Search Results (555)

Neurological complications, particularly seizures, represent a significant and often under-recognized clinical challenge in pediatric hematologic malignancies. Distinguishing CNS leukemia-associated epilepsy from chemotherapy-induced neurotoxicity is critical for optimizing therapy but remains difficult due to overlapping clinical presentations. This review highlights the distinct molecular mechanisms underlying these two entities. CNS leukemia-associated seizures are primarily driven by blood–brain barrier (BBB) disruption following leukemic infiltration, which triggers a neuroinflammatory cascade involving pro-inflammatory cytokines such as IL-6 and TNF-α, and impairs glutamate homeostasis. In contrast, chemotherapy-induced seizures, particularly those associated with high-dose methotrexate, arise from disrupted folate metabolism, intracellular oxidative stress, and subsequent N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. We provide a comparative analysis of these pathways, integrating current evidence on pharmacogenomic susceptibility—including polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and drug transporter genes—as well as epigenetic factors. By synthesizing these molecular insights, we propose a mechanistic framework for precise clinical differentiation, which may inform biomarker-driven diagnostic approaches and targeted neuroprotective strategies in this vulnerable population. Full article

Background: Infective endocarditis (IE) remains associated with high morbidity and mortality despite advances in diagnostic and therapeutic strategies. Markers reflecting both inflammatory burden and nutritional status may improve early risk stratification. The hemoglobin-albumin-lymphocyte-platelet (HALP) score is a composite index integrating hematologic and nutritional parameters; however, its prognostic value in IE has not been well established. Methods: This two-center retrospective cohort study included 218 adult patients hospitalized with IE between January 2016 and January 2025. HALP score was calculated from admission laboratory values. The primary outcome was in-hospital mortality, and 1-year mortality was evaluated as a secondary outcome. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value. Patients were categorized into low- and high-HALP groups, and survival was assessed using Kaplan–Meier analysis. Cox regression analyses were performed to identify independent predictors of in-hospital mortality. Results: A total of 218 patients were analyzed. In-hospital mortality occurred in 38.5% of patients. HALP score was significantly lower in non-survivors and was independently associated with in-hospital mortality. ROC analysis demonstrated good discriminatory performance (AUC 0.784), with an optimal cut-off value of 15.1 (sensitivity 73.9%, specificity 73.8%). Low HALP scores were associated with more advanced functional status, more frequent intracardiac complications, and higher rates of acute heart failure, renal failure, and septic shock. One-year mortality was also higher in the low-HALP group (42.9% vs. 18.2%, p = 0.005). Conclusions: HALP score is independently associated with in-hospital mortality in patients with IE and identifies a subgroup with more severe disease and worse outcomes. As an easily calculated parameter, it may serve as a complementary tool for risk stratification and clinical decision-making. Full article

Background: Malignant lymphoma is the most common hematological malignancy; however, primary central nervous system lymphoma accounts for only a small percentage of non-Hodgkin lymphoma (NHL). Among these, primary cauda equina lymphoma (CEL) is extremely uncommon. Its rarity and atypical clinical presentation often make diagnosis challenging. Case Presentation: An 80-year-old man presented with progressive gait disturbance, lower-extremity weakness, and numbness. MRI revealed diffuse swelling and homogeneous gadolinium enhancement of the cauda equina at T12–L1; additionally, CSF cytology identified malignant lymphocytes. Open biopsy confirmed a diagnosis of diffuse large B-cell lymphoma. At diagnosis, the patient was classified as Ann Arbor stage IV, and the clinical parameters corresponded to a high-risk International Prognostic Index (IPI) category. The patient received five courses of immunochemotherapy with rituximab, methotrexate, vincristine, and procarbazine (R-MPV), resulting in marked radiological improvement and functional recovery, achieving a complete response. However, consolidation therapy was discontinued as the patient did not wish to continue. Unfortunately, intracranial relapse occurred four months later, and the patient ultimately succumbed to infectious complications. Only 29 cases of primary CEL have been reported. For all cases, a biopsy with histopathological examination is required for a definitive diagnosis. Currently, combined chemotherapy and radiotherapy are considered the standard treatment. This case was diagnosed through nerve biopsy with cauda equina at T12 to L1 levels, and immunochemotherapy successfully reduced the lesion while improving lower extremity function. Conclusions: Despite the considerable burden on patients, nerve biopsy is necessary for primary CEL to obtain a diagnosis and an early therapeutic approach for both neurological and vital prognoses. Full article

