Hematological Research Articles

Bone Marrow and Metabolic Bone Disease.

The bone marrow represents one of the largest organs in the body, with a relevant metabolic role that continues to be investigated. Numerous studies have focused on marrow adipose tissue (MAT). Evidence indicates that the bone marrow adipocytes do not only work as storage tissue but also consist of endocrine and paracrine cells, with the potential to contribute to local and systemic metabolism. MAT plays a role in bone health through its interaction with the other components of bone. Many metabolic disorders (osteoporosis, obesity, diabetes) have a complex and still not well-established or understood relationship with bone health. This article surveys the literature on the relationship of bone marrow and metabolic disorders, and how it is being studied using imaging techniques, with a special focus on bone health.

Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

Procedural Complications of Central Venous Catheter Placement in Pediatric Oncology Practice (a Clinical Case Series)

The availability of central venous access is the cornerstone of contemporary pediatric oncology and hematology. As a result, the percentage of pediatric patients receiving infusion chemotherapy who require a central line remains high. Central venous catheter insertion can be associated with procedural complications, including life-threatening ones.Aim — to investigate the potential factors leading to complications during central venous catheterization in order to develop preventive strategies.Materials and methods. The study included 1,512 original cases of patients aged 1 month to 20 years treated at the D. Rogachev National Research Medical Center between 2019 and 2022. The following 10 complications were examined: failed first venipuncture attempt, guidewire/catheter malpositioning, guidewire knotting, lifethreatening arrhythmias, guidewire entrapment in the trabecular network of the right ventricle, arterial puncture, pneumothorax, hemothorax, puncture of lung parenchyma, Horner's syndrome. In addition, four rare complications were noted, including phrenic nerve injury, cardiac tamponade, alveolar hemorrhage, and arterial pseudoaneurysm.Results. The primary cause of all complications was direct mechanical injury to anatomical structures by a needle or guidewire/catheter. When inadvertent vascular injury and bleeding occur, the resulting hematoma may lead to further damage by compressing soft tissues. Excessively deep insertion of the guidewire may cause its knotting or cardiac arrhythmias. Adequate physician training and strict adherence to procedural protocols are essential to avoid these complications.Conclusion. Central venous catheterization remains a procedure with potential complications. Although ultrasound guidance does not eliminate all risks, it increases the likelihood of successful venipuncture at the first attempt, thereby reducing complication rates. Recognizing the potential causes of procedural complications during central venous access placement, including uncommon ones, facilitates early diagnosis and appropriate medical intervention.

Improving childhood cancer care in South Africa using the Paediatric Oncology Facility Integrated Local Evaluation (PrOFILE) tool

Aim Using the St. Jude Paediatric Oncology Facility Integrated Local Evaluation (PrOFILE) tool, the South African Association of Paediatric Haematology Oncology (SAAPHO) collaborated with St Jude Children’s Research Hospital to evaluate the delivery of health services and provide evidence-based assessments to inform and prioritise action plans to improve childhood cancer care. Methods PrOFILE was used to assess paediatric oncology care in thirteen public-sector hospitals comprehensively. Following that, representatives from each of the thirteen public-sector hospitals and from SAAPHO, the National Department of Health, the World Health Organization, St. Jude Global, and Childhood Cancer Foundation South Africa participated in a national stakeholder prioritisation workshop. Participants were assigned one of the PrOFILE components (Context, Workforce, Diagnostics, Multidisciplinary Team, Therapy, or Patients and Outcomes), forming six working groups to assess, map, and evaluate childhood cancer topics. Using a modified implementation mapping approach and through participation in structured co-designed activities, each group designed multi-level health interventions: prioritising initiatives identified by the SAAPHO, setting goals for each priority, co-designing project-specific logic models, reviewing potential barriers to implementation, and developing a post-workshop agenda. Results Individual hospital reports and a national aggregate report were compiled to discuss opportunities and priorities. The goal of the workshop was to utilise evidence-based assessments to achieve, a) objective assessment data to inform prioritisation exercises conducted by stakeholders, and b) priorities and action plans to inform childhood cancer control activities and demonstrate national organisation, human resources capabilities, and technical support to improve childhood cancer care. Through structured discussion and voting, six priority areas were identified and assigned to working groups: redrafting the organisation’s constitution, standardising multidisciplinary reporting, developing protocols and treatment guidelines, establishing fever-management guidelines, strengthening chemotherapy safety practices, and enhancing hospital-based cancer registries. Conclusions An implementation map enabled stakeholders to develop actionable plans, the success of which is demonstrated by the active implementation of the identified priorities by the focused working groups. This could serve as a model for countries with identified priorities but need more means to implement them. Based on mapping and outputs from the PrOFILE workshop, the NDoH will facilitate the creation of a childhood cancer committee to sustain progress on the key themes and priorities identified through the PrOFILE mapping process.

