oyesegun R
Samson ML
Sanni A
Sharma A
Sowunmi A
Sulaiman AT
Adebukola OT
Wuraola F
Adeleye AO
Adewunmi OL
Zarami AB
Kingham TP
Du M

Humans
Risk Factors
Nigeria
Male
Case-Control Studies
Female
Colorectal Neoplasms
Middle Aged
Adult
Aged
Diet
Life Style
Incidence


Patient-reported early continence recovery after robot-assisted radical prostatectomy in elderly men

Abstract: We evaluated the impact of chronological age on early urinary continence recovery following robot-assisted radical prostatectomy (RARP) using EPIC-26 and quantified discordance between patient-reported and surgeon-assessed continence. A total of 144 consecutive patients underwent RARP and were stratified into Group A (< 70 years, n = 74), Group B (70-<75 years, n = 36), and Group C (≥ 75 years, n = 34). Continence was assessed using EPIC-26 and independent surgeon evaluation at 1, 2, 3, 4, and 6 months postoperatively. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models; proportional hazards assumptions were verified using Schoenfeld residuals. Longitudinal domain trajectories were analyzed using generalized estimating equations (GEE). Social continence rates at 3 months were 85.1%, 72.2%, and 58.1% in Groups A, B, and C, increasing to 97.3%, 94.4%, and 77.4% at 6 months (p = 0.0004). Pad-free rates increased from 39.7%, 36.7%, and 29.4% to 77.8%, 76.7%, and 52.9% (p = 0.110). Age independently predicted delayed social continence recovery (HR 0.953, 95% CI: 0.933-0.973; p < 0.001). Recovery trajectories were slower in Group C (p = 0.008), whereas Groups A and B showed comparable trajectories. At 3 months, surgeon-assessed pad-free continence was 69.3% compared with 37.3% by EPIC-26, representing a 32-percentage-point difference with only fair agreement (κ = 0.38; p = 0.034). Although age was associated with delayed early recovery, meaningful recovery with partial narrowing of between-group differences was observed. Age alone should not automatically preclude surgical consideration in appropriately selected elderly patients, and surgeon assessments substantially overestimated patient-reported continence, supporting routine use of validated PROMs.

Yoon SG
Yun SW
Jin HJ
Noh TI
Shim JS
Park MG
Kang SH
Kang SG

Humans
Male
Prostatectomy
Robotic Surgical Procedures
Aged
Urinary Incontinence
Recovery of Function
Middle Aged
Patient Reported Outcome Measures
Prostatic Neoplasms
Age Factors
Time Factors


Deciphering the regulatory role of ADAM8 in the PDAC tumor microenvironment

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options, driven in part by its immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) and neutrophils (TANs) contribute to tumor progression and immune evasion. A Disintegrin and Metalloproteinase 8 (ADAM8), a zinc-dependent protease, is strongly upregulated in PDAC and correlates with poor clinical outcomes, suggesting a regulatory role in tumor progression. Wild-type (WT) and Adam8 knockout (A8KO) PDAC cell lines were generated using the CRISPR-Cas9 technique, and PDAC mouse models with or without Adam8 expression were established to investigate the role of ADAM8 in tumor and immune cells. In vitro assays, including Western blotting, qPCR, migration and invasion assays, proliferation assays, ELISA, cytokine and proteome analyses, as well as co-culture experiments with PDAC cells and either macrophages or neutrophils, were employed to assess the effects of ADAM8 on tumor-immune cell crosstalk. In parallel, in vivo WT and A8KO KPC models were generated, genotyped, and monitored to evaluate the impact of ADAM8 on survival, tumor growth, and immune cell recruitment within the PDAC TME. ADAM8 deletion reduced tumor cell proliferation and migration, associated with reduced activation of FAK/Src/STAT3 signaling and altered secretion of cytokines including GM-CSF, M-CSF, ICAM-1, and TNF-α. Co-culture assays demonstrated that ADAM8 enhanced reciprocal signaling between tumor cells and TAMs/TANs, promoting pro-oncogenic activation. Migration assays and in vivo analyses revealed that ADAM8 facilitated recruitment of macrophages and neutrophils in PDAC TME, while Adam8KO tumors exhibited reduced immune infiltration and altered macrophage polarization. Our findings demonstrate that ADAM8 promotes PDAC aggressiveness by enhancing tumor cell proliferation and migration, activating FAK/Src/STAT3 signaling, and driving macrophage and neutrophil recruitment through cytokine regulation. By orchestrating both tumor-intrinsic pathways and tumor-immune interactions, ADAM8 emerges as a key determinant of PDAC progression and a systemic target for therapeutic intervention.