Invasive infections caused by Magnusiomyces spp. are rare, but are associated with severe complications in hematopoietic cell transplantation (HCT) recipients and hospital outbreaks. Following a Magnusiomyces clavatus outbreak in our HCT unit, a prospective targeted screening protocol was implemented, which included pharyngeal and rectal swabs cultured on yeast-selective media with prolonged incubation. Clinical and microbiological data were analyzed, and whole-genome sequencing (WGS) was performed on the available isolates. During the study period (September 2022–July 2023), five colonizations and five invasive breakthrough Magnusiomyces infections were identified. Despite prompt initiation of antifungal treatment, 4/5 patients (80%) died. WGS demonstrated clonal relatedness among four M. clavatus isolates, supporting clonal transmission, although no environmental sources were identified. An enhanced two-phase screening strategy involving 71 patients showed limited benefit, identifying only one additional colonization case compared to routine surveillance cultures. A retrospective review (2007–2021) identified 58 Magnusiomyces spp. episodes, with only 10% occurring in patients with hematological malignancies. Our study describes a prolonged clonal outbreak confined to an HCT unit and provides a detailed evaluation of a targeted screening approach in this setting, highlighting the challenges of early identification and prediction of invasive infections. Further studies are needed to define the optimal surveillance and prevention strategies. Full article

Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients. Full article

Background: Rapidly progressive glomerulonephritis (RPGN) is a severe nephrological emergency, frequently secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. In older adults, the coexistence of comorbidities and monoclonal gammopathy of undetermined significance (MGUS) makes it difficult to distinguish between ANCA vasculitis and monoclonal gammopathy of renal significance (MGRS), which differ in prognosis and treatment. The coexistence of PR3-ANCA-associated vasculitis and MGUS is uncommon and sparsely documented. Case Presentation: A 72-year-old woman with hypertension and type 2 diabetes presented with acute deterioration and rapidly progressive renal failure, requiring hemodialysis. She had subnephrotic proteinuria, hematuria, and an active urinary sediment. The autoimmune workup showed ANCA negativity using immunofluorescence, but PR3-ANCA positivity using ELISA. Hematologic characterization documented an IgG kappa monoclonal spike; no bone lesions, amyloidosis, or criteria for multiple myeloma were found; and the patient was classified as MGUS. Renal biopsy revealed necrotizing extracapillary pauci-immune glomerulonephritis with cellular and fibrocellular crescents and no monoclonal deposits, consistent with PR3-ANCA vasculitis. Induction therapy with methylprednisolone pulses and oral prednisone was initiated; cyclophosphamide was not administered because of catheter-associated Staphylococcus aureus bacteremia and upper gastrointestinal bleeding complicated by disseminated intravascular coagulation. The patient died on day 25 due to infectious and hemorrhagic complications. Conclusions: This case provides additional documentation of an uncommon overlap between PR3-ANCA-associated vasculitis and MGUS in a Latin American patient and highlights the role of renal biopsy in distinguishing MGRS from pauci-immune vasculitis in the presence of paraproteinemia. It also underscores the need to tailor immunosuppression in frail older adults, balancing disease control against the risk of severe infection. Full article

Thrombocytopenia is a frequent complication of patients presenting emergently across the world for a wide array of etiologies. From patients who develop thrombocytopenia due to invasive neoplastic disease affecting the bone marrow to patients who develop immune complications secondary to the formation of auto-antibody responses that drive patients’ platelet counts lower or even cause infection, these patients stress the clearest need for prompt tests to discern the more likely thrombocytopenic-inducing cause. It is in this setting that looking at other platelet variables easily obtainable from modern hematology analyzers has gained traction. One of the elements found in extended platelet profiles are immature platelets (youngest and newly released platelets), also known as reticulated platelets, which are readily measurable from a complete blood count. One of the advantages of obtaining these counts is that they represent the immediate response of the bone marrow to the thrombocytopenia and, depending on etiology inducing the thrombocytopenia, they also provide information on the marrow’s response to therapeutic approaches. It is in this context that this review will present information of how these relatively novel platelet parameters can be used in clinical practice and how they can be a rapid gauge of the body’s response to disease processes leading to platelet losses. Thrombocytopenias resulting from infection (sepsis, viremia), autoantibody formation (immune thrombocytopenia and immune-mediated thrombotic thrombocytopenic purpura), immune dysregulation (systemic lupus erythematosus), and iatrogenic (drug-induced) will be discussed and used to explain how these young platelet measurements can provide valuable clinical information. Full article