Postoperative pancytopenia in a patient with giant parathyroid adenoma and brown tumor: a case report

BackgroundParathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies.Case presentationWe present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal.ConclusionsPancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

Chemotherapy-Induced Febrile Neutropenia Managed on an Outpatient Basis at the Pediatric Hematology and Oncology Department of the Ibn Sina Children’s Hospital in Rabat

Introduction: Febrile neutropenia (FN) is an important cause of morbidity and mortality in patients with cancer. The general objective of this study was to collect data and analyze the factors influencing management of the febrile neutropenia at the day hospital at the pediatric department of Hematology and Oncology (SHOP) of Rabat.

Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.

Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs.

Evaluation of disease activity in systemic lupus erythematosus using standard deviation of lymphocyte volume combined with red blood cell count and lymphocyte percentage

Systemic lupus erythematosus (SLE) commonly damages the blood system and often manifests as blood cell abnormalities. The performance of biomarkers for predicting SLE activity still requires further improvement. This study aimed to analyze blood cell parameters to identify key indicators for a SLE activity prediction model. Clinical data of 138 patients with SLE (high activity, n = 40; moderate activity, n = 44; mild activity, n = 37; low activity, n = 17) and 100 healthy controls (HCs) were retrospectively analyzed. Data from 89 paired admission–discharge patients with SLE were collected. Differences and associations between blood cell parameters and disease indicators, as well as the relationship between the these parameters and organ damage, were examined. Machine-learning methods were employed to develop a prediction model for disease activity evaluation. Most blood cell parameters (22/26, 84.62%) differed significantly between patients with SLE and HCs. Analysis of 89 paired patients with SLE revealed significant changes in most blood cell parameters at discharge. The standard deviation of lymphocyte volume (SD-V-LY), red blood cell (RBC) count, lymphocyte percentage (LY%), hemoglobin(HGB), hematocrit(HCT), and neutrophil percentage(NE%) correlated with disease activity. By employing machine learning, an optimal model was established to predict active SLE using SD-V-LY, RBC count, and LY% (area under the curve [AUC] = 0.908, sensitivity = 0.811). External validation indicated impressive performance (AUC = 0.940, sensitivity = 0.833). Correlation analysis revealed that SD-V-LY was positively correlated with ESR, IgG, IgA, and IgM but was negatively correlated with C3 and C4. The RBC count was linked to renal and hematopoietic system impairments, whereas LY% was associated with joint/muscle involvement. In conclusion, SD-V-LY is associated with SLE disease activity. SD-V-LY combined with RBC count and LY% contributes to a prediction model, which can be utilized as an effective tool for assessing SLE activity.

Basic coagulation parameters and platelet count among malaria patients attending at Addis Zemen Primary Hospital, Northwest Ethiopia.