Cellular oncology (Dordrecht, Netherlands)

Zandieh K
Cook L
Zhao K
Nagl C
Gao Y
diFazio P
Bartsch DK
Bauer UM
Meixner M
Yildiz D
Keber C
Nimsky C
Bartsch JW

Animals
Tumor Microenvironment
Humans
ADAM Proteins
Membrane Proteins
Cell Line, Tumor
Carcinoma, Pancreatic Ductal
Cell Movement
Pancreatic Neoplasms
Cell Proliferation
Signal Transduction
Neutrophils
Mice, Knockout
STAT3 Transcription Factor
Mice
Macrophages
src-Family Kinases
Focal Adhesion Kinase 1
Antigens, CD


STK11 c.1062 C > G germline variant in medullary thyroid carcinoma: implications for familial predisposition and genetic counseling

Abstract: Medullary thyroid carcinoma (MTC) is characterized by frequent RET mutations, while non-RET alterations remain less well studied. Previous reports have identified a recurrent STK11 c.1062 C > G (p.Phe354Leu) variant in MTC, but its clinicopathologic and functional significance remains uncertain. A total of 129 MTCs (128 families) were analyzed by Sanger sequencing to screen for the STK11 c.1062 C > G variant. Germline status was assessed in cases with available normal tissue. Targeted next-generation sequencing was performed in 30 tumors (29 families). Functional effects of the STK11 c.1062 C > G variant were evaluated using an overexpression model in TT cells, with assessment of AMPKα phosphorylation. Progression-free survival was analyzed using Kaplan-Meier methods. The STK11 c.1062 C > G variant was identified in 12 of 129 MTCs (9.3%) and in 11 of 128 families (8.6%). It was significantly enriched in hereditary cases compared with sporadic tumors: 27.8% (5/18) vs. 7.7% (1/12) for individual MTC cases, and 23.5% (4/17) vs. 7.7% (1/12) for families. In evaluable cases, the variant was confirmed to be germline. Tumors harboring STK11 c.1062 C > G showed a mutational spectrum predominantly involving RET, whereas variant-negative tumors exhibited more heterogeneous alterations, including genes related to DNA repair and chromatin remodeling. No significant difference in progression-free survival was observed between groups (P = 0.54). In vitro, the STK11 c.1062 C > G variant was associated with reduced AMPKα phosphorylation compared with wild-type STK11. Given the population frequency and ClinVar benign/likely benign classification of this variant, our data do not support STK11 c.1062 C > G as a primary driver of MTC; rather, it may represent a recurrent germline variant that could act as a low-penetrance modifier in a subset of patients, warranting cautious interpretation and further validation.