Purpose: A scoping review of the published risk stratification scores for febrile neutropenia (FN) was performed to provide a basis for further research and optimization of risk stratification models that can support evidence-based clinical decision-making with a combined individual patient and health resource perspective. Methods: The scoping review utilized the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR). Studies reporting risk stratification models for FN and published in the PubMed and/or Scopus databases between 2000 and 2024 were retrieved and reviewed. Study eligibility criteria were adult cancer patients and articles utilizing FN risk stratification methods. Two researchers reviewed all relevant studies separately to determine if they were eligible for inclusion and extracted the necessary data. Results: A total of 210 papers was screened by title and abstract. A further 158 were screened by retrieval and eligibility, and 14 studies were found eligible after reviewing full papers. Studies have different cohort sizes (min 31, max 4434), age and gender distributions, cancer types (1 hematological, 3 gynecological, 10 mixtures of hematological and solid cancers), definitions of FN and complication, study type (2 retrospective, 12 prospective). The resulting papers mostly focused on validating CISNE and MASCC scores. Additionally, they investigated possible improvements by evaluating revised versions of the MASCC score. Conclusions: The scoping review revealed inconsistencies in key definitions when using risk stratification scores. It is concluded that the field could benefit from more consensus in definitions and research approaches to secure the generalizability and utility of the research. Full article

Background/Objectives: Oral mucositis (OM) is a common complication in onco-hematological patients undergoing chemotherapy and hematopoietic stem cell transplantation, negatively affecting comfort, nutrition, and quality of life. Despite existing assessment tools and recommendations, OM management—particularly non-pharmacological approaches—remains inconsistent, and evidence on nurses’ perspectives and contextual factors is limited. This study explored nurses’ perceptions and experiences regarding non-pharmacological treatments for OM, including educational needs and barriers and facilitators to implementation in clinical practice. Methods: A qualitative descriptive study using inductive content analysis was conducted. Semi-structured interviews were carried out with nurses working in onco-hematological settings in Italy. Data were analysed according to the Elo and Kyngäs framework. Results: Twelve nurses with extensive experience in onco-hematology and transplant care participated in the study. Five main themes emerged: (1) education and training pathways; (2) approaches to mucositis management; (3) nursing competence in OM care; (4) interprofessional collaboration; and (5) governance of practice, including protocols and guidelines. Findings highlighted strong experiential competence, high levels of nursing autonomy in assessment and patient education, and effective interprofessional collaboration, particularly in specialised settings. However, training pathways were predominantly informal, and the availability and use of protocols varied widely across clinical contexts. Conclusions: Non-pharmacological management of OM appears to be sustained primarily by advanced nursing competence and a specialised clinical culture rather than by structured education and standardised governance. Addressing educational gaps and promoting shared protocols may enhance the consistency, quality, and equity of supportive care while ensuring that the findings are clearly reflective of nurses’ experiences. Full article

Background/Objectives: Delayed umbilical cord clamping (DCC) is widely recommended for neonatal benefit; however, concerns persist among professionals that DCC may increase the risk of postpartum hemorrhage. There is a higher risk of postpartum hemorrhage in women with hypertensive disorders of pregnancy (HDP). We aimed to evaluate the association between umbilical cord clamping timing and maternal blood loss in term pregnancies, including those complicated by HDP. Methods: We conducted a cross-sectional study of women delivering at three major hospitals in Almaty, Kazakhstan (August 2020–March 2021). The primary outcome was maternal blood loss. Secondary outcomes included hemoglobin (Hb) and red blood cell (RBC) change from pre-delivery to discharge. Multivariable models were adjusted for maternal age, parity and hypertension category. Results: Two hundred and seven women were analyzed (early cord clamping ≤ 60 (ECC) n = 21; delayed cord clamping 60–119 s (DCC60s) n = 161; delayed cord clamping ≥ 120 s (DCC120s) n = 25). Baseline characteristics were similar across groups except for hypertension distribution. Median blood loss did not differ significantly (255–260 mL; p = 0.9128). Adjusted models confirmed no association between clamping category and blood loss (RoM: ECC vs. DCC60s 0.97; 95% CI 0.93–1.01; DCC120s vs. DCC60s 1.01; 95% CI 0.96–1.07). Conclusions: Among term births in Almaty, including HDP-affected pregnancies, delayed umbilical cord clamping was not associated with increased maternal blood loss or hematologic decline. These findings indicate that DCC does not appear to increase maternal bleeding risk in high-risk obstetric populations and are broadly in line with current international recommendations. Further prospective research is warranted to evaluate specific subgroups, including severe preeclampsia. Full article