Malaria is an intravascular parasitic-related blood disease that causes bleeding, coagulopathy, and thrombocytopenia. However, limited data shows the effect of Plasmodium species infection on basic coagulation parameters and platelet count. Thus, this study aimed to assess basic coagulation parameters and platelet count among malaria patients. A cross-sectional study was conducted among 240 study participants (120 cases and 120 controls) from June 1, 2021, to February 30, 2022. A convenient sampling technique was employed to select study participants. The blood sample was collected by a trained laboratory technologist for platelet counts, prothrombin time (PT), partial thromboplastin time (PTT), international normalization ratio (INR), blood film, and serological testing. The collected data were analyzed in SPSS version 23. Data were analyzed by the Mann-Whitney U test, Kruskal Wallis H, and Spearman's rank-order correlation tests. Descriptive findings were presented through median, tables, and chart. In all cases, a P-value < 0.05 was considered statistically significant. The percentage of mild, moderate, and high malaria parasitemia levels per microliter of blood was 21.7%, 20%, and 58.3%, respectively. The overall median malaria parasitemia was 10,304 per microliter of blood. Among malaria patients, 77.5%, 61.7%, and 51.7% had prolonged PT, INR, and APTT, respectively as compared to control. Moreover, 26.7% of Plasmodium-infected participants had mild thrombocytopenia as compared to the control group (P < 0.001). The value of PT, APTT, and INR were significantly elevated, whereas the level of platelet count was inversely reduced when the malaria parasitemia level increased as compared to controls (p < 0.001).

About the Need to Study the Effect of Soil Salinity on Diseases

The article is devoted to the issues of diseases and their development characteristic of the conditions of saline lands, which have received little attention so far. Due to deficiencies in irrigated agriculture, salinization is increasing more and more. In some countries, the share of saline land is 32% - 78% of the total used land. As a result of some studies, it was found that in areas with a lot of saline land, there is a higher incidence of diseases of the digestive organs and even cancer. In Mingbuloq District, Namangan Region of Uzbekistan, there was a high incidence of “Certain disorders related to the immune mechanism of diseases of blood and blood-forming organs (including anemia)” in adolescents under 14 years of age. Almost 2 times more was found. Judging from statistical data, it is possible to note a high level of infant mortality in many countries with saline lands. These data indicate that the study of the effects of salt-flooded lands on diseases is the most urgent problem.

Nurse-Driven Interventions Reduce Central Line-Associated Bloodstream Infection Close to Zero in One Pediatric Oncologic Facility: A Single-Center Retrospective Observational Study.

Central line-associated bloodstream infections (CLABSIs) are critical infectious complications among pediatric hematology-oncology patients, and the management of central venous catheters (CVCs) by healthcare personnel can significantly influence the incidence of these infections. This study evaluates the impact of nurse-led changes in CVC management on the incidence of CLABSIs. This single-center, retrospective observational study was conducted at an urban, tertiary referral, and academic center serving pediatric patients. The study cohort comprised 239 patients and 323 CVCs seen between 2012 and 2022. CLABSI was defined according to the Centers for Disease Control and Prevention definitions. Oncology nurse leaders developed CVC-specific educational modules for CLABSI prevention. All the relevant information during the CVC maintenance period was noted in the patient's CVC logbook. A total of 24 (7%) cases of confirmed CLABSI were identified. The incidence of CVC-related infections was 0.32 cases per 1000 catheter days (95%CI: 0.19-0.45). The incidence decreased by 40% between the first and second three-year study period. Documented exit-site infection was reported in 32 (10%) cases. The correlation between exit-site infection and CLABSI was found in 9 (28%) cases. Our CVC-related infection rates are significantly lower than the incidence reported by the Italian Association of Pediatric Hematology and Oncology, which settles at 3-5 cases per 1000 catheter days. Our data confirm the effectiveness of local CVC management guidelines in preventing CVC-related infectious complications.

Children With Acute Lymphoblastic Leukemia in Romania: Results From a Decade-Long Single-Center Study.

Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in children, with continuously improving survival rates. As few studies in Romania have analyzed ALL patients and disease characteristics or survival, we conducted a retrospective study on 158 patients diagnosed with ALL admitted to the Department of Pediatric Oncology and Hematology at the Emergency Hospital for Children, Cluj-Napoca, Romania, from January 2011 until April 2021. The most important objectives of the study are to establish full profiles of the patients and ALL, remission rates, relapses, and deaths, an epidemiology analysis to determine the incidence of ALL for comparison with the standard European population, and also to assess survival by the most important parameters, including minimal residual disease (MRD). This was a retrospective study that focused on patients with newly diagnosed ALL from January 2011 to April 2021 in the Department of Pediatric Hematology and Oncology of the Emergency Hospital for Children, Cluj-Napoca, Romania. The inclusion criteria were: patients with de novo ALL, patients who were younger than 18 years of age, and patients with signed informed consents. The exclusion criteria included patients who were older than 18 years of age; patients with relapsed ALL; and patients who did not have a signed informed consent. A total of 158 patients were included in the study, aged between 0 and 17 years. The information about patient characteristics and all variables was taken from the patients' files, where informed consent is mandatorily stored. Descriptive statistics were used to evaluate variables such as age, gender, leukocyte number, immunophenotype, prednisone response, risk group assessment, cytogenetics, relapse, and MRD. Kaplan-Meier curves were used to assess survival, for which patients were divided into two subcohorts: a 2011-2015 subcohort and a 2016-2020 subcohort. The statistical analyses used Prism version 10.2.3 (GraphPad Software, La Jolla, CA). For the analysis, we used Kaplan-Meier curves, the log-rank (Mantel-Cox) test, the log-rank test for trends, the Gehan-Breslow-Wilcoxon test, survival proportions, the chi-square test, and correlations. A shift in risk groups was observed after the introduction of MRD testing in 2017, with more patients being stratified in the medium-risk group (MRG) and high-risk group (HRG). At the survival analyses between bone marrow (BM) aspiration and MRD on day 15, we discovered that patients with MRD>10% had much higher overall survival (OS) and event-free survival (EFS) compared to patients with >25% blasts in the BM; 24(11.4%) patients relapsed, of which, nine (3.8%) were very early relapses and 10 (4.1%) were late relapses. The five-year OS and EFS for patients with the T-cell immunophenotype of ALL and those with leukocyte counts >100,000/mm3were identical to those at one year. The OS of the 2016-2020 subcohort was higher than that of the 2011-2015 subcohort, and more patients were stratified into MRG and HRGs due to the implementation of MRD testing. Minimal residual disease testing helped to improve significantly the survival rates of patients with more than 10% residual disease. None of the patients with very early relapses entered complete remission (CR), but all late relapses achieved CR. All events experienced by patients with the T-cell immunophenotype, or leukocyte counts of >100,000/mm3 occurred in the first year after diagnosis.

The relationship between the severity and complications of Henöch-Schönlein purpura in children and dietary inflammatory index: a retrospective cohort study.

To investigate the association between the Dietary Inflammatory Index (DII) and disease severity as well as complications in children diagnosed with Henöch-Schönlein purpura (HSP), shedding light on the potential influence of dietary factors on HSP. A retrospective cohort study was conducted, enrolling children aged 2-14 years diagnosed with HSP. Participants were divided into low and Pro-inflammatory dietary groups based on their DII scores. Biomarkers, nutrient intake, blood lipid profiles and disease complications were compared between the two groups. Spearman correlation analysis was performed to assess the relationship between DII and complications. A total of 115 patients, including 56 patients with anti-inflammatory dietary and 59 with pro-inflammatory dietary, were included. The pro-inflammatory dietary group demonstrated significantly elevated of C-reactive protein, tumor necrosis factor-α, interleukin-6, erythrocyte sedimentation rate, white blood cell count, eosinophils, IgE, consumption of total calories, protein, carbohydrates, fiber, fat intake, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, VLDL cholesterol, complications of renal, skin, gastrointestinal, coagulation and respiratory in comparison to the anti-inflammatory dietary group. DII was positively correlated with renal, skin, gastrointestinal, coagulation and respiratory complications. The study highlights the potential influence of dietary inflammatory potential, as quantified by the DII, on disease severity and complications in children with HSP. Understanding the interplay between dietary patterns and inflammatory responses in pediatric vasculitis has implications for the management of HSP, emphasizing the relevance of considering dietary interventions to optimize clinical outcomes and improve the overall well-being of affected children.