Kong W
Bao L
Wang M
Zhao X
Gu H
Pan X
Zhang X
Zhang T
Xing X
Wang J

Humans
Thyroid Neoplasms
Protein Serine-Threonine Kinases
Germ-Line Mutation
AMP-Activated Protein Kinase Kinases
Female
Carcinoma, Neuroendocrine
Genetic Predisposition to Disease
Male
Middle Aged
Adult
Aged
Young Adult


Analytical validation of a modified wild-type blocker qpcr assay for the sensitive DNA-based detection of NPM1 type A in acute myeloid leukemia

Abstract: This study describes the development and analytical validation of a DNA-based quantitative PCR (qPCR) assay for detecting the NPM1 Type A mutation (NPM1-A mut) in acute myeloid leukemia (AML). The assay employs a modified wild-type blocker (WTB) to preferentially suppress amplification of wild-type (WT) alleles, thereby enriching mutant targets. The modified WTB was synthesized as a 3'-ddC-terminated LNA/DNA chimera and used together with a 6-FAM-MGB-Eclipse hydrolysis probe. The analytical performance of the WTB-qPCR assay was compared with that of an otherwise identical qPCR assay lacking WTB. Key parameters such as linearity, precision, limit of detection (LoD), and limit of quantification (LoQ) were evaluated following the guidelines outlined in CLSI EP17-A2. Concurrently, modified WTB was implemented in Sanger sequencing to improve the sensitivity of mutation detection. Incorporation of WTB yielded an LoD of 0.00302% and an LoQ of 0.00528%, corresponding to approximately 3.02 and 5.28 NPM1-Amut copies, respectively, per 100,000 WT copies. This represented a clear improvement over the non-WTB assay. The WTB-qPCR showed excellent linearity (R2 > 0.999) and precision (CV < 5%), with 100% analytical specificity and no detectable cross-reactivity. Application of modified WTB in Sanger sequencing increased analytical sensitivity to ~ 0.1% mutant allele frequency. The modified WTB-qPCR assay offers a rapid, highly sensitive, and cost-effective DNA-based method for MRD monitoring in NPM1-A-mutated AML. Its strong analytical performance and straightforward workflow support its implementation as a routine diagnostic tool in clinical laboratories.

Hamedi-Asl P
Hamedi-Asl D
Rostami S
Barati M
Amini A
Jafari D
Damerchiloo F
Manafi R
Safa M

Nucleophosmin
Leukemia, Myeloid, Acute
Humans
Nuclear Proteins
Mutation
Real-Time Polymerase Chain Reaction
Limit of Detection
Sensitivity and Specificity
Alleles
Reproducibility of Results
DNA Mutational Analysis


Moving toward precision communication in pediatric oncology clinical trials: An outline of a conceptual framework to support caregiver decision-making

Abstract: Pediatric oncology clinical trials (POCTs) are the cornerstone of therapeutic progress in childhood cancer. Yet, poor accrual and retention remain persistent challenges contributing to early termination of POCTs, limiting the advancement of novel therapies. These challenges reflect a convergence of system, protocol, clinician, and family-level factors, among which caregivers' psychosocial decision-making processes represent a potentially modifiable but underexplored contributor. Caregivers making POCT-related decisions must navigate complex medical information under conditions of heightened emotional distress and uncertainty. Psychosocial factors such as distress, comprehension, trust, values, and social context are known to influence decision-making. However, the field still lacks an integrated framework to explain how these factors may shape decisional trajectories and outcomes throughout POCT participation. This commentary reframes POCT enrollment not as a discrete informed-consent event, but as a dynamic, psychosocial decision-making process that unfolds over time. We present an outline of a conceptual Precision Communication Framework designed to support care teams in aligning communication priorities with caregivers' psychosocial and decisional contexts at key decision points throughout trial participation. Rather than seeking to address all causes of poor accrual or withdrawal, this framework focuses on reducing preventable decisional uncertainty and regret in contexts where psychosocial processes are central drivers of caregiver experiences. By presenting an outline of a conceptual model that would link psychosocial-decisional profiles to communication strategies to prioritize, this commentary aims to inform future empirical research and lay the groundwork for identifying communication strategies to prioritize to reduce caregiver decisional burden and promote sustained participation in POCTs.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

Levesque A
Blackall G
Axson SA
Van Scoy LJ
Sholler GS

Humans
Caregivers
Decision Making
Neoplasms
Clinical Trials as Topic
Communication
Child
Uncertainty