Immunotherapy with immune checkpoint inhibitors (ICIs) has represented a major breakthrough in the treatment of multiple solid and hematological malignancies, significantly improving survival and tumor control. However, the blockade of immune regulatory pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) is associated with the development of immune-related adverse events, among which immune-mediated colitis (IMC) constitutes one of the most relevant gastrointestinal complications due to its frequency, potential severity, and impact on the continuation of oncologic treatment. IMC typically presents with diarrhea, abdominal pain, and gastrointestinal bleeding, and may progress to severe, life-threatening forms. Its incidence varies according to the type of ICI, and is higher with CTLA-4 inhibitors and particularly elevated with combination therapies. The pathophysiology is complex and multifactorial, involving dysregulated activation of proinflammatory T lymphocytes, impairment of immune regulatory mechanisms, disruption of the intestinal epithelial barrier, and a key modulatory role of the gut microbiota. Diagnosis requires a high index of clinical suspicion and relies on endoscopy with biopsies, given the poor correlation between clinical severity and endoscopic or histological findings. Fecal biomarkers, such as calprotectin and lactoferrin, are useful for risk stratification and disease monitoring. Treatment is based on a stepwise immunosuppressive approach, with corticosteroids as first-line therapy and biologic agents such as infliximab or vedolizumab in refractory cases. Emerging strategies, including fecal microbiota transplantation, offer new therapeutic perspectives. This article provides a comprehensive review of the current evidence on the epidemiology, pathophysiology, diagnosis, and management of IMC, as well as future challenges and opportunities in its clinical management. Full article

Background and Objectives: Effective postoperative analgesia is essential for enhanced recovery after bariatric surgery. The erector spinae plane block (ESPB) has emerged as a promising regional anesthesia technique, but its impact on postoperative pain control, opioid requirement, patient and surgeon satisfaction, and stress response in obese patients undergoing sleeve gastrectomy remains unclear. This study aimed to evaluate the effects of bilateral ESPB on postoperative analgesia requirements, pain scores, patient and surgeon satisfaction, hemodynamic stability, postoperative stress response, and perioperative hematologic and biochemical parameters in ASA II–III patients with a body mass index (BMI) > 30 undergoing sleeve gastrectomy. Study design was a prospective, randomized, single-blind clinical trial. Materials and Methods: After obtaining ethics committee approval (Şanlıurfa Harran University Hospital, date: 23 January 2023; decision no: HRÜ/23.02.09) and written/verbal informed consent, 60 patients aged 18–65 years, BMI > 30, ASA II–III scheduled for elective sleeve gastrectomy were included. Patients were randomized into two groups: those receiving bilateral ESPB (Group E, n = 30) and those without ESPB (Group C, n = 30). Demographic characteristics, ASA scores, comorbidities, and surgical duration were recorded. Preoperative venous samples were collected into hemogram (WBC, lymphocyte, neutrophil) and biochemistry tubes (CRP, cortisol, glucose). Standard monitoring (ECG, SpO₂, NIBP) was applied intraoperatively, and vital parameters (HR, MAP) were recorded throughout. Postoperatively, HR, MAP, Numerical Rating Scale (NRS) scores at 0, 2, 4, 8, and 24 h, opioid requirement, patient and surgeon satisfaction (Likert scale), postoperative hemogram and biochemistry values, and side effects or complications were documented. All patients received dexketoprofen as baseline analgesia, with tramadol HCl administered as rescue analgesic. Results: All 60 patients completed the study. There were no statistically significant differences between the groups regarding age, BMI, or surgery duration. Comorbidities were similar between groups. Intraoperative and postoperative HR and MAP values showed no significant differences. Postoperative NRS scores at the 0, 2, 8, and 24 hours were significantly lower in Group E compared with Group C. Both patient and surgeon satisfaction scores were higher in Group E. Rescue analgesic (tramadol HCl) consumption in the postoperative ward was significantly reduced in Group E. Cortisol levels, particularly at the 24th postoperative hour, showed a significantly smaller increase in Group E, suggesting a reduced surgical stress response. No significant differences were found between the groups regarding postoperative side effects or complications. Conclusions: Preoperative bilateral ESPB is an effective component of multimodal analgesia in sleeve gastrectomy. The block significantly reduces postoperative pain intensity, lowers NRS scores, improves patient and surgeon satisfaction, and decreases opioid requirements. Additionally, ESPB appears to attenuate the postoperative stress response, as reflected by smaller increases in cortisol levels. These findings support the routine incorporation of ESPB in perioperative pain management strategies for gastric sleeve surgery. Full article