Numerical-experimental estimation of the deformability of human red blood cells from rheometrical data

The deformability of human red blood cells (RBCs), which comprise almost 99% of the cells in whole blood, is largely related not only to pathophysiological blood flow but also to the levels of intracellular compounds. Therefore, statistical estimates of the deformability of individual RBCs are of paramount importance in the clinical diagnosis of blood diseases. Although the microscale hydrodynamic interactions of individual RBCs lead to non-Newtonian blood rheology, there is no established method to estimate individual RBC deformability from the rheological data of RBC suspensions, and the possibility of this estimation has not been proven. To address this issue, we conducted an integrated analysis of a model of the rheology of RBC suspensions, coupled with macrorheological data of human RBCs suspended in plasma. Assuming a nonlinear curve of the relative viscosity of the suspensions as a function of the cell volume fraction, the statistical average of the membrane shear elasticity was estimated for individual intact RBCs or hardened RBCs. Both estimated values reproduced well the experimentally observed shear-thinning non-Newtonian behavior in these suspensions. We hereby conclude that our complementary approach makes it possible to estimate the statistical average of individual RBC deformability from macrorheological data obtained with usual rheometric tests.

Key blood disease indicator can be estimated with rheological blood test data

Estimation method allows red blood cell deformability to be determined from the viscosity of blood.

Whole Exome Sequencing of Adult Indians with Apparently Acquired Aplastic Anaemia: Initial Experience at Tertiary Care Hospital

Aplastic anaemia (AA) is a rare hypocellular bone marrow disease with a large number of mutations in the telomerase reverse transcriptase gene (TERT), leading to bone marrow failure. We used our benchmarked whole exome sequencing (WES) pipeline to identify variants in adult Indian subjects with apparently acquired AA. For 36 affected individuals, we sequenced coding regions to a mean coverage of 100× and a sufficient depth was achieved. Downstream validation and filtering to call mutations in patients treated with Cyclosporin A (CsA) identified variants associated with AA. We report four mutations across the genes associated with the AA, TERT and CYP3A5, in addition to other genes, viz., IFNG, PIGA, NBS/NBN, and MPL. We demonstrate the application of WES to discover the variants associated with CsA responders and non-responders in an Indian cohort.

SARS-CoV-2 infection induces hyaluronan production in vitro and hyaluronan levels in COVID-19 patients relate to morbidity and long-term lung impairment: a prospective cohort study.

We previously demonstrated that the lungs of deceased COVID-19 patients were filled with a clear hydrogel consisting of hyaluronan (HA). In this translational study, we investigated the role of HA at all stages of COVID-19 disease to map the consequences of elevated HA on morbidity and identify the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced HA production. A reduced alveolar surface area was observed in the lungs of deceased COVID-19 patients compared to healthy controls, as visualized by a 3D rendering of lung morphology using light-sheet fluorescence microscopy. We confirmed the presence of HA in lung biopsies and found large quantities of proinflammatory fragmented HA. The association of systemic HA in blood plasma and disease severity was assessed in patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS, 6-9) during the acute and convalescent phases and related to lung function. We found that systemic levels of HA were high during acute COVID-19 disease, remained elevated during convalescence, and were associated with a reduced diffusion capacity. In vitro 3D-lung models, differentiated from primary human bronchial epithelial cells, were used to study the effects of SARS-CoV-2 infection on HA metabolism, and transcriptomic analyses revealed a dysregulation of HA synthases and hyaluronidases, both contributing to increased HA in apical secretions. Furthermore, corticosteroid treatment reduced the inflammation and downregulated HA synthases. Our findings demonstrate that HA plays a role in COVID-19 morbidity and that sustained elevated HA concentrations may contribute to long-term respiratory impairment.IMPORTANCEThis study provides insights into the role of hyaluronan (HA) in the severity and long-term impact of COVID-19 on lung function. Through extensive morphological examination of lung tissues and a multicenter study, we identified that HA levels are significantly elevated in COVID-19 patients, correlating with a reduced lung diffusion capacity during convalescence. Using a 3D-lung model, we further uncovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection causes a dysregulated HA metabolism, leading to increased HA production. Our findings provide valuable insights into the pathogenesis of SARS-CoV-2 and suggest that targeting HA metabolism could offer new therapeutic avenues for managing COVID-19, particularly to prevent long-term lung impairment. Additionally, HA holds potential as a biomarker for predicting disease severity, which could guide personalized treatment strategies.

Low Magnetic Field Exposure Alters Prostate Cancer Cell Properties.

