Search Results (1,026)

Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m²), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks. Full article

Background and Clinical Significance: Obstructive sleep apnea (OSA) is a common comorbidity in patients with cardiac and metabolic disorders. The coexistence of central sleep apnea with Cheyne–Stokes breathing (CSA-CSB) in heart failure patients, especially those with preserved ejection fraction (HFpEF), represents a diagnostic and therapeutic challenge. Data on continuous positive airway pressure (CPAP) failure and successful adaptation to servo-ventilation (ASV) in the context of complex comorbidities remain limited. Case Presentation: We present the case of a 74-year-old male with a history of type 2 diabetes mellitus, paroxysmal atrial fibrillation, HFpEF, essential hypertension, and bladder carcinoma. He was referred for pre-operative OSA screening, reporting excessive daytime sleepiness, insomnia, and witnessed apneas. Initial respiratory polygraphy revealed severe sleep-disordered breathing with dominant CSA-CSB and moderate OSA. Laboratory investigations also revealed severe iron-deficiency anemia, which was managed with parenteral iron supplementation. The patient underwent CPAP titration, which led to modest improvement and residual high apnea–hypopnea index (AHI). After persistent symptoms and an inadequate CPAP response, an ASV device was initiated with significant clinical and respiratory improvement, demonstrating normalization of hypoxic burden and optimal adherence. Conclusions: CSA-CSB in HFpEF patients with anemia poses unique therapeutic difficulties. This case highlights the importance of individualized diagnostic and therapeutic strategies, including transitioning to ASV in CPAP-refractory cases, which can lead to improved adherence, reduced hypoxia, and better overall outcomes in high-risk patients. Full article

Background/Objectives: The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand crosslinks and maintenance of genomic stability. Germline loss of FA pathway function in the inherited Fanconi anemia syndrome leads to increased DNA damage and a range of clinical phenotypes, including a heightened risk of head and neck squamous cell carcinoma (HNSCC). Non-synonymous FA gene mutations are also observed in up to 20% of sporadic HNSCCs. The mechanistic target of rapamycin (mTOR) is known to stimulate cell growth, anabolic metabolism including protein synthesis, and survival following genotoxic stress. Methods/Results: Here, we demonstrate that FA− deficient (FA−) HNSCC cells exhibit elevated intracellular amino acid levels, increased total protein content, and an increase in protein synthesis indicative of enhanced translation. These changes are accompanied by hyperactivation of the mTOR effectors translation initiation factor 4E Binding Protein 1 (4E-BP1) and ribosomal protein S6. Treatment with the mTOR inhibitor rapamycin reduced the phosphorylation of these targets and blocked translation specifically in FA− cells but not in their isogenic FA− proficient (FA+) counterparts. Rapamycin-mediated mTOR inhibition sensitized FA− but not FA+ cells to rapamycin under nutrient stress, supporting a therapeutic metabolism-based vulnerability in FA− cancer cells. Conclusions: These findings uncover a novel role for the FA pathway in suppressing mTOR signaling and identify mTOR inhibition as a potential strategy for targeting FA− HNSCCs. Full article

Background/Objectives: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia exhibiting 90% mortality without prompt treatment. The aim of this study was to investigate the association of therapeutic plasma exchange (TPE)-treated TTP in end-stage renal disease (ESRD) patients with mortality, demographics, and clinical comorbidities. We queried the United States Renal Data System for ESRD patients starting dialysis between 1 January 2005 and 31 December 2018, using International Classification of Diseases (ICD)-9 and ICD-10 codes for thrombotic microangiopathy, with a TPE procedure code entered within 7 days. Methods: Cox proportional hazards models were used to assess mortality, adjusting for demographic and clinical factors. Results: Among 1,155,136 patients, increased age [adjusted odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.94–0.96]; black race (OR = 0.67, CI: 0.51–0.89); and Hispanic ethnicity (OR = 0.43, CI: 0.28–0.66) were associated with a lower risk of TPE-treated TTP diagnosis, whereas female sex (OR = 1.59, CI: 1.25–2.02) and tobacco use (OR = 2.08, CI: 1.58–2.75) had a higher risk. A claim for TPE-treated TTP carried a lower risk of death (adjusted hazard ratio = 0.024, CI: 0.021–0.028). Female sex, black race, Hispanic ethnicity, and hypothyroidism were also associated with decreased all-cause mortality. Conclusions: These findings suggest that ESRD patients with TPE-treated TTP are significantly protected from mortality compared with ESRD patients without this diagnosis. Full article

Background/Objectives: Pica, the compulsive ingestion of non-nutritive substances, has long been observed in patients with iron deficiency anemia (IDA). This behavior is particularly noted in adults, including pregnant women, and poses both diagnostic and management challenges. We conducted a review of studies from the past decade to evaluate the epidemiology and nature of pica in adult IDA patients and the outcome of various treatment strategies on anemia and pica behaviors. Methods: We searched PubMed, Scopus, and Cochrane Library for peer-reviewed articles (including observational studies, clinical trials, and reviews) published in English between 2015 and 2025. Inclusion criteria targeted studies of adult populations with IDA that reported on pica prevalence, characteristics, or treatment outcomes. We also reviewed clinical guidelines and meta-analyses on IDA treatment in adults for recommended management approaches. Results: Pica was found to be a prevalent symptom among individuals with IDA, but was readily treatable with appropriate iron deficiency treatment. Among treatment options, both oral and parenteral iron supplementation were found to be effective in resolving iron deficiency and pica. Choice of treatment depends on tolerance to oral iron, speed of resolution required, and comorbid conditions. Conclusions: Pica is closely intertwined with IDA; our review highlighted the prevalence of pica among individuals with IDA, which serves as both a clinical clue to underlying anemia and a potential source of complications. Crucially, the treatment of IDA is also effective for pica. We recommend oral iron therapy on alternate-day dosing as first-line therapy to minimize side effects, alongside dietary optimization. If IDA and pica are resistant to oral iron supplementation or oral iron cannot be tolerated, parenteral iron therapy can be considered. Full article

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG⁺/C3d⁺) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R > 10,000 pg/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein–Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6/IFN-γ overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality. Full article

The precipitation of cryoglobulins, serum immunoglobulins, below 37 °C defines the clinical cryoglobulinemic syndrome, a systemic vasculitis usually characterized by purpura, weakness, and arthralgia. In most cases, this condition is associated with chronic infection by the hepatitis C virus (HCV) and can evolve into B-cell dysregulation and malignancies. The current literature on non-HCV-associated cryoglobulinemia is very limited, and little is known about the immunological and serological profile of affected patients. The cryoglobulinemic syndrome not associated with HCV infection is often found concomitantly with other infections, autoimmune diseases, and B-cell lymphoproliferative disorders. The cryoprecipitation of fibrinogen has been described as a rare disorder, perhaps underestimated and not fully understood, causing thrombotic occlusion and ischemia in different rheumatic disorders. Cold temperature plays a pathogenetic role in autoimmune hemolytic anemias, in which the presence of cold agglutinins produced by B cells at the lymphoplasmacytic cell stage may promote agglutination of red blood cells in the coldest parts of the circulation, even at mild room temperatures, undergoing hemolysis. Laboratory methods for the detection and quantification of cryoproteins are downright critical, and their concurrent detection is pivotal for the diagnosis. In this review, we summarize the clinical involvement of cryoglobulins, cryofibrinogen, and cold agglutinins in non-HCV autoimmune diseases, underlining the crucial steps of the most employed analytic methods. Full article

Patient blood management (PBM) is a multidisciplinary approach aimed at improving patient outcomes through targeted anemia treatment that minimizes allogeneic blood transfusions, employs blood conservation techniques, and avoids inappropriate use of blood product transfusions. Viscoelastic testing (VET) techniques, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), have led to significant advancements in PBM. These techniques offer real-time whole-blood assessment of hemostatic function. This provides the clinician with a more complete hemostasis perspective compared to that provided by conventional coagulation tests (CCTs), such as the prothrombin time (PT) and the activated partial thromboplastin time (aPTT), which only assess plasma-based coagulation. VET does this by mapping the complex processes of clot formation, stability, and breakdown (i.e., fibrinolysis). As a result of real-time whole-blood coagulation assessment during hemorrhage, hemostasis can be achieved through targeted transfusion therapy. This approach helps fulfill an objective of PBM by helping to reduce unnecessary transfusions. However, challenges remain that limit broader adoption of VET, particularly in hospital settings. Of these, standardization and the high cost of the devices are those that are faced the most. This discussion highlights the potential of VET application in PBM to guide blood-clotting therapies and improve outcomes in patients with coagulopathies from various causes that result in hemorrhage. Another aim of this discussion is to highlight the limitations of implementing these technologies so that appropriate measures can be taken toward their wider integration into clinical use. Full article

Background and Objectives: Thrombocytopenia and hemolytic anemia are common but non-criteria manifestations of antiphospholipid syndrome (APS). However, their relationship with specific immunological profiles remains poorly characterized. This study aimed to evaluate these hematologic manifestations and identify their serological associations in patients with APS. Materials and Methods: We retrospectively reviewed 346 patients diagnosed with APS. Demographic, clinical, and laboratory characteristics were analyzed. Logistic regression was used to identify risk factors associated with hemolytic anemia. Results: The mean age was 47.1 ± 13.1 years, and 71.7% were female. Thrombocytopenia was present in 34.5%, and hemolytic anemia in 16.5% of patients. Lupus anticoagulant (LAC) was the most common antibody (66.8%). In univariate analysis, hemolytic anemia was significantly associated with LAC positivity (OR 4.216, 95% CI: 2.326–7.640, p < 0.001), anticardiolipin IgG (OR 7.170, p = 0.007), triple positivity (OR 3.638, p = 0.002), and diabetes mellitus (OR 2.084, p = 0.007). DIAPS showed a protective trend (OR 0.547, p = 0.002). In multivariate analysis, only LAC remained an independent risk factor for hemolytic anemia (adjusted OR 3.557, 95% CI: 1.355–9.335, p = 0.003). Conclusions: LAC positivity is an independent predictor of hemolytic anemia in APS. These findings suggest a distinct immunologic profile among patients with hematologic involvement and highlight the need for further investigation into non-criteria manifestations. Full article

Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including apoptosis and autophagy, but its cytotoxicity to RBCs has not been investigated. Colorimetric and fluorometric techniques were used to assess eryptosis and hemolysis in control and CEP-treated RBCs. Cells were labeled with Fluo4/AM and annexin-V-FITC to measure Ca²⁺ and phosphatidylserine (PS) exposure, respectively. Forward scatter (FSC) was detected to estimate cell size, and extracellular hemoglobin along with lactate dehydrogenase and aspartate transaminase activities were assayed to quantify hemolysis. Physiological manipulation of the extracellular milieu and various signaling inhibitors were tested to dissect the underlying mechanisms of CEP-induced RBC death. CEP increased PS exposure and hemolysis indices and decreased FSC in a concentration-dependent manner with prominent membrane blebbing. Although no Ca²⁺ elevation was detected, chelation of intracellular Ca²⁺ by BAPTA-AM reduced hemolysis. Whereas SB203580, D4476, acetylsalicylic acid, necrosulfonamide, and melatonin inhibited both PS exposure and hemolysis, staurosporin, L-NAME, ascorbate, caffeine, adenine, and guanosine only prevented hemolysis. Interestingly, sucrose had a unique dual effect by exacerbating PS exposure and reversing hemolysis. Of note, blocking KCl efflux augmented PS exposure while aggravating hemolysis only under Ca²⁺-depleted conditions. CEP activates Ca²⁺-independent pathways to promote eryptosis and hemolysis. The complex cytotoxic profile of CEP can be mitigated by targeting the identified modulatory pathways to potentiate its anticancer efficacy. Full article

Despite being highly prevalent among women of reproductive age, the psychological dimensions of iron deficiency anemia (IDA) often go unrecognized. While the hematological consequences of IDA are well established, emerging evidence suggests that it may also adversely affect emotional processing, mental health, and overall quality of life. This study aimed to systematically assess levels of alexithymia, anxiety, depressive symptoms, and quality of life in women diagnosed with IDA compared to age-matched healthy controls. A total of 151 women with confirmed IDA and 150 healthy controls were recruited. Participants underwent laboratory testing and completed validated questionnaires, including the Beck Depression Scale (BDS), State-Trait Anxiety Inventory (STAI), WHOQOL-BREF-TR, and the Toronto Alexithymia Scale (TAS-20). Women with IDA demonstrated significantly higher alexithymia and anxiety scores and lower quality of life compared to controls. Within the IDA group, probable alexithymia was associated with more severe anemia parameters and poorer psychological outcomes. These findings indicate that IDA is not only a hematological disorder but also one with a substantial psychological burden. Recognizing and addressing these psychological dimensions in clinical practice is critical. A multidisciplinary management approach that integrates both hematological treatment and mental health interventions may be essential to improve overall patient outcomes among women with IDA. Full article

Iron deficiency (ID) is the most prevalent micronutrient deficiency globally, affecting approximately one in four individuals, with a particularly high burden among children, women of reproductive age, and populations in low- and middle-income countries. It contributes significantly to the global burden of disease, with consequences ranging from impaired cognitive and motor development in children to increased risks during pregnancy, including low birth weight, preterm delivery, and maternal mortality, as well as reduced physical performance and quality of life in adults. ID often precedes iron deficiency anemia (IDA), though clinical and functional impairments—such as cognitive deficits, immune dysfunction, and fatigue—can occur even in the absence of anemia. Despite its widespread nature, challenges remain in precisely defining, diagnosing, and treating ID effectively. Advances in diagnostic tools allow for earlier detection, while novel therapeutic strategies, including updated oral dosing regimens and modern intravenous iron formulations, offer improved efficacy and tolerability. These approaches are particularly valuable in minimizing gastrointestinal side effects and enhancing patient adherence. This review is based on a comprehensive literature search conducted primarily through PubMed and Scopus, emphasizing studies published within the past 10–15 years. It is thematically structured to explore the epidemiology, health consequences, diagnostic complexities, and therapeutic developments related to ID. It highlights the multifactorial nature of ID and underscores the urgent need for early identification, targeted interventions, and updated clinical guidelines to reduce the long-term health and societal impacts of this preventable and treatable condition. Full article

Background: Fanconi Anemia (FA) is a rare disorder, characterized by chromosomal instability, congenital abnormalities, progressive bone marrow failure, and predisposition to cancer. FA is caused by pathogenic variants in any of the 23 (FANCA-FANCY) linked genes. Procedure: Retrospective analysis of 13 FA patients with a causative variant was performed. Patients (6 boys and 7 girls) aged from 9 to 26 years old, (mean age of 7.3 years), at diagnosis. Results: Phenotype evaluation demonstrated in 11/13 patients’ congenital anomalies, with pigmentary changes and short stature, present in 90% of cases. Hematological abnormalities were present in 10/11 patients, with thrombocytopenia being the prominent finding. Genetic analysis for the most common complementation group FA-A revealed that 12/13 patients belonged to this group and only one patient was found to be FA-E. Exon deletions, single nucleotide variations, and duplications were identified. Familial patterns, due to consanguinity, were evident in one case. Twelve patients underwent hematopoietic stem cell transplantation (HSCT), with variable pre-HSCT supportive treatments. Post-HSCT data showed that 9 out of 10 patients for whom follow up data was available, survived for a median time of 5.4 years. Complications like acute graft-versus-host disease were noted. Conclusions: Our study highlights the importance of genotype towards tailored monitoring for children and families with FA. Full article

Belzutifan is a hypoxia-inducible factor-2α (HIF-2α) inhibitor that received FDA approval in 2021 for treating cancers resulting from von Hippel-Lindau (VHL) disease, including clear cell renal cell carcinoma (ccRCC), followed by approval in 2023 for sporadic ccRCC that has progressed through multiple lines of therapy. HIF-2α is a promising drug target, as VHL is commonly inactivated in ccRCC, which results in HIF-2α-mediated signaling that is considered central to tumorigenesis. Belzutifan has demonstrated efficacy in clinical trials in the first-line and subsequent line settings, and in combination with tyrosine kinase inhibitors. Despite being overall well tolerated, belzutifan has a distinct safety profile because of its unique mechanism of action. Anemia was the most common adverse event observed in clinical trials and is considered an on-target effect. Hypoxia is also frequently observed and commonly results in dose reductions, treatment discontinuation, and supplemental oxygen use. This review summarizes the rates of hypoxia seen in clinical trials of belzutifan in ccRCC. As the cause of hypoxia is not well understood, this review also discusses possible mechanisms of hypoxia based on preclinical studies of the HIF pathway and HIF-2α inhibitors. Finally, this review proposes monitoring and management recommendations for clinicians prescribing belzutifan to ccRCC patients. Full article

(1) Background: Wilms’ tumor (WT) is the most common pediatric renal malignancy. Although survival outcomes have improved with multimodal therapy, the optimal sequence of surgery and chemotherapy remains debated, particularly in resource-limited settings. This study evaluates the effect of treatment strategy on surgical complications and survival, utilizing two decades of data from Thai tertiary centers. (2) Methods: A retrospective cohort study was conducted on 83 children who underwent radical nephrectomy for WT between 2002 and 2022 at two university hospitals in Thailand. Patients were grouped by treatment protocol: primary nephrectomy (n = 59) or neoadjuvant chemotherapy (n = 24). Clinical, pathological, operative, and follow-up data were analyzed to identify predictors of surgical complications and survival. (3) Results: Short-term postoperative complications occurred in 16.9% of cases, more frequently in males and in patients with hypoalbuminemia, anemia, or large tumors. Estimated blood loss greater than 5 mL/kg, serum albumin less than 3.5 g/dL, and hemoglobin lower than 10 g/dL were independent predictors of complications. The five-year overall survival (OS) and progression-free survival (PFS) rates were 82.4% and 68.1%, respectively. Patients with unfavorable histology or short-term complications experienced significantly poorer OS. Neoadjuvant chemotherapy was associated with increased nutritional compromise and a trend toward higher complication rates, although it was not directly linked to inferior OS. (4) Conclusions: In pediatric WT, the perioperative nutritional and hematologic statuses significantly influence surgical outcomes. While neoadjuvant chemotherapy may assist in tumor downsizing, it might also compromise surgical fitness. Customized preoperative risk assessment and nutritional support can enhance outcomes, particularly in low- and middle-income countries. Full article