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology, arising from complex interactions between tumor biology, host factors, and anticancer therapies. Growing evidence indicates that biological sex and gender-related factors modulate both thrombotic risk and clinical expression of venous thromboembolism (VTE) in patients with cancer. In this narrative review, we summarize current epidemiological, biological, and clinical data on sex- and gender-related differences in CAT across solid and hematologic malignancies. Men generally exhibit a higher overall incidence of VTE, whereas women may experience earlier, treatment-associated thrombotic events, with variability according to cancer type, stage, and therapy. Biological factors linked to coagulation and inflammation differ between sexes and may contribute to these patterns, although mechanistic evidence remains incomplete. Sex-related disparities also emerge in treatment-associated complications, including bleeding risk and abnormal uterine bleeding in anticoagulated women of reproductive age. In contrast, evidence for sex differences in oncohematology-associated thrombosis is limited and inconsistent. Gender-related inequalities in clinical trial participation further constrain the interpretation of available data. Overall, current evidence supports sex as a clinically relevant modifier of CAT risk, underscoring the need for systematic sex- and gender-informed research, to improve mechanistic understanding, and sex-stratified reporting to advance precision medicine in thrombosis and oncology. Full article

Hepatic encephalopathy is a severe complication of liver failure, traditionally investigated through brain–liver interactions; however, the involvement of extrahepatic organs remains poorly understood. This study examined splenic histopathological changes in a mouse model of acute hepatic encephalopathy induced by ammonium acetate administration, focusing on iron metabolism and macrophage activation. Although conventional hematoxylin and eosin staining revealed no overt structural abnormalities, unstained spleen sections demonstrated abundant black deposits, predominantly in the red pulp. Prussian blue staining confirmed a significant increase in hemosiderin-positive cells; however, a subset of black deposits was iron-negative. Immunohistochemical analyses revealed that these iron-negative pigments were localized within F4/80-positive macrophages and colocalized with heme oxygenase-1 (HO-1), suggesting enhanced heme degradation. Ultrastructural observations further identified electron-dense granules consistent with hematin accumulation in splenic macrophages. Hematological analyses revealed significant reductions in red blood cell count and hemoglobin levels, indicating accelerated erythrocyte destruction. Collectively, these findings demonstrate that acute hepatic encephalopathy induces splenic macrophage activation, accompanied by disordered iron metabolism and hematin accumulation. This study highlights the spleen as a previously underappreciated extrahepatic organ involved in the pathophysiology of hepatic encephalopathy and suggests that splenic heme–iron handling may represent a novel therapeutic target. Full article

Background: Pediatric-onset Evans syndrome (pES) is a rare autoimmune disorder defined by the coexistence or sequential development of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), frequently accompanied by autoimmune neutropenia (AIN) and characterized by a relapsing, multilineage course. Increasing evidence suggests that pES may represent a broader immune dysregulation phenotype rather than an isolated hematologic disorder. Methods: We conducted a retrospective, single-center study of children diagnosed with pES and followed for up to 13 years at a tertiary referral center. Clinical data regarding hematologic evolution, extra-hematological immunopathological manifestations, treatment requirements, infectious complications, and genetic findings were analyzed descriptively. Results: Six children (4 males) were included, with a median age at first cytopenia of 7 years (range 3–15) and a median follow-up of 8 years (range 1–13). ITP preceded AIHA in 3/6 patients (50%), one patient (16.7%) developed AIHA first, and two (33.3%) showed partial or evolving multilineage disease with DAT positivity prior to overt hemolysis. AIN occurred in 3/6 patients (50%). Extra-hematological immunopathological manifestations occurred in 5/6 patients (83.3%), with two (33.3%) developing more than one. Second-line therapy was required in 3/6 patients (50%). Infectious episodes occurred in 83.3% of patients, predominantly viral or mild bacterial infections, with no life-threatening events. Whole-exome sequencing performed in three patients identified a heterozygous TNFAIP3 variant of uncertain significance in one case; no pathogenic variants were detected. Conclusions: pES demonstrates clinical heterogeneity, frequent multilineage cytopenia, and substantial extra-hematological immune involvement. Multisystem manifestations may be associated with increased treatment burden. Long-term multidisciplinary monitoring and cautious interpretation of genetic findings are essential for individualized pediatric care. Full article