Prostate cancer is the second most common neoplasia and fifth-leading cause of cancer death in men worldwide. Electromagnetic and magnetic fields have been classified as possible human carcinogens, but current understanding of molecular and cellular pathways involved is very limited. Effects due to extremely low magnetic/hypomagnetic fields (LMF) are furthermore poorly understood. Extracellular vesicles (EVs) are crucial mediators of cellular communication with multifaceted roles in cancer progression, including via transport and uptake of various protein and microRNA (miRNA) EV-cargoes. miRNAs regulate gene expression and are implicated in cancer-related processes such as proliferation, metastasis, and chemoresistance. This study investigated the effects of LMF exposure (20 nT) by magnetic shielding on the prostate cancer cell line PC3 compared to the prostate epithelial cell line PNT2 under short-term (4 h) conditions. We examined EV profiles following a 4 h LMF exposure alongside associated functional enrichment KEGG and GO pathways for the EV proteomes. The 4 h LMF exposure significantly reduced cellular EV release and modified PC3 EV cargoes to a more inflammatory and metastatic profile, with 16 Disease Pathways and 95 Human Phenotypes associated specifically with the LMF-treated PC3 EV proteomes. These included cancerous, metabolic, blood, skin, cardiac and skeletal Disease Pathways, as well as pain and developmental disorders. In the normal PNT2 cells, less EV protein cargo was observed following LMF exposure compared with cells not exposed to LMF, and fewer associated functional enrichment pathways were identified. This pointed to some differences in various cellular functions, ageing, defence responses, oxidative stress, and disease phenotypes, including respiratory, digestive, immune, and developmental pathways. Furthermore, we analysed alterations in matrix metalloproteinases (MMPs) and miRNAs linked to metastasis, as this is crucial in cancer aggressiveness. The 4 h LMF exposure caused a significant increase in MMP2 and MMP9, as well as in onco-miRs miR-155, miR-210, miR-21, but a significant reduction in tumour-suppressor miRs (miR-200c and miR-126) in the metastatic PC3 cells, compared with normal PNT2 cells. In addition, 4 h LMF exposure significantly induced cellular invasion of PC3 cells. Overall, our findings suggest that changes in magnetic field exposures modulate EV-mediated and miR-regulatory processes in PCa metastasis, providing a basis for exploring novel therapeutic strategies.

Autoinflammatory disorders with symptoms that resemble malignant blood diseases – Schnitzler syndrome, adult Still disease, SAPHO and VEXAS syndrome

Autoinflammatory disorders with symptoms that resemble malignant blood diseases – Schnitzler syndrome, adult Still disease, SAPHO and VEXAS syndrome

Central Nervous System Fungal Diseases in Children with Malignancies: A 16-Year Study from the Infection Working Group of the Hellenic Society of Pediatric Hematology Oncology.

We analyzed data on pediatric invasive fungal diseases of the central nervous system (CNS-IFDs) reported by five of a total of eight Pediatric Hematology-Oncology Departments in Greece for 16 years (2007-2022). A total of twelve patients (11 boys, median age: 9.5 years, range: 2-16) were reported suffering from CNS-IFDs. The underlying malignancy was acute lymphoblastic leukemia in 9/12 and acute myeloid leukemia, Ewing sarcoma, and rhabdomyosarcoma in one each. Eleven patients presented with CNS-related symptoms (i.e., seizures, headache, cerebral palsy, ataxia, hallucination, seizures, blurred vision, amaurosis). All patients had pathological MRI findings. Multifocal fungal disease was observed in 6/12 patients. Nine proven and three probable CNS-IFD cases were diagnosed. Causative pathogens in proven cases were Aspergillus spp. and Candida albicans (n = 2 each), Mucor spp., Rhizopus arrhizus, Absidia spp., Fusarium oxysporum and Cryptococcus neoformans (n = 1 each). Causative pathogens in probable cases were Aspergillus spp. (n = 2) and Candida spp. (n = 1). All patients received appropriate antifungal therapy (median duration: 69.5 days, range 19-364). Two patients underwent additional surgical treatment. Six patients were admitted to the Intensive Care Unit due to complications. Three patients (25%) died, two due to IFD and one due to an underlying disease. Early recognition and prompt intervention of CNS-IFDs may rescue the patients and improve overall